Search Results (1,083)

Background: CDK4/6 inhibitors induce G1/S cell-cycle arrest in bladder cancer; however, adaptive resistance limits their therapeutic efficacy. The role of the m⁶A reader IGF2BP3 in regulating sensitivity to CDK4/6 inhibition remains largely unknown. Methods: Transcriptomic profiling was performed in palbociclib-treated bladder cancer cell lines (T24, RT112, and UMUC-3) to identify m⁶A regulators associated with drug response. The expression and clinical significance of IGF2BP3 were evaluated using The Cancer Genome Atlas (TCGA) data and an independent clinical cohort. Gain- and loss-of-function assays were conducted to investigate the effects of IGF2BP3 on cell proliferation and cell-cycle progression. Mechanistic studies, including RNA-binding, mRNA stability, ubiquitination, and in vivo tumorigenesis assays, were performed to elucidate the underlying regulatory network. Results: IGF2BP3 was identified as the only m⁶A regulator differentially expressed following palbociclib treatment. IGF2BP3 expression was significantly elevated in bladder cancer tissues compared with normal tissues and was associated with poor prognosis and Ki67 positivity. Functionally, IGF2BP3 overexpression (OE) promoted G1/S transition, increased MYC and downstream cell-cycle regulators, and partially rescued palbociclib-induced cell-cycle arrest, whereas IGF2BP3 knockdown (KD) suppressed cell proliferation in an MYC-dependent manner. Mechanistically, IGF2BP3 bound to MYC mRNA in an m⁶A-dependent manner and enhanced its stability. Furthermore, MKRN2 was identified as an E3 ubiquitin ligase that directly interacted with IGF2BP3, promoted its ubiquitination, and facilitated its proteasomal degradation. In vivo, MKRN2 co-overexpression attenuated IGF2BP3-driven tumor growth and synergized with palbociclib to maximally suppress tumor volume, reduce MYC and Ki67 expression, and induce apoptosis. Conclusions: These findings establish the MKRN2–IGF2BP3–MYC axis as a critical regulator of CDK4/6 inhibitor sensitivity in bladder cancer. Targeting IGF2BP3 or enhancing MKRN2 activity may represent a promising strategy to overcome adaptive resistance and improve the therapeutic efficacy of CDK4/6 inhibitors. Full article

Collagen peptides have been widely studied for their beneficial effects on skin health; however, their potential role in hair growth remains insufficiently explored. This study aimed to investigate the effects of orally administered low-molecular-weight fish collagen peptide (SH-GT) on hair regrowth and its underlying mechanisms in a hair-removed C57BL/6J mouse model. Mice were administered SH-GT (100, 300, or 600 mg/kg body weight) or a positive control (Pansidil, 400 mg/kg) daily for 28 days. SH-GT significantly enhanced hair regrowth, as evidenced by the increased hair growth area. Histological analysis revealed increased dermal thickness and visible hair follicle structures in SH-GT-treated groups. At the molecular level, SH-GT upregulated proliferation-related proteins, including PCNA and Cyclin D1, and activated Wnt/β-catenin signaling. In addition, SH-GT enhanced PI3K/Akt/mTOR signaling, suggesting improved cellular growth and survival. Conversely, SH-GT suppressed hair growth inhibitory pathways by reducing BMP4 expression and decreasing Smad phosphorylation. Furthermore, SH-GT increased the mRNA expression of growth factors such as IGF-1, HGF, VEGF, EGF, and FGF7. In conclusion, SH-GT promotes hair regrowth by simultaneously activating proliferation-related signaling pathways and suppressing inhibitory mechanisms, thereby improving the dorsal skin microenvironment associated with hair regrowth. These findings suggest that SH-GT may serve as a promising functional ingredient for improving hair growth. Full article

We investigated the biocompatibility of a novel oral herbal formulation containing Rhus coriaria (sumac) extract plus propolis compared with a propolis-only formulation using zebrafish embryos. Zebrafish embryos (AB/AB strain) were exposed to 3,4-dichloroaniline (DCA), a propolis-only formulation, or a combined sumac–propolis formulation from 24 to 72 h post-fertilization. Biochemical endpoints—including lipid peroxidation (LPO), nitric oxide (NO), acetylcholinesterase (AChE), and superoxide dismutase (SOD)—were evaluated, while gene expression levels of fabp10a, cyp1a, vtg, bax, bcl2, gfap, erg, and igf2 were quantified using RT–PCR. Statistical analysis was performed using one-way ANOVA with a significance threshold of p < 0.05. DCA increased oxidative stress (LPO: p < 0.001; NO: p < 0.01) with reduced SOD (p < 0.01). The propolis-only formulation increased LPO (p < 0.01) and decreased SOD (p < 0.05) versus control, whereas the sumac + propolis formulation showed milder edema, normalized LPO and NO (both p < 0.05 vs. DCA), and increased SOD versus control (p < 0.05), DCA (p < 0.001), and propolis-only (p < 0.001); AChE was unchanged (p > 0.05). At the transcript level, DCA upregulated fabp10a/cyp1a/vtg (all p < 0.0001) and bax (p < 0.0001) while downregulating bcl2 (p < 0.001), erg (p < 0.0001), and igf2 (p < 0.01); these alterations were largely mitigated by the sumac + propolis formulation (vtg lower vs. DCA p < 0.0001 and vs. propolis-only p < 0.001; igf2 higher vs. DCA p < 0.001 and vs. propolis-only p < 0.01). Overall, incorporating sumac into a propolis-based formulation improved biocompatibility in zebrafish embryos, supporting further evaluation of this strategy for oral mucositis-oriented applications. Full article

The global push to eliminate antibiotic growth promoters in poultry has accelerated the demand for effective natural alternatives. β-Glucans—branched polysaccharides derived from Saccharomyces cerevisiae cell walls—enhance immunity and gut health; however, their mechanistic effect on the somatotropic axis and meat quality in broilers remains unresolved. Herein, the hypothesis that dietary β-glucan modulates somatotropic signaling to improve growth performance and breast muscle quality was tested with 240 one-day-old Ross 308 chicks allocated to three groups—untreated control, 250 mg β-glucan/kg feed, and 1 g β-glucan/kg feed—and reared for 35 d. Growth performance, plasma growth hormone (GH) and prolactin (PRL), somatotropic axis gene expression in liver and breast muscle, and postmortem meat quality were assessed. β-Glucan supplementation significantly elevated final body weight, breast muscle weight, and plasma GH and PRL, and upregulated hepatic IGF-1 and muscle GH receptor mRNA at 35 d, and hepatic GH receptor mRNA at 17 d. Muscle pH was higher and relative drip loss lower in supplemented birds 72 h postmortem. These results support the hypothesis and identify 1 g β-glucan/kg feed as an effective dose for improving growth and meat quality through somatotropic axis modulation—a novel mechanistic demonstration in broiler chickens. Full article

Umbilical cord mesenchymal stromal cells (UC-MSCs) are a key element of regenerative medicine due to their ability to secrete growth factors that stimulate proliferation and angiogenesis, and modulate the inflammatory response. Despite their widespread use, the influence of the perinatal microenvironment on their biological properties remains poorly understood. The aim of this study was to assess the influence of pH and blood gas parameters in umbilical cord blood on the global transcriptomic profile of UC-MSCs and to analyze the correlation between the metabolic status of the newborn and the expression of key trophic factors: EGF, FGF2, FGFR1, FGFR3, GDNF, HGF, IGF1, NES, NGF, and PGF. Methods: The study was conducted in two stages. In the first phase, transcriptomic screening was performed using Affymetrix HuGene 2.0 ST microarray on cells isolated from three environmental groups defined by cord blood pH: acidic (pH < 7.35), physiological (7.35–7.39), and alkaline (pH ≥ 7.4). In the second phase, the results were validated using qPCR on an expanded study group (N = 50). Gene expression levels (RQ) were related to blood gas parameters (pH, pCO₂, pO₂, cHCO₃) and the presence of clinical features of threatened neonatal asphyxia. Results: Microarray analysis revealed that environmental pH acts as a molecular phenotypic switch. Under low pH conditions (<7.35), a shift in cell profile from proliferative to structural–migratory was observed. Significant overexpression of genes responsible for extracellular matrix (ECM) organization and adhesion (e.g., COMP, DCN, LUM, FMOD) was observed, while pathways related to cell cycle and cell division (↓CDK1, AURKA, TOP2A) were downregulated. qPCR validation confirmed these observations, demonstrating a strong positive correlation between blood pH and the expression of regenerative mediators: FGFR1 (r = 0.28), EGF (r = 0.30), NGF (r = 0.39), and IGF1 (r = 0.30). A negative correlation was also found between carbon dioxide pressure (pCO₂) and the expression of NGF, FGFR1, and EGF. A significant clinical finding was that in newborns diagnosed with threatened asphyxia, EGF, FGFR1, and NGF gene expression was significantly reduced, indicating impaired trophic potential of the cells in response to metabolic stress. Conclusions: These results indicate that cord blood gas parameters are critical regulators of the genetic activity of UC-MSCs. Metabolic and respiratory acidosis not only inhibit the cells’ proliferative potential but also force them into a matrix remodeling mode, permanently modifying their transcriptomic profile. This suggests that the neonatal acid–base status may serve as an objective indicator of the “biological quality” of isolated stromal cells, which has significant implications for their future applications in cell therapies. Full article

Leptin (LEP) is an adipocyte-derived cytokine that integrates nutritional status, metabolism, and reproduction in cattle, with particular relevance for modern high-producing dairy cows. In ruminants, LEP and its receptors are widely expressed in metabolic and reproductive tissues, including adipose tissue, liver, hypothalamus, pituitary, ovary, uterus, and placenta, where LEP modulates energy homeostasis, neuroendocrine function, and local tissue responses. Changes in circulating LEP concentrations during the transition period reflect changes in body fat reserve, insulin and GH-IGF-1 dynamics, thyroid hormones, and inflammation and contribute to coordinated metabolic adaptations supporting the onset of lactation. At the reproductive level, LEP influences the hypothalamic–pituitary–gonadal axis, affects the pulsatility of luteinizing hormone (LH) under nutritional stress, and exerts direct effects on ovarian steroidogenesis, folliculogenesis, oocyte competence, embryo development, and uterine immune function. New evidence also links LEP profiles to major peripartum disorders, including subclinical ketosis, insulin resistance, postpartum ovarian inactivity, and uterine inflammatory diseases, and emphasises its potential as part of a panel evaluating the risk of metabolic and reproductive disorders. Furthermore, polymorphisms within the bovine LEP gene and its signalling network have been associated with milk production, feed efficiency, body condition, and fertility traits, suggesting opportunities to incorporate markers into genomic selection schemes aimed at improving robustness and reproductive performance. This review summarises current knowledge on LEP biology in cattle, with an emphasis on dairy cows, and discusses perspectives on translating this information into practical tools for nutritional management, health monitoring, and genetic improvement in bovine production systems. Full article

Sudden cardiac death (SCD) in athletes often represents the first manifestation of an underlying inherited cardiovascular disorder exposed by adrenergic stress, altered calcium cycling, mechanical loading, and metabolic demand during intense exercise. This review focuses on the molecular architecture that links genotype to arrhythmogenic phenotype in athletes, emphasizing sarcomeric force generation and energetic inefficiency in hypertrophic cardiomyopathy, desmosomal failure and Hippo/Wnt/transforming growth factor-beta (TGF-β) signaling in arrhythmogenic cardiomyopathy, and ion-channel and calcium/calmodulin-dependent protein kinase II (CaMKII)calcium handling abnormalities in inherited channelopathies. This review further examines how exercise-induced physiological remodeling intersects with these pathways through insulin-like growth factor-1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling, mitochondrial biogenesis, oxidative stress, inflammatory signaling, and epigenetic regulation. Attention is given to the molecular basis of genotype-positive/phenotype-negative states, variable penetrance, and exercise-mediated disease expression. Finally, the integration of molecular biology with genomic data, polygenic risk, and emerging digital phenotyping is discussed to refine mechanism-based risk stratification and identify future therapeutic targets for prevention of SCD in athletes. Full article

Background: Esophageal squamous cell carcinoma (ESCA) represents one of the most common aggressive malignancies worldwide. Insulin-like growth factor binding protein 1 (IGFBP1), a typical member of the IGF superfamily, is closely linked to adverse prognosis in numerous cancers. Up to now, little is known about its functional relevance to cell migration and tumor progression in ESCA. This work focuses on clarifying the relationship between IGFBP1 expression and the progression and migratory characteristics of ESCA. Methods: mRNA expression profiles from ESCA patients were obtained from the TCGA and GEO databases. Differential expression analysis was performed using R software(version 4.2.2), followed by an intersection of DEGs between datasets. The STRING database was applied to establish PPI networks. Cytoscape software(Version 3.7.2) was then used for visual presentation and hub gene identification. IGFBP1 expression was validated in ESCA tissues versus adjacent normal tissues. Prognostic correlation was assessed using GEPIA, while diagnostic and predictive values were evaluated through ROC analysis and Cox regression. Genetic alterations of IGFBP1 were analyzed via cBioPortal. Immune cell infiltration patterns were investigated using TIMER. Functional enrichment analyses (GO, KEGG) were performed on IGFBP1-associated DEGs. In the in vitro experiments, esophageal cancer cell lines (such as Eca109 and TE-1) and normal human esophageal epithelial cell lines (such as HEEC) were selected. The transcriptional level of IGFBP1 was examined using RT-qPCR, while Western blot analysis was conducted to validate its protein expression changes. Changes in the proliferative capacity of cancer cells after IGFBP1 silencing were detected by the CCK-8 assay, and cell migration capacity was determined via wound scratch assays to clarify the related biological effects. Results: Overall, 2870 DEGs were screened from the GEO database, 153 DEGs were screened from the TCGA database, and 34 genes were found to be common to both databases; 10 core genes were screened from the PPI network. IGFBP1 was abnormally expressed in esophageal cancer. Cox regression confirmed that IGFBP1 is an independent risk factor, and prognostic analysis indicated that IGFBP1 is closely associated with poor prognosis. Gene mutation analysis showed that amplification mutations are the most common type of IGFBP1 gene mutation, and genetic alterations in IGFBP1 in ESCA patients are significantly associated with overall survival (OS) (p = 0.0002568). GO analysis indicated that IGFBP1-related differentially expressed genes were enriched in organic anion transport, epidermal development, apical cell components, and metal ion transmembrane transporter activity. Pathway enrichment based on the KEGG database illustrated the main enrichment of target genes in neuroactive ligand–receptor interactions, calcium signaling and cAMP signaling pathways. Additionally, remarkable differences in immune cell infiltration were observed between IGFBP1 high-expression and low-expression subgroups through tumor immune profiling. IGFBP1 expression differed significantly between esophageal cancer cells and normal esophageal epithelial cells, as detected by RT-qPCR (p < 0.05). Moreover, knockdown of IGFBP1 markedly inhibited the proliferation (p < 0.05) and migration abilities (p < 0.05) of TE-1 and Eca109 cells. Conversely, IGFBP1 overexpression facilitated these cellular processes. Conclusions: As a key oncogenic driver for ESCA, IGFBP1 may participate in the oncogenesis of ESCA, possibly influencing clinical outcomes via IGF signaling and the tumor microenvironment. Its dual functions in tumor and immune systems suggest it might be a candidate for ESCA immunotherapy research. Full article

During development, stem cells rapidly proliferate and differentiate to form the embryo and the placenta, requiring intensive increases in cellular protein synthesis and changes to the cell architecture. Chaperone proteins, including the small heat shock proteins (HSPs), are critical assistants to protein folding, preventing protein aggregation, and promoting autophagy. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) is a stress-activated kinase that promotes fetal and placental growth. MAP3K4 directly activates p38 and JNK in trophoblast stem (TS) cells by phosphorylating MAP2K3 and MAP2K4/7, respectively. In addition, MAP3K4 promotes activation of the Akt signaling pathway by controlling Igf1r expression. TS cells differentiate to placental trophoblasts comprising the junctional zone (JZ) and labyrinth (LAB) placental layers. In this study, we demonstrate that JZ differentiation transiently increases JNK activity, whereas LAB differentiation induces sustained p38, JNK, and Akt activation. Each of these pathways is inhibited in MAP3K4 kinase-inactive (KI) LAB^KI trophoblasts. JZ and LAB differentiation also induces HSP22 and HSP27 expression and HSP27 phosphorylation; these are also reduced in TS^KI and LAB^KI cells. JZ and LAB differentiation induces GABARAP-positive autophagosomes that are deficient in KI cells. Altogether, our findings demonstrate that MAP3K4 is critical for responses during differentiation in placental trophoblasts. Full article

Background: Dietary protein optimization is an important nutritional strategy for improving growth and physiological responses, and antioxidant homeostasis in fish. Methods: In this study, 540 black carp (initial body weight: 10.50 ± 1.00 g) were randomly assigned into recirculating tanks (500 L) fed with six dietary protein levels (30–44% crude protein) for an 8-week feeding trial with triplicates per treatment and 30 fish per replicate. After the trial, fish body, blood, hepatopancreas, and intestinal samples were collected for body composition, serum biochemical parameters, metabolism, and antioxidant indices’ analyses. Results: Results showed fish fed 38% protein (PT38) exhibited the highest weight gain (p < 0.05), with no further improvement at higher protein levels. Compared with PT30 group, PT38 group significantly promoted protein deposition by upregulating transcript levels of insulin-like growth factors (IGFs) via activating mechanistic target of rapamycin (mTOR) signaling pathway. PT38 could improve fatty acid oxidation by heightening levels of carnitine palmitoyl transferase 1α (CPT1α), peroxisome proliferator-activated receptor α (PPARα) and PPARδ. Meanwhile, PT38-PT41 significantly inhibit expression of fatty acid synthesis and lipid droplet deposition-related genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and perilipin 2 (p < 0.05). PT38 significantly enhanced antioxidant homeostasis by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Conclusions: Overall, Under the current experimental conditions, 38% dietary protein is suitable for promoting growth performance, improving protein and lipid metabolism, and enhancing antioxidant homeostasis in black carp. Full article

Cancer research is pivotal for understanding cancer biology, discovering new therapeutic targets, and advancing precision medicine. However, it faces challenges such as data complexity, dispersed analytical tools, and the lack of a unified platform. To address these issues, we developed the GEO Cancer Analysis Suite (GCAS), an R package and visualization interface via shinyApp. GCAS includes four main modules: differential gene expression analysis, correlation studies, pan-cancer analysis, and immune infiltration and drug sensitivity analysis. These modules facilitate the identification of potential cancer biomarkers, elucidation of gene regulatory networks, comprehensive multi-cancer analysis, and assessment of gene expression in relation to immune cell infiltration and drug sensitivity. Using GCAS, GAPDH was found to be upregulated in multiple lung cancer and breast datasets and positively correlated with the m⁶A regulatory gene IGF2BP3. Further in vitro assays suggested that IGF2BP3 regulates GAPDH mRNA stability. Immune infiltration analysis indicated a negative correlation between GAPDH expression and CD4 T cell infiltration scores. Drug sensitivity analysis revealed a significant negative correlation between GAPDH expression and sensitivity to EGFR-targeting drugs, particularly Erlotinib. GCAS is a crucial tool in cancer research, simplifying data analysis and enhancing the discovery of novel biomarkers, immune landscape profiles, and drug sensitivity predictions, significantly contributing to cancer research and precision medicine. Full article

This study examined the protective mechanisms of oleanolic acid (OA) against high-fat diet (HFD)-induced hepatic steatosis and intestinal dysbiosis in Nile tilapia. Fish were allocated to four groups: normal diet (ND), HFD, and OA-supplemented HFD (50 and 250 mg/kg). After 42 days, physiological, biochemical, and histological assessments demonstrated that OA markedly reduced hepatic lipid accumulation, mitochondrial injury, and intestinal shortening. Transcriptomic analysis revealed that OA alleviated lipid dysregulation by inhibiting de novo lipogenesis and promoting lipid trafficking and β-oxidation, effectively reversing HFD-induced changes in the PPAR, MAPK, mTOR, and autophagy-lysosome signaling pathways. 16S rRNA sequencing indicated that OA increased microbial alpha diversity, suppressing HFD-associated taxa (e.g., Nordella) while enriching beneficial genera such as Clavibacter, Bosea, and Bdellovibrio. Importantly, OA treatment restored HFD-induced depletion of intestinal butyric acid and suppressed hepatic pro-inflammatory cytokines (tnf-α, il-1β), while upregulating growth-related factors (igf1). Correlation analysis confirmed strong associations between microbial alterations (Nordella and Phreatobacter) and hepatic lipid metabolism and inflammatory gene expression. Overall, OA mitigates metabolic stress in Nile tilapia by reconfiguring the gut–liver axis, integrating microbial restoration with precise regulation of hepatic nutrient-sensing and inflammatory pathways, providing a potential therapeutic strategy for lipid metabolism disorders in aquaculture. Full article

Insulin-like growth factor 1 (IGF-1) signaling plays a complementary role to insulin signaling in glucose metabolism homeostasis. This study characterized the physiological roles of the IGF1 receptor A (Igf1ra) and B (Igf1rb) in zebrafish. The transcripts of igf1ra and igf1rb were detected in multiple zebrafish tissues, including the liver, muscle, and brain. Zebrafish lacking igf1ra or igf1rb were generated using CRISPR/Cas9 technology. Both igf1ra^−/− and igf1rb^−/− zebrafish exhibited stunted growth. Reduced BMI was found in igf1ra^−/− zebrafish, while BMI increased in igf1rb^−/− zebrafish. Hyperglycemia and increased hepatic glycogen were observed in igf1ra^−/− zebrafish, while blood glucose levels in igf1rb^−/− zebrafish were normal. No significant difference in whole-body or hepatic triglyceride content was observed in igf1ra^−/− zebrafish, while the whole-body and hepatic triglyceride content of igf1rb^−/− zebrafish increased compared to their wild-type control siblings. Further analyses of the expression patterns of key genes involved in glucose and lipid metabolism were conducted on igf1r mutants. Decreased levels of genes involved in glucose absorption and glycolysis and increased levels of genes involved in gluconeogenesis and glycogen synthesis were observed in igf1ra^−/− zebrafish, but not in igf1rb^−/− zebrafish. Conversely, significantly decreased levels of transcripts involved in lipolysis and increased levels of transcripts involved in the lipogenesis process were observed in igf1rb^−/− zebrafish, but not in igf1ra^−/− zebrafish. Restricted cell growth and protein synthesis signaling, including AKT and mTOR activation, was also detected in igf1ra^−/− zebrafish, while a moderate elevation in AKT and mTOR activity was seen in igf1rb^−/− zebrafish. Taken together, our results suggest that functional divergence occurred after the duplication of the zebrafish igf1r gene, with igf1ra primarily modulating glucose absorption and utilization, and igf1rb primarily affecting lipid metabolism in the somatotropic axis. Full article

The renin–angiotensin system (RAS) regulates inflammation, tissue homeostasis, and barrier integrity in lung and colon epithelial cells. Beyond classical pathways, non-canonical components including angiotensin-converting enzyme 2 (ACE2), epidermal growth factor receptor (EGFR), insulin-like growth factor 2 receptor (IGF2R) and aminopeptidase N (ANPEP) are implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and bacterial sepsis due to their roles in tissue repair and signaling. Despite their similar inflammatory and coagulopathic features, their impact on RAS-associated non-immune gene expression in epithelial tissues remains unclear. This study investigates the regulation of these targets in lung (BEAS-2B) and colon (CRL-1831) cells following exposure to recombinant SARS-CoV-2 spike protein N-terminal domain fragment (S1-NTD) and Pseudomonas aeruginosa-derived lipopolysaccharide (LPS). Cells were treated with 100 ng/mL of S1-NTD or LPS for 12–72 h. Viability was assessed via XTT assays, and molecular changes were analyzed through qRT-PCR and Western blotting. Both stimuli induced a time and dose-dependent decrease in metabolic activity. ACE2 was significantly downregulated in lung cells, while transient upregulation occurred in colon cells at 24 h. EGFR expression increased in colon cells following LPS exposure but decreased in lung cells after S1-NTD treatment. Both IGF2R and ANPEP were upregulated by S1-NTD in lung cells at 72 h, whereas colon cells showed earlier upregulation at 24–48 h. Our findings reveal that viral and bacterial stimuli elicit distinct, tissue-specific regulatory patterns in RAS-associated pathways. These alterations may contribute to epithelial barrier dysfunction and inflammation, highlighting these proteins as potential targets for managing secondary bacterial infections and inflammatory lung–gut complications in COVID-19. Full article

Growing evidence suggests an important pathogenetic role of brain-specific gangliosides in the mechanisms underlying Alzheimer’s disease (AD), the most common form of dementia. Nutritional strategies targeting ganglioside sialylation—for example, through agglutinin-mediated modulation—have therefore attracted increasing research interest. In particular, wheat malt extract (WME), a food-derived source of wheat germ agglutinin (WGA) with high affinity for gangliosides, may influence molecular pathways involved in AD pathogenesis. Twelve-month-old female APPswe/PS1E9 transgenic mice, a model of AD, and wild-type (WT) littermates received WME or tap water for three weeks. Behavioral performance was subsequently assessed. Amyloid plaque burden and astrocyte activation were evaluated using Congo red staining and GFAP immunoreactivity, respectively. Gene expression of selected AD markers in the brain was quantified by RT–qPCR. Aged WT mice exhibited robust, region-specific molecular responses to WME, including upregulation of activity-dependent and synaptic plasticity genes (Arc, Egr1, Bdnf, Syp), enhancement of metabolic and insulin-related signaling (Pgc1a, Sirt1, Igf1r, Irs2), increased Cldn5 expression, and reduced pro-inflammatory Il1β expression. APP/PS1 mice exhibited limited response to WME, suggesting more persistent transcriptional signatures of synaptic impairment, metabolic dysregulation, and neuroinflammation than in WT mice. We found no significant effects of WME treatment on amyloid plaque density and behavior in APP/PS1 mice. No effects on astrocyte activation were observed in either group. These findings demonstrate that dietary WME counteracts abnormal behaviors and molecular changes in neuron plasticity, metabolic, and vascular markers under conditions of normal aging but fails to improve the hallmarks of AD pathology. This highlights the potential of WGA-containing nutrients as a preventive nutritional approach targeting pathogenic mechanisms of aging and, potentially, AD pathology. Full article