The aim of this study was to investigate the effect of evodiamine (EV) on dexamethasone-induced osteoporosis in zebrafish. Zebrafish larvae were exposed to different concentrations of dexamethasone to obtain the osteoporosis in zebrafish. Calcium, phosphorus, and alizarin red staining determination were performed to evaluate the effects of EV on bone mineralization. Alkaline phosphatase (ALP), hydroxyproline (HP), and tartrate resistant acid phosphatase (TRAP) were also measured by commercial kits. The expression of MMP3-OPN-MAPK pathway in zebrafish was measured by Western blot. RT-PCR was used to determine mRNA levels of MMP3, OPN, and MAPK. EV could significantly increase the content of calcium and phosphorus. The results of alizarin red staining showed that EV could significantly increase the calcium sink of horse fish, increasing the area of bone formation. EV could increase the content of hydroxyproline in zebrafish. EV also increased ALP and TRAP in zebrafish. Western blot and RT-PCR results showed that EV restored the MMP3-OPN-MAPK pathway in zebrafish. In conclusion, we found that EV can alleviate dexamethasone-induced osteoporosis in zebrafish. The mechanism is related to activating MMP3-OPN-MAPK pathway and then activating bone remodeling.

Osteoporosis is a chronic inflammatory disease that severely affects quality of life. Cornus officinalis is a Chinese herbal medicine with various bioactive ingredients, among which morroniside is its signature ingredient. Although anti-bone resorption drugs are the main treatment for bone loss, promoting bone anabolism is more suitable for increasing bone mass. Therefore, identifying changes in bone formation induced by morroniside may be conducive to developing effective intervention methods. In this study, morroniside was found to promote the osteogenic differentiation of bone marrow stem cells (BMSCs) and inhibit inflammation-induced bone loss in an in vivo mouse model of inflammatory bone loss. Morroniside enhanced bone density and bone microstructure, and inhibited the expression of IL6, IL1β, and ALP in serum (p < 0.05). Furthermore, in in vitro experiments, BMSCs exposed to 0–256 μM morroniside did not show cytotoxicity. Morroniside inhibited the expression of IL6 and IL1β and promoted the expression of the osteogenic transcription factors Runx2 and OCN. Furthermore, morroniside promoted osteocalcin and Runx2 expression and inhibited TRAF6-mediated NF-κB and MAPK signaling, as well as osteoblast growth and NF-κB nuclear transposition. Thus, morroniside promoted osteogenic differentiation of BMSCs, slowed the occurrence of the inflammatory response, and inhibited bone loss in mice with inflammatory bone loss.

Plant-derived extracellular vesicles (PDEVs) are bioactive nanoscale vesicles secreted by plant cells, which have recently gained attention as promising therapeutic agents in tissue engineering owing to their low immunogenicity, inherent biological activities, and potential as drug delivery vehicles. This review comprehensively outlines the general properties, application-specific characteristics, and isolation techniques of PDEVs, with a particular emphasis on their roles in facilitating cell proliferation, differentiation, and immunomodulation to promote tissue regeneration. We further discuss the therapeutic efficacy of PDEVs derived from various plant sources across different tissue engineering contexts, as well as the application of engineered PDEVs in tailored regenerative strategies. In comparison to mammalian extracellular vesicles, PDEVs present distinct advantages, including minimized ethical concerns and reduced risks of immune rejection. Nevertheless, challenges remain for their clinical translation, such as the lack of standardized isolation protocols and inadequate assessment of long-term in vivo safety. This article synthesizes current understanding of PDEVs, underscores their multifunctional potential, and offers perspectives on engineering approaches aimed at enhancing their therapeutic performance. With continued development, PDEVs may emerge as innovative tools in tissue engineering, facilitating tissue repair and regeneration either through their innate bioactivity or as engineered drug delivery systems.

Background: Emerging research indicates that gut microbiota (GM) are pivotal in the regulation of immune-mediated bone diseases. Nonunion, a bone metabolic disorder, has an unclear causal relationship with GM and immune cells. This study aims to elucidate the causal relationship between GM and nonunion using Mendelian Randomization (MR) and to explore the mediating role of immune cells.Methods: Using a two-step, two-sample Mendelian randomization approach, this study explores the causal link between GM and nonunion, as well as the mediating role of immune cells in this relationship. Data were sourced from multiple cohorts and consortiums, including the MiBioGen consortium. GM data were derived from a recently published dataset of 473 gut microbiota, and nonunion data were obtained from genome-wide association studies (GWAS).Results: MR analysis identified 12 bacterial genera with protective effects against nonunion and seven bacterial genera associated with a higher risk of nonunion, including Agathobacter sp000434275, Aureimonas, Clostridium M, Lachnospirales, Megamonas funiformis, and Peptoccia. Reverse MR analysis indicated that nonunion does not influence GM. Additionally, MR analysis identified 12 immune cell types positively associated with nonunion and 14 immune cell types negatively associated with nonunion. Building on these findings, we conducted mediation MR analysis to identify 24 crucial GM and immune cell-mediated relationships affecting nonunion. Notably, Campylobacter D, Megamonas funiformis, Agathobacter sp000434275, Lachnospirales, Clostridium E sporosphaeroides, and Clostridium M significantly regulated nonunion through multiple immune cell characteristics.Conclusions: To our knowledge, our research results are the first to emphasize a causal relationship between the gut microbiome and nonunion, potentially mediated by immune cells. The correlations and mediation effects identified in our study provide valuable insights into potential therapeutic strategies targeting the gut microbiome, informing global action plans.

The genus Ligustrum (Oleaceae) encompasses woody plants with both medicinal and edible uses, distinguished by a wide range of bioactive compounds, including triterpenoids, phenylethanoid glycosides, flavonoids, and other active constituents. These metabolites demonstrate multi-target pharmacological effects, such as anti-inflammatory, antioxidant, antitumor, and anti-osteoporotic activities. In traditional medicine, species like L. lucidum and L. robustum are well-documented for their therapeutic roles in nourishing the liver and kidneys, enhancing vision, darkening hair, and serving as functional tea ingredients. Beyond their medicinal and health-promoting properties, Ligustrum species are also employed as ornamental plants, bioindicators of atmospheric pollution, algicidal agents, and feed additives. Given the increasing global demand and underutilization of Ligustrum resources, there is an urgent need to establish a sustainable supply framework focused on alternative strategies such as metabolic engineering, synthetic biology, and environmentally friendly manufacturing. This review encapsulates recent progress in the exploration of chemical diversity, pharmacological characteristics, omics-based analyses, and biosynthetic research pertaining to Ligustrum . It proposes an integrated methodology that amalgamates multi-omics approaches, synthetic biology, and environmentally sustainable manufacturing processes to advance strategies for whole-plant valorization and germplasm conservation. The objective is to establish a theoretical framework and technical paradigm to facilitate the comprehensive exploitation and sustainable utilization of Ligustrum as a medicinal resource.

Acrylamide is a widespread environmental and dietary contaminant, and hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) serve as objective biomarkers of internal exposure. However, the association between acrylamide exposure and rheumatoid arthritis (RA) has not been well characterized at the population level. We analyzed data from 4 cycles of the US National Health and Nutrition Examination Survey (2003–2006 and 2013–2016), including 1972 adults aged ≥20 years with complete information on RA status and acrylamide hemoglobin adduct measurements. Multivariable logistic regression models accounting for the complex survey design were used to examine associations between HbAA, HbGA, total adducts (HbAA + HbGA), the metabolic ratio (HbGA/HbAA), and RA prevalence. Restricted cubic spline models were applied to explore potential nonlinear exposure–response relationships. Nonlinear associations were observed between acrylamide-related hemoglobin adducts and the prevalence of RA. HbAA exhibited a J-shaped association, with higher odds observed at intermediate exposure levels. In contrast, HbGA and total adduct concentrations showed increasing associations across higher exposure ranges. The HbGA/HbAA ratio was positively associated with RA prevalence. Restricted cubic spline analyses supported these non-monotonic exposure–response patterns. Subgroup analyses showed variability in point estimates across behavioral and clinical strata, but estimates were often imprecise and should be interpreted as exploratory. In this nationally representative cross-sectional study, HbAA was nonlinearly associated with the prevalence of RA among US adults. These findings support an epidemiological association between internal biomarkers of acrylamide exposure and RA. Prospective studies with repeated exposure assessment and mechanistic measurements are needed to clarify temporal relationships and underlying biological pathways.