Search Results (6,847)

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

The Caco-2 in vitro model of the intestinal barrier is a well-established system for the investigation of the intestinal fate of orally ingested chemicals and drugs, and it has been used for over ten years by pharmaceutical industries as a model for absorption in preclinical studies. The Caco-2 model shows a fair correlation with in vivo drug absorption, though some inherent biases remain unresolved. Its main limitation lies in the lack of structural complexity, as it does not replicate the diverse cell types and mucus layer present in the human intestinal epithelium. Consequently, the development of advanced in vitro models of the intestinal barrier, that more structurally resemble the human intestinal epithelium physiology, has increased the potential applications of these models. Recently, Caco-2-based advanced intestinal models have proven effective in predicting nanomaterial uptake and transport across the intestinal barrier. The aim of this review is to provide a state-of-the-art of human in vitro intestinal barrier models for the study of translocation/uptake of nanoparticles relevant for oral exposure, including inorganic nanomaterials, micro/nano plastic, and fiber nanomaterials. The main effects of the above-mentioned nanomaterials on the intestinal barrier are also reported. Full article

Polymicrobial biofilms involving fungal and bacterial species are increasingly recognized as contributors to persistent infections, particularly in the oral cavity. Candida albicans and Aggregatibacter actinomycetemcomitans are two commensals that can turn into opportunistic pathogens and are able to form robust biofilms. Objectives: This study aimed to assess the interaction dynamics between these two microorganisms and to evaluate their susceptibility to fluconazole and azithromycin in single- and mixed-species forms. Methods: Biofilm biomass was quantified using crystal violet assays, while biofilm cell viability was assessed through CFU enumeration (biofilm viability assay). To assess the resistance properties of single versus mixed-species coincubations, we applied the antimicrobial susceptibility test (AST) to each drug, and analysed spatial organization with confocal laser scanning microscopy, using PNA-FISH. Results: The results indicated that both species can coexist without significant mutual inhibition. However, a non-reciprocal synergism was also observed, whereby mixed-species biofilm conditions promoted the growth of A. actinomycetemcomitans, while C. albicans growth remained stable. As expected, antimicrobial tolerance was elevated in mixed cultures, likely due to enhanced extracellular matrix production and potential quorum-sensing interactions, contributing to increased resistance against azithromycin and fluconazole. Conclusions: This study provides novel insights into previously rarely explored interactions between C. albicans and A. actinomycetemcomitans. These findings underscore the importance of investigating interspecies interactions within polymicrobial biofilms, as understanding their mechanisms, such as quorum-sensing molecules and metabolic cooperation, can contribute to improved diagnostics and more effective targeted therapeutic strategies against polymicrobial infections. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Toothpaste is an essential oral hygiene product commonly used to sustain oral health due to its incorporation of antimicrobial agents. Numerous functional toothpastes enriched with antimicrobial agents have been developed and are available to consumers. This study evaluates the antimicrobial and antibiofilm efficacy of 12 commercially available toothpaste products, including those with specialized functions. Statistical significance was assessed to validate the differences observed among the toothpaste samples. Their effects on Streptococcus mutans, the primary pathogen responsible for dental caries, were evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and bacterial growth was measured to compare antimicrobial activities. Toothpaste containing 1000 μg/mL fluoride and whitening toothpaste exhibited the strongest antimicrobial effects, effectively inhibiting S. mutans growth. Additionally, bamboo salt-enriched and tartar-control toothpaste demonstrated inhibitory effects on bacterial growth. Assays to evaluate the ability of cells to form biofilms and the expression of genes involved in biofilm formation revealed a partial correlation between biofilm formation and spaP, gtfB, gtfC, and gtfD expression, although some showed opposite trends. Collectively, this study provides valuable insights into the antimicrobial and biofilm inhibition capabilities of commercial toothpastes against S. mutans, offering a foundation for evaluating the efficacy of functional toothpaste products. Full article

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Background/Objectives: Early gut colonization by bifidobacteria, occurring more favorably in vaginally born infants than in those delivered via C-section, is crucial for maintaining overall health. The study investigated the health-promoting properties of Limosilactobacillus vaginalis BC17 both as viable cells and as postbiotics (i.e., cell-free supernatant and heat-killed cells), with the purpose of developing oral formulations to support intestinal health. Methods: The safety, effects on the adhesion of bifidobacteria and enteropathogens to intestinal cells, and anti-inflammatory properties of L. vaginalis BC17 viable cells and postbiotics were evaluated. Fast-disintegrating tablets were formulated by freeze-drying cell-free supernatant in combination with heat-killed or viable cells alongside maltodextrins. Results: The formulations were shown to be non-genotoxic and compatible with intestinal cell lines (Caco-2 and HT-29). BC17 viable cells survived in co-culture with intestinal cells up to 48 h and exhibited moderate adhesion to the cell lines. Notably, both BC17 viable cells and postbiotics enhanced the adhesion of beneficial bifidobacteria to Caco-2 cells by up to 250%, while reducing enteropathogens adhesion by 40–70%. Moreover, they exerted significant anti-inflammatory effects, reducing nitric oxide production in macrophages by 40–50% and protecting intestinal cells from SDS-induced damage. The formulations allowed administration of at least 10⁹ BC17 cells in infants and adults through easy and rapid dispersion in milk or water, or directly in the oral cavity without chewing, and preserved their functional properties for up to 3 months of storage. Conclusions: L. vaginalis BC17 viable cells and postbiotics, as well as fast-disintegrating tablets, showed promising functional and safety profiles. Although further in vivo validation is needed, this approach represents a compelling strategy for promoting gut health. Full article

Quinoa protein isolate (QPI) and sodium alginate (SA) have excellent biocompatibility and functional properties, making them promising candidates for food-grade delivery systems. In this study, we developed, for the first time, a QPI/SA complex-stabilized Pickering emulsion for curcumin encapsulation. The coacervation behavior of QPI and SA was investigated from pH 1.6 to 7.5, and the structural and interfacial characteristics of the complexes were analyzed using zeta potential measurements, Fourier-transform infrared spectroscopy, scanning electron microscopy, and contact angle analysis. The results showed that the formation of QPI/SA complexes was primarily driven by electrostatic interactions, hydrogen bonding, and hydrophobic interactions, with enhanced amphiphilicity observed under optimal conditions (QPI/SA = 5:1, pH 5). The QPI/SA-stabilized Pickering emulsions demonstrated excellent emulsification performance and storage stability, maintaining an emulsification index above 90% after 7 d when prepared with 60% oil phase. In vitro digestion studies revealed stage-specific curcumin release, with sustained release in simulated gastric fluid (21.13%) and enhanced release in intestinal fluid (88.21%). Cytotoxicity assays using HeLa cells confirmed the biocompatibility of QPI/SA complexes (≤500 μg/mL), while curcumin-loaded emulsions exhibited dose-dependent anticancer activity. These findings suggest that QPI/SA holds significant potential for applications in functional foods and oral delivery systems. Full article

Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article

Simian foamy virus (SFV) is a retrovirus that infects primates. However, epidemiological studies of SFV are often limited to captive populations. The southeastern Brazilian Atlantic Forest is home to both an endemic, endangered species, Leontopithecus rosalia, and an introduced species, Leontopithecus chrysomelas, to which no data on SFV exist. In this study, we assessed the molecular prevalence of SFV, their viral load, and their phylogenetic relationship in these two species of primates. Genomic DNA was extracted from 48 oral swab samples of L. chrysomelas and 102 of L. rosalia. Quantitative PCR (qPCR) was performed to diagnose SFV infection and quantify viral load. SFV prevalence was found to be 23% in L. chrysomelas and 33% in L. rosalia. No age-related differences in prevalence were observed; however, L. rosalia showed a higher mean viral load (3.27 log10/10⁶ cells) compared to L. chrysomelas (3.03 log10/10⁶ cells). The polymerase gene sequence (213 pb) of L. rosalia (SFVlro) was clustered within a distinct SFV lineage found in L. chrysomelas. The estimated origin of SFVlro dated back approximately 0.0836 million years ago. Our study provides the first molecular prevalence data for SFV in free-living Leontopithecus populations while offering insights into the complex evolutionary history of SFV in American primates. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and currently is the second-leading cause of cancer-related mortality globally. Current front-line systemic therapies for advanced HCC offer only modest improvements in patient overall survival. HCC is a sexually dimorphic disease, and cancer progression is driven in part by AR activity. Here, we present novel niclosamide pro-drugs for use in advanced HCC based upon niclosamide’s known anti-AR activity and additional anti-cancer pathway efficacy. Methods: Niclosamide analogs were evaluated for their impacts on the AR protein in two HCC cell lines with different AR phenotypes. Amino acid conjugates of niclosamide were developed, and pharmacokinetic (PK) analyses were conducted to determine improvements in clearance and oral exposure. Finally, niclosamide analogs and amino acid conjugates were evaluated in an in vivo model of HCC. Results: Niclosamide analogs maintained anti-AR properties in HCC. Valine-conjugated niclosamide showed improved oral exposure, positioning it as a potential therapeutic in advanced HCC. Conclusions: Valine–niclosamide improves upon niclosamide’s poor solubility and oral bioavailability, increasing its utility for a variety of therapeutic uses. Further study of valine–niclosamide in advanced HCC and in other cancers or diseases is warranted. Full article

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article