INTERNATIONAL ENDODONTIC JOURNAL
·
2016
·Vol. 50
·期 9
·885-894
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IF 2.842
S. Su,Y. Zhu,S. Li,Y. Liang,J. Zhang
Aim To investigate the role of cAMP response element-binding protein (CREB) in the regulation of odonto/osteogenic differentiation of stem cells from the apical papilla (SCAPs). Methodology Stem cells from the apical papilla were obtained from human impacted third molars ( n = 15). Isolated SCAPs were transfected with CREB overexpressing/silenced lentivirus. Transfected cells were stained with alizarin red to investigate mineralized nodule formation. The expression of the mineralization-related genes, alkaline phosphatase (ALP), collagen type I (Col I), runt-related transcription factor 2 (RUNX2), osterix (OSX) and osteocalcin (OCN), was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Protein expression of the odontogenic-related marker dentine sialoprotein (DSP) and the osteogenic-related marker RUNX2 was measured by Western blotting analysis. One-way analysis of variance ( anova ) and Student's t -test were used for statistical analysis ( a = 0.05). Results The overexpression of CREB enhanced mineralized nodule formation and up-regulated ( P < 0.05) the mRNA levels of odonto/osteogenic-related markers, including ALP, Col I, RUNX2, OSX and OCN, and also increased ( P < 0.05) the protein expression of DSP and RUNX2. In contrast, the silencing of CREB inhibited ( P < 0.05) the mineralization capacity of the SCAPs and decreased ( P < 0.05) the expression of odonto/osteogenic-related markers. Conclusion Up-regulation of CREB expression promoted odonto/osteogenic differentiation of SCAPs and provided a potential method for the regeneration of the dentine–pulp complex.
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Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xiong Huacui,Zhao Fujian,Peng Yuqi,Li Meimei,Qiu Huanhuan,Chen Ke
Repair of critical-size bone defects remains a considerable challenge in the clinic. The most critical cause for incomplete healing is that osteoprogenitors cannot migrate to the central portion of the defects. Herein, stem cells from exfoliated deciduous teeth (SHED) with the properties of easy attainability and low immunogenicity were loaded into gelatin/bioactive glass (GEL/BGM) scaffolds to construct GEL/BGM + SHED engineering scaffolds. An in vitro study showed that BGM could augment the osteogenic differentiation of SHED by activating the AMPK signaling cascade, as confirmed by the elevated expression of osteogenic-related genes, and enhanced ALP activity and mineralization formation in SHED. After implantation in the critical bone defect model, GEL/BGM + SHED scaffolds exhibited low immunogenicity and significantly enhanced new bone formation in the center of the defect. These results indicated that GEL/BGM + SHED scaffolds present a new promising strategy for critical-size bone healing.
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Food Bioscience
·
2026
·
IF 6.2
Zhiyuan Li,Lei Jiang,Yuqi Li,Huifen Li,Shihan Zhang,Lijuan Han
Chemotherapy-induced mesenchymal stem cell (MSC) senescence impairs tissue repair and limits regenerative therapies. Probiotic-derived extracellular vesicles (EVs) have emerged as biocompatible nanocarriers, yet the molecular determinants of their therapeutic efficacy remain poorly defined.Culturing Lactobacillus rhamnosus PB LR76 with mangiferin (MGF) loads MGF into extracellular vesicles (EVs, 2.66% w/w) and remodels their proteome, generating multimodule anti senescence cargo. PB LR76 MGF EVs (50 μg/mL protein, 1.33 μg/mL MGF) significantly attenuated doxorubicin induced mesenchymal stem cell (MSC) senescence: they reduced ROS, DNA damage (γ-H2AX), and p53/p21 activation, while preserving mitochondrial membrane potential. In an eight group, three strain comparison (PB LR76, probiotic LGG, nonprobiotic ATCC 4356), only probiotic strain EVs preserved osteogenic and chondrogenic differentiation (Alizarin Red S/Alcian Blue; Runx2, ALP, COL1A1, OSX, ACAN, COL2A1, SOX9), confirming strain specificity. DIA Hyper quantitative proteomics (549 proteins, n = 3) identified 134 differentially abundant proteins enriched in PB LR76 MGF EVs, coordinated across four functional modules: redox/stress proteins (thioredoxin, NADH dehydrogenase FC = 30.8), six glycolytic moonlighting enzymes, DnaK GrpE/GroEL chaperones, and metabolic/ribosomal moonlighting proteins. PubMed cross referencing mapped 21 of 26 probiotic EV effector categories, 11 enriched in PB LR76 MGF EVs, to 10 human pathways, including TLR2/NF-κB, integrin/FAK survival, and NAD+/sirtuin dependent p53 deacetylation. These findings establish a proteome to phenotype framework for probiotic EV bioactivity and position PB LR76 MGF EVs as a food grade nanotherapeutic strategy against chemotherapy induced tissue damage.
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ACS Applied Bio Materials
·
2025
·
IF 4.7
Ying He,Tianze Sun,Jiazhou Wu,Zexian Liu,Yingzhuan Ye,Jie Li,Tao Qian,Xiantong Hu,Jiayi Wang,Xiaomei Bie,Gang Xu,Yantao Zhao
The clinical repair of bone defects is hindered by limitations in donor material and complications arising from autologous bone grafting. Consequently, the development of efficient bone regeneration materials is of great clinical importance. The present study investigated a three-dimensional microporous demineralized bone matrix (DBM) combined with bone marrow mesenchymal stem cells (BMSCs) to enhance the outcomes of bone defect repair. The DBM has been developed to enhance the collagen preparation process, with the aim of retaining the collagen fiber network of the natural bone matrix and forming a three-dimensional microporous structure with good mechanical property. In vitro experiments demonstrated that the biocompatibility of DBM was superior to that of traditional cancellous and cortical bone materials, and they promoted cell adhesion, proliferation, and osteogenic differentiation as well as osteogenesis-related genes. In vivo experimentation was conducted to verify the efficacy of the treatment on a critical-sized cranial bone defect in nude mice. Micro-CT and histological analysis showed more formation of bone at 4 weeks and 8 weeks postsurgery. The DBM with optimized pore structure, degradation rate, and bioactivity enhanced the efficiency of bone defect repair by synergizing the osteogenic activity of BMSCs. The DBM with a porous and cross-linked structure could provide BMSCs with more internal surface area for attachment space to promote cell adhesion and growth and create advantages for the bone formation. Moreover, the DBM contains multifarious osteoinductive growth factors such as transforming growth factor-β (TGF-β), fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and insulin growth factors (IGFs), which can enhance osteogenic differentiation of BMSCs. This study may provide an innovative strategy for bone regeneration and bone defect repair.
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Biomaterials Advances
·
2026
·
IF 6
Mingyu Jia,Zhihong Chen,Huajian Zhou,Haoran Jiang,Yukang Zhang,Yangyang Liu,Min Wu
Bone defect repair remains a significant challenge faced in clinical practice. Bone tissue engineering has emerged as an effective approach for bone defect repair due to its ample donor source and remarkable repair efficacy. In this study, we combined Abaloparatide (ABL) with bone marrow-derived mesenchymal stem cells (BMSCs) and utilized methacrylated gelatin (GelMA) as a matrix to successfully develop a bio-scaffold with dual activity (ABL@GelMA/BMSCs). BMSCs regulate the bone microenvironment by secreting cytokines, which promote bone repair through a paracrine mechanism. The addition of ABL not only facilitated the osteogenic differentiation and paracrine function of BMSCs but also significantly enhanced the bone induction capability of the scaffold, as evidenced by the marked upregulation of osteogenic markers (ALP, RUNX2, OCN). Furthermore, this bio-scaffold was able to upregulate the Foxp3 gene, inducing Foxp3+ regulatory T cells, thereby modulating the local immune microenvironment to promote bone formation. After implantation of this bio-scaffold into a critical-sized cranial defect model, histological results demonstrated a higher bone mineral density (BMD), and CT reconstruction indicated good healing of the defect. In summary, this bio-scaffold exhibits a powerful capacity for bone defect repair while improving the bone microenvironment through the synergistic modulation of regulatory T cells, providing a new strategy for bone defect repair.
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ACS Applied Bio Materials
·
2026
·
IF 5.6
Wenjing Zhang,Xiaoyang Chen,Ziyi Lin,Shangyang Pan,Zufa sabeel,Wenxin Li,Heyun Shen,Zhao Yang
Breast cancer (BC) remains the most prevalent and deadly malignancy among women worldwide. While photothermal therapy (PTT) and chemodynamic therapy (CDT) offer tumor-specific and minimally invasive advantages, their standalone efficacy is limited. Ligustilide (LIG) can exert antitumor effects by generating •O2–, but its bioavailability is poor, thus necessitating improved delivery strategies. Here, we reported a multifunctional nanoplatform (FeD@LIG) integrating PTT, CDT, and chemotherapy for the simultaneous elimination of breast cancer stem cells (BCSCs) and non-BCSCs. FeD@LIG was synthesized via one-step oxidative polymerization of dopamine, co-loading Fe3+ and LIG. The nanospheres exhibited excellent photothermal conversion efficiency (52.8%) and pH/GSH-responsive drug release. Upon near-infrared (NIR) irradiation, FeD@LIG triggered ROS generation via Fenton-like reactions and elevated local temperature, leading to enhanced oxidative stress, apoptosis, and LIG release. In vitro, FeD@LIG reduced cell viabilities of MCF-7 and MDA-MB-231 cells to 12.5 and 7.9%, respectively, and significantly inhibited BCSCs’ self-renewal. In vivo, FeD@LIG achieved a tumor inhibition rate of 92.8% with minimal toxicity. Mechanistic studies revealed activation of the BAX/BCL-2/Caspase-3 pathway and suppression of Hedgehog signaling. Overall, FeD@LIG represents a promising nanotherapeutic strategy for overcoming drug resistance and recurrence by inhibiting both BCSCs and non-BCSCs through multimodal synergistic therapy.
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ANIMAL FEED SCIENCE AND TECHNOLOGY
·
2026
·
IF 3.2
Xi-Yue Ding,Yu-Hang Hong,Zi-Yan Liu,Guo-He Cai,Pan Wang,Chuang-Zhong Zhu,Hong-Ling Yang,Yun-Zhang Sun
BFPS and EBFPS improved growth performance, feed utilization, and serum immunity. • EBFPS showed better potential in improving intestinal morphology and microbial homeostasis than BFPS. • EBFPS activated TLRs signaling and inhibited intestinal inflammation, while conversely in BFPS. A 56-day feeding trial was carried out to compare the effects of king oyster mushroom ( Pleurotus eryngii ) and soybean meal (SM) fermented by microorganisms ( Saccharomyces cerevisiae Sa, Bacillus pumilus SE5, and Lactobacillus lactis 17, BFPS) alone or in combination with enzymes (cellulase and protease, EBFPS) on growth performance, serum biochemistry, and intestinal health in large yellow croaker ( Larimichthys crocea ). Large yellow croaker was randomly assigned to three groups (control, BFPS, and EBFPS) with four replicates (160 fish per replicate) per group. Results showed that BFPS and EBFPS improved growth performance and feed utilization, but did not affect organ-somatic indices. Dietary BFPS and EBFPS decreased serum aspartate transaminase and alanine transferase activities, implying superior liver health of croakers. Moreover, there were significant enhancements of serum alkaline phosphatase and acid phosphatase activities in BFPS and EBFPS groups, as well as immunoglobulin M content in EBFPS group. In terms of inflammatory cytokines, serum IL-1β and TGF-β1 contents were reduced in croakers fed with BFPS-contained diet, while croakers fed with EBFPS-contained diet showed reduction of serum IL-1β content, but not TGF-β1. Dietary BFPS decreased MT, VH, VW, and expressions of occlidin and jam , while enhanced MT, VH, VW, and zo-1 mRNA level were observed in fish fed with EBFPS-contained diet. Dietary BFPS resulted in significant up-regulation of pro-inflammatory il-1β and il-6 mRNA levels, as well as significant down-regulation of il-4/13a , il-4/13b , il-10 and tgf-β1 , tlr1 and tlr2b mRNA levels. Inconsistently, dietary EBFPS up-regulated il-4/13a , il-10 , tlr1 , tlr2a , and tlr2b mRNA levels. EBFPS, rather than BFPS, increased α-diversity of intestinal microbiota, and β-diversity revealed that the cluster of the EBFPS group was notably separated from the control and BFPS groups' cluster. Furthermore, the enhancement of beneficial Firmicutes and the reduction of pathogenic Proteobacteria and Brevinema were observed in croakers fed with EBFPS-contained diet. BFPS increased Proteobacteria and reduced Brevinema . Overall, EBFPS, as a functional protein source, could efficiently improve growth, immunity, and intestinal health of large yellow croaker ( L. crocea ) compared to BFPS.
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Progress in Biomaterials
·
2023
·Vol. 12
·期 2
·75-86
·
IF 4.9
Jafarimanesh Mohammad Amin,Ai Jafar,Shojaei Shahrokh,Khonakdar Hossein Ali,Darbemamieh Goldis,Shirian Sadegh
Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague–Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups ( n = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210 nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40 nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Shaoyi Lin,Yunyun Zhu,Tingting Hu,Kaihan Wang,Xiaomin Chen
Acute myocardial infarction (AMI) has caused cardiac vascular disease to emerge in recent years, and heart failure is the leading cause of death worldwide and modern medicine offers a number of treatments for AMI. In the present investigation, we created a new hydrogel material for the treatment of acute MI repair that combines mesenchymal stem cell (MSCs)-derived exosomes (EX) and selenium nanoparticles (Se NPs)-loaded collagen type 1 (COL-I)/tannic acid (TA) hydrogel. The physico-chemical characterizations of prepared Se NPs were systematically analysed by efficient analytical and spectroscopic methods. In vitro cytocompatibility analyses, established that prepared hydrogel samples have greater cell viability by MTT and LDH assays, which described that the suitability of hydrogel for the AMI treatment. In vitro cell migration assay exhibited that ∼95% of cell migration ability for Se-EX/Hydrogel when compared to the other groups on cardiac endothelial cells (cECs). The qRT-PCR analysis revealed that Se-EX/Hydrogel provided 3-fold decreasing of pro-inflammatory factors expressions when compared to the LPS induced cell models (cECs and Raw 264.7 cells). In vitro cell apoptosis observations demonstrated that developed Se-EX/Hydrogel effectively reduced the LPS-induced cell apoptosis (13.59 ± 1.2) when compared to the other groups (LPS = 29.51 ± 0.9; LPS + EX = 17.65 ± 1.0; LPS + Se NPs = 18.38 ± 0.8). When blended Se-EX/Hydrogel group were injected into AMI rat models, in vivo observation revealed that improved cardiac function through increased LV wall thickness (2.46 ± 0.6 mm) and significantly reduced infarct size (12.05 ± 1.0%) when compared to the AMI group. The outcome of the results demonstrated that introduced injectable hydrogel had a significant impact on the recovery of infarcted heart.
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Bioresources and Bioprocessing
·
2022
·Vol. 9
·期 1
·1-14
·
IF 4.983
Wang Jin,He Wubo,Tan Wen-Song,Cai Haibo
Epigallocatechin-3-gallate (EGCG) is a plant-derived flavonoid compound with the ability to promote the differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts. However, the effect of EGCG on the osteogenic differentiation of the human umbilical cord-derived mesenchymal stem cells (HUMSCs) is rarely studied. Therefore, in this study, the osteogenic effects of EGCG are studied in the HUMSCs by detecting cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition and the expression of relevant osteogenic markers. The results showed that EGCG can promote the proliferation and osteogenic differentiation of the HUMSCs in vitro at a concentration of 2.5–5.0 μM. Unfortunately, the EGCG is easily metabolized by cells during cell culture, which reduces its bioavailability. Therefore, in this paper, EGCG-loaded microspheres (ECM) were prepared and embedded in chitosan/carboxymethyl cellulose/montmorillonite (CS/CMC/MMT) scaffolds to form CS/CMC/MMT-ECM scaffolds for improving the bioavailability of EGCG. The HUMSCs were cultured on CS/CMC/MMT-ECM scaffolds to induce osteogenic differentiation. The results showed that the CS/CMC/MMT-ECM scaffold continuously released EGCG for up to 22 days. In addition, CS/CMC/MMT-ECM scaffolds can promote osteoblast differentiation. Taken together, the present study suggested that entrainment of ECM into CS/CMC/MMT scaffolds was a prospective scheme for promotion osteogenic differentiation of the HUMSCs. Graphical Abstract
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PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Bing Liang,Xiongbin Chen,Min Li,Lingling Zhang,Xia Yang,Liangqin Shi,Yanju Gong,Yuanyuan Gong,Huan Xu,Xiao Wu,Zhong Jin,Yanru Wang,Luwei Liu,Xiaohong Yi,Lushuang Xie,Hua Zhong,Chongyang Shen,Yong Wang,Lan Yang
Context Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP).Objective To explore the effects and mechanisms of action of LWDH in PMOP.Materials and methods Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated.Results LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62.Discussion and conclusions LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.
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BMC Complementary Medicine and Therapies
·
2021
·Vol. 21
·期 1
·1-12
·
IF 0
Bian Wei,Xiao Shunqiang,Yang Lei,Chen Jun,Deng Shifang
Background Quercetin and H19 can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, whether quercetin regulates H19 expression to promote osteogenic differentiation of BMSCs is unclear.Methods BMSC proliferation, matrix mineralization, and alkaline phosphatase (ALP) activity were assessed using the Cell Counting Kit-8, ALP assay kit, and alizarin red staining kit, respectively. Expression of H19, miR-625-5p, BMP-2, osteocalcin, and RUNX2 were measured by qRT-PCR; β-catenin protein level was measured by western blotting.Results Quercetin promoted BMSC proliferation, enhanced ALP activity, and upregulated the expression of BMP-2, osteocalcin, and RUNX2 mRNAs, suggesting that it promoted osteogenic differentiation of BMSCs. Moreover, quercetin increased H19 expression, while the effect of quercetin on BMSCs was reversed by silencing H19 expression. Additionally, miR-625-5p, interacted with H19, was downregulated during quercetin-induced BMSC osteogenic differentiation, which negatively correlated with H19 expression. Silencing miR-625-5p expression promoted BMSC proliferation and osteogenic differentiation, whereas miR-625-5p overexpression weakened the effect of quercetin on BMSCs. Finally, quercetin treatment or downregulation of miR-625-5p expression increased β-catenin protein level in BMSCs. Upregulation or downregulation of miR-625-5p or H19 expression, respectively, inhibited β-catenin protein level in quercetin treated-BMSCs.Conclusion H19 promotes, while miR-625-5p inhibits BMSC osteogenic differentiation. Quercetin activates the Wnt/β-catenin pathway and promotes BMSC osteogenic differentiation via the H19/miR-625-5p axis.
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