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Journal of Functional Foods · 2026 · IF 3.9

Menthol, a dietary bioactive monoterpene, alleviates LPS-induced intestinal inflammation in a weaned piglet model: potential involvement of the Piezo1/TPH1/5-HT axis

Li Dong,You Wu,Yangshu Zhou,Hongrong Wang,Lihuai Yu

Menthol is a widely consumed dietary monoterpene found in peppermint oil, yet its effects on intestinal health under inflammatory conditions remain poorly understood. This study investigated the protective effects of dietary menthol against lipopolysaccharide (LPS)-induced intestinal inflammation in a weaned piglet model, focusing on the enteroendocrine Piezo1/TPH1/5-HT signaling axis. Sixty 28-day-old Duroc × (Landrace × Large White) weaned piglets were randomly assigned to five groups: a non-challenged control (CON), an LPS-challenged group, and three LPS-challenged groups receiving menthol at 12.5, 25, or 50 mg/kg of diet in a 22-day trail (21-day feeding +6 h post-LPS). Supplementation with 25 mg/kg menthol of diet significantly increased average daily body weight gain (ADG) and average daily feed intake (ADFI) while reducing the incidence of diarrhea before LPS challenge ( P  < 0.05). After LPS administration, menthol markedly attenuated intestinal injury, as evidenced by reduced serum lactate dehydrogenase (LDH) activity and lower levels of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in both serum and intestinal tissues ( P  < 0.05). Morphologically, menthol increased villus height and the villus height to crypt depth ratio (VH/CD), decreased crypt depth ( P  < 0.05), and preserved microvilli density, tight junction integrity, and nuclear morphology of the small intestine. Notably, menthol partially restored the LPS-induced loss of enteroendocrine cells and normalized gut hormone profiles, specifically reducing serotonin (5-HT) and gastrin while increasing somatostatin. Mechanistically, menthol appeared to suppress the LPS-induced upregulation of the mechanosensor Piezo1, the 5-HT-synthesizing enzyme tryptophan hydroxylase 1 (TPH1), and the 5-HT3 receptor at both the gene and protein levels ( P  < 0.05). These findings suggested that dietary menthol, particularly at 25 mg/kg of diet, alleviated intestinal inflammation, potentially by preserving enteroendocrine cell homeostasis and downregulating the Piezo1/TPH1/5-HT signaling pathway. This study provides new evidence for the potential application of menthol as a functional food ingredient to support gut health.

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Nanoscale · 2023 ·Vol. 15 ·期 8 ·4123-4136 · IF 6.7

Magnetic nanocomposites for magneto-promoted osteogenesis: from simulation auxiliary design to experimental validation

Lili Hao,Jiaxiang Li,Peng Wang,Zongliang Wang,Yu Wang,Yongzhan Zhu,Min Guo,Peibiao Zhang

Magnetically actuated mechanical stimulation, as a novel form of intelligent responsive force stimulation, has a great potential for remote spatiotemporal regulation of a variety of life processes. Hence, the optimal design of magnetic nanomaterials for generating magneto-mechanical stimuli becomes an important driving force in the development of magneto-controlled biotherapy. This study aims to clarify the general rule that the surface modification amount of magnetic nanoparticles (NPs) affects the biological behavior (e.g., cell adhesion, proliferation and differentiation) of pre-osteoblast cells. First of all, course-grained molecular dynamics simulations predict that 23.3% graft modification of the NPs can maximize the heterogeneity of the dynamics of the polymer matrix, which may generate enhanced mechanical stimuli. Then, experimentally, iron oxide (IO) NPs grafted with different amounts of poly(γ-benzyl-L-glutamate) (PBLG) were prepared to obtain homogeneous magnetic nanocomposites with improved mechanical properties. Further in vitro cell experiments demonstrate that the grafting amounts of 21.46% and 32.34% of PBLG on IO NPs are the most beneficial for the adhesion and osteogenic differentiation of cells. Simultaneously, the maximized upregulation of the Piezo1 gene indicates that the cells receive the strongest magneto-mechanical stimuli. The consistent conclusion of the experiments and simulations indicates that 20–30% PBLG grafted on the IO surface could maximize the ability of magnetic stimuli to regulate the biological behavior of the cells, which validates the feasibility of simulation auxiliary material design and is of great importance for promoting the application of magneto-controlled biotherapy in bioengineering and biomedicine.

CAS / MDL: 10025-77-1 32315-10-9
研究领域: 生物工程 · 生物医学工程 · 材料科学 · 细胞生物学
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ADVANCED FUNCTIONAL MATERIALS · 2023 · IF 19

4D Oriented Dynamic Scaffold for Promoting Peripheral Nerve Regeneration and Functional Recovery

Mouyuan Sun,Dongqi You,Ning Zhan,Chao Liu,Xiaoting Zhang,Lining Lin,Jingyu Zhang,Yiting Lou,Yuewei Chen,Chundi Liu,Huiming Wang,Yong He,Mengfei Yu

Neurological function recovery after peripheral nerve injury (PNI) is exceptionally challenging, chiefly because neurons cannot efficiently proliferate, differentiate, and form regenerated axons to pass through the defect region expeditiously and transmit neurological signals. In this study, a four-dimensional (4D) oriented dynamic scaffold is constructed based on shape memory polymer (SMP), which can regulate spatiotemporally controllable neuronal early adequate proliferation, subsequently effective differentiation and axon formation by synergizing the on-demand microtopography and deformation force-based mechanical stimuli (DFMS). This dynamic scaffold can accelerate the restoration of large segmental nerve defects, elevate the neural signaling efficiency by 60% compared with static scaffold, and finally form the functionalized robust regenerating nerve fascicles with comparable therapeutic effects on autologous nerve transplantation. Furthermore, the crucial role of Piezo1/Camk2b modulated neuronal differentiation and axon extension is also revealed through deep transcriptomic analysis. In summary, the 4D oriented dynamic scaffold can precisely and remotely regulate neuronal behavior and fate in a non-invasive way, which has excellent potential for clinical application in peripheral nerve restoration.

CAS / MDL: 68-12-2
研究领域: 生物医学工程 · 神经科学 · 组织工程 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Injectable, viscoelastic hydrogel precisely regulates developmental tissue regeneration

Zihan Wu,Zhaogang Yang,Dongyong Sha,Yifan Ma,Betty Y.S. Kim,Wen Jiang,Yuan Yuan,Changsheng Liu

Extracellular matrix viscoelasticity is a crucial parameter for designing biomaterials in tissue regeneration. However, the precise control of viscoelastic properties for reproducing the mechanical environment that cells experience in vivo remains a challenge. Here, we developed a series of injectable, viscoelastic PEGylated poly (glycerol sebacate) (PEGS-OH) hydrogels crosslinked via click chemistry and investigated the role of viscoelasticity in developmental tissue regeneration. We found that, compared to 100% and 60% crosslink degrees, 80% crosslinked PEGS-OH with incomplete network slipping promoted a striking increase in the adhesion and differentiation of bone mesenchymal stem cells (BMSCs). Moreover, with PEG segments increasing, the elastic hydrogel turned into viscous state and regulated BMSCs differentiation from osteogenesis to adipogenesis. Further studies revealed that the crosslink degree- and PEG segment-induced BMSCs response was greatly relied on the mechanosensitive Piezo1 mechanism. With in vivo cartilago articularis and skull defect regeneration as models, tendencies from experiments in vitro were further confirmed. Our findings highlight a potential material-biological strategy to precisely regulate cell fate and ensuing tissue regeneration, and provide insight into the relevance of material viscoelasticity in the fate of stem cell differentiation.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 力学生物学
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Nanoscale · 2019 ·Vol. 11 ·期 48 ·23423-23437 · IF 6.97

Synergistic osteogenesis promoted by magnetically actuated nano-mechanical stimuli

Lili Hao,Linlong Li,Peng Wang,Zongliang Wang,Xincui Shi,Min Guo,Peibiao Zhang

Functional biomaterials with magnetic properties are considerably useful for regulating cell behavior and promoting bone regeneration. And the combination of such biomaterials with physical environmental cues (such as magnetic fields and mechanical stress) might be more favorable for the regulation of cell function. This study is aimed at investigating the combined effects of magnetically responsive materials and a static magnetic field (SMF) on the osteogenic differentiation of osteoblasts and the potential mechanism involved. In this study, oleic acid modified iron oxide nanoparticles (IO-OA NPs) were utilized to generate homogeneous magnetic nanocomposites with poly(lactide-co-glycolide) (PLGA) used as the base and to enhance the mechanical properties of the composites. In vitro experimental results show that in the presence of an external SMF, cell attachment and osteogenic differentiation were significantly improved using the IO-OA/PLGA composites, as indicated by enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated bone-associated gene expression (ALP, OCN, and BMP2), in a dose- and time-dependent manner. Furthermore, the upregulated expression levels of piezo-type mechanosensitive ion channel component 1 (Piezo1), a key receptor for sensing mechanical stimuli, implied that the synergistically enhanced osteogenic differentiation was mainly caused as a result of the mechanical stimuli. Such magnetically actuated mechanical stimuli were induced through the nano-deformation of the magnetic substrate under a SMF, which was directly characterized via in situ scanning using atomic force microscopy (AFM). This study demonstrates that magnetically actuated nano-mechanical stimuli may underpin the synergistic effects of magnetic composites and magnetic stimuli to enhance osteogenic differentiation, and they could form the basis of a potential strategy to accelerate bone formation for bone tissue engineering and regenerative medicine applications.

研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学
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