Search Results (568)

Extracellular vesicles (EVs), nanoscale membrane-enclosed particles, are natural carriers of proteins and nucleic acids. Microalgae are widely used as a source of bioactive substances in the food and cosmetic industries and definitely have a potential to be used as the producers of EVs for biomedical applications. In this study, the extracellular vesicles isolated from the culture medium of two unicellular microalgae, Chlamydomonas reinhardtii (Chlamy-EVs) and Parachlorella kessleri (Chlore-EVs), were characterized by atomic force microscopy (AFM), cryo-electronic microscopy (cryo-EM), and nanoparticle tracking analysis (NTA). The biocompatibility with human cells in vitro (HEK-293T, DF-2 and A172) and biodistribution in mouse organs and tissues in vivo were tested for both microalgal EVs. An exogenous therapeutic protein, human heat shock protein 70 (HSP70), was successfully loaded to Chlamy- and Chlore-EVs, and its efficient delivery to human glioma and colon carcinoma cell lines has been confirmed. Additionally, in order to search for potential therapeutic biomolecules within the EVs, their proteomes have been characterized. A total of 105 proteins were identified for Chlamy-EVs and 33 for Chlore-EVs. The presence of superoxide dismutase and catalase in the Chlamy-EV constituents allows for considering them as antioxidant agents. The effective delivery of exogenous cargo to human cells and the possibility of the particle yield optimization by varying the microalgae growth conditions make them favorable producers of EVs for biotechnology and biomedical application. Full article

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

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Fusobacterium nucleatum and activating mutations in the Kirsten rat sarcoma virus oncogene homolog (KRAS) are increasingly recognized as cooperative drivers of colorectal cancer (CRC). F. nucleatum promotes tumorigenesis via adhesion to epithelial cells, modulation of the immune microenvironment, and delivery of virulence factors, while KRAS mutations—present in 60% of CRC cases—amplify proliferative signaling and inflammatory pathways. Here, we review the molecular interplay by which F. nucleatum enhances KRAS-driven oncogenic cascades and, conversely, how KRAS mutations reshape the tumor niche to favor bacterial colonization. We further discuss the use of KRAS as a prognostic biomarker and explore promising non-antibiotic interventions—such as phage therapy, antimicrobial peptides, and targeted small-molecule inhibitors—aimed at selectively disrupting F. nucleatum colonization and virulence. This integrated perspective on microbial–genetic crosstalk offers novel insights for precision prevention and therapy in CRC. Full article

Soil salinization poses a critical threat to global agriculture, necessitating innovative strategies for sustainable remediation. This review synthesizes advances in leveraging plant–microbe interactions to remediate saline–alkali soils, focusing on oilseed crops—Brassica napus, Glycine max, Arachis hypogaea, Helianthus annuus, and Sesamum indicum—as keystone species for ecosystem restoration. These crops exhibit unique adaptive strategies, including root architectural plasticity and exudate-mediated recruitment of stress-resilient microbiomes (Proteobacteria, Actinobacteria, and Ascomycota), which collectively stabilize soil structure and enhance nutrient cycling, ion homeostasis, and soil aggregation to mitigate soil salinity and alkalinity. Emerging technologies further amplify these natural synergies: nanomaterials optimize nutrient delivery and microbial colonization, while artificial intelligence (AI) models predict optimal plant growth-promoting rhizobacteria (PGPR) combinations and simulate remediation outcomes. This integration establishes a roadmap for precision microbiome engineering, offering scalable strategies to restore soil health and ensure food security in saline–alkali ecosystems. Full article

Nanomaterials have emerged as a transformative technology in agricultural science, offering innovative solutions to improve plant–microbe interactions and crop productivity. The unique properties, such as high surface area, tunability, and reactivity, of nanomaterials, including nanoparticles, carbon-based materials, and electrospun fibers, render them ideal for applications such as nutrient delivery systems, microbial inoculants, and environmental monitoring. This review explores various types of nanomaterials employed in agriculture, focusing on their role in enhancing microbial colonization and soil health and optimizing plant growth. Key nanofabrication techniques, including top-down and bottom-up manufacturing, electrospinning, and nanoparticle synthesis, are discussed in relation to controlled release systems and microbial inoculants. Additionally, the influence of surface properties such as charge, porosity, and hydrophobicity on microbial adhesion and colonization is examined. Moreover, the potential of nanocoatings and electrospun fibers to enhance seed protection and promote beneficial microbial interactions is investigated. Furthermore, the integration of nanosensors for detecting pH, reactive oxygen species, and metabolites offers real-time insights into the biochemical dynamics of plant–microbe systems, applicable to precision farming. Finally, the environmental and safety considerations regarding the use of nanomaterials, including biodegradability, nanotoxicity, and regulatory concerns, are addressed. This review emphasizes the potential of nanomaterials to revolutionize sustainable agricultural practices by improving crop health, nutrient efficiency, and environmental resilience. Full article

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homing to mineralized tissues. We then outline the sequential establishment of the pre-metastatic niche, driven by EV-mediated processes including fibronectin deposition, stromal cell reprogramming, angiogenesis, neurogenesis, metabolic reconfiguration, and immune modulation, specifically, the expansion of myeloid-derived suppressor cells and impaired lymphocyte function. Within the bone microenvironment, tumor-derived EVs carrying microRNAs and proteins shift the balance toward osteoclastogenesis, inhibit osteoblast differentiation, and disrupt osteocyte signaling. These alterations promote osteolytic destruction or aberrant bone formation depending on tumor type. We also highlight cutting-edge imaging modalities and single-EV omics technologies that resolve EV heterogeneity and identify potential biomarkers detectable in plasma and urine. Finally, we explore therapeutic approaches targeting EVs, such as inhibition of nSMase2 or Rab27A, extracorporeal EV clearance, and delivery of engineered, bone-targeted vesicles, while addressing translational challenges and regulatory considerations. This review offers a roadmap for leveraging EV biology in predicting, preventing, and treating skeletal metastases by integrating advances across basic biology, bioengineering, and translational science. Full article

Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections globally, significantly contributing to gastritis, peptic ulcers, and gastric malignancies. Its pathogenesis involves a complex array of virulence factors—including cagA, vacA, and urease—which facilitate mucosal colonization, immune evasion, and persistent inflammation. A major challenge in vaccine development is the bacterium’s ability to manipulate both innate and adaptive immune responses, resulting in limited natural clearance and long-term persistence. This review synthesizes H. pylori pathogenesis and host immune dynamics, highlighting their implications for vaccine design. By elucidating the molecular and cellular mechanisms underlying host–pathogen interactions, we explore how these insights inform antigen selection, adjuvant optimization, and delivery strategies. By integrating basic science with translational objectives, this review aims to support the development of an effective H. pylori vaccine, addressing global health needs, particularly in regions with a high infection burden and limited access to treatment. Full article

Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45⁺, CD4⁺CD3⁺, and CD8⁺CD3⁺ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy. Full article

Ferulic acid (FA) exhibits beneficial properties in ulcerative colitis (UC) pathogenesis, while sensitivity to the environment and enzymes limits its use in UC therapy. Therefore, this study aims to develop a colon-targeted nanocomplex delivery system using FA and investigate its protective effects and underlying regulatory mechanisms in UC mice. A novel Zein/FA–pectin (PEC)/chitosan (CS) nanocomplex was successfully fabricated in this study. Through systematic adjustment of the PEC/CS-to-Zein/FA ratio, optimal encapsulation efficiency (60.1%) and loading capacity (26.2%) were achieved. The characterized data indicated that hydrogen bonds, electrostatic interactions, and hydrophobic forces were the main driving forces maintaining the formation of the nanocomplexes, accompanied by alterations in the secondary structure of Zein. The Zein/FA–PEC/CS nanocomplexes demonstrated excellent thermal/storage particle size stability and exhibited both protective and sustained-release effects of FA during simulated gastrointestinal digestion. Furthermore, the results demonstrated that the nanocomplexes potentially alleviate UC by regulating inflammatory cytokines, oxidative stress, and gut microbiota. Compared to unencapsulated FA, the nanocomplexes have a better effect on alleviating UC symptoms. In summary, Zein/FA–PEC/CS nanocomplexes have promising prospects in alleviating colitis in UC mice. Full article

Probiotics, as live microbial agents, play a pivotal role in modulating host microbiota balance, enhancing immunity, and improving gastrointestinal health. However, their application is hindered by critical challenges, such as inactivation during processing, storage, and gastrointestinal delivery, as well as low colonization efficiency. This article comprehensively reviews recent advances in probiotic delivery systems, focusing on innovative technologies, including hydrogels, nanocoatings, emulsions, and core–shell microgels. It provides an in-depth analysis of natural polyphenol-based nanocoatings and metal–phenolic network (MPN) single-cell encapsulation strategies for enhancing bacterial survival rates while highlighting the unique potential of microalgae-based bio-carriers in targeted delivery. Research demonstrates that well-designed edible delivery systems can effectively preserve probiotic viability and enable controlled intestinal release, offering novel strategies to reshape a healthy gut microbiome. While these systems show promise in maintaining probiotic activity and gut colonization, challenges remain in safety, scalable production, and clinical translation. Overcoming these barriers is crucial to fully harnessing probiotics for human health. Full article

Background/Objectives: Keratins form a crucial component of the epithelial cytoskeleton, playing an essential role in maintaining tissue architecture and coordinating key cellular functions. KRT80 is a type II keratin that has emerged as an oncogenic driver in several malignancies, yet its involvement in colorectal cancer (CRC) remains unclear. Here, we investigated the molecular interaction between miR-195-5p, KRT80 expression, and CRC growth. Methods: Potential miR-195-5p binding sites in the KRT80 3′-UTR were identified through the use of integrated bioinformatic analyses, while publicly available datasets confirmed a significant overexpression of KRT80 in CRC tissues compared to normal mucosa. This finding was further validated through the use of mRNA and protein analysis in paired tumor and adjacent normal samples from CRC patients. Results: Functional assays involving CRC cell lines showed that transfection with miR-195-5p mimics led to a significant downregulation of KRT80 expression, reflecting the effects of direct KRT80 silencing by siRNA. Both molecular approaches induced G₁-phase cell cycle arrest, concomitantly with reductions in G₂/M populations. Furthermore, the in vivo delivery of miR-195-5p mimics in a mouse model of colitis-associated CRC resulted in a significant reduction in Krt80 expression in the colon. Conclusions: Collectively, our results reveal that miR-195-5p negatively regulates KRT80 expression, contributing to its tumor-suppressive activity in colorectal cancer and highlighting a molecular mechanism with potential therapeutic relevance. Full article

This study reports, for the first time, the successful application of chitosan oligosaccharide (COS) and 2-hydroxyethyl cellulose (HEC) coatings on electrospun poly(3-hydroxybutyrate) (PHB) materials for the immobilization of non-conventional yeast strains with fungal biocontrol potential. The coatings enhanced the surface wettability of PHB fibers, facilitating efficient yeast adhesion and viability maintenance. Among the tested strains, Pichia acaciae YD6 was newly isolated and characterized, while Pichia fermentans YP6 and Zygosaccharomyces bailii YE1 had previously been identified as endophytic colonizers. All three strains demonstrated high adaptability, efficient immobilization, and antagonistic activity, confirming their potential for biocontrol applications. COS-coated PHB fibers promoted greater colony expansion than those coated with HEC. Antifungal assays of the yeast-containing biocarriers showed significant inhibition of F. graminearum growth. These findings underscore the potential of PHB-based fibrous materials as sustainable, bioactive carriers for yeast immobilization, with desirable biological properties. This approach offers a promising and eco-friendly strategy for pest control and bioactive agent delivery in agricultural applications. Full article

Human milk (HM) is a complex biological fluid that plays a significant role in infant health, influenced by maternal dietary habits and body composition. This study aimed to explore how maternal diet and nutritional status affect the microbial composition of HM. In this pilot study, 15 mothers were recruited from a maternity ward and assessed for dietary habits through a semi-structured food frequency questionnaire and a 3-day dietary record. Maternal body composition was evaluated using bioelectrical impedance analysis. HM samples were collected for microbiota analysis, focusing on the diversity and composition of bacterial communities via 16S rRNA sequencing. The study identified that maternal nutrient intake significantly correlated with the composition of HM microbiota. Specifically, Firmicutes abundance showed positive correlations with animal protein (τ = 0.39; p = 0.043), total carbohydrates (τ = 0.39; p = 0.043), and vitamin A (τ = 0.429; p = 0.026). Bacteroidota was positively correlated with retinol (τ = 0.39; p = 0.043). Higher consumption of dietary fiber (>24 g/day) did not yield significant differences in bacterial composition compared to lower intake (<24 g/day) (p = 0.8977). Additionally, no significant differences were found in overall bacterial abundance across different maternal characteristics such as age, mode of delivery, or breastfeeding type. This study underscores the importance of maternal diet in shaping the HM microbiota, which may have implications for infant health. Dietary modifications during lactation could be a strategic approach to promote beneficial microbial colonization in HM. Further research is warranted to confirm these findings and explore the underlying mechanisms. Full article