Acta Biomaterialia
·
2022
·
IF 10.633
Nanfang Nie,Lin Gong,Deming Jiang,Yanshan Liu,Jingwei Zhang,Jiaqi Xu,Xudong Yao,Bingbing Wu,Yu Li,Xiaohui Zou
Severe damage to the uterine endometrium , which results in scar formation and endometrial dysfunction, eventually leads to infertility or pregnancy-related complications. No effective therapeutic treatment is currently available for such injuries owing to the structural complexity, internal environment, and function of the uterus. Three-dimensional (3D) bio-printing to engineer biomimetic structural constructs provides a unique opportunity for tissue regeneration . Herein, using 3D extrusion-based bioprinting (EBB), we constructed a bilayer endometrial construct (EC) based on a sodium alginate-hyaluronic acid (Alg-HA) hydrogel for functional regeneration of the endometrium. The upper layer of the 3D bio-printed EC is a monolayer of endometrial epithelial cells (EECs), while the lower layer has a grid-like microstructure loaded with endometrial stromal cells (ESCs). In a partial full-thickness uterine excision rat model, our bilayer EC not only restored the morphology and structure of the endometrial wall (including organized luminal/ glandular epithelium, stroma, vasculature and the smooth muscle layer), but also significantly improved the reproductive outcome in the surgical area after implantation (75%, 12/16, p < 0.01). Therefore, repair of the uterine endometrium using the developed 3D bio-printed bilayer EC may represent an effective regenerative treatment for severe endometrial injury. Statement of significance Achieving structural and functional recovery of the endometrium following severe injury is still a challenge. Here, we designed a 3D bio-printed endometrial construct (EC) to mimic the native bilayer structure and cellular components of the endometrium. The bio-printed EC consists of a dense upper layer with endometrial epithelial cells and a lower layer with endometrial stromal cells. In particular, the 3D bio-printed EC significantly improved the reproductive outcome in the surgical area (75%, 12/16) compared to that of the cell-loaded non-printed group (12.5%, 2/16). This study demonstrates that a biomimetic bilayer construct can facilitate endometrial repair and regeneration. Therefore, an endometrial cells-loaded 3D-bioprinted EC is a promising therapeutic option for patients suffering from severe endometrial damage.
研究领域:
组织工程
·
生殖医学
·
生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jinlong Qin,Min Sun,Jiajing Cheng,Huici Jiang,Mingchen Lv,Jianxing Jing,Ran Chen,Zhen Fan,Jianzhong Du
Unavoidable damage to the basal layer of the endometrium has a huge negative impact on a woman’s reproductive health and menstrual cycle. However, it is difficult for medicine to penetrate a series of biological barriers toward the basal layer in the deeper area of the endometrium. To meet this challenge, we developed an ultrasound-responsive hydrogel incorporated with a transforming growth factor-beta (TGF-β) mimetic peptide to enhance pregnancy outcomes by restoring the function of a wounded endometrium due to its deep-tissue-penetration capability. In vitro studies revealed that the TGF-β-mimetic-peptide-loaded hydrogel could achieve 64.35% of cell migration under ultrasound stimulation even in phosphate-buffered saline of pH 6.0. Upon in situ sonication at the uterus, carboxymethyl chitosan can be released from degraded hydrogel to open tight junctions with reduced interstitial pressure by ultrasound to promote deep penetration. Rat studies revealed that the penetration capability of TGF-β-mimetic-peptide-loaded hydrogel with sonication was 1.6 times higher than that of the control group. Besides the rat uterine model, ex vivo human uterine tissue was also collected and imaged, demonstrating up to ∼700 μm of tissue penetration depth. In addition, compared to control groups, effective uterus recovery without intrauterine stenosis and endometrial cavity fluid was observed from rats with severe uterine injury treated by TGF-β-mimetic-peptide-loaded hydrogel. In addition, fertility restoration in the endometrial injury model was observed after treatment with such an ultrasound-responsive hydrogel incorporated with TGF-β mimetic peptides. Overall, this work provides an effective approach to treating endometrial injury for enhanced pregnancy outcomes.
研究领域:
生物医学工程
·
生殖医学
·
组织工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2020
·
IF 4.049
Ke Ye,QiXin Jiang,Yawen Lu,Xiaodong Wen,Jie Yang
Prostaglandins (PGs) are vitally important unsaturated fatty acids involved in arachidonic acid (AA) metabolism, participating in numerous pathophysiological processes, especially in maintaining the homeostasis of uterus. Therefore, quantitative analysis of PGs is of great importance for uncovering potential mechanisms of PGs related diseases. However, methods for determining PGs in uterine samples have not been reported. In this study, an ultra high-performance liquid chromatography/mass spectrometry (UHPLC-MS/MS) method was established to quantify PGs in uterine samples, using N,N-Dimethylethylenediamine (DMED) and N,N-Diethylethylenediamine (DEED) as derivatization reagents. The derivatization could be finished at 37 °C for 30 min catalyzed by 1-N,N,N',N'-Tetramethyl-O-(7-azabenzotriazol-1-yl) uronium hexafluorophosphate (HATU). This is a mild condition suitable for most of biological samples. The DMED labeling of PGs could significantly enhance their response compared to those of underived ones. This method exhibited excellent linearity (R 2 > 0.997) and precision for the determination of PGs in uterine samples (CV ≤ 12.9%). The extraction recoveries of PGs were ranged from 83.0 to 100% and matrix effects were ranged from 86.3 to 106%, indicating DEED labeled standards could be used as internal standards for PGs quantification. With the proposed method, we successfully quantified PGs in rat uterus. The results showed their levels were significant changed in abnormal uterine bleeding (AUB) rats, suggesting that PGs might be involved in the pathological process of AUB. This established analogous reagents derivatization based UHPLC-MS/MS method could be used as a powerful tool to monitor PGs, providing insights to the precise mechanism of PG action on the endometrium.
研究领域:
生物化学
·
医学
✓ 已验证
DOI
高影响因子
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
·
2020
·Vol. 106
·期 2
·526-538
·
IF 5.399
Wu Ying-Ting,Ma Si-Yu,Sun Wen-Qin,Shen Wei-Wei,Zhu Hui-Ting,Zhang Qin,Chen Hui-Fen
BackgroundEndometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM.MethodsTRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis.ResultsWe found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin β1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin β1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model.ConclusionIn conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM.
研究领域:
妇科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS
·
2018
·Vol. 25
·期 2
·1-9
·
IF 3.367
Caiyun Li,Huajiang Wei,Yanping Zhao,Guoyong Wu,Huaimin Gu,Zhouyi Guo,Hongqin Yang,Yonghong He,Shusen Xie
This study aims to monitor and assess the penetration and accumulation of titanium dioxide nanoparticles (TiO
2
NPs) (25 nm and 60 nm) and the penetration of the TiO
2
NPs assisted by diode laser radiation (LR) in human normal endometrium (NE) and uterine leiomyoma (UL) tissues. In the 210 min ex vivo experiments, optical coherence tomography (OCT) and diffuse reflectance (DR) spectral measurement were used to study the changes in optical properties of tissues after TiO
2
NPs suspension administering. The results show that TiO
2
NPs make the OCT signal intensities and DR spectra of both NE and UL tissues increase with time, and larger NPs produce greater signal enhancement. In addition, there are significant differences between NE and UL tissues in terms of the values of attenuation coefficients. The experiment results indicate that the same size of the NPs penetrate faster in UL tissues than that in NE tissues, and 25 nm TiO
2
NPs allow larger penetration depth than 60 nm TiO
2
NPs in tissues. LR can remarkably increase the penetration of TiO
2
NPs in two types of tissues, especially in UL tissues. Analysis of attenuation coefficients and reflectance intensity reveals that the accumulation of the TiO
2
NPs in NE and UL tissues has great influence on the tissue optical properties.
研究领域:
生物医学工程
·
纳米医学
·
妇科学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Linfang Wu,Jing Wang,Yonghuan Yan,Lu Wang,Qi Huang,Jinyong Peng,Lili Li
Endometritis is a prevalent condition of the reproductive system that leads to significant tissue damage in the uterus, thereby seriously impacting the health and quality of life of these patients. Hesperidin (HES), a natural flavonoid glycoside, displays various biological activities. Nonetheless, the protective effect of HES treatment against endometritis remains uncertain. In this study, we examined the protective effects of HES on endometritis induced by lipopolysaccharide (LPS) both in vivo and in vitro . In vitro experimental results showed that HES reduced the levels of inflammatory factors, improved mitochondrial morphology, increased mitochondrial activity and inhibited ROS levels; moreover, it activated the AMPK/PGC-1 α signalling pathway in LPS-induced human endometrial endothelial cells (HEECs). AMPK served as a potential target of HES, which was further validated using molecular docking, molecular dynamic simulation, CETSA and SPR. Moreover, in vivo experimental results indicated that HES significantly mitigated the histopathological alterations in the uterus caused by LPS, as well as reduced the levels of inflammatory factors, MPO activity, the expression levels of CD38, and CD138 and activated the AMPK/PGC-1α signalling pathway. Overall, HES mitigated mitochondrial oxidative stress and inflammatory response primarily through activation of the AMPK/PGC-1α signalling pathway, thereby exerting protective effects against endometritis.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
分子生物学
·
妇产科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Xinyue Zhou,Zhenyu Chen,Lipeng Pei,Jingli Sun
Emerging evidence has exhibited an obvious decreased expression of miR-106a-5p in the ectopic endometrial tissue of endometriosis (EMS) patients. Thus far, the pathophysiological function of miR-106a-5p in EMS is unknown. A previous study showed an increased FOXC1 expression in the ectopic endometrial tissue of patients with EMS. Moreover, we found that there was a binding site of miR-106a-5p on the 3ʹUTR of FOXC1 through bioinformatics predictions. Hence, we speculated that miR-106a-5p might affect the development of EMS via targeting FOXC1. We first showed a decreased level of miR-106a-5p and an increased level of FOXC1 mRNA in ectopic endometrial tissues compared with normal tissues. Functionally, we transfected ectopic endometrial stromal cells (ESCs) with miR-106a-5p mimics or NC mimics and indicated an inhibitory role of miR-106a-5p on ESC proliferation, invasion, and migration. Mechanistically, FOXC1 was found to be a target gene of miR-106a-5p. To confirm whether miR-106a-5p exerted an inhibitory activity in ESCs via targeting FOXC1, miR-106a-5p mimic was co-transfected into ESCs with the FOXC1-plasmid or vector. We found that FOXC1 overexpression evidently reversed the results caused by a miR-106a-5p mimic in ESCs. Additionally, our results demonstrated that miR-106a-5p mimic inhibited the expression of p-Akt and p-PI3K. Collectively, these results revealed that miR-106a-5p inhibited the proliferative, migratory, and invasive ability of ESCs via directly binding to FOXC1, likely through the suppression of the PI3K and its downstream signaling pathway, which offered a potential and novel therapeutic strategy for EMS treatment.
研究领域:
妇科学
·
分子生物学
·
细胞生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Ming Chen,Xuemin Liu,Xiaoxia Song,Xiaofeng Ye,Zeshen Liang,Guoqing Chen,Peixian Cheng,Huihua Yang,Ling Shuai,Dongdong Li,Liping Wang
Thin endometrium (TE), a major cause of embryo implantation failure, increases the risk of early miscarriage, ectopic pregnancy, and perinatal complications. Owing to the poor utilization and short-term effectiveness of current stem cell therapies, their efficacy in improving reproductive outcomes in patients with TE is limited. Endometrial extracellular matrix (EMECM) modified hemispherical hydrogels (ECMHPs) are developed to deliver menstrual blood-derived stem cells (MenSCs) to promote TE repair. The irregular porous structure on one side of the hemispherical hydrogel microspheres significantly enhances their retention capability on the uterine wall, whereas the bioactive decellularized EMECM promotes MenSCs proliferation and paracrine function. In vitro experiments demonstrate that ECMHPs@MenSCs promote the proliferation of damaged human endometrial stromal cells (HESCs) while inhibiting their fibrosis and apoptosis. In TE rat models, intrauterine transplantation of the ECMHPs delivering MenSCs system (ECMHPs@MenSCs) extends retention time, promotes endometrial thickness by 2.3-fold, increases glandular number by 3.7-fold, inhibits endometrial fibrosis. Additionally, this system improves endometrial regeneration markers and uterine receptivity, and restores fertility, with a mean gestational sac number of 11.0 ± 2.8 compared with only 2.3 ± 2.1 in the untreated group. This study provides an efficient and convenient therapeutic strategy for TE repair and fertility restoration.
研究领域:
生殖医学
·
组织工程
·
干细胞治疗
·
生物材料
·
再生医学
·
妇产科学
·
细胞治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Jingwen Shi,Wenda Jing,Yueyun He,Ying Huang
Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.
研究领域:
妇科学
·
分子生物学
·
转录因子
·
疾病发病机制
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产品关联
DOI
PubMed
高影响因子
Science of Advanced Materials
·
2022
·Vol. 14
·期 2
·263-271
·
IF 1.067
Fan Jing,Wu Dan,Zhao Depeng,Hu Rui,Fu Zhihong,Li Xuemei
In this study, a novel small molecule estradiol guanidine derivative (Guanidoestradiol, GDT) for female reproductive system targeting and nitric oxide (NO) release has been constructed by conjugating 17β-estradiol and L-arginine through an esterification reaction. After
intraperitoneal administration in female mice, the serum Griess assay and immunohistochemical analysis of ovary and uterus were performed. GDT effectively increased NO concentration in the blood and produced some bio-effects that are beneficial to the reproductive system. The specific advantages
are as follows: (1) the introduction of guanidine groups and amino groups improves the water solubility and bioavailability of estradiol and is expected to exert other biofunctions; (2) the estradiol residue of GDT gives the NO donor the ability for ovarian and uterine targeting; (3) combined
administration of estradiol and NO to the uterus and ovary promoted endometrial thickening and expression of vascular proliferation markers; (4) the abundance of iNOS in tissues was reduced after treatment with NO donors. We suggest that Guanidoestradiol is a promising small-molecule drug
to enhance normal endometrial and ovarian function and may play a role in promoting reproduction.
研究领域:
药理学
·
生殖生物学
·
内分泌学
✓ 已验证
DOI
高影响因子
LASER PHYSICS
·
2016
·Vol. 26
·期 5
·055604
·
IF 1.102
P C Gu,M Ye,H J Wei,G Y Wu,Z Y Guo,H Q Yang,Y H He,S S Xie,L P Zhou
The aims of this study were to monitor and contrast the diffusion of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles' (NPs) penetration and accumulation in human normal endometrium (NE) tissues and uterine leiomyoma (UL) tissues combined with microneedles (MN) in vitro using optical coherence tomography (OCT) and diffuse reflectance (DR) spectral. Continuous OCT and DR spectra monitoring showed that, after application of ZnO or TiO2 NPs, the OCT signal intensities of NE and UL both increase with time, and the TiO2 NPs tend to produce a greater signal enhancement than ZnO NPs in the same type of tissue. And for the same type of NPs, they penetrate faster in NE tissue compared with UL tissue. In addition, the use of MN can significantly enhance the penetration of topically applied ZnO or TiO2 NPs in the tissue. The attenuation coefficients of NE tissue are about 5.01 ± 0.35 mm−1 for ZnO NPs treatment at 195 min and 4.62 ± 0.29 mm−1 for ZnO NPs/MN at 179 min, 4.73 ± 0.30 mm−1 for TiO2 NPs at 183 min, 4.05 ± 0.25 mm−1 for TiO2 NPs/MN at 147 min when the penetration process reached the stable state. And the attenuation coefficients of UL tissue are about 5.0 ± 0.34 mm−1 for ZnO NP treatment at 191 min and 4.20 ± 0.26 mm−1 for ZnO NPs/MN at 169 min, 4.33 ± 0.27 mm−1 for TiO2 NPs at 176 min, 3.53 ± 0.20 mm−1 for TiO2 NPs/MN at 141 min when the penetration process reached the stable state. This suggests that TiO2 NPs penetrate faster and reach the maximum amount of penetration earlier than ZnO NPs with the same condition. The results of attenuation coefficients and reflectance intensity of NE and UL tissue suggests that the accumulation of the TiO2 or ZnO NPs in both NE and UL tissue greatly influenced the tissue optical properties.
研究领域:
生物医学工程
·
纳米医学
·
成像技术
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR HUMAN REPRODUCTION
·
2023
·
IF 4
Dong Xiaoyu,Xu Le,Wang Shuang,Jiao Xue,Yan Shumin,Huang Yufei,Yuan Ming,Wang Guoyun
Ferroptosis is an iron-dependent programmed cell death process characterised by the accumulation of lethal oxidative damage. Localised iron overload is a unique clinical phenomenon in ovarian endometriosis. However, the role and mechanism of ferroptosis in the course of ovarian endometriosis remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian endometriosis and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells. Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse endometriosis model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian endometriosis can activate autophagy-related ferroptosis in endometrial stromal cells, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the endometriosis environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian endometriosis.
研究领域:
妇科学
·
细胞生物学
·
分子生物学
·
病理生理学
✓ 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）