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
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Plant Signaling & Behavior
·
2022
·
IF 2.734
Rui Zhou,Menglong Fan,Mei Zhao,Xinqiang Jiang,Qinghua Liu
Leaves are the main vegetative organs of the aboveground part of plants and play an important role in plant morphogenesis. KNOTTED-LIKE HOMEOBOX (KNOX) plays a crucial role in regulating leaf cell fate and maintaining leaf development. In this study, we analyzed LtKNOX1 from Lilium tsingtauense and illustrated its function in transgenic plants. Tissue-specific expression analysis indicated that LtKNOX1 was highly expressed in stems, young flower buds, and shoot apical meristems (SAMs). Ectopic overexpression of LtKNOX1 in Nicotiana benthamiana suggested that transformants with mild phenotypes were characterized by foliar wrinkles and mildly curled leaves; transformants with intermediate phenotypes showed severely crimped blades and narrow leaf angles, and the most severe phenotypes lacked normal SAMs and leaves. Moreover, the expression levels of genes involved in the regulation of KNOX in transgenic plants were detected, including ASYMMETRIC LEAVES1, PIN-FORMED 1, GA20-oxidase, CUP-SHAPED COTYLEDON 2, CLAVATA 1 and WUSCHEL(WUS), and the expression of other genes were down-regulated except WUS. This study contributes to our understanding of the LtKNOX1 function.
研究领域:
植物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
Reproductive and Developmental Medicine
·
2024
·Vol. 9
·期 1
·22
·
IF 0.7
Chen Xi,Zuo Wei-Wen,Zhang Guo-Dong,Xu Cong-Jian
Objective: Immune dysfunction plays an important role in the pathogenesis of endometriosis. C5a, a by-product of complement activation, binds to its receptor (C5a receptor 1, C5aR1) in various cells, including macrophages. The combination of C5a and C5aR1 in macrophages induces M2 polarization. There is no consistent conclusion regarding macrophage polarization status and its participation in the pathogenesis of endometriosis. Methods: We analyzed the expression of C5aR1 and the immunophenotype of macrophages in samples from patients with endometriosis using immunohistochemistry and flow cytometry. We tested the equivalent item in a mouse model and the THP-1 cell line in vivo and in vitro . Single-cell RNA sequencing (scRNA-seq) from the Gene Expression Omnibus (GEO, GSE213216) was used to investigate the phenotype and function of C5aR1 + macrophages. Results: The infiltration of C5aR1 + macrophages was associated with the severity of endometriosis. C5aR1 + macrophages polarized more toward the M2 phenotype and transformed into an immunosuppressive state. Inhibiting C5aR1 using PMX-53 decreased the expression of C5aR1 + macrophages and reduced their polarization to the M2 phenotype, consequently shrinking lesion size in a mouse model. Conclusion: Our study emphasizes the importance of C5aR1 and the macrophage phenotype in the pathogenesis of endometriosis. We propose PMX-53 as a potential therapeutic agent for endometriosis.
研究领域:
免疫学
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生殖医学
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分子生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Dazhen Zhang,Xinzhe Qu,Fuchao Chu,Zhenxin Wang,Jie Mou,Feng Yuan
Background Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective. Methods A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes. Results Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone. Conclusion This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.
研究领域:
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE BIOMEDICINE ONLINE
·
2021
·
IF 3.828
Qiuju Li,Ming Yuan,Xue Jiao,Miaomiao Ji,Yufei Huang,Jing Li,Dong Li,Guoyun Wang
Research question Which metabolites are altered in the peritoneal cavity of women with endometriosis? Could the mouse endometriosis model simulate these alterations? Design Thirteen women with endometriosis and seven women with other benign gynaecological diseases, who underwent laparoscopic surgery, were included in this study. None had received hormonal therapy for 3 months before surgery. For the animal experiments, six and five mice were included in the endometriosis and control groups, respectively. Peritoneal fluid from the patients and peritoneal lavage fluid from the mice was collected and analysed. Non-targeted metabolomics via liquid chromatography with tandem mass spectrometry was used to identify the altered metabolites in the peritoneal fluid of endometriosis patients and mouse models. MetaboAnalyst 4.0 was used to visualize the data. Results Several metabolites in the peritoneal cavity were significantly altered in both humans and mice with endometriosis. Concentrations of lysophosphatidylcholine (LysopC) ( P =0.017 in patients and P =0.041 in the mouse model) and derivatives of phosphoethanolamine (1-arachidonoyl-sn-glycero-3-phosphoethanolamine in patients, P =0.027; 1-oleoyl-sn-glycero-3-phosphoethanolamine in patients, P =0.0086; and phosphorylethanolamine in the mouse model, P =0.0027) were significantly up-regulated in both, whereas concentrations of acylcarnitines ( l -palmitoylcarnitine, P =0.047; and stearoylcarnitine, P =0.029) and kynurenine ( P =0.045) were significantly increased only in humans. The human and mouse samples shared three altered enriched metabolite sets. Conclusions Women with endometriosis show an altered metabolic state in the abdominal cavity. The endometriosis mouse model shared half of the significantly altered metabolite sets found in the abdominal cavity of humans.
研究领域:
妇科学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
INFLAMMATION RESEARCH
·
2025
·Vol. 74
·期 1
·1-18
·
IF 5.4
Li Jue,Wu Zhijing,Li Nan,Wang Jianhong,Huang Meihua,Zhu Li,Wan Guiping,Zhang Zhenzhen
Endometriosis, a persistent inflammatory disease, is associated with pelvic or abdominal pain. The immune system and sensory nervous system show a synergistic effect on regulation of pain. In particular, Interleukin-33 (IL-33) is released as a danger signal and drives key hallmarks of severe endometriosis. To explore the mechanistic involvement of IL-33 in pain associated with endometriosis, both an in vivo murine endometriosis model and in vitro experiments with RAW 264.7 cells and dorsal root ganglion (DRG) neurons were utilized. In vivo, we demonstrated that IL-33 significantly exacerbated endometriosis and induced hyperalgesia in mice. By interacting with the ST2 receptor in macrophages, IL-33 enhanced the release of tumor necrosis factor α (TNF-α) and Interleukin 1β (IL-1β). This process set off an inflammatory cascade, which further facilitated macrophages recruitment and neurogenesis in ectopic lesions. As an ion channel expressed by nociceptors, transient receptor potential vanilloid 1 (TRPV1) expression was significantly increased in DRG in the presence of IL-33. In vitro, we confirmed that IL-33 elevated the release of TNF-α in macrophages. Ultimately, macrophage-derived TNF-α increased TRPV1 protein level in DRG neuronal cells through the TNFR1/p38 MAPK signaling pathway. Overall, these results revealed an inductive role of IL-33 in pain associated with endometriosis, and highlighted the interaction between macrophages and sensory neurons.
研究领域:
免疫学
·
神经科学
·
妇产科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SOLID STATE SCIENCES
·
2019
·
IF 2.155
Hu Jingyu,Yang Ran,Li Zhaohui,Sun Yuanqiang,Qu Lingbo,Alexander Nti Kani
The zinc oxide/graphitic carbon nitride (ZnO/g-C 3 N 4 ) heterostructured nanocomposite was successfully synthesized by a facile two-step process involving thermal condensation of melamine and hydrothermal in situ growth of globular zinc oxide (ZnO) nanoparticles on the surface of graphitic carbon nitride (g-C 3 N 4 ). The morphologies, chemical compositions, and optical properties of the prepared ZnO/g-C 3 N 4 were investigated via a series of characterization techniques. SEM and TEM validate the grafting of ZnO globular with a diameter of 40–50 nm on the surface of g-C 3 N 4 . The visible photodegradation activity of the nanocomposite was assessed via tetracycline and oxytetracycline as target pollutants. Under visible light irradiation, 15 wt% ZnO globular-g-C 3 N 4 exhibits high photocatalytic activity with 78.4% of tetracycline degraded in 50 min and 63.5% of oxytetracycline in 50 min which was much faster photocatalytic degradation efficiency than that of the reported materials. Reactive species scavenging experiments revealed that photogenerated holes are the main reason for the photocatalytic degradation. After six recycles, the ZnO globular-g-C 3 N 4 resulted in 70% degradation efficiency of TC suggesting its high stability and reusability. This work proved a new insight for constructing novel high-performance photocatalysts for TC degradation.
研究领域:
材料科学
·
环境科学
✓ 已验证
DOI
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2021
·Vol. 28
·期 36
·50500-50509
·
IF 4.223
He Qian,Huang Shengxiong,Luo Wei,Su Yifeng,Xia Mao,Zhou Nan,Zhou Zhi
In-situ catalytic pyrolysis has simple process configuration and low cost. Ex-situ catalytic pyrolysis can optimize the pyrolysis capacity and upgrade catalysis, and the catalytic can be reused. But there have been few studies researched on compare in-situ and ex-situ catalytic pyrolysis of the OS performed in similar reactor with two kinds of catalytic. This paper study the pyrolysis of oily sludge (OS) uses CaO and oily pyrolysis char as catalytic at 700 °C. Through analysis the pyrolysis oil (PO), pyrolysis solid (PS) and pyrolysis gas (PG) during pyrolysis procedure to research the difference between in-situ and ex-situ catalytic pyrolysis. The gas chromatography-mass spectrometry (GC-MS) results show that CaO was conducive to the synthesis of aromatics, which content more than aliphatics and heterocyclics in CaO-i (i: in-situ) and CaO-e (e: ex-situ) groups. However, char greatly inhibits the production of aromatic compounds and promotes the production of aliphatic compounds. Gas chromatography (GC) results present that the char and CaO can greatly increase the content of combustible gas and the content reach to 85.85%, the pyrolysis gas (PG) keep at the highest combustion performance in char-CaO-i group. Meanwhile, compared with uncatalyzed groups, the content of CH 4 and CO increased about 2.05% and 3.93%, respectively. Fourier transform infrared spectroscopy (FT-IR) show that char and CaO reduce the function groups number of pyrolysis solid (PS), and it shows that the pyrolysis reaction is more complete. This research is expecting to provide theory support for catalytic pyrolysis of OS.
研究领域:
环境科学
·
能源工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Meng Zhang,Yiqing Ye,Zhengyun Chen,Xiaodong Wu,Yue Chen,Pengfei Zhao,Mengdan Zhao,Caihong Zheng
Endometriosis seriously affects 6–10% of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. In vitro studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. In vivo experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs. Statement of Significance Macrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.
研究领域:
妇科学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Min He,Qian Wang,Zhenqiang Shi,Yi Xie,Weifeng Zhao,Changsheng Zhao
Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin. A porous structure of the attached hydrogel layer was observed by scanning electron microscopy, and the presence of drug molecules in the hydrogel layer was confirmed by X-ray photoelectron spectroscopy and UV–vis absorption spectra . The drug release could be triggered under the mimicking inflammation environment, and the release rate was responsive to the inflammation degree. In addition, after attaching the hydrogel coating, the substrate showed low cytotoxicity, and high promotion for cell adhesion and proliferation. The excellent hemocompatibility of the hydrogel coating was also demonstrated by prolonged clotting time and suppressed platelet adhesion. This work suggests that the inflammation-responsive indometacin conjugated hydrogel coating has great potential to be used for prophylaxis HO.
研究领域:
生物材料学
·
药剂学
·
组织工程学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR HUMAN REPRODUCTION
·
2018
·Vol. 25
·期 1
·5-16
·
IF 3.449
Sun Huihui,Li Dong,Yuan Ming,Li Qiuju,Zhen Qianwei,Li Ni,Wang Guoyun
STUDY QUESTIONDo exosomes play a role in the pathogenesis of endometriosis in a murine model?SUMMARY ANSWERExosomes from endometriosis (EMS) can alternatively activate macrophages and thus contribute to the development of lesions in mice.WHAT IS KNOWN ALREADYThe pathogenesis of endometriosis, an inflammatory disease, possibly involves peritoneal macrophages. Exosomes are recognized as a new communicator among cells and a key modulator in several inflammatory diseases.STUDY DESIGN, SIZE, DURATIONWe performed in vitr and in vivo experiments to demonstrate the role of exosomes in modulating macrophages. RAW264.7 cells (macrophages) were used to examine the effects of exosomes on macrophages in vitro. An experiment was also conducted in vivo, as follows. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group). The experimental group was injected i.p. with EMS-exosomes derived from eutopic stromal cells, starting on Day-7 then every day for 1 week. The control group received CON-exosomes from mice without endometriosis. Peritoneal macrophages were assessed over the next 6 days. On Day 0, all mice were injected i.p. with endometrium to establish the endometriosis model. On Day 14, all mice were sacrificed, ectopic lesions were counted and measured.PARTICIPANTS/MATERIALS, SETTING, METHODSExosomes were isolated from endometrial stromal cells (ESCs) by ultracentrifugation and characterized through transmission electron microscopy, nanoparticle tracking analysis and western blot. After treatment with exosomes, the polarization and phagocytic ability of the macrophages were detected by flow cytometry analysis, immunofluorescent staining and RT-PCR. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of endometrial segments.MAIN RESULTS AND THE ROLE OF CHANCEAfter treatment with EMS-exosomes, the macrophages were polarized into an M2-like phenotype and their phagocytic ability decreased (P < 0.05 versus treatment with CON-exosomes). The total weight and volume of the lesions in mice treated with EMS-exosomes significantly increased compared with those in mice treated with CON-exosomes (P < 0.05). The infiltration of M2-like macrophages was enhanced in the EMS-exosome group (P < 0.001 versus treatment with CON-exosomes).LARGE SCALE DATAN/ALIMITATIONS, REASONS FOR CAUTIONDetection of endometriosis following exosome treatment was only performed in a murine endometriosis model. Clinical data and additional mechanism studies must be conducted to understand the role of exosomes in the pathogenesis of endometriosis.WIDER IMPLICATIONS OF THE FINDINGSThis study emphasizes the importance of EMS-exosomes in the pathogenesis of endometriosis. Further investigations on the exosome signaling pathways may contribute to the development of effective treatments for endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This research was supported by grants (Nos. 81571417 and 81771552) from the National Science Foundation of China. The authors report no conflict of interest.
研究领域:
生殖生物学
·
免疫学
·
妇科学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）