DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 7
·597-605
·
IF 4.4
Ting Wu,Lu Li,Wenhong Zhou,Guofang Bi,Xiaowen Jiang,Manlan Guo,Xiao Yang,Jianhong Fang,Jianxin Pang,Shicheng Fan,Huichang Bi
Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist pregnenolone 16α-carbonitrile (PCN) for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbia. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP, and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiments further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly.
研究领域:
药理学
·
微生物学
·
肝脏病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Horizons
·
2024
·
IF 12.2
Wenping Ma,Yi Zheng,Guangzhen Yang,Hongjian Zhang,Mingxia Lu,Hongshi Ma,Chengtie Wu,Hongxu Lu
Organoids, which are 3D multicellular constructs, have garnered significant attention in recent years. Existing organoid culture methods predominantly utilize natural and synthetic polymeric hydrogels. This study explored the potential of a composite hydrogel mainly consisting of calcium silicate (CS) nanowires and methacrylated gelatin (GelMA) as a substrate for organoid formation and functionalization, specifically for intestinal and liver organoids. Furthermore, the research delved into the mechanisms by which CS nanowires promote the structure formation and development of organoid. It was discovered that CS nanowires can influence the stiffness of the hydrogel, thereby regulating the expression of the mechanosensory factor Yes-associated protein (YAP). Additionally, the bioactive ions released by CS nanowires in the culture medium could accelerate Wnt/β-catenin signaling, further stimulating organoid development. Moreover, bioactive ions were found to enhance the nutrient absorption and ATP metabolic activity of intestinal organoids. Overall, the CS/GelMA composite hydrogel proves to be a promising substrate for organoid formation and development. This research suggested that inorganic biomaterials hold significant potential in organoid research, offering bioactivities, biosafety, and cost-effectiveness.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Tissue Engineering
·
2023
·
IF 8.2
Weifeng Li,Pinghui Zhou,Bomin Yan,Meiyao Qi,Yedan Chen,Lijun Shang,Jianzhong Guan,Li Zhang,Yingji Mao
Modulating a favorable inflammatory microenvironment that facilitates the recovery of degenerated discs is a key strategy in the treatment of intervertebral disc (IVD) degeneration (IDD). More interestingly, well-mechanized tissue-engineered scaffolds have been proven in recent years to be capable of sensing mechanical transduction to enhance the proliferation and activation of nucleus pulposus cells (NPC) and have demonstrated an increased potential in the treatment and recovery of degenerative discs. Additionally, existing surgical procedures may not be suitable for IDD treatment, warranting the requirement of new regenerative therapies for the restoration of disc structure and function. In this study, a light-sensitive injectable polysaccharide composite hydrogel with excellent mechanical properties was prepared using dextrose methacrylate (DexMA) and fucoidan with inflammation-modulating properties. Through numerous in vivo experiments, it was shown that the co-culture of this composite hydrogel with interleukin-1β-stimulated NPCs was able to promote cell proliferation whilst preventing inflammation. Additionally, activation of the caveolin1-yes-associated protein (CAV1-YAP) mechanotransduction axis promoted extracellular matrix (ECM) metabolism and thus jointly promoted IVD regeneration. After injection into an IDD rat model, the composite hydrogel inhibited the local inflammatory response by inducing macrophage M2 polarization and gradually reducing the ECM degradation. In this study, we propose a fucoidan-DexMA composite hydrogel, which provides an attractive approach for IVD regeneration.
研究领域:
组织工程
·
生物医学材料
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再生医学
·
骨科
·
炎症生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 40
·9314-9324
·
IF 5.344
Maowen Chen,Yan Hu,Yanhua Hou,Menghuan Li,Maohua Chen,Lu Tan,Caiyun Mu,Bailong Tao,Zhong Luo,Kaiyong Cai
The high surface elastic modulus of the titanium (Ti) implant is one of the critical factors causing poor osteointegration between the implant surface and surrounding bone tissue. To address this challenge, spherical silica nanoparticles (SSNs) and spherical titania nanoparticles (STNs) with different sizes were synthesized and embedded into Ti surfaces via a micro-arc oxidation (MAO) technique. There were no significant changes in the surface roughness and protein adsorption behaviors before and after the embedding of spherical silica nanoparticles and titania nanoparticles into the Ti implant. However, the surface elastic modulus of Ti-SSNs decreased from 93 GPa to 6.7 GPa, while there was still no change in surface elastic modulus between Ti and Ti-STN groups. In vitro experiments showed that Ti-SSNs, especially Ti-SSN3, significantly stimulated the expression level and nuclear localization of the transcription factor YAP. YAP/TAZ could further inhibit the phosphorylation of AKT and mTOR proteins in MSCs, leading to higher LC3-II protein expression and osteogenic differentiation of MSCs. Ti-SSNs also showed a higher level of autophagosome formation, ALP activity and mineralization capability compared to the other groups. Our results showed that the surface elasticity modulus of an implant plays an important role in the regulation of MSC behaviors. Therefore, designing an implant with an optimal elastic modulus at the surface might have great clinical potential in the bone repair field.
研究领域:
生物材料
·
组织工程
·
干细胞生物学
·
生物力学
·
骨科研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE AMERICAN CERAMIC SOCIETY
·
2024
·Vol. 107
·期 9
·5993-6003
·
IF 3.5
Liang Su,Jiaxiang Lu,Huan Zhang,Xilin Li,Jinbo Wang,Haolun Wang,Sen Lin
The integration of thermal and electromagnetic interference (EMI) insulation is of great significance for fields such as aerospace that face extreme environments. The challenge lies in ensuring that the protective layer is lightweight while simultaneously possessing the ability to suppress heat conduction, heat convection, thermal radiation, and electromagnetic radiation. To address these challenges, we propose a novel ultralight all-fiber-structure composite sponge, yttria-stabilized zirconia/polyvinyl butyral-supported silver (YAP) nanofiber sponge, with ultralight mass (∼65 mg/cm 3 ), exceptionally low thermal conductivity (21 mW/m K at 25°C, and 329 mW/m K at 500°C), and remarkable EMI shielding effectiveness (∼62.6 dB). Moreover, benefiting from its all-fiber-structure, the YAP nanofiber sponge can endure 100 cycles of compression up to 50% of its original volume while retaining its mechanical properties with minimal degradation. These characteristics render YAP nanofiber sponge an ideal material for integrated thermal and EMI insulation, offering a promising solution to the rigorous demands of extreme environment protection such as space exploration.
研究领域:
材料科学
·
纳米技术
·
航空航天工程
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热工学
·
电磁学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF CELL BIOLOGY
·
2024
·
IF 4.5
Yiheng Zhang,Mulan Xing,Fansheng Meng,Ling Zhu,Qingchuan Huang,Tianle Ma,Huihua Fang,Xujing Gu,Suzhou Huang,Xinyu Wu,Gaohong Lv,Jun Guo,Li Wu,Xin Liu,Zhipeng Chen
In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca 2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.
研究领域:
肝病学
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xiaomeng Li,Shuaibing Liu,Shanshan Han,Qingqing Sun,Jianmin Yang,Yuhang Zhang,Yongchao Jiang,Xiaofeng Wang,Qian Li,Jianglin Wang
Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through three-dimensional (3D) and spatiotemporal changes in vivo. The matrix stiffness as a crucial factor during bone tissue development is dynamic stiffening. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, we create a dynamic and controllable stiffening 3D biomimetic model to regulate the osteoblastic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. Our findings showed that these dynamic hydrogels allowed cells to spread and volume expansion prior to secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, presented the significantly elevated osteogenic ECM secretion, gene expression, and YAP/TAZ nuclear localization. In vivo evaluation of animal experiments further indicated that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promoted bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo. This article is protected by copyright. All rights reserved
研究领域:
生物材料
·
组织工程
·
再生医学
·
细胞生物学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Ziang Li,Jincheng Tang,Liang Zhou,Jiannan Mao,Wei Wang,Ziyan Huang,Lichen Zhang,Jie Wu,Xinzhao Jiang,Zhouye Ding,Kun Xi,Feng Cai,Yong Gu,Liang Chen
The extracellular matrix (ECM) stores signaling molecules and facilitates mechanical and biochemical signaling in cells. However, the influence of biomimetic “rejuvenation” ECM structures on aging- and degeneration-related cellular activities and tissue repair is not well understood. We combined physical extrusion and precise “on–off” alternating cross-linking methods to create anisotropic biomaterial microgels (MicroRod and MicroSphere) and explored how they regulate the cell activities of the nucleus pulposus (NP) and their potential antidegenerative effects on intervertebral discs. NP cells exhibited aligned growth along the surface of the MicroRod, enhanced proliferation, and reduced apoptosis. This suggests an adaptive cellular response involving adhesion and mechanosensing, which causes cytoskeletal extension via environmental cues. NP cells maintain nuclear membrane integrity through the YAP/TAZ pathway, which activates the cGAS-STING pathway to rectify the aging mechanisms. In vivo, MicroRod carries NP cells and reduces inflammatory factor and protease secretion in degenerated intervertebral discs, inhibiting degeneration and promoting NP tissue regeneration. Our findings highlight the role of mechanical stress in maintaining cellular activity and antiaging effects in harsh environments, providing a foundation for further research and development of antidegenerative biomaterials.
研究领域:
生物材料
·
组织工程
·
力学生物学
·
细胞衰老
·
退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2023
·Vol. 8
·期 1
·1-17
·
IF 39.3
Liu Yi,Ji Yanhong,Jiang Ruiyi,Fang Chao,Shi Gang,Cheng Lin,Zuo Yinan,Ye Yixin,Su Xiaolan,Li Junshu,Wang Huiling,Wang Yuan,Lin Yi,Dai Lei,Zhang Shuang,Deng Hongxin
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.
研究领域:
胃肠病学
·
肿瘤学
·
老年医学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Xingyu Zhou,Junhui Jiang,Junbo Dang,Yilong Wang,Ruibo Hu,Chen Shen,Tianhao Zhao,Dahui Sun,Guibin Wang,Mei Zhang
Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/β-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.
研究领域:
生物材料
·
组织工程
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Haitao Guan,Wei Wang,Zichao Jiang,Boyu Zhang,Zhipeng Ye,Judun Zheng,Wei Chen,Yuhui Liao,Yingze Zhang
Osteoporosis, characterized by an imbalance in bone homeostasis, is a global health concern. Bone defects are difficult to heal in patients with osteoporosis. Classical drug treatments for osteoporotic bone defects have unsatisfactory efficacy owing to side effects and imprecise delivery problems. In this study, a magnetic aggregation-induced bone-targeting poly(lactic-co-glycolic acid, PLGA)-based nanocarrier (ZOL-PLGA@Yoda1/SPIO) is synthesized to realize dual-targeted delivery and precise Piezo1-activated therapy for osteoporotic bone defects. Piezo1 is an important mechanotransducer that plays a key role in regulating bone homeostasis. To achieve dual-targeting properties, ZOL-PLGA@Yoda1/SPIO is fabricated using zoledronate (ZOL)-decorated PLGA, superparamagnetic iron oxide (SPIO), and Piezo1-activated molecule Yoda1 via the emulsion solvent diffusion method. Bone-targeting molecular mediation and magnetic aggregation-induced properties can jointly and effectively achieve precise delivery to localized bone defects. Moreover, Yoda1 loading enables targeted and efficient mimicking of mechanical signals and activation of Piezo1. Experiments in vivo and in vitro demonstrate that ZOL-PLGA@Yoda1/SPIO can activate Piezo1 in bone defect areas of osteoporotic mice, improve osteogenesis through YAP/β-catenin signaling axis, promote a well-coordinated osteogenesis–angiogenesis coupling, and significantly accelerate bone reconstruction within the defects without noticeable side effects. Overall, this novel dual-targeting nanocarrier provides a potentially effective strategy for the clinical treatment of osteoporotic bone defects.
研究领域:
生物医学工程
·
纳米技术
·
骨生物学
·
力学生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
npj Science of Food
·
2023
·Vol. 7
·期 1
·1-13
·
IF 6.4
Xu Enbo,Niu Ruihao,Lao Jihui,Zhang Shengliang,Li Jie,Zhu Yiyuan,Shi Huimin,Zhu Qingqing,Chen Yijian,Jiang Yuyan,Wang Wenjun,Yin Jun,Chen Qihe,Huang Xiao,Chen Jun,Liu Donghong
Tissue-like cultured meats of some livestock have successfully been established by different approaches. However, the production of a structure similar to fish fillets is still challenging. Here, we develop tissue-like cultured fish fillets by assembly of large yellow croaker muscle fibers and adipocytes with 3D-printed gel. Inhibition of Tgf-β and Notch signals significantly promoted myogenic differentiation of piscine satellite cells (PSCs). The mixture of fish gelatin and sodium alginate combined with a p53 inhibitor and a Yap activator supported PSC viability and proliferation. Based on the texture of fish muscle tissue, a 3D scaffold was constructed by gelatin-based gel mixed with PSCs. After proliferation and differentiation, the muscle scaffold was filled with cultured piscine adipocytes. Finally, tissue-like fish fillets with 20 × 12 × 4 mm were formed, consisting of 5.67 × 10 7 muscles and 4.02 × 10 7 adipocytes. The biomanufacture of tissue-like cultured fish fillet here could be a promising technology to customize meat production with high fidelity.
研究领域:
生物技术
·
食品科学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）