Search Results (1,846)

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging. Full article

Background/Objectives: This study aimed to investigate the protective effects and underlying molecular mechanisms of cyanidin-3-O-glucoside (C3G) against cognitive impairment in aging mice induced by D-galactose (D-gal). Methods: Spatial learning and memory, hippocampal histopathology, oxidative stress and inflammatory markers, as well as underlying regulatory pathways, were assessed in C3G-treated D-galactose-induced aging mice via Morris water maze, H&E staining, biochemical assays, qRT-PCR and Western blot. Results: Results showed C3G improved cognitive function by reducing escape latency and increasing target quadrant time along with platform crossings, while also alleviating hippocampal damage. It dose-dependently enhanced total antioxidant capacity and activities of key antioxidant enzymes (GSH-Px and SOD), reduced malondialdehyde, and inhibited pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). At the molecular level, C3G treatment was associated with changes in the Nrf2 and NF-κB pathways at mRNA and protein levels. It enhanced Nrf2 expression and reduced Keap1 expression, accompanied by upregulated mRNA levels of Nqo1 and Hmox1. Meanwhile, C3G decreased IKKβ and p65 protein expression and downregulated mRNA levels of Ikbkb, Nfkb1, and RelA. The combined contribution of these pathways in reducing ROS and inflammation may constitute the molecular basis underlying the neuroprotective effects of C3G. Conclusions: C3G alleviates cognitive dysfunction and brain damage in D-gal-induced aging mice, with effects associated with modulation of Nrf2 and NF-κB pathways. These findings offer preliminary insights for its dietary application in brain aging intervention. Full article

D-allulose is a rare low-calorie sugar with considerable health benefits and industrial potential. Compared with chemical synthesis and free enzyme catalysis, microbial production using engineered cells offers a low-cost and highly stable solution. Therefore, we investigated the reaction pathway underlying the synthesis of D-allulose from D-glucose. Specifically, the enhancement of glucose isomerase-catalyzed reactions and their role in D-allulose synthesis were evaluated. First, a mutant strain with significantly increased glucose isomerase from Anoxybacillus kamchatkensis G10 (AGGI) expression was obtained through ultraviolet mutagenesis combined with high-throughput flow cytometry. A 4.55-fold increase in AGGI activity and a D-fructose conversion yield of 51.2% were obtained. A dual-enzyme pathway was subsequently constructed by co-expressing AGGI and D-allulose 3-epimerase (DAEase) in the optimized host. After balancing the catalytic requirements of both enzymes through optimization of reaction conditions, CRISPR-associated transposase was employed to efficiently integrate the glucose transporter gene galP into the genome, further enhancing substrate supply. The final engineered Escherichia coli strain achieved a D-allulose conversion rate of 15% from 20 g/L D-glucose. This demonstrates the crucial role of glucose isomerase in microbial D-allulose production and advances the optimization and development of D-allulose synthesis strategies using D-glucose as a substrate. Full article

The sodium–galactose cotransporter from Vibrio parahaemolyticus (vSGLT) was first cloned and functionally characterized by the laboratory of Ernest M. Wright in 2000, establishing a one-to-one Na⁺:sugar coupling stoichiometry and pioneering a bacterial model for human SGLTs. Here, we revisit vSGLT using solid-supported membrane electrophysiology on the Nanion SURFE²R N1, providing a modern, non-radioactive kinetic analysis of Na⁺-coupled sugar transport. Rapid transient currents were observed upon substrate application to proteoliposomes containing purified vSGLT. D-galactose elicited the largest Na⁺-dependent responses, followed by D-glucose and D-fucose, while no transport was observed in K⁺-based solutions. Apparent kinetic parameters recapitulate the overall trends observed in the original radiolabeled uptake assays, with K_m(Na⁺) ≈ 18 mM and K_m(gal) ≈ 9.8 mM. These findings validate the SURFE²R N1 SSM system as a quantitative, label-free method for Na⁺ symport characterization and demonstrate that vSGLT retains its canonical substrate selectivity and stoichiometry. Full article

The α-gal epitope is synthesized in non-primate mammals and New-World monkeys by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT), encoded by the GGTA1 gene. Ancestral Old-World monkeys and apes synthesizing α-gal epitopes underwent extinction 20–30 million years ago. Their mutated offspring, with the inactivated GGTA1 gene, survived and produced the natural anti-Gal antibody, specifically binding α-gal epitopes. Anti-Gal protected the surviving offspring from lethal viruses presenting α-gal epitopes, which killed α-gal-synthesizing parental primates. Anti-Gal constitutes ~1% of human immunoglobulins and is also produced in Old-World monkeys and apes. α-Gal epitopes can serve as therapeutic agents in several clinical disciplines: 1. Cancer immunotherapy: Engineering cancer cells to express α-gal epitopes results in anti-Gal binding to these cells and localized activation of the complement system that kills these cancer cells and recruits the antigen-presenting cells (APCs) dendritic cells and macrophages. Anti-Gal bound to cancer cells targets them for robust uptake by APCs, which process internalized tumor antigens (TAs) and transport them to lymph nodes for activation of cytotoxic T-cells. These T-cells kill TA-presenting metastatic tumor cells. Clinical trials demonstrated that such engineering is achieved by intra-tumoral injection of α-gal glycolipids, the use of recombinant α1,3GT, or the use of oncolytic viruses containing the GGTA1 gene. 2. Viral vaccines: Inactivated whole-virus vaccines presenting α-gal epitopes bind anti-Gal, which targets them for extensive uptake by APCs, thereby increasing their immunogenicity by ~100-fold. 3. Injured-tissue regeneration: Anti-Gal binding to α-gal-presenting nanoparticles administered to wounds, into the post-myocardial infarction (MI) injured myocardium and into injured spinal cord, activates the complement system that recruits pro-regenerative macrophages, which orchestrate regeneration by recruiting stem cells and the secretion of pro-regenerative cytokines. All these findings suggest that α-gal/anti-Gal antibody interaction can serve as a novel therapeutic approach, applicable to various clinical settings. Full article

Background: Aging-related cognitive decline is closely associated with microglial senescence and the resulting chronic neuroinflammation. Emerging evidence identifies the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway as a pivotal innate immune signaling pathway linking DNA damage to cellular senescence and the senescence-associated secretory phenotype (SASP), particularly in microglia. Targeting the formation or selective clearance of senescent cells thus emerges as a promising therapeutic approach to ameliorate cognitive dysfunction. Resveratrol has shown promise in modulating immune response and exerting anti-aging effects. However, the therapeutic potential and underlying mechanisms of resveratrol in mitigating age-associated microglial senescence and cognitive decline are not fully understood. Methods: In the present study, we employed a well-established murine model of accelerated aging induced by chronic intraperitoneal injection of D-galactose (D-gal) to elicit pronounced senescence-associated phenotypes and neuroinflammation. Resveratrol was administered via oral gavage daily for three weeks following D-gal injections. Behavioral assays were conducted to assess cognitive performance. Immunohistochemistry, quantitative PCR, and Western blot analyses were used to evaluate markers of cellular senescence, microglial activation and pro-inflammatory cytokine expression. In addition, in vitro assays in cultured microglia coupled with RNA sequencing were used to investigate the downstream signaling events following resveratrol treatment. Results: Chronic D-gal treatment induced significant cognitive impairment, enhanced microglial activation, elevated pro-inflammatory cytokine levels, and increased markers of cellular senescence in the brain. Resveratrol administration remarkably attenuated these effects, as evidenced by improved memory performance, reduced microglial senescence markers, and suppressed expression of Cxcl-10, Il-1β, and other SASP factors. Mechanistically, unbiased transcriptomic analysis revealed that the cGAS-STING signaling and neuroinflammation pathways were prominently dysregulated with double-stranded DNA-induced cellular senescence, which was effectively normalized by resveratrol in cultured microglia. Interestingly, resveratrol inhibited the translocation of STING from the endoplasmic reticulum to the Golgi apparatus and suppressed phosphorylation of TBK1, thereby blocking downstream STING signaling. Conclusions: These findings demonstrate that resveratrol mitigates microglial senescence and neuroinflammation and preserves cognitive function in D-gal-induced aging mice, at least partly through modulation of the cGAS-STING signaling. Therefore, targeting this pathway may represent a promising therapeutic strategy for age-related neuroinflammatory and cognitive disorders. Full article

Background: Endometriosis is a complex condition that impairs women’s quality of life and reproductive potential. Its diagnosis remains significant challenge for clinicians. The aim of the study was to investigate cancer-like immune evasion mechanisms in endometriosis and to develop a novel diagnostic model using machine learning. Methods: In this study, we measured the levels of soluble forms of the following immune markers in blood serum and peritoneal fluid (PF): sMICA, sMICB, sEng, sCD25, s4-1BB, sB7.2, sCTLA-4, sPD-L1, sPD-1, sTIM-3, sLAG-3, and sGal-9. Results: sMICB levels in PF differed across endometriosis stages and were higher in patients with endometriosis-associated adhesions. sMICA levels in PF were elevated in women with endometriosis-associated infertility. The disease severity was inversely correlated with serum sB7.2 levels and positively correlated with serum sTIM-3 levels. A logistic regression model achieved an accuracy = 0.79, AUC = 0.94, and F1-score = 0.88, whereas XGBoost performed better with accuracy = 0.94, AUC = 0.95, and F1-score = 0.96. The key predictive features in both models were sMICB serum level and patients’ pain score. Conclusions: Our results demonstrate the potential role of sMICA and sMICB shedding in endometriosis and present a novel, minimally invasive diagnostic approach. Full article

Inflammation and cellular senescence are fundamental contributors to aging and neurodegenerative disorders. Marine algae are increasingly acknowledged for their content of bioactive molecules capable of influencing inflammation and cellular aging. In this research, we examined the capacity of Sargassum siliquastrum aqueous extract (SSE) to counteract inflammatory responses in RAW 264.7 macrophages stimulated by lipopolysaccharide, as well as aging-related changes in a mouse model of D-galactose (D-gal)-induced aging. SSE treatment markedly lowered levels of pro-inflammatory cytokines, prostaglandin E₂, and nitric oxide. Furthermore, SSE attenuated the transcriptional activities of nuclear factor kappa-B (NF-κB) and activator protein 1, while modulating protein expression associated with NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in RAW 264.7 cells. In vivo, SSE reduced the phosphorylation levels of MAPKs in the hippocampus of D-gal-treated mice. Additionally, SSE modulated the expression of genes associated with cellular senescence and inflammation in the hippocampus and cerebral cortex. However, the apparent molecular effects were not accompanied by significant improvement in passive avoidance performance, which showed only a non-significant trend between the model control and SSE-administrated groups. Collectively, these findings suggest that SSE exerts anti-inflammatory effects in vitro and provide preliminary evidence of its potential to modulate D-gal-induced aging-related neuroinflammatory changes in mice. Full article

H-NS (histone-like nucleoid-structuring protein) is a global regulator affecting diverse bacterial processes. This study aimed to elucidate the regulatory role of H-NS in the virulence of Klebsiella pneumoniae (K. pneumoniae), particularly in relation to capsule synthesis and anchoring. A clinically isolated ST11-KL64 strain of K. pneumoniae FK6741 with low virulence was used. The role of H-NS was evaluated using colony morphology, the string test, viscosity measurement, capsule quantification, transmission electron microscopy, growth curve, biofilm assay, a mouse infection model, transcriptomic analysis, and RT-qPCR. Deletion of hns converted FK6741 into a hypermucoid phenotype in the positive string test; capsule quantification and transmission electron microscopy (TEM) showed increased polysaccharide chains but a reduced and tightly bound capsule. The mutant was initially found to grow slowly but formed stronger biofilms. In vivo, it displayed reduced virulence but induced stronger inflammation. Molecular assays revealed upregulation of capsule synthesis genes (galF, wzi, wcaJ, and wzc) and downregulation of wabG, which is involved in capsule anchoring. H-NS represses capsule synthesis genes, limiting capsule formation in K. pneumoniae. In contrast, loss of H-NS downregulates wabG, a key gene involved in GalA-mediated capsule anchoring, resulting in unstable surface attachment and loss of capsular polysaccharides. Consequently, these unanchored polysaccharides fail to confer effective protection, resulting in reduced bacterial virulence. Full article

Background/Objectives: Saponins have recently emerged as promising natural products that enhance toxin-based anticancer therapeutics by improving cytosol uptake. This study aimed to identify structurally defined novel natural saponins and evaluate their ability to enhance anticancer cytotoxicity. Methods: The roots of Saponaria officinalis L. were extracted with aqueous ethanol and purified by silica gel column chromatography and reverse-phase high-performance liquid chromatography (RP HPLC). The structures of new saponins were elucidated by NMR spectroscopy and mass spectrometry. Biological activity was assessed in vitro using multiple cancer cell lines. Results: Two pairs of structurally defined pure saponins were obtained: SO1406 and SO1448, and SO1684 and SO1726. Structural elucidation revealed that SO1684 and SO1726 share the core structure 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Qui-(1→4)-[β-D-Xyl-(1→3)-β-D-Xyl-(1→4)]-α-L-Rha-(1→2)-β-D-Fuc, with SO1684 acetylated at Qui O-4 and SO1726 bearing additional acetylation at Qui O-3. Deacetylation of either SO1684 or SO1726 afforded a known saponin SA1641 isolated from Saponinum album (Merck). Similarly, SO1406 and SO1448 were identified as 3-O-β-D-Gal-(1→2)-[β-D-Xyl-(1→3)]-β-D-GlcA-gypsogenin-28-O-β-D-Xyl-(1→4)-α-L-Rha-(1→2)-β-D-Fuc derivatives, each acetylated at Fuc O-4, with SO1448 containing an additional acetyl group at Fuc O-3. Among the isolated compounds, SO1684 is a known saponin and SO1406 exhibited the most pronounced biological activity, significantly enhancing the cytotoxicity of the ribosome-inactivating protein saporin (SAP) in the MDA-MB231 (triple-negative breast cancer) cell line. Conclusions: SO1406 demonstrates strong cytotoxicity-enhancing activity, highlighting the significant potential of structurally defined natural saponins to advance intracellular delivery and improve the therapeutic performance of protein-based anticancer agents. Full article

Invariant natural killer T (iNKT) cells are a unique lymphocyte subset that bridge innate and adaptive immunity through recognition of glycolipid antigens presented by CD1d. Upon activation by ligands such as α-galactosylceramide (α-GalCer), iNKT cells rapidly secrete cytokines, including IFN-γ and TNF-α, thereby activating dendritic cells, natural killer (NK) cells, and cytotoxic T lymphocytes (CTLs) to promote antitumor immunity. Despite their therapeutic promise, clinical translation has been limited by rapid α-GalCer clearance, induction of iNKT cell anergy following repeated stimulation, and the immunosuppressive tumor microenvironment (TME). Recent advances in lipid-engineered nanoparticle systems offer solutions to these challenges by improving ligand stability, enhancing antigen-presenting cell targeting, and enabling controlled release that sustains Th1-biased activation while reducing anergy. Liposomal and polymer-based nano-formulations enhance bioavailability and promote more durable IFN-γ-mediated responses. In parallel, chimeric antigen receptor (CAR)-engineered iNKT cells provide antigen-specific tumor targeting while preserving intrinsic CD1d-restricted immunomodulatory functions, demonstrating encouraging safety and efficacy in early-phase studies. Combination strategies further strengthen iNKT-based immunotherapy. Integration with chemotherapy, immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4, and cytokine support enhances effector activation, counteracts TME-induced suppression, and improves therapeutic outcomes. However, challenges remain, including optimization of dosing, control of off-target immune activation, scalable manufacturing, and long-term safety evaluation. Collectively, the convergence of nanotechnology, CAR engineering, and rational combination approaches establishes iNKT cell-based therapy as a promising next-generation immunotherapeutic strategy. Continued refinement of delivery systems, genetic engineering platforms, and translational protocols may enable durable immune reprogramming and improved clinical outcomes in resistant and immunosuppressive cancers. Full article

Gastrointestinal acute graft-versus-host disease (GI aGvHD) remains a leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Current diagnostic methods rely on invasive procedures with limited sensitivity. While circulating biomarkers have been proposed, little is known about the local transcriptomic landscape within inflamed GI tissue. We performed integrated profiling of mRNA and microRNA expression in colonoscopically resected GI biopsies from n = 8 HSCT patients, including n = 3 with histologically confirmed GI aGvHD and n = 5 without. Using NanoString nCounter technology, we quantified 770 immune-related mRNAs and 799 mature human microRNAs. Differential expression analysis, pathway enrichment, cell type deconvolution, and machine learning–based biomarker prioritisation were conducted to define disease-specific molecular signatures. GI aGvHD was marked by upregulation of inflammatory genes (e.g., IL1B, IL17RA, HLA-DRA) and immune-regulatory microRNAs (e.g., miR-155-3p, miR-223-3p), alongside downregulation of epithelial and anti-inflammatory markers (ST6GAL1, THBS1, miR-1915-3p, miR-145-5p). Enrichment analyses revealed activation of IL2/STAT5, JAK/STAT3, TCR signalling, and antigen presentation pathways. Machine learning identified LCN2, CXCL13, and miR-1269b as top-ranked biomarker candidates. Cell deconvolution showed increased M0 macrophage and decreased dendritic cell signatures in aGvHD tissue. This is the first study to integrate mRNA and microRNA profiling in GI tissue using NanoString technology to characterise the immune and epithelial transcriptomic landscape of aGvHD. Our findings reveal dysregulated immune pathways, altered myeloid cell populations, and novel biomarker candidates, offering tissue-specific insights into disease pathogenesis and potential diagnostic targets. Larger validation studies and functional assays are warranted to confirm clinical utility. Full article

Lotus leaf provides unique nutritional properties to the traditional Chinese dish Jiao Hua Ji. However, its functional polysaccharides remain inadequately characterized. This study evaluates the physicochemical properties and hypoglycemic effects of lotus leaf polysaccharides in Jiao Hua Ji. Ultrasonic-assisted enzymatic extraction significantly improved the yield of polysaccharides to 10.35 ± 0.39%. The yield of the polysaccharides as well as uronic acid content demonstrated a strong correlation with the bioactivity. FTIR analysis confirmed the characteristic infrared spectral features associated with glucans. Four polysaccharides were purified and characterized as 719 kDa (Glc/Gal/Ara 98.91:0.44:0.65), 1010 kDa (Glc/Gal/Ara 98.43:1.18:0.39), 447 kDa (Glc/Gal/Ara 97.17:2.02:0.82), and 327 kDa (Glc/Gal/Ara 97.54:2.06:0.4). The purified polysaccharides exhibited enhanced inhibition of α-amylase, positively correlating with molecular weight and glucose content. Molecular docking studies revealed that the polysaccharide successfully occupies the hydrophobic pocket of α-amylase through hydrogen bonds, with a low binding energy of −6.548 kcal/mol. Notably, the purified polysaccharide significantly improved glucose utilization by 157.5% without cytotoxicity. This study may provide a foundational basis for the application of Jiao Hua Ji in hypoglycemic dietary intervention. Full article

Background/Objectives: Senescence has been recently described in brain cells following ischemic stroke. The potential of targeting senescence as an effective therapeutic approach in the treatment of ischemic stroke requires further investigation. This study evaluated the effects of the senolytic drug navitoclax after experimental ischemic stroke. Methods: Navitoclax was injected into male young Wistar rats at doses of 10 and 30 mg/kg (i.p.). to evaluate its pharmacokinetics, cerebral levels and potential to cause thrombocytopenia. Subsequently, a second group of rats underwent 60 min of transient middle cerebral artery occlusion (tMCAO). Navitoclax (10 mg/kg, i.p.) or vehicle was injected every other day between days 3 and 13 after tMCAO. Neurofunctional performance, infarct size, and senescence markers were assessed on day 14. Results: Navitoclax (10 mg/kg) administration resulted in a maximum plasma concentration of 0.702 mg/L and half-life of 11.33 h. Additionally, a brain concentration of 0.04 ± 0.02 µg/g was detected. Moderate thrombocytopenia was induced by 10 mg/kg, and to a greater extent by 30 mg/kg. Navitoclax (6 × 10 mg/kg) improved neurofunctional impairment, as indicated by significant decrease by 66% in the total time for the tape removal test, and significantly reduced infarct area by 52% when compared to vehicle. Moreover, navitoclax significantly reduced levels of SA-β-gal (by 80%), lipofuscin (by 91%), and Checkpoint kinase 2 (Chk2; by 69%) in the ischemic hemisphere. Conclusions: Navitoclax protects the brain after ischemic stroke by improving neurofunctional outcome and reducing infarct size, which is associated with reducing senescence markers. Although moderate thrombocytopenia warrants caution, targeting senescence emerges as a promising therapeutic strategy for ischemic stroke. Full article

Differential light shift (DLS) is an important error term that limits the atom interferometer’s measurement precision, especially for the case of the electro-optic modulator (EOM)-based scheme, where multiple laser sidebands exist, and their ratios are hard to control synchronously. This article carried out an experimental and theoretical study on this subject. By conducting long-term gravity measurement, we find that the gravity exhibits drifts of about 13.13 μGal, and is strongly correlated to the Raman laser’s sidebands. A model of the DLS-induced gravity error is established and a DLS compensation method is proposed to suppress the gravity drift to 2.54 μGal. Besides the compensation method, we propose a Dual-Sideband Ratio Locking scheme to more robustly eliminate the gravity measurement drift. By feeding back to both the EOM microwave power and the tapered amplifier’s temperature, this method locks both the ±1 order sideband to a stability level of ${10}^{-5}$, which corresponds to a gravity error of less than 0.1 μGal. Long-term gravity measurement is carried out after the locking method, showing a long-term stability of 1.6 μGal. The proposed methods will benefit the suppression of the DLS effect for high-precision atom interference measurement. Full article