Comparison of nanovesicles derived from Panax notoginseng at different size: physical properties, composition, and bioactivity.

Aim: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. Methods: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Results: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Conclusion: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

A unilateral increase in the occlusal vertical dimension of growing rats results in mandibular deviation.

OBJECTIVE: The effects of unilateral increased occlusal vertical dimension (iOVD) on bilateral craniofacial, mandibular and alveolar development in growing rats were investigated via cone-beam computed tomography (CBCT). The role of Wnt/ß-catenin signalling in this process was examined. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were randomly allocated into unilateral iOVD and sham groups. At 2, 4 and 8 weeks, the rats were scanned via CBCT to analyse cranial, maxillary, mandibular and dental morphology. Changes in temporomandibular joint (TMJ) cartilage histology and Wnt/ß-catenin signalling were assessed by histochemical and immunohistochemical staining and qRT-PCR. RESULTS: Dorsal cephalograms revealed that the mandible in the iOVD group tilted approximately 4° to the right. Unilateral iOVD had little effect on cranial and maxillary growth but inhibited mandibular growth (mandibular length and ramal height), especially on the deviated side (DS). Moreover, unilateral iOVD increased the length of the lower incisors and decreased the height of the molars on the DS. Unilateral iOVD induced bilateral osteoarthritis-like changes in the bilateral TMJ condylar cartilage and activated Wnt/ß-catenin signalling in the condylar cartilage, especially on the contralateral side (CLS). CONCLUSION: Occlusion with unilateral iOVD induced mandibular deviation, significantly inhibited mandibular growth and produced compensatory changes in the alveolar bone. In the iOVD group, the mandibular body length and ramal height were greater on the CLS than on the DS. Moreover, the greater ß-catenin protein expression in the TMJ condylar cartilage on the CLS than on the DS may account for the difference in asymmetrical mandibular development.

Effect of different approaches of direct radiation on the surface structure and caries susceptibility of enamel.

It is not clear whether different radiation methods have different effects on enamel. The purpose of this study was to compare the effects of single and fractionated radiation on enamel and caries susceptibility and to provide an experimental basis for further study of radiation­related caries. Thirty-six caries-free human third molars were collected and randomly divided into three groups (n = 12). Group1 (control group) was not exposed to radiation. Group 2 received single radiation with a cumulative dose of 70 Gy. Group 3 underwent fractionated radiation, receiving 2 Gy/day for 5 days followed by a 2-day rest period, for a total of 7 weeks with a cumulative dose of 70 Gy. Changes in microhardness, roughness, surface morphology, bacterial adhesion and ability of acid resistance of each group were tested. Scanning electron microscope revealed that the enamel surface in both radiation groups exhibited unevenness and cracks. Compared with the control group, microhardness and acid resistance of enamel decreased, while roughness and bacterial adhesion increased in both the single radiation and fractionated radiation groups. Compared with the single radiation group, the enamel surface microhardness and acid resistance decreased in the fractionated radiation group, while roughness and bacterial adhesion increased. Both single radiation and fractionated radiation resulting in changes in the physical and biological properties of enamel, with these changes being more pronounced in the fractionated radiation group. Therefore, fractionated radiation is recommended as a more suitable method for constructing a radiation­related caries model in vitro.

Evaluating stability and bioactivity of Rehmannia-derived nanovesicles during storage.

Plant-derived nanovesicles (PDNVs) have garnered growing attention in the biomedical field owing to their abundance in plant-derived ribonucleic acids (RNA), proteins, lipids and metabolites. The question about the preservation of PDNVs is a crucial and unavoidable concern in both experiments' settings and their potential clinical application. The objective of this research was to examine the impact of varying storage temperatures on the stability and bioactivity of Rehmannia-derived nanovesicles (RDNVs). The results showed that RDNVs aggregated after 2 weeks of storage period at 4 °C, and the particle size of some RDNVs gradually increased with time, along with the increase of solution potential. After 2 months of storage, all RDNVs exhibited varying levels of aggregation irrespective of storage temperature. The bioactivities of nanovesicles under different temperature storage conditions revealed a gradual decline in cell proliferation inhibition bioactivity over time, significantly lower than that of freshly prepared RDNVs. In contrast, the preservation of anti-migratory activity in RDNVs was found to be more effective when subjected to rapid freezing in liquid nitrogen followed by storage at - 80 °C, as opposed to direct storage at - 80 °C. These findings suggest that temperature alone may not be sufficient in safeguarding the activity and stability of RDNVs, highlighting the necessity for the development of novel protective agents for PDNVs.

The dynamic progression of temporomandibular joint osteoarthritis-like lesions elicited by mandibular shift in a rat model.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) presents significant challenges due to its complex etiology, often insidious onset, high incidence, and progressive structural deterioration. While research has explored genetic and molecular factors, treatment outcomes remain suboptimal, emphasizing the need for a deeper understanding of disease progression. OBJECTIVE: This study employs a specific mandibular shift rat model to explore the dynamic progression of TMJ-OA-like lesions and evaluate the potential for self-repair at different stages, aiming to inform early diagnosis and preventative strategies. METHODS: Seventy-two female Sprague-Dawley rats were randomized into three groups: a control group (n=24; average weight: 157.23±1.63 g) receiving sham surgery. an experimental group (n=24; average weight: 157.78±1.88 g) subjected to mandibular shift induction, and a removal group (n=24; average weight: 158.11±2.20 g) experiencing mandibular shift for one, two, or four weeks followed by a one-month recovery period (designated as 1w Removal, 2w Removal and 4w Removal, respectively). Histomorphological and molecular analyses were conducted at designated time points. RESULTS: Rats in the 1-week removal group exhibited substantial recovery in condylar morphology, cartilage thickness, extracellular matrix composition, and expression of OA-related genes. Conversely, the 4-week removal group mirrored the experimental group, indicating limited self-repair capacity at later stages. The 2-week removal group presented with variable outcomes, with some animals showing signs of recovery and others resembling the experimental group, indicating a potential transitional phase in the disease process. CONCLUSION: Recovery from early-stage TMJ-OA involves eliminating provoking factors such as occlusal interference or reducing joint loading. However, advanced stages exhibit diminished self-repair capabilities, necessitating additional therapeutic interventions. These findings emphasize the importance of early diagnosis and intervention in TMJ-OA management.

O-carboxymethyl chitosan in biomedicine: A review.

O-carboxymethyl chitosan (O-CMC) is a chitosan derivative produced through the substitution of hydroxyl (-OH) functional groups in glucosamine units with carboxymethyl (-CH2COOH) substituents, effectively addressing the inherent solubility issues of chitosan in aqueous solutions. O-CMC has garnered significant interest due to its enhanced solubility, elevated viscosity, minimal toxicity, and advantageous biocompatibility properties. Furthermore, O-CMC demonstrates antibacterial, antifungal, and antioxidant characteristics, rendering it a promising candidate for various biomedical uses such as wound healing, tissue engineering, anti-tumor therapies, biosensors, and bioimaging. Additionally, O-CMC is well-suited for the fabrication of nanoparticles, hydrogels, films, microcapsules, and tablets, offering opportunities for effective drug delivery systems. This review outlines the distinctive features of O-CMC, offers analyses of advancements and future potential based on current research, examines significant obstacles for clinical implementation, and foresees its ongoing significant impacts in the realm of biomedicine.

Exploring new avenues of health protection: plant-derived nanovesicles reshape microbial communities.

Symbiotic microbial communities are crucial for human health, and dysbiosis is associated with various diseases. Plant-derived nanovesicles (PDNVs) have a lipid bilayer structure and contain lipids, metabolites, proteins, and RNA. They offer unique advantages in regulating microbial community homeostasis and treating diseases related to dysbiosis compared to traditional drugs. On the one hand, lipids on PDNVs serve as the primary substances that mediate specific recognition and uptake by bacteria. On the other hand, due to the multifactorial nature of PDNVs, they have the potential to enhance growth and survival of beneficial bacterial while simultaneously reducing the pathogenicity of harmful bacteria. In addition, PDNVs have the capacity to modulate bacterial metabolism, thus facilitating the establishment of a harmonious microbial equilibrium and promoting stability within the microbiota. These remarkable attributes make PDNVs a promising therapeutic approach for various conditions, including periodontitis, inflammatory bowel disease, and skin infection diseases. However, challenges such as consistency, isolation methods, and storage need to be addressed before clinical application. This review aims to explore the value of PDNVs in regulating microbial community homeostasis and provide recommendations for their use as novel therapeutic agents for health protection.

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical ß-catenin pathway.

BACKGROUND: 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection. METHODS: 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. RESULTS: In this study, the WNT/ß-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. CONCLUSIONS: These data underscored the activation of the WNT/ß-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.

Investigating diagnostic potential of long non-coding RNAs in head and neck squamous cell carcinoma using TCGA database and clinical specimens.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and prognostically challenging cancer worldwide. The role of long non-coding RNAs (lncRNAs) in cancer regulation is progressively being understood. This study aims to identify lncRNAs with diagnostic potential as biomarkers for HNSCC. Statistical analysis was performed on expression data from the Cancer Genome Atlas (TCGA) database to identify potential lncRNAs associated with HNSCC. Four selected lncRNAs were validated using real-time quantitative reverse transcription polymerase chain reaction and correlated with clinical factors. Functional roles were further investigated. A total of 488 differentially expressed lncRNAs were identified in TCGA-HNSC. After rigorous evaluation based on p-values, survival analysis, and ROC analysis, 24 lncRNAs were prioritized for additional investigation. LINC00460, LINC00941, CTC-241F20.4, and RP11-357H14.17 were established as candidate diagnostic biomarkers. These lncRNAs exhibited elevated expression in HNSCC tissues and were associated with poor prognosis. Combining them showed high diagnostic accuracy. Notably, LINC00460 and CTC-241F20.4 demonstrated a significant elevation in the advanced stages of HNSCC. We constructed an lncRNA-mRNA regulatory network, and the array of significant regulatory pathways identified included focal adhesion, regulation of epithelial cell migration, and others. Additionally, these lncRNAs were found to influence immune responses by modulating immune cell infiltration in the HNSCC microenvironment. Our research indicates that LINC00460, LINC00941, RP11-357H14.17, and CTC-241F20.4 may have diagnostic and prognostic importance in HNSCC. Furthermore, we have gained insights into their potential functional roles, particularly about immune responses and interactions in the microenvironment.

MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.

The p53 tumor suppressor protein plays an important role in physiological and pathological processes. MDM2 and its homolog MDMX are the most important negative regulators of p53. Many studies have shown that MDMX promotes the growth of cancer cells by influencing the regulation of the downstream target gene of tumor suppressor p53. Studies have found that inhibiting the MDMX-p53 interaction can effectively restore the tumor suppressor activity of p53. MDMX has growth-promoting activities without p53 or in the presence of mutant p53. Therefore, it is extremely important to study the function of MDMX in tumorigenesis, progression and prognosis. This article mainly reviews the current research progress and mechanism on MDMX function, summarizes known MDMX inhibitors and provides new ideas for the development of more specific and effective MDMX inhibitors for cancer treatment.

Anti-Microbial Effect of AgBr-NP@CTMAB on Streptococcus Mutans and Assessment of Surface Roughness Hardness and Flexural Strength of PMMA.

Purpose: To investigate the inhibition of Streptococcus mutans (S.mutans) and its biofilm by AgBr-nanoparticles (NP) @CTMAB (cetyltrimethyl-ammonium bromide) and evaluate the changes in Polymethyl methacrylate (PMMA)'s surface roughness (Ra), microhardness, and flexural strength during prolonged immersion in AgBr-NP@CTMAB for application in the denture cleaning industry. Patients and Methods: The antibacterial activity of AgBr-NP@CTMAB against S.mutans was measured colony formation assay, OD600 and laser confocal microscopy. Changes in the specimens' values for surface roughness, microhardness, and flexural strength (MPa) were measured after immersion solutions for 180 or 360 days. Results: The AgBr-NP@CTMAB solution exhibited a robust antibacterial effect on planktonic S. mutans, with a minimum bactericidal concentration of 5 µg/mL. The 10 µg/mL AgBr-NP@CTMAB solution efficiently inhibited S. mutans biofilm formation. (2) No significant difference in surface roughness after immersion in AgBr-NP@CTMAB (10 µg/mL and 20 µg/mL) comparing with distilled water (P > 0.05) and Polident had significantly higher than distilled water (P < 0.05). There was a significant decrease in the surface hardness of the PMMA specimens that were immersed in the Polident compared with those in distilled water (P < 0.05). While, no significant differences in surface hardness after immersion in the AgBr-NP@CTMAB (P > 0.05). The result of flexural strength suggested that there was no statistically significant difference (P < 0.05) between AgBr-NP@CTMAB as well as Polident and water. Conclusion: AgBrNP@CTMAB can efficiently inhibit the growth of plankton S.mutans and biofilm formation, without affecting the flexural strength, microhardness, or surface roughness of PMMA. Therefore, AgBrNP@CTMAB holds promise as a new denture cleaning agent.

The Association Between Vitamin D and Early Childhood Caries: A Systematic Review and Meta-Analysis.

PURPOSE: Previous surveys have reported that children with vitamin D deficiency were likely to suffer from early childhood caries (ECC). The aim of this systematic review and meta-analysis was to determine 1. whether the status of vitamin D is intrinsically related to the occurrence of ECC and 2. the optimal level of vitamin D for the prevention of ECC. MATERIALS AND METHODS: The database of PubMed, Web of Science, Cochrane, Embase and Google scholar were searched for targeted literature. The eligibility criteria were observational studies in which children with ECC were compared to children without ECC in terms of their vitamin D status. Applying the Newcastle-Ottawa tool, study selection, data extraction, and risk of bias assessment were performed by 2 reviewers independently. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.4 software. RESULTS: 501 articles were retrieved from the electronic databases; 11 studies were finally included in systematic review, 10 studies of which were submitted to meta-analysis. The 25(OH)D levels in the ECC group were statistically significantly lower compared with that in the caries-free group (WMD = -13.96, 95% CI: [-19.88,-8.03], p < 0.001), especially in regard to the association between S-ECC and vitamin D (WMD = -18.64, 95% CI: [-20.06,-17.22], p < 0.001). The subgroup analyses in terms of geographical region demonstrated that children with a level of 25(OH)D of 50-75 nmol/l were more likely to have ECC than those with over 75 nmol/l (OR = 1.42, 95% CI: [1.26,1.60], p < 0.001), with data from Asia and Europe combined for analysis Conclusions: The level of vitamin D was lower in children with ECC than in caries-free children, and the correlation between S-ECC and vitamin D was even stronger. The optimal 25(OH)D level for preventing occurrence and development of ECC was ≥ 75 nmol/l. Thus, clinicians should view the development of early caries also from a systemic perspective.

IL-8 activates fibroblasts to promote the invasion of HNSCC cells via STAT3-MMP1.

Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling.

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-ß-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Regulation of the Notch signaling pathway by natural products for cancer therapy.

The Notch signaling pathway is an evolutionarily conserved pathway that modulates normal biological processes involved in cellular differentiation, apoptosis, and stem cell self-renewal in a context-dependent fashion. Attributed to its pleiotropic physiological roles, both overexpression and silencing of the pathway are associated with the emergence, progression, and poorer prognosis in various types of cancer. To decrease disease incidence and promote survival, targeting Notch may have chemopreventive and anti-cancer effects. Natural products with profound historical origins have distinguished themselves from other therapies due to their easy access, high biological compatibility, low toxicity, and reliable effects at specific physiological sites in vivo. This review describes the Notch signaling pathway, particularly its normal activation process, and some main illnesses related to Notch signaling pathway dysregulation. Emphasis is placed on the effects and mechanisms of natural products targeting the Notch signaling pathway in diverse cancer types, including curcumin, ellagic acid (EA), resveratrol, genistein, epigallocatechin-3-gallate (EGCG), quercetin, and xanthohumol and so on. Existing evidence indicates that natural products are feasible solution to fight against cancer by targeting Notch signaling, either alone or in combination with current therapeutic agents.

Exploring the Role of Wnt Ligands in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.

OBJECTIVES: This study aimed to investigate the functions of 19 types of Wnt ligands during the process of osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs), with particular attention to WNT3A and WNT4. MATERIALS AND METHODS: The expression levels of 19 types of Wnt ligands were examined using real-time quantitative polymerase chain reaction (real-time qPCR) during hPDLSCs osteogenic differentiation at 7, 10, and 14 days. Knockdown of WNT3A and WNT4 expression was achieved using adenovirus vectors, and conditioned medium derived from WNT3A and WNT4 overexpression plasmids was employed to investigate their roles in hPDLSCs osteogenesis. Osteogenic-specific genes were analyzed using real-time qPCR. Alkaline phosphatase (ALP) and alizarin red S activities and staining were employed to assess hPDLSCs' osteogenic differentiation ability. RESULTS: During hPDLSCs osteogenic differentiation, the expression of 19 types of Wnt ligands varied, with WNT3A and WNT4 showing significant upregulation. Inhibiting WNT3A and WNT4 expression hindered hPDLSCs' osteogenic capacity. Conditioned medium of WNT3A promoted early osteogenic differentiation, while WNT4 facilitated late osteogenesis slightly. CONCLUSION: Wnt ligands, particularly WNT3A and WNT4, play an important role in hPDLSCs' osteogenic differentiation, highlighting their potential as promoters of osteogenesis. CLINICAL RELEVANCE: Given the challenging nature of alveolar bone regeneration, therapeutic strategies that target WNT3A and WNT4 signaling pathways offer promising opportunities. Additionally, innovative gene therapy approaches aimed at regulating of WNT3A and WNT4 expression hold potential for improving alveolar bone regeneration outcomes.

Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair.

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Antitumor effect of toosendanin on oral squamous cell carcinoma via suppression of p-STAT3.

BACKGROUND: Toosendanin (TSN) exhibits potent antitumor activity against various tumor cell lines. However, its efficacy against oral squamous cell carcinoma (OSCC) remains unknown. Here, we investigated the effects of TSN on OSCC cells in vitro and verified them in vivo using a patient-derived xenograft (PDX) model. METHODS: The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by western blotting. An OSCC PDX model was constructed to further investigate the role of TSN in regulating the function of OSCC. RESULTS: The cell viability of CAL27 and HN6 cells decreased as the concentration of TSN increased within the experimental range. Compared with controls, TSN at lower doses inhibited cell proliferation and induced apoptosis through S-phase cell cycle arrest. TSN inhibited OSCC cell proliferation by downregulating the STAT3 pathway through the inhibition of STAT3 phosphorylation. After successful construction of the OSCC PDX model with high pathological homology to the primary tumor and treatment with an intraperitoneal injection of TSN, we showed that TSN significantly reduced the tumor size of the PDX model mice without obvious toxicity. CONCLUSIONS: Both in vitro and in vivo, TSN significantly inhibits the proliferation and promoted apoptosis of OSCC cells. Furthermore, TSN demonstrates potent inhibition of STAT3 phosphorylation, indicating its potential as a promising therapeutic agent for OSCC. Therefore, TSN holds great promise as a viable drug candidate for the treatment of OSCC.

Engineered Plant-Derived Nanovesicles Facilitate Tumor Therapy: Natural Bioactivity Plus Drug Controlled Release Platform.

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

The Emerging Roles of Ferroptosis in Neonatal Diseases.

Ferroptosis is a novel type of programmed cell death involved in many diseases' pathological processes. Ferroptosis is characterized by lipid peroxidation, reactive oxygen species accumulation, and iron metabolism disorder. Newborns are susceptible to ferroptosis due to their special physiological state, which is prone to abnormal iron metabolism and the accumulation of reactive oxygen species. Recent studies have linked ferroptosis to a variety of diseases in the neonatal period (including hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis). Ferroptosis may become an effective target for the treatment of neonatal-related diseases. In this review, the ferroptosis molecular mechanism, metabolism characteristics of iron and reactive oxygen species in infants, the relationship between ferroptosis and common infant disorders, and the treatment of infant diseases targeted for ferroptosis are systematically summarized.