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ENVIRONMENTAL POLLUTION · 2025 · IF 7.3

The exposure to nandrolone changed the expression of genes associated with sexual differentiation and disrupted the levels of hormones in the hypothalamic-pituitary-gonadal (HPG) axis, ultimately inducing male differentiation in zebrafish (Danio rerio)

Yufei Xie,Qiuyu Liu,Wenting Lin,Yuan Ren,Lingtian Xie

Various anabolic androgenic steroids (AAS) are frequently detected in aquatic environments, yet the potential ecotoxicological impacts of their increased load have not received adequate attention. This study investigates the effects of exposure to the androgen nandrolone on sex differentiation, gonadal development, and the expression of hormones, enzymes, and proteins related to the hypothalamic-pituitary-gonadal (HPG) axis in zebrafish. The results indicate that exposure to nandrolone at 60 days post-fertilization promotes the maturation of spermatogonia, inhibits the development of oocytes, and induces their apoptosis. Additionally, there were dose-dependent changes in male differentiation and hormone levels within the HPG axis: in the high-dose group (5 μg/L), males constituted 73 % of the population, and levels of E2 hormones in gonadal tissues decreased by 33 %, while T hormone levels increased by 55 %. Furthermore, the expression of genes essential for ovarian differentiation were downregulated, whereas the expression of testicular differentiation-related genes were upregulated. The molecular docking results show that the drug can form hydrogen bonds with key proteins, which have high affinity, and are more likely to cause conformational changes in the proteins, thereby altering their activity. KEGG analysis suggests that the MAPK signaling pathway is likely the target pathway through which nandrolone exposure induces reproductive toxicity.

CAS / MDL: 64-18-6 67-56-1
研究领域: 生态毒理学 · 分子生物学 · 内分泌学
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Materials · 2023 ·Vol. 16 ·期 15 ·5335 · IF 3.4

A Double Cross-Linked Injectable Hydrogel Derived from Muscular Decellularized Matrix Promotes Myoblast Proliferation and Myogenic Differentiation

Zhao Huang,Jianwen Cheng,Wei Su

Injectable hydrogels possess tremendous merits for use in muscle regeneration; however, they still lack intrinsic biological cues (such as the proliferation and differentiation of myogenic cells), thus considerably restricting their potential for therapeutic use. Herein, we developed a double cross-linked injectable hydrogel composed of methacrylamidated oxidized hyaluronic acid (MOHA) and muscular decellularized matrix (MDM). The chemical composition of the hydrogel was confirmed using1H NMR and Fourier transform infrared spectroscopy. To achieve cross-linking, the aldehyde groups in MOHA were initially reacted with the amino groups in MDM through a Schiff-based reaction. This relatively weak cross-linking provided the MOHA/MDM hydrogel with satisfactory injectability. Furthermore, the methacrylation of MOHA facilitated a second cross-linking mechanism via UV irradiation, resulting in improved gelation ability, biomechanical properties, and swelling performance. When C2C12 myogenic cells were loaded into the hydrogel, our results showed that the addition of MDM significantly enhanced myoblast proliferation compared to the MOHA hydrogel, as demonstrated by live/dead staining and Cell Counting Kit-8 assay after seven days of in vitro cultivation. In addition, gene expression analysis using quantitative polymerase chain reaction indicated that the MOHA/MDM hydrogel promoted myogenic differentiation of C2C12 cells more effectively than the MOHA hydrogel, as evidenced by elevated expression levels of myogenin, troponin T, and MHC in the MOHA/MDM hydrogel group. Moreover, after four to eight weeks of implantation in a full-thickness abdominal wall-defect model, the MOHA/MDM hydrogel could promote the reconstruction and repair of functional skeletal muscle tissue with enhanced tetanic force and tensile strength. This study provides a new double cross-linked injectable hydrogel for use in muscular tissue engineering.Keywords:hydrogels;biomaterials;muscular decellularized matrix;proliferation;myogenic differentiation

研究领域: 生物材料学 · 组织工程学
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ANALYTICA CHIMICA ACTA · 2017 · IF 4.95

Chiral differentiation of amino acids through binuclear copper bound tetramers by ion mobility mass spectrometry

Xiangying Yu,Zhong-Ping Yao

In this study, travelling wave ion mobility mass spectrometry has been used to investigate chiral differentiation of common chiral amino acids , through separation of binuclear copper bound tetrameric ions formed with chiral selector tryptophan , proline , tyrosine , phenylalanine or histidine . Significant chiral recognition was observed for amino acids with aromatic rings or long and active side chains, with peak-to-peak resolutions up to 1.826. Tryptophan and histidine offered better enantioselectivity , compared to other chiral selectors. The results suggested that the mechanism for chiral recognition in ion mobility mass spectrometry might be significantly different from that in tandem mass spectrometry . Linear calibration curves were also established to allow determination of enantiomeric excess of the analytes by the approach. This study showed that higher assembly of chiral analyte and chiral selector might enable better chiral discrimination and ion mobility mass spectrometry could be a powerful technique for provide qualitative, quantitative and structural information of chiral analysis.

CAS / MDL: 7447-39-4
研究领域: 分析化学 · 生物化学
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EXPERIMENTAL ANIMALS · 2022 · IF 1.798

Lrrc32 accelerates tenogenic differentiation of tendon-derived stem cells and promotes Achilles tendon repair in rats

Kai KANG,Lukuan CUI,Qian ZHANG,Shijun GAO

Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group. Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.

CAS / MDL: 28718-90-3
研究领域: 干细胞生物学 · 组织工程 · 再生医学 · 骨科
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Biomedical Materials · 2021 ·Vol. 16 ·期 3 ·035033 · IF 3.715

Bladder muscle regeneration enhanced by sustainable delivery of heparin from bilayer scaffolds carrying stem cells in a rat bladder partial cystectomy model

Chengyuan Wang,Hui Wang,Qianping Guo,Xiaojie Ang,Bin Li,Fengxuan Han,Yingxi Fu,Weiguo Chen

In bladder tissue engineering, regeneration of muscle is of equal importance to epithelial regeneration. However, as yet there is no effective strategy for promoting bladder muscle regeneration. In this study we aim to promote bladder muscle regeneration by sustainably delivering heparin from a bilayer scaffold carrying stem cells. The bilayer scaffold [heparin–polycaprolactone (PCL)/bladder decellularized matrix (BAM) Hep-PB/PCL] comprises an electrospun layer (Hep-PB electrospun membrane) and a three-dimensional (3D) printed layer (PCL scaffold), fabricated via coaxial-electrospinning and 3D printing, respectively. Heparin was encapsulated into the core of the Hep-PB fibers with a core–shell structure to sustain its release. The morphology of the bilayer scaffold and the microstructure of the electrospun fibers were characterized. The release behavior of heparin from various electrospun membranes was evaluated. The role of Hep-PB in promoting myogenic differentiation of the adipose-derived stem cells (ADSCs) through sustainable release of heparin was also evaluated. After 7 d culture, Hep-PB/PCL scaffolds carrying ADSCs (defined as ASHP) were used for bladder reconstruction in a rat partial cystotomy model. The result shows that the PCL printed scaffold has ordered macropores (∼370 μm), unlike the compact microstructure of electrospun films. The Hep-PB membrane exhibits a sustained release behavior for heparin. This membrane also shows better growth and proliferation of ADSCs than the other membranes. The polymerase chain reaction results show that the expression of smooth muscle cell markers in ADSCs is enhanced by the Hep-PB scaffold. The results of retrograde urethrography and histological staining indicate that the bladder volume in the ASHP group recovers better, and the regenerated bladder muscle bundles are arranged in a more orderly fashion compared with the direct suture and bladder decellularized matrix groups. Therefore, findings from this study show that bladder muscle regeneration could be enhanced by bilayer scaffolds delivering heparin and carrying stem cells, which may provide a new strategy for bladder tissue engineering.

CAS / MDL: 64-19-7 920-66-1
研究领域: 组织工程 · 再生医学 · 生物医学工程 · 干细胞生物学
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ACS Applied Bio Materials · 2024 · IF 4.6

Tendon Decellularized Matrix Modified Fibrous Scaffolds with Porous and Crimped Microstructure for Tendon Regeneration

Jianping Zhao,Di Zhang,Qiumei Lan,Gang Zhong,Yisi Liu,Nathaniel Holwell,Xiang Wang,Jinzhi Meng,Jun Yao,Brian G. Amsden,Yin Yu,Fei Chen

Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.

研究领域: 组织工程 · 生物医学工程 · 再生医学 · 生物材料 · 干细胞生物学
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Biomaterials Science · 2021 ·Vol. 10 ·期 3 ·753-769 · IF 6.843

Bioinspired bimodal micro-nanofibrous scaffolds promote the tenogenic differentiation of tendon stem/progenitor cells for achilles tendon regeneration

Zhiwei Yin,Lu Sun,Liyang Shi,Hemin Nie,Jianwu Dai,Can Zhang

Poor tendon repair remains a clinical problem due to the difficulties in replicating the complex multiscale hierarchical structure of native tendons. In this work, a bioinspired fibrous scaffold with bimodal micro-nanofibers and a teno-inductive aligned topography was developed to replicate microscale collagen fibers and nanoscale collagen fibrils that compose native tendons. The results showed indicated that the combination of micro- and nanofibers enhanced the mechanical properties. Furthermore, their biological performance was assessed using tendon stem/progenitor cells (TSPCs). Micro-nanofibers induced a higher cell aspect ratio and enhanced the tenogenic differentiation of TSPCs compared to micro- and nanocontrols. Interestingly, it was observed that scaffold nanotopography and microstructures promoted tenogenesis via activating the TGF-β/Smad2/3-mediated signaling pathway. The in situ implantation study confirmed that micro-nanofibrous scaffolds promoted the structural and mechanical properties of the regenerated Achilles tendon. Overall, our study shows that the bimodal micro-nanofibrous scaffold developed here presents a promising potential to improve the outcomes of tendon tissue engineering.

CAS / MDL: 68441-17-8
研究领域: 组织工程 · 生物材料 · 再生医学 · 细胞生物学 · 机械工程
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Small · 2019 ·Vol. 15 ·期 25 ·1901397 · IF 10.856

Highly Porous Microcarriers for Minimally Invasive In Situ Skeletal Muscle Cell Delivery

Ranjith Kumar Kankala,Jia Zhao,Chen-Guang Liu,Xiao-Jie Song,Da-Yun Yang,Kai Zhu,Shi-Bin Wang,Yu Shrike Zhang,Ai-Zheng Chen

Microscale cell carriers have recently garnered enormous interest in repairing tissue defects by avoiding substantial open surgeries using implants for tissue regeneration. In this study, the highly open porous microspheres (HOPMs) are fabricated using a microfluidic technique for harboring proliferating skeletal myoblasts and evaluating their feasibility toward cell delivery application in situ. These biocompatible HOPMs with particle sizes of 280–370 µm possess open pores of 10–80 µm and interconnected paths. Such structure of the HOPMs conveniently provide a favorable microenvironment, where the cells are closely arranged in elongated shapes with the deposited extracellular matrix, facilitating cell adhesion and proliferation, as well as augmented myogenic differentiation. Furthermore, in vivo results in mice confirm improved cell retention and vascularization, as well as partial myoblast differentiation. These modular cell-laden microcarriers potentially allow for in situ tissue construction after minimally invasive delivery providing a convenient means for regeneration medicine.

研究领域: 组织工程 · 再生医学 · 生物医学工程
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Frontiers in Bioscience-Landmark · 2023 ·Vol. 28 ·期 7 ·139 · IF 3.1

HnRNP A1 Suppresses the Odontogenic Differentiation and the Inclusion of RUNX2 Exon 5 of Dental Mesenchymal Cells

Yanan Zhang,Junjun Huang,Lingyan Yan,Rong Jia,Jihua Guo

Background: RUNX2 (Runt-related transcription factor 2) acts as a key regulator in the odontogenic differentiation of human dental pulp stem cells (hDPSCs). Moreover, the inclusion of exon 5 is important for RUNX2 function. Our previous study showed that Y-Box Binding Protein 1 (YBX1) promoted RUNX2 exon 5 inclusion and mineralization of hDPSCs. However, the regulatory mechanism of RUNX2 exon 5 alternative splicing needed further exploration. Methods: The expression level of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) during the odontogenic differentiation of hDPSCs was analyzed by RT-PCR and Western blot. The roles of hnRNP A1 in the alternative splicing of RUNX2 exon 5 and the odontogenic differentiation of dental mesenchymal cells were analyzed by gain- and loss-of-function experiments. Results: Surprisingly, we found an alternative splicing factor, hnRNP A1, which had an opposite role to YBX1 in regulating RUNX2 exon 5 inclusion and odontogenic differentiation of hDPSCs. Through gain- and loss-of-function assay, we found that hnRNP A1 suppressed the inclusion of RUNX2 exon 5, resulting in the inhibition of odontoblastic differentiation. The overexpression of hnRNP A1 can inhibit the expression of ALP (alkaline phosphatase) and OCN (osteocalcin), and the formation of mineralized nodules during the odontogenic differentiation of both hDPSCs and mouse dental papilla cells (mDPCs), whereas the opposite results were obtained with an hnRNP A1 knockdown preparation. Conclusions: The present study indicated that hnRNP A1 suppressed RUNX2 exon 5 inclusion and reduced the odontogenic differentiation ability of hDPSCs and mDPCs.

CAS / MDL: 123-03-5
研究领域: 分子生物学 · 干细胞研究 · 牙科学 · 转录调控 · 可变剪接
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Biomimetic mineralized collagen scaffolds enhancing odontogenic differentiation of hDPSCs and dentin regeneration through modulating mechanical microenvironment

Wenjing Jin,Haiyan Wu,Jue Shi,Zihe Hu,Yanyan Zhou,Zhuo Chen,Changyu Shao,Ruikang Tang,Zhijian Xie

Dentin regeneration is a huge challenge because of its complicated structure and the shortage of odontoblasts. Unlike in vitro remineralization of dentin through supersaturation of calcium phosphate, the materials of mineralized collagen scaffolds could recruit the human dental pulp stem cells (hDPSCs) and induce their differentiation in vivo and achieve dentin repair. Inspired by the biomineralization of dentin, herein, mineralized collagen fibrils with various mineralization degrees and mechanical properties were prepared through biomolecule hyaluronic acid (HA) modification, and first time find the mechanical properties have a positive correlation with mineralization degree. When 1.2 mg/mL HA was used to modification, the mineralized HA-modified collagen scaffolds (HA-MCS) with similar modulus and stiffness to that of natural dentin could be obtained. Furthermore, testing ALP activity and alizarin red S staining experiments confirmed the HA-MCS with a biomimetic mechanical microenvironment could enhance the proliferation and differentiation of hDPSCs. Additionally, in vivo experiments performed on the beagle model further proved this point that HA-MCS with a biomimetic mechanical microenvironment could promote dentin regeneration. These results not only elucidate that the modulation of mechanical properties of biomaterials could enhance the proliferation and differentiation of stem cells, but also provide a strategy for hard tissue regeneration.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 牙科材料 · 再生医学
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Applied Materials Today · 2019 · IF 8.013

Tendon ECM modified bioactive electrospun fibers promote MSC tenogenic differentiation and tendon regeneration

Tian Tu,Yanbing Shen,Xiansong Wang,Wenjie Zhang,Guangdong Zhou,Yanzhong Zhang,Wenbo Wang,Wei Liu

Proper niche environment is the key factor for mesenchymal stem cells (MSCs) involved tendon-lineage differentiation and regeneration. In the present study, soluble tendon derived extracellular matrix (sTECM) was used to modify aligned electrospun fibers with acid neutralizing effect in order to create an optimal niche environment for tendon regeneration, and its efficacy was evaluated using mouse MSC tenogenic differentiation in vitro and rat Achilles tendon regeneration in vivo . The results showed that sTECM modified ultrafine fibers were more cytocompatible and capable of inducing a predominant tenogenic phenotype of mouse MSCs with the enhanced expression of tendon markers including scleraxis , tenomodulin , collagen III , mohawk homeobox , decorin , fibromodulin and biglycan . By contrast, pure sTECM components led to enhanced multi-lineage differentiation of mouse MSCs including tenogenic lineage. This inductive effect was further enhanced when unilateral mechanical loading was applied in vivo. Moreover, the implantation of sTECM modified scaffold created an ideal niche environment including bioactive sTECM components, topological and mechanical signals, upon in vivo implantation for in situ tendon regeneration. As the results, sTECM modified scaffold in comparison with the non-modified one regenerated higher quality tendon tissue with the features of more mature tissue structure, better tissue organization, cell density and alignment as well as better collagen ultrastructure. Quantitative analysis demonstrated significantly bigger collagen fibril diameter, stronger mechanical property and better tissue grading score and higher expression levels of tenogenic markers when compared to those of control scaffold (p < 0.05). This study demonstrated that sTECM modified pH-neutral ultrafine fibers may represent a novel bioactive scaffold for in situ tendon regeneration, which deserves further investigation in large animals.

CAS / MDL: 57-13-6
研究领域: 组织工程 · 生物材料 · 干细胞生物学 · 再生医学
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