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41 pages, 8942 KB  
Article
Synthesis, Computational Studies, and Structural Analysis of 1-(3,5-Dimethoxyphenyl)azetidin-2-ones with Antiproliferative Activity in Breast Cancer and Chemoresistant Colon Cancer
by Azizah M. Malebari, Shubhangi Kandwal, Abdirahman Ali, Darren Fayne, Brendan Twamley, Daniela M. Zisterer and Mary J. Meegan
Pharmaceuticals 2025, 18(9), 1330; https://doi.org/10.3390/ph18091330 - 5 Sep 2025
Viewed by 287
Abstract
Background/Objectives: A series of 1-(3,5-dimethoxyphenyl)azetidine-2-ones were synthesised to evaluate their antiproliferative activity in MCF-7 breast cancer cells and HT-29 chemoresistant colon cancer cells. The 1,4-diarylazetidin-2-ones were designed by replacing the characteristic 3,4,5-trimethoxyphenyl Ring A of the antimitotic stilbene combretastatin CA-4 with a [...] Read more.
Background/Objectives: A series of 1-(3,5-dimethoxyphenyl)azetidine-2-ones were synthesised to evaluate their antiproliferative activity in MCF-7 breast cancer cells and HT-29 chemoresistant colon cancer cells. The 1,4-diarylazetidin-2-ones were designed by replacing the characteristic 3,4,5-trimethoxyphenyl Ring A of the antimitotic stilbene combretastatin CA-4 with a 3,5-dimethoxyphenyl substituent at N-1, together with phenyl, hydroxyl, and phenoxy substituents at C-3 of the four-membered ring. Methods: A panel of 12 novel compounds was synthesized and evaluated in estrogen receptor (ER)- and progesterone receptor (PR)-positive MCF-7 breast cancer cells followed with the more potent compounds further evaluated in HT-29 chemoresistant colon cancer cells. Cytotoxicity was determined by LDH assay. The structures of the 1-(3,5-dimethoxyphenyl)azetidine-2-ones 12i, 12k, 12o, 12p together with the 1-(3,5-dimethoxyphenyl)azetidine-2-one 12s were determined by X-ray crystallography. The trans configuration of the C-3 and C-4 substituents of the β-lactam ring was confirmed for compounds 12k and 12u. Molecular modelling and molecular dynamics studies examined the molecular interactions of the compounds with the colchicine binding site of tubulin. Results: The 1-(3,5-Dimethoxyphenyl)-4-(4-ethoxyphenyl)-3-hydroxyazetidin-2-one 12l was identified as the most potent antiproliferative compound in the series (with an IC50 value of 10 nM in MCF-7 breast cancer cells and 3 nM in HT-29 colon cancer cells) and with greater potency than CA-4 in the chemoresistant HT-29 cells. Computational docking studies predicted binding conformations for 12l and the related series of compounds in the colchicine binding site of tubulin and rationalised the impact of the 3,5-dimethoxyphenyl substituent at N-1 of the azetidine-2-one on activity. Conclusions: These findings indicate that the novel 1-(3,5-dimethoxyphenyl)-2-azetidinone 12l is a suitable candidate for further investigation as a potential antiproliferative microtubule-targeting agent for breast and chemoresistant colon cancers. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry: 2nd Edition)
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13 pages, 609 KB  
Article
Circulating microRNAs as Early Biomarkers of Colon Cancer: A Nested Case-Control Study Within a Prospective Cohort
by Lisa Padroni, Giorgia Marmiroli, Laura De Marco, Valentina Fiano, Lucia Dansero, Saverio Caini, Giovanna Masala, Luca Manfredi, Lorenzo Milani, Fulvio Ricceri and Carlotta Sacerdote
Int. J. Mol. Sci. 2025, 26(16), 7893; https://doi.org/10.3390/ijms26167893 - 15 Aug 2025
Viewed by 332
Abstract
Circulating microRNAs (miRNAs) have emerged as non-invasive biomarkers that may be associated with cancer risk, but their role in the development of colon cancer is still not well understood. We conducted a nested case-control study within the EPIC-Italy cohort to investigate the association [...] Read more.
Circulating microRNAs (miRNAs) have emerged as non-invasive biomarkers that may be associated with cancer risk, but their role in the development of colon cancer is still not well understood. We conducted a nested case-control study within the EPIC-Italy cohort to investigate the association between pre-diagnostic serum levels of eight candidate miRNAs (Let7, Mir21, Mir155, Mir181, Mir222, Mir145, Mir92, and Mir20) and subsequent colon cancer occurrence. A total of 104 incident colon cancer cases were matched to 104 controls by center, sex, age, recruitment date, and vital status. miRNA expression was quantified using RT-qPCR and normalized to Mir484. Logistic regression models were applied to estimate odds ratios, 95% confidence intervals, and p-values, adjusting for age at recruitment, smoking status, body mass index, physical activity, adherence to a Mediterranean diet, and socioeconomic position. Elevated expression of Let7 (OR = 0.91; 95% CI: 0.84–1.00; p = 0.04) was associated with slightly lower odds of colon cancer in unadjusted models. Mir21 and Mir222 showed borderline associations (p = 0.07 and p = 0.09, respectively), but these did not remain significant after Bonferroni correction. This result was consistent in the multivariate logistic model: higher levels of Let7 (OR = 0.91; 95% CI: 0.82–1.00; p = 0.06) and Mir222 (OR = 0.75; 95% CI: 0.57–1.00; p = 0.05) are suggestive of an association with lower odds of colon cancer. Our findings highlight the challenges of using circulating miRNAs as very early biomarkers, particularly when samples are collected nearly a decade before diagnosis. Future studies with larger sample sizes, serial blood collections, and integration with inflammatory and immune markers will be crucial to clarify the temporal dynamics of circulating miRNA alterations and their potential role in risk-adapted screening strategies. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 2407 KB  
Article
Mechanisms of Cultivation Chronosequence on Distribution Characteristics of Arbuscular Mycorrhizal Fungi in Tea Plantations, South Henan, China
by Xiangchao Cui, Dongmeng Xu, Shuping Huang, Wei Wei, Ge Ma, Mengdi Li and Junhui Yan
Microbiol. Res. 2025, 16(8), 188; https://doi.org/10.3390/microbiolres16080188 - 12 Aug 2025
Viewed by 302
Abstract
The vital role of arbuscular mycorrhizal (AM) fungi in tea plant growth is well established; however, the mechanisms underlying how increasing cultivation chronosequence (CC) influences AM fungal distribution remain unclear. An investigation was conducted to investigate the temporal dynamics of AM fungal indices [...] Read more.
The vital role of arbuscular mycorrhizal (AM) fungi in tea plant growth is well established; however, the mechanisms underlying how increasing cultivation chronosequence (CC) influences AM fungal distribution remain unclear. An investigation was conducted to investigate the temporal dynamics of AM fungal indices and soil properties across a 100-year tea CC (10-, 30-, 60-, and 100-year CC) in Xinyang Maojian tea (Camellia sinensis L.) plantations (Xinyang, Henan Province, China). Principal coordinate analysis was conducted to reveal the significant reorganization of AM fungal indices during early-to-mid stages (PCoA1: 89.2%, p < 0.05), with triphasic development. Mycorrhizal colonization (MC), hypha biomass (hypha), and spore density (SD) surged by 100% during 10–30 years; SD peaked at 60 years (164 spores g−1) before declining, while glomalin-related soil protein (GRSP) accumulated significantly only at 100 years (p < 0.05). Concurrently, soil acidification (pH decreased from 6.37 to 4.84) and phosphorus depletion (AP from 119.6 mg kg−1 to 32 mg kg−1) intensified by 60 years, contrasting with the significant accumulations of soil organic organisms (SOM) (from 10.6 g kg−1 to 36.4 g kg−1), electrical conductivity (EC) (from 0.019 to 0.050 mS·cm−1), and microaggregate accumulation (MAR) (from 25.8% to 40.3%) during the period. The linear regression model was performed to validate the significant effects (p < 0.05) of CC on the AM indices (MC, SD, hypha, and GRSP) and soil physiochemical characteristics (EC, moisture, and SOM). Variance partitioning attributed 97.4% of the total variation, while interactions among cultivation ages, nutrient characteristics (SOM and AP), and non-nutrient characteristics (pH, EC, moisture, and aggregates) accounted for 23.0%. To identify the driving factors of AM fungi indices, Pearson correlation and redundancy analysis (RDA) were performed, and EC (26.5%) and pH (20.9%) were identified as the paramount regulators of hyphal integrity and colonization efficiency. It was found that 60 years worked as a critical transition point for targeted interventions (e.g., organic amendments and pH buffering) to mitigate rhizosphere dysfunction and optimize mycorrhizal services in perennial monocultures. Full article
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20 pages, 3519 KB  
Article
Hylocereus polyrhizus Pulp Residues Polysaccharide Alleviates High-Fat Diet-Induced Obesity by Modulating Intestinal Mucus Secretion and Glycosylation
by Guanghui Li, Kit-Leong Cheong, Yunhua He, Ahluk Liew, Jiaxuan Huang, Chen Huang, Saiyi Zhong and Malairaj Sathuvan
Foods 2025, 14(15), 2708; https://doi.org/10.3390/foods14152708 - 1 Aug 2025
Viewed by 541
Abstract
Although Hylocereus polyrhizus pulp residues polysaccharides (HPPP) have shown potential in improving metabolic disorders and intestinal barrier function, the mechanism by which they exert their effects through regulating O-glycosylation modifications in the mucus layer remains unclear. Therefore, this study established a HFD-induced obese [...] Read more.
Although Hylocereus polyrhizus pulp residues polysaccharides (HPPP) have shown potential in improving metabolic disorders and intestinal barrier function, the mechanism by which they exert their effects through regulating O-glycosylation modifications in the mucus layer remains unclear. Therefore, this study established a HFD-induced obese colitis mouse model (n = 5 per group) and combined nano-capillary liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) technology to quantitatively analyze the dynamic changes in O-glycosylation. Additionally, through quantitative O-glycosylation proteomics and whole-proteome analysis, we identified 155 specifically altered O-glycosylation sites in colon tissue, with the glycosylation modification level of the MUC2 core protein increased by approximately 2.1-fold. The results indicate that HPPP alleviates colonic mucosal damage by regulating interactions between mucus O-glycosylation. Overall, we demonstrated that HPPP increases HFD-induced O-glycosylation sites, improves intestinal mucosal structure in obese mice, and provides protective effects against obesity-induced intestinal mucosal damage. Full article
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17 pages, 4148 KB  
Article
Contribution of the Gravity Component and Surface Type During the Initial Stages of Biofilm Formation at Solid–Liquid Interfaces
by Elisavet Malea, Maria Petala, Margaritis Kostoglou and Theodoros Karapantsios
Water 2025, 17(15), 2277; https://doi.org/10.3390/w17152277 - 31 Jul 2025
Viewed by 633
Abstract
Water systems are highly vulnerable to biofilm formation, which can compromise water quality, operational efficiency, and public health. Factors such as surface material properties and gravitational orientation of the surface play critical roles in the early stages of microbial attachment and biofilm development. [...] Read more.
Water systems are highly vulnerable to biofilm formation, which can compromise water quality, operational efficiency, and public health. Factors such as surface material properties and gravitational orientation of the surface play critical roles in the early stages of microbial attachment and biofilm development. This study examines the impact of gravity and surface composition on the initial adhesion of Pseudomonas fluorescens AR11—a model organism for biofilm research. Focusing on stainless steel (SS) and polycarbonate (PC), two materials commonly used in water and wastewater infrastructure, bacterial adhesion was evaluated at surface inclinations of 0°, 45°, 90°, and 180° to assess gravitational impact. After three hours of contact, fluorescence microscopy and image analysis were used to quantify surface coverage and cluster size distribution. The results showed that both material type and orientation significantly affected early biofilm formation. PC surfaces consistently exhibited higher bacterial adhesion at all angles, with modest variations, suggesting that material properties are a dominant factor in initial colonization. In contrast, SS showed angle-dependent variation, indicating a combined effect of gravitational convection and surface characteristics. These insights contribute to a deeper understanding of biofilm dynamics under realistic environmental conditions, including those encountered in space systems, and support the development of targeted strategies for biofilm control in water systems and spaceflight-related infrastructure. Full article
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15 pages, 1274 KB  
Review
Engineered Bifidobacterium Strains Colonization at Tumor Sites: A Novel Approach to the Delivery of Cancer Treatments
by Rhea Amonkar, Ashley Ann Uy, Pablo Ramirez, Harina Patel, Jae Jin Jeong, Nicole Oyinade Shoyele, Vidhi Vaghela and Ashakumary Lakshmikuttyamma
Cancers 2025, 17(15), 2487; https://doi.org/10.3390/cancers17152487 - 28 Jul 2025
Viewed by 844
Abstract
Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a [...] Read more.
Bacteria-mediated cancer therapy represents a novel and promising strategy for targeted drug delivery to solid tumors. Multiple studies have demonstrated that various Bifidobacterium species can selectively colonize the hypoxic microenvironments characteristic of solid tumors. Leveraging this property, Bifidobacterium has been explored as a delivery vector for a range of anti-cancer approaches such as immunotherapy, nanoformulated chemotherapeutics, and gene therapy. Notably, anti-angiogenic genes such as endostatin and tumstatin have been successfully delivered to colorectal tumors using Bifidobacterium infantis and Bifidobacterium longum, respectively. Additionally, Bifidobacterium bifidum has been employed to transport doxorubicin and paclitaxel nanoparticles to breast and lung tumor sites. Furthermore, both Bifidobacterium longum and Bifidobacterium bifidum have been utilized to deliver nanoparticles that act as synergistic agents for high-intensity focused ultrasound (HIFU) therapy, significantly enhancing tumor ablation, particularly in triple-negative breast cancer (TNBC) models. While these pre-clinical findings are highly encouraging, further clinical research is essential. Specifically, studies are needed to investigate the colonization dynamics of different Bifidobacterium species across various tumor types and to evaluate their potential in delivering diverse cancer therapies in human patients. Full article
(This article belongs to the Special Issue Advances in Drug Delivery for Cancer Therapy)
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25 pages, 8335 KB  
Article
Integrative In Silico and In Vivo Analysis of Banhasasim-Tang for Irritable Bowel Syndrome: Mechanistic Insights into Inflammation-Related Pathways
by Woo-Gyun Choi, Seok-Jae Ko, Jung-Ha Shim, Chang-Hwan Bae, Seungtae Kim, Jae-Woo Park and Byung-Joo Kim
Pharmaceuticals 2025, 18(8), 1123; https://doi.org/10.3390/ph18081123 - 27 Jul 2025
Viewed by 626
Abstract
Background/Objectives: Banhasasim-tang (BHSST) is a traditional herbal formula commonly used to treat gastrointestinal (GI) disorders and has been considered a potential therapeutic option for irritable bowel syndrome (IBS). This study aimed to explore the molecular targets and underlying mechanisms of BHSST in IBS [...] Read more.
Background/Objectives: Banhasasim-tang (BHSST) is a traditional herbal formula commonly used to treat gastrointestinal (GI) disorders and has been considered a potential therapeutic option for irritable bowel syndrome (IBS). This study aimed to explore the molecular targets and underlying mechanisms of BHSST in IBS using a combination of network pharmacology, molecular docking, molecular dynamics simulations, and in vivo validation. Methods: Active compounds in BHSST were screened based on drug-likeness and oral bioavailability. Potential targets were predicted using ChEMBL, and IBS-related targets were obtained from GeneCards and DisGeNET. A compound–target–disease network was constructed and analyzed via Gene Ontology and KEGG pathway enrichment. Compound–target interactions were further assessed using molecular docking and molecular dynamics simulations. The in vivo effects of eudesm-4(14)-en-11-ol, elemol, and BHSST were evaluated in a zymosan-induced IBS mouse model. Results: Twelve BHSST-related targets were associated with IBS, with enrichment analysis identifying TNF signaling and apoptosis as key pathways. In silico simulations suggested stable binding of eudesm-4(14)-en-11-ol to TNF-α and kanzonol T to PIK3CD, whereas elemol showed weak interaction with PRKCD. In vivo, eudesm-4(14)-en-11-ol improved colon length, weight, stool consistency, TNF-α levels, and pain-related behaviors—effects comparable to those of BHSST. Elemol, however, showed no therapeutic benefit. Conclusions: These findings provide preliminary mechanistic insight into the anti-inflammatory potential of BHSST in IBS. The integrated in silico and in vivo approaches support the contribution of specific components, such as eudesm-4(14)-en-11-ol, to its observed effects, warranting further investigation. Full article
(This article belongs to the Special Issue Network Pharmacology of Natural Products, 2nd Edition)
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16 pages, 2230 KB  
Article
Three-Dimensional-Printed Biomimetic Scaffolds for Investigating Osteoblast-Like Cell Interactions in Simulated Microgravity: An In Vitro Platform for Bone Tissue Engineering Research
by Eleonora Zenobi, Giulia Gramigna, Elisa Scatena, Luca Panizza, Carlotta Achille, Raffaella Pecci, Annalisa Convertino, Costantino Del Gaudio, Antonella Lisi and Mario Ledda
J. Funct. Biomater. 2025, 16(8), 271; https://doi.org/10.3390/jfb16080271 - 24 Jul 2025
Viewed by 888
Abstract
Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to [...] Read more.
Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research. Polylactic acid scaffolds with physiological (P) and osteoporotic-like (O) trabecular architectures were 3D-printed by means of fused deposition modeling technology. Morphometric characterization was performed using micro-computed tomography. Human osteoblast-like SAOS-2 and U2OS cells were cultured on the scaffolds under static and dynamic simulated microgravity conditions using a rotary cell culture system (RCCS). Scaffold biocompatibility, cell viability, adhesion, and metabolic activity were evaluated through Bromodeoxyuridine incorporation assays, a water-soluble tetrazolium salt assay, and an enzyme-linked immunosorbent assay of tumor necrosis factor-α secretion. Both scaffold models supported osteoblast-like cell adhesion and growth, with an approximately threefold increase in colonization observed on the high-porosity O scaffolds under dynamic conditions. The dynamic environment facilitated increased surface interaction, amplifying the effects of scaffold architecture on cell behavior. Overall, sustained cell growth and metabolic activity, together with the absence of detectable inflammatory responses, confirmed the biocompatibility of the system. Scaffold microstructure and dynamic culture conditions significantly influence osteoblast-like cell behavior. The combination of 3D-printed scaffolds and a RCCS bioreactor provides a promising platform for studying bone remodeling in osteoporosis and microgravity-induced bone loss. These findings may contribute to the development of advanced in vitro models for biomedical research and potential countermeasures for bone degeneration. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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16 pages, 2108 KB  
Article
Decoding the JAK-STAT Axis in Colorectal Cancer with AI-HOPE-JAK-STAT: A Conversational Artificial Intelligence Approach to Clinical–Genomic Integration
by Ei-Wen Yang, Brigette Waldrup and Enrique Velazquez-Villarreal
Cancers 2025, 17(14), 2376; https://doi.org/10.3390/cancers17142376 - 17 Jul 2025
Cited by 1 | Viewed by 574
Abstract
Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC [...] Read more.
Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC. The platform integrates clinical, genomic, and treatment data to support dynamic, hypothesis-generating analyses for precision oncology. Methods: AI-HOPE-JAK-STAT combines large language models (LLMs), a natural language-to-code engine, and harmonized public CRC datasets from cBioPortal. Users define analytical queries in plain English, which are translated into executable code for cohort selection, survival analysis, odds ratio testing, and mutation profiling. To validate the platform, we replicated known associations involving JAK1, JAK3, and STAT3 mutations. Additional exploratory analyses examined age, treatment exposure, tumor stage, and anatomical site. Results: The platform recapitulated established trends, including improved survival among EOCRC patients with JAK/STAT pathway alterations. In FOLFOX-treated CRC cohorts, JAK/STAT-altered tumors were associated with significantly enhanced overall survival (p < 0.0001). Stratification by age revealed survival advantages in younger (age < 50) patients with JAK/STAT mutations (p = 0.0379). STAT5B mutations were enriched in colon adenocarcinoma and correlated with significantly more favorable trends (p = 0.0000). Conversely, JAK1 mutations in microsatellite-stable tumors did not affect survival, emphasizing the value of molecular context. Finally, JAK3-mutated tumors diagnosed at Stage I–III showed superior survival compared to Stage IV cases (p = 0.00001), reinforcing stage as a dominant clinical determinant. Conclusions: AI-HOPE-JAK-STAT establishes a new standard for pathway-level interrogation in CRC by empowering users to generate and test clinically meaningful hypotheses without coding expertise. This system enhances access to precision oncology analyses and supports the scalable, real-time discovery of survival trends, mutational associations, and treatment-response patterns across stratified patient cohorts. Full article
(This article belongs to the Special Issue AI-Based Applications in Cancers)
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20 pages, 10628 KB  
Article
Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
by Qi Xu, Aikun Fu, Nan Wang and Zhizhen Zhang
Microorganisms 2025, 13(7), 1632; https://doi.org/10.3390/microorganisms13071632 - 10 Jul 2025
Viewed by 730
Abstract
Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, [...] Read more.
Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, and 7- weeks post-tumor implantation through 16S rRNA gene sequencing. Breast tumor progression was associated with lung metastasis and splenomegaly, accompanied by distinct tissue-specific microbial dynamics. While alpha diversity remained stable in tumors, mammary tissue, and cecal contents, it significantly increased in the spleen (p < 0.05). Longitudinal analysis revealed a progressive rise in Firmicutes and a decline in Proteobacteria abundance within tumors, mammary tissue, and cecum, whereas the spleen microbiota displayed unique phylum-level compositional shifts. Tissue- and time-dependent microbial signatures were identified at phylum, genus, and species levels during breast tumor progression. Strikingly, the spleen microbiota integrated nearly all genera enriched in other sites, suggesting its potential role as a microbial reservoir. Gut-associated genera (Lactobacillus, Desulfovibrio, Helicobacter) colonized both cecal contents and the spleen, with Lactobacillus consistently detected across all tissues, suggesting microbial translocation. The spleen exhibited uniquely elevated diversity and compositional shifts, potentially driving splenomegaly. These results delineated the trajectory of microbiota translocation and colonization, and demonstrated tissue-specific microbial redistribution during breast tumorigenesis, offering valuable implications for advancing microbiome-targeted cancer therapies. Full article
(This article belongs to the Special Issue Host–Microbiome Cross-Talk in Cancer Development and Progression)
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19 pages, 3977 KB  
Article
Genome-Wide Analysis of the CDPK Gene Family in Populus tomentosa and Their Expressions in Response to Arsenic Stress and Arbuscular Mycorrhizal Fungi Colonization
by Minggui Gong, Jiajie Su, Shuaihui Wang, Youjia Wang, Weipeng Wang, Xuedong Chen and Qiaoming Zhang
Agronomy 2025, 15(7), 1655; https://doi.org/10.3390/agronomy15071655 - 8 Jul 2025
Viewed by 460
Abstract
Calcium-dependent protein kinases (CDPKs) are crucial regulators in calcium-mediated signal transduction pathways, playing a pivotal role in plant response to abiotic stresses. However, there is still limited knowledge regarding the genes of the Populus tomentosa CDPK family and their underlying functions in response [...] Read more.
Calcium-dependent protein kinases (CDPKs) are crucial regulators in calcium-mediated signal transduction pathways, playing a pivotal role in plant response to abiotic stresses. However, there is still limited knowledge regarding the genes of the Populus tomentosa CDPK family and their underlying functions in response to arsenic (As) stress and arbuscular mycorrhizal fungi (AMF) colonization. In our study, 20 PtCDPKs were identified in the P. tomentosa genome. Phylogenetic analysis categorized these PtCDPK genes into four subgroups based on sequence homology. Motif analysis revealed that PtCDPK genes within the same group share a similar exon–intron structure, conserved domains, and composition. The promoters of PtCDPK genes were found to contain a multitude of cis-acting elements, including light-response elements, phytohormone-response elements, and stress-response elements. The analysis of genes provided insights into the evolutionary dynamics and expansion of the PtCDPK gene family within P. tomentosa. The PtCDPK genes exhibited a strong collinear relationship with the CDPK genes of two model plants, namely, Arabidopsis thaliana and Oryza sativa L. Specifically, 10 gene pairs showed collinearity with Arabidopsis; in contrast, 14 gene pairs were collinear with rice. Transcriptome analysis of gene expression levels in P. tomentosa roots under both As stress and arbuscular mycorrhizal fungi (AMF) colonization conditions revealed that 20 PtCDPK genes had differential expression patterns. Under As stress, AMF inoculation led to the upregulation of 11 PtCDPK genes (PtCDPKSK5, X2, 1-3, 20-1, 24, 26-X1-1, 26-X1-2, 29-1, 29-2, 32, and 32-X1) and the downregulation of 8 PtCDPK genes, including PtCDPK1-1, 1-2, 8-X1, 10-X4, 13, 20-2, 26-X2, and 26-X3. The RT-qPCR results for 10 PtCDPK genes were consistent with the transcriptome data, indicating that AMF symbiosis plays a regulatory role in modulating the expression of PtCDPK genes in response to As stress. The principal findings of this study were that PtCDPK genes showed differential expression patterns under As stress and AMF colonization, with AMF regulating PtCDPK gene expression in response to As stress. Our study contributes to developing a deeper understanding of the function of PtCDPKs in the Ca2+ signaling pathway of P. tomentosa under As stress and AMF inoculation, which is pivotal for elucidating the molecular mechanisms underlying As tolerance in AMF-inoculated P. tomentosa. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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22 pages, 9642 KB  
Article
Bacillus thuringiensis Exopolysaccharide BPS-2 Ameliorates Ulcerative Colitis in a Murine Model Through Modulation of Gut Microbiota and Suppression of the NF-κB Cascade
by Zexin Gao, Huan Li, Jungang Wen, Wenping Ding, Jie Yu, Yue Zhang, Xiaojuan Song and Jianrong Wu
Foods 2025, 14(13), 2378; https://doi.org/10.3390/foods14132378 - 4 Jul 2025
Viewed by 560
Abstract
This study investigated the therapeutic potential of Bacillus thuringiensis extracellular polysaccharide BPS-2 in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) murine models. BPS-2 demonstrated significant efficacy in ameliorating UC-associated pathologies through three principal mechanisms: (1) attenuating histopathological damage while preserving colon epithelial integrity, [...] Read more.
This study investigated the therapeutic potential of Bacillus thuringiensis extracellular polysaccharide BPS-2 in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) murine models. BPS-2 demonstrated significant efficacy in ameliorating UC-associated pathologies through three principal mechanisms: (1) attenuating histopathological damage while preserving colon epithelial integrity, (2) modulating immune marker expression patterns in colon tissues, and (3) restoring gut microbiota homeostasis. BPS-2 exhibited multi-faceted protective effects on the gut by mitigating oxidative stress responses and enhancing short-chain fatty acid biosynthesis, leading to an improved gut microbial community structure. Molecular docking analysis displayed strong binding affinity (ΔG = −7.8 kcal/mol) between the BPS-2U fragment and the Nuclear Factor κB (NF-κB) p50/p65 heterodimer, suggesting the potential disruption of NF-κB signaling pathways. Complementary molecular dynamics simulations revealed exceptional conformational stability in the p65-BPS-2U complex. These findings establish BPS-2 as a natural food additive that modulates the microbiota-barrier–inflammation axis through dietary intervention, offering a novel strategy to alleviate UC. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Structure and Health Functions)
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20 pages, 3709 KB  
Article
An Effective Oral Nanodelivery Material for Curcumin: Ingenious Utilization of Gastrointestinal Absorption Characteristics
by Qiuxu An, Yuanyuan Liu, Guodong Liang, Yuewu Wang, Fengying Liang, Yunyang Bai, Chaolu Eerdun, Riqing Cheng, Haifeng Zhang and Xiaojie Lv
Molecules 2025, 30(12), 2536; https://doi.org/10.3390/molecules30122536 - 10 Jun 2025
Viewed by 574
Abstract
Curcumin exhibits compromised bioavailability upon oral administration due to its inherent limitations, including low aqueous solubility, poor membrane permeability, and chemical instability. Inspired by the efficient mechanism by which viruses penetrate mucus and cells, we constructed an electrically neutral and hydrophilic nanocarrier (C60-CPP5/Pser@CUR) [...] Read more.
Curcumin exhibits compromised bioavailability upon oral administration due to its inherent limitations, including low aqueous solubility, poor membrane permeability, and chemical instability. Inspired by the efficient mechanism by which viruses penetrate mucus and cells, we constructed an electrically neutral and hydrophilic nanocarrier (C60-CPP5/Pser@CUR) using fullerene C60 as the matrix modified with cell-penetrating peptides and phosphoserine. CPP5 facilitates efficient cellular internalization of therapeutic agents, while the incorporation of phosphoserine serves as a charge reversal strategy. This design enables dynamic surface charge modulation to enhance curcumin’s trans-barrier delivery efficiency. Systematic in vitro and in vivo evaluations demonstrated that the synthesized carrier significantly improved the synergistic effects of mucus penetration and cellular uptake. The Caco-2 cellular uptake of curcumin-loaded carriers was 2.26 times higher than that of free drugs. In a single-pass intestinal perfusion study in rat models, this nanocarrier significantly enhanced the absorption of curcumin in the duodenal and colonic regions. In the in vivo experiments, compared with free curcumin, its Cmax and AUC0–t achieved improvements of 2.60 times and 14.70 times, respectively. This virus-mimetic platform dynamically adapts to micro-environmental demands through charge reversal mechanisms, effectively overcoming sequential biological barriers and providing a robust strategy for oral delivery of hydrophobic therapeutics. Full article
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13 pages, 1068 KB  
Article
Styrene–Maleic Acid Copolymer-Based Nanoprobes for Enhanced Boron Neutron Capture Therapy
by Mingjie Zhang, Shanghui Gao, Kai Yang, Benchun Jiang, Wei Xu, Waliul Islam, Shinnosuke Koike, Yusei Kinoshita, Hiroto Nakayama, Jianrong Zhou, Kazumi Yokomizo and Jun Fang
Pharmaceutics 2025, 17(6), 738; https://doi.org/10.3390/pharmaceutics17060738 - 4 Jun 2025
Viewed by 595
Abstract
Background/Objectives: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene–maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which [...] Read more.
Background/Objectives: Boron neutron capture therapy (BNCT) is a promising, less-invasive anticancer treatment. However, the development of effective boron-based agents (BNCT probes) remains a critical and challenging issue. Previously, we developed a styrene–maleic acid (SMA) copolymer conjugated with glucosamine, encapsulating boronic acid, which exhibited tumor-targeted distribution via the enhanced permeability and retention (EPR) effect. Building upon this approach, in this study, we designed and synthesized a series of SMA-based polymeric probes for BNCT and evaluated their biological activities, with a particular focus on tumor-targeting properties. Methods: Two SMA-based BNCT nanoprobes, SMA–glucosamine conjugated Borax (SG@B) and SMA-conjugated aminophenylboronic acid encapsulating tavaborole (S-APB@TB), were designed and synthesized. The boron content in the conjugates was quantified using inductively coupled plasma mass spectrometry (ICP-MS), while particle sizes were measured via dynamic light scattering (DLS). In vitro cytotoxicity was assessed using the MTT assay in mouse colon cancer C26 cells. The tissue distribution of the conjugates was analyzed in a mouse sarcoma S180 solid tumor model using ICP-MS. Results: Both SG@B and S-APB@TB formed nanoformulations with average particle sizes of 137 nm and 99 nm, respectively. The boron content of SG@B was 2%, whereas S-APB@TB exhibited a significantly higher boron content of 14.4%. Both conjugates demonstrated dose-dependent cytotoxicity against C26 cells, even in the absence of neutron irradiation. Notably, tissue distribution analysis following intravenous injection revealed higher boron concentrations in plasma and tumor tissues compared to most normal tissues, with S-APB@TB showing particularly favorable tumor accumulation. Conclusions: These findings highlight the tumor-targeting potential of SMA-based BNCT nanoprobes. Further investigations are warranted to advance their clinical development as BNCT agents. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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16 pages, 4625 KB  
Article
Lactobacillus Re-Engineers Gut Microbiota to Overcome E. coli Colonization Resistance in Mice
by Jianlei Jia, Pengjia Bao, Qinran Yu, Ning Li, Hao Ren, Qian Chen and Ping Yan
Vet. Sci. 2025, 12(5), 484; https://doi.org/10.3390/vetsci12050484 - 16 May 2025
Cited by 1 | Viewed by 797
Abstract
The intestinal health and functionality of animals play pivotal roles in nutrient digestion and absorption, as well as in maintaining defense against pathogenic invasions. These biological processes are modulated by various determinants, including husbandry conditions, dietary composition, and gut microbial ecology. The excessive [...] Read more.
The intestinal health and functionality of animals play pivotal roles in nutrient digestion and absorption, as well as in maintaining defense against pathogenic invasions. These biological processes are modulated by various determinants, including husbandry conditions, dietary composition, and gut microbial ecology. The excessive use of anthropogenic antibiotics may disrupt intestinal microbiota composition, potentially leading to dysbiosis that directly compromises host homeostasis. While Lactobacillus species are recognized for their immunomodulatory properties, their precise mechanisms in regulating host anti-inflammatory gene expression and influencing mucosal layer maturation, particularly regarding E. coli colonization resistance, require further elucidation. To investigate the regulatory mechanisms of Lactobacillus in relation to intestinal architecture and function during E. coli infection, we established a colonic infection model using Bal b/c mice, conducting systematic analyses of intestinal morphology, inflammatory mediator profiles, and microbial community dynamics. Our results demonstrate that Lactobacillus supplementation (Pediococcus acidilactici) effectively mitigated E. coli O78-induced enteritis, with co-administration during infection facilitating the restoration of physiological parameters, including body mass, intestinal histoarchitecture, and microbial metabolic functions. Microbiome profiling revealed that the Lactobacillus intervention significantly elevated Lactococcus abundance while reducing Weissella populations (p < 0.05), concurrently enhancing metabolic pathways related to nutrient assimilation and environmental signal processing (including translation mechanisms, ribosomal biogenesis, amino acid transport metabolism, and energy transduction systems; p < 0.05). Mechanistically, Lactobacillus administration attenuated E. coli-induced intestinal pathology through multiple pathways: downregulating pro-inflammatory cytokine expression (IL-1β, IL-1α, and TNF-α), upregulating epithelial junctional complexes (Occludin, Claudin-1, and ZO-1), and stimulating mucin biosynthesis (MUC1 and MUC2; p < 0.05). These modifications collectively enhanced mucosal barrier integrity and promoted epithelial maturation. This investigation advances our comprehension of microbiota–host crosstalk during enteropathogenic infections under probiotic intervention, offering valuable insights for developing novel nutritional strategies and microbial management protocols in animal husbandry. Full article
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