Intratumoral bacteria have attracted considerable attention as critical components of the tumor microenvironment (TME) that influence tumor initiation, progression, therapeutic efficacy, and immune responses. Conventional antibiotic approaches for eradicating intratumoral bacteria are limited by severe side effects, disruption of microbial homeostasis, and the emergence of multidrug resistance, while offering no direct tumoricidal effects. Here, we developed bimetallic Copper-Tin nanozymes (CuSn nanozymes) with a galvanic cell effect to overcome bacteria-associated challenges, overcome drug resistance, and enhance cancer therapy. The nanozymes can generate highly active electrons and metal ions at tumor sites without external stimulation, achieving massive reactive oxygen species (ROS) production and effective tumor eradication. The released electrons disrupt bacterial electron transport chains (ETC), thereby inhibiting energy synthesis and achieving potent antibacterial effects. The release of copper ions further enhances ROS-mediated antibacterial activity. Moreover, bacterial eradication promotes antitumor immune activation, further enhancing therapeutic outcomes. Using breast, endometrial, and liver cancer models, we demonstrated the broad applicability of this approach. This work not only offers a new paradigm for designing innovative bimetallic nanozymes with enhanced catalytic activity but also provides a potential therapeutic approach for simultaneously eliminating bacteria and tumors, overcoming chemoresistance, and offering effective treatment without reliance on conventional antibiotics or chemotherapeutics for microbiota-enriched tumors.

Salpingitis and subsequent conditions such as hydrosalpinx and tissue damage are significant causes of female infertility. Currently, beyond pharmacological and surgical interventions, there is a lack of highly effective therapeutic strategies, highlighting an urgent need for biomaterials that meet clinical demands. In this study, we developed a thermosensitive CS-RC-GP-ZnO hydrogel loaded with nanoparticles. This material undergoes a sol-gel transition at physiological temperature, enabling it to physically fill the infected fallopian tube while sustainably releasing antibacterial, anti-inflammatory, and pro-regenerative components. In vitro validation confirmed that CS-RC-GP-ZnO exhibits biocompatibility, biodegradability, the ability to promote cell proliferation and migration, induction of macrophage polarization, and effective antimicrobial properties. A rat model of salpingitis was established by combining mixed bacterial infection with mechanical injury. Using this model, CS-RC-GP-ZnO treatment was associated with activation of the cAMP/PKA/CREB pathway and a shift in macrophage-related markers toward an M2-like polarization state. This significantly enhances antibacterial and anti-inflammatory effects, promotes tissue repair, and subsequently remodels the immune microenvironment, thereby achieving notable therapeutic outcomes. In summary, the CS-RC-GP-ZnO hydrogel shows promising efficacy in treating salpingitis and other female reproductive diseases, indicating considerable potential for clinical translation. STATEMENT OF SIGNIFICANCE: To address the shortage of effective clinical therapies for salpingitis, a thermosensitive CS-RC-GP-ZnO hydrogel was developed by incorporating recombinant humanized collagen for enhanced tissue regeneration and zinc oxide nanoparticles for antibacterial and anti-inflammatory functions. A clinically relevant rat salpingitis model was established using mixed bacterial infection combined with mechanical injury to mimic ascending infection and pelvic inflammatory compression. The hydrogel restored immune homeostasis by synergistically promoting antibacterial activity, inflammation resolution, tissue repair, and macrophage polarization toward the M2 phenotype, offering a promising therapeutic strategy for salpingitis and related gynecological disorders.

Tumor therapy remains one of the major challenges in medicine. Tumor-associated bacteria have recently emerged as crucial regulators of the tumor microenvironment, profoundly influencing the occurrence, development, immune response, and therapeutic efficacy of tumors, including intratumoral and intracellular bacteria. In particular, intratumoral and intracellular bacteria could be the effective targets to boost tumor therapy. However, several limitations remain for both antimicrobial therapy and tumor therapy in clinical, including drug resistance, low therapy efficiency, high recurrence rates, etc. Encouragingly, stimuli-responsive nanomaterials have significantly contributed to overcome these limitations. In this review, the different types of intratumoral and intracellular bacteria present in the tumor microenvironment were first introduced. Next, it summarizes the mechanisms by which these bacteria affect the biological activity of tumor cells. Then, the applications and mechanisms of various stimuli-responsive nanomaterials in antimicrobial therapy to enhance tumor therapy are discussed. Subsequently, advances in improving tumor therapy by intratumoral and intracellular antibacterial strategies are highlighted. Additionally, the future concerns and solutions of stimuli-responsive nanomaterials are examined. Finally, the current challenges associated with using antibacterial strategies for tumor therapy are revealed, along with prospective future development directions.

Unintended pregnancy remains a significant concern in women's healthcare. Although current short-term contraceptive methods, particularly hormonal approaches, are effective in preventing unintended pregnancy, their potential long-term adverse effects necessitate the development of safer alternatives. A nanostrategy that interrupts early pregnancy by inhibiting embryonic trophoblast cell proliferation presents a promising non-hormonal approach with minimal adverse effects on female reproductive system. In this study, we further advanced this strategy by designing a highly effective, low-dose contraceptive using vitamin B13 copper metal-organic framework (VB13 Cu-MOF) as the active agent. VB13 Cu-MOF exhibited rapid dissolution in aqueous environments with a sustained and low Cu²⁺ release rate, facilitating preferential uptake by embryonic trophoblast cells due to their tumor-like characteristics. Upon contact with cells in the in vitro cellular model, the released Cu²⁺ was transported into cells via proteins on cell membrane in two pathways, direct Cu²⁺ intracellular transport, and Cu²⁺ reduction to Cu⁺ and Cu+ intracellular transport. Both Cu²⁺ and Cu⁺ in cells triggered parallel Fenton-like reactions, resulting in excessive reactive oxygen species generation, mitochondrial damage, apoptosis, and ferroptosis. RNA-seq analysis identified the key biological processes and the associated genes involved in these interactions. In vivo experiments in rat models demonstrated contraceptive efficacy using VB13 Cu-MOF at an ultra-low dose (65 μg/mL) and its hydrogel formulation, without inducing adverse effects on serum copper levels, estrogen concentrations, inflammatory markers, or organ morphology. These findings establish VB13 Cu-MOF as a promising non-hormonal contraceptive with strong potential to prevent unintended pregnancies while minimizing risks to women's health. STATEMENT OF SIGNIFICANCE: Vitamin 13 copper metal-organic Framework (VB13 Cu-MOF) was designed and developed as a bioactive material for female non-hormonal contraceptives. As a new source of copper ions, VB13 Cu-MOF demonstrated a controlled release of copper ions, effectively targeting and inducing trophoblast cell death to achieve high contraceptive efficacy in a rat model at low dosage, without causing adverse effects in vitro or in vivo. Moreover, VB13 can increase the histocompatibility of Cu-MOF to normal cells. VB13 Cu-MOF was employed to validate a novel contraceptive mechanism targeting trophoblast cells to interrupt the pregnancy process 5-8 days after mating. Significantly, this demonstrates its potential as a promising non-hormonal contraceptive for clinical use, contributing to enhanced women's healthcare.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (R--CH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, Xray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 mu M exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu2 + . To minimize the burst release, in this study, we designed a series of Cu-Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu-Fe alloys and UFG Cu-Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and in vitro cytotoxicity. With careful comparison and selection, we chose the CG Cu-5Fe and UFG Cu-5Fe for in vivo tests using rat model, including tissue biocompatibility, in vivo corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu-5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu-5Fe alloys exhibited dramatic suppression of Cu2 + release in simulated uterine fluid for the long-term immersion process. The in vivo tissue compatibility was significantly improved with both CG and UFG Cu-5Fe alloys implanted in the rats' uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu-5Fe alloys can be the promising candidate material for Cu-IUD.

The normal aging process is accompanied by cognitive decline, and previous studies have indicated the crucial role of the hypothalamus in regulating both aging and cognition. However, the precise molecular mechanism underlying this relationship remains unclear. Therefore, this present study aimed to identify potential predictors of cognitive decline associated with aging specifically within the hypothalamus. To achieve this, we employed Morris water maze (MWM) testing to assess learning and memory differences between young and aged mice. Additionally, transcriptome sequencing was conducted on the hypothalamus of young and aged mice to identify potential genes. Subsequently, GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways. Finally, the results obtained from sequencing analysis were further validated using qRT-PCR. Notably, MWM testing revealed a significant decrease in spatial learning and memory ability among aged mice. According to KEGG analysis, the DEGs primarily encompassed various biochemical signaling pathways related to immune system (e.g., C3; C4b; Ccl2; Ccl7; Cebpb; Clec7a; Col3a1; Cxcl10; Cxcl2; Fosb; Fosl1; Gbp5; H2-Ab1; Hspa1a; Hspa1b; Icam1; Il1b; Itga5; Itgax; Lilrb4a; Plaur; Ptprc; Serpine1; Tnfrsf10b; Tnfsf10), neurodegenerative disease (e.g., Atp2a1; Creb5; Fzd10; Hspa1a; Hspa1b; Il1b; Kcnj10; Nxf3; Slc6a3; Tubb6; Uba1y; Wnt9b), nervous system function (e.g., Chrna4; Chrna6; Creb5; Slc6a3),and aging (e.g., Creb5; Hspa1a; Hspa1b) among others. These identified genes may serve as potential predictors for cognitive function in elderly individuals and will provide a crucial foundation for further exploration into the underlying molecular mechanisms.

Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.

Preventing unintentional pregnancy is one of the goals of a global public health policy to minimize effects on individuals, families, and society. Various contraceptive formulations with high effectiveness and acceptance, including intrauterine devices, hormonal patches for females, and condoms and vasectomy for males, have been developed and adopted over the last decades. However, distinct breakthroughs of contraceptive techniques have not yet been achieved, while the associated long-term adverse effects are insurmountable, such as endocrine system disorder along with hormone administration, invasive ligation, and slowly restored fertility after removal of intrauterine devices. Spurred by developments of nanomaterials and bionanotechnologies, advanced contraceptives could be fulfilled via nanomaterial solutions with much safer and more controllable and effective approaches to meet various and specific needs for women and men at different reproductive stages. Nanomedicine techniques have been extended to develop contraceptive methods, such as the targeted drug delivery and controlled release of hormone using nanocarriers for females and physical stimulation assisted vasectomy using functional nanomaterials via photothermal treatment or magnetic hyperthermia for males. Nanomaterial solutions for advanced contraceptives offer significantly improved biosafety, noninvasive administration, and controllable reversibility. This review summarizes the nanomaterial solutions to female and male contraceptives including the working mechanisms, clinical concerns, and their merits and demerits. This work also reviewed the nanomaterials that have been adopted in contraceptive applications. In addition, we further discuss safety considerations and future perspectives of nanomaterials in nanostrategy development for next-generation contraceptives. We expect that nanomaterials would potentially replace conventional materials for contraception in the near future.

Menstruation is a specific physiological phenomenon in female humans that is regulated by complex molecular mechanisms. However, the molecular network involved in menstruation remains incompletely understood. Previous studies have suggested that C-X-C chemokine receptor 4 (CXCR4) is involved; however, how CXCR4 participates in endometrial breakdown remains unclear, as do its regulatory mechanisms. This study aimed to clarify the role of CXCR4 in endometrial breakdown and its regulation by hypoxia-inducible factor-1 alpha (HIF1A). We first confirmed that CXCR4 and HIF1A protein levels were significantly increased during the menstrual phase compared with the late secretory phase using immunohistochemistry. In our mouse model of menstruation, real-time PCR, western blotting, and immunohistochemistry showed that CXCR4 mRNA and protein expression levels gradually increased from 0 to 24 h after progesterone withdrawal during endometrial breakdown. HIF1A mRNA and HIF1A nuclear protein levels significantly increased and peaked at 12 h after progesterone withdrawal. Endometrial breakdown was significantly suppressed by the CXCR4 inhibitor AMD3100 and the HIF1A inhibitor 2-methoxyestradiol in our mouse model, and HIF1A inhibition also suppressed CXCR4 mRNA and protein expression. In vitro studies using human decidual stromal cells showed that CXCR4 and HIF1A mRNA expression levels were increased by progesterone withdrawal and that HIF1A knockdown significantly suppressed the elevation in CXCR4 mRNA expression. CD45+ leukocyte recruitment during endometrial breakdown was suppressed by both AMD3100 and 2-methoxyestradiol in our mouse model. Taken together, our preliminary findings suggest that endometrial CXCR4 expression is regulated by HIF1A during menstruation and may promote endometrial breakdown, potentially via leukocyte recruitment.

The comprehensively adopted copper-containing intrauterine devices (Cu-IUDs) present typical adverse effects such as bleeding and pain at the initial stage of post-implantation. The replacement of Cu material is demanded. Zinc and its alloys, the emerging biodegradable materials, exhibited contraceptive effects since 1969. In this work, we evaluated the feasibility of bulk Zn alloys as IUD active material. Using pure Cu and pure Zn as control groups, we investigated the contraceptive performance of Zn-0.5Cu and Zn-1Cu alloys via in vitro and in vivo tests. The results showed that the main corrosion product of Zn-Cu alloys is ZnO from both in vitro and in vivo studies. CaZn2(PO4)2·2H2O is formed atop after long-term immersion in simulated uterine fluid, whereas CaCO3 is generally formed atop after implantation in the rat uterine environment. The cytocompatibility of the Zn-1Cu alloy was significantly higher than that of the pure Zn and pure Cu to the human endometrial epithelial cell lines. Furthermore, the in vivo results showed that the Zn-1Cu alloy presented much improved histocompatibility, least damage and the fastest recovery on endometrium structure in comparison to pure Zn, Zn-0.5Cu and pure Cu. The systematic and comparing studies suggest that Zn-1Cu alloy can be considered as a possible candidate for IUD with great biochemical and biocompatible properties as well as high contraceptive effectiveness. STATEMENT OF SIGNIFICANCE: The existing adverse effects with the intrinsic properties of copper materials for copper-containing intrauterine devices (Cu-IUD) are of concerns in their employment. Such as burst release of cupric ions (Cu2+) at the initial stage of the Cu-IUD. Zinc and its alloys which have been emerging as a potential biodegradable material exhibited contraceptive effects since 1969. In this study, Zn-1Cu alloys displayed significantly improved biocompatibility with human uterus cells and a decreased inflammatory response within the uterus. Therefore, high antifertility efficacy of the Zn-1Cu alloy was well maintained, while the adverse effects are significantly eased, suggesting that the Zn-1Cu alloy is promising for IUD.

Copper intrauterine device is one of the most adopted contraceptive methods with high effectiveness (over 99 %), low cost, spontaneous reversibility and long-lasting usage. However, the side effects induced from the initial burst release of copper ions (Cu2+) hinder the continuation of the Cu-IUD made of Coarse-Grained Copper (CG Cu). We proposed to tailor the bio-corrosion behaviors of better control of Cu2+ release via the addition of bioactive Mg into the Ultra-Fine Grained (UFG) Bulk Cu. Thus, UFG bulk Cu with 0.4 wt.% Mg was produced via equal-channel angular pressing. The microstructures of the UFG Cu-0.4Mg was observed using electron backscatter diffraction and transmission electron microscopy techniques. The in vitro long-term corrosion behaviors in simulated uterine fluid, cytotoxicity to four cell lines, in vivo biocompatibility and contraceptive efficacy were all studied on CG Cu, UFG Cu and UFG Cu-0.4Mg materials. The results demonstrate that both the ultrafine grains and the addition of bioactive Mg into Cu contribute to the suppression of the burst release of Cu2+ in the initial stage and the maintenance of high level Cu2+ in long-term release. Moreover, the UFG Cu-0.4Mg also exhibited much improved cell and tissue biocompatibility from both the in vitro and in vivo evaluations. Therefore, the contraceptive efficacy of UFG Cu-0.4Mg is still maintained as high as the CG Cu and UFG Cu while the side effects are significantly eased, suggesting the high potential of the UFG Cu-0.4Mg alloy as a new upgrading or alternative material for Cu-IUD. Statement of significance The side effects from burst release of Cu2+ at the initial implantation stage of Cu-containing intrauterine devices (Cu-IUD) is one of the main drawbacks of these devices. In this work, an ultra-fine-grained Cu (UFG Cu) alloyed with a low amount of bioactive Mg was used for a Cu-IUD. The UFG Cu-0.4Mg alloy exhibited suppressed burst release of Cu2+ at initial implantation, while active Cu2+ release for long-term usage was maintained, comparable to coarse-grained pure Cu. Furthermore, the UFG Cu-0.4Mg alloy displayed significantly improved biocompatibility with human uterus cells and a much decreased inflammatory response within the uterus. Therefore, the side effects from Cu-IUD were eased, while high antifertility efficacy of the UFG Cu-0.4Mg alloy was maintained. The UFG Cu-0.4Mg alloy is promising for Cu-IUD. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Significant advances have been achieved in the research evaluating Zn and its alloys as degradable metallic biomaterials mainly for application in bone and blood vessels. In the present study, the degradation behaviors of Zn-0.1Li and Zn-0.8Mg alloys in simulated uterine fluid (SUF) were systematically investigated for 300 days. In vitro viability assays were conducted in different uterine cells (HUSMCs, HEECs, and HESCs), and histological examination after the in vivo implantation into the uterine cavity was performed using pure Zn as control. The immersion test results indicated that both Zn-0.1Li and Zn-0.8Mg alloys exhibited better corrosion resistance than pure Zn, with Zn3(PO4)2⋅4H2O and CaZn2(PO4)2⋅2H2O being the main corrosion products detected in the SUF in addition to ZnO. The cell cytotoxicity assays revealed that Zn-0.1Li and Zn-0.8Mg exhibited better cytocompatibility than Zn. Moreover, the in vivo experiments demonstrated that the Zn-0.1Li and Zn-0.8Mg alloys induced less inflammation in the uterine tissue than pure Zn, with CaCO3 and Zn(HPO4)⋅3H2O being the major biocorrosion products in addition to ZnO. According to these results, zinc alloys appear to be suitable potential candidate materials for future intrauterine biomedical devices.

Activating transcription factor 6 (ATF6), also known as ACHM7, ATF6A, encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. It functions as nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is presented in the promoters of genes encoding ER chaperones. Studies have shown that endoplasmic reticulum stress (ERS) can cause damage to spermatozoa and testes, leading to male sterility. And we find that the expression of ATF6 in spermatozoa of some infertile patients is significantly reduced. Then, we construct the Atf6 knockout mice model and interestingly find a decline in male fertility. The downstream gene testis-specific serine/threonine-protein kinase 4 (Tssk4) is screened based on transcriptome sequencing. We use Western blot and real-time PCR to confirm this result in both 293T cells and Atf6 knockout mice. TSSK4 is essential in male germ cell genesis and sperm maturation. Our results suggest that the expression of TSSK4 may be regulated by ATF6. The effect of Atf6 knockout on the reproductive development of male mice may be related to the low expression of TSSK4, which further verify that there may be some relationship between ERS and male reproduction.

Background: Cervical cancer is the leading cause of cancer-related death in women worldwide. However, the mechanisms mediating the development and progression of cervical cancer are unclear. In this study, we aimed to elucidate the roles of microRNAs and a1-chimaerin (CHN1) protein in cervical cancer progression. Methods: The expression of miR-205 and CHN1 protein was investigated by in situ hybridisation and immunohistochemistry. We predicted the target genes of miR-205 using software prediction and dual luciferase assays. The expression of mRNAs and proteins was tested by qRT-PCR and western blotting respectively. The ability of cell growth, migration and invasion was evaluated by CCK-8 and transwell. Cell apoptosis was analysed by flow cytometry analysis. Results: We found that miR-205 and CHN1 were highly expressed in human cervical cancer tissue compared with paired normal cervical tissues. The CHN1 gene was shown to be targeted by miR-205 in HeLa cells. Interestingly, transfection with miR-205 mimic upregulated CHN1 mRNA and protein, while miR-205 inhibitor downregulated CHN1 in high-risk and human papilloma virus (HPV)-negative human cervical cancer cells in vitro ,. These data suggested that miR-205 positively regulated the expression of CHN1. Furthermore, the miR-205 mimic promoted cell growth, apoptosis, migration, and invasion in high-risk and HPV-negative cervical cancer cells, while the miR-205 inhibitor blocked these biological processes. Knockdown of CHN1 obviously reduced the aggressive cellular behaviours induced by upregulation of miR-205 , suggesting that miR-205 positively regulated CHN1 to mediate these cell behaviours during the development of cervical cancer. Furthermore, CHN1 was correlated with lymph node metastasis in clinical specimens. Conclusions: Our findings showed that miR-205 positively regulated CHN1 to mediate cell growth, apoptosis, migration, and invasion during cervical cancer development, particularly for high-risk HPV-type cervical cancer. These findings suggested that dysregulation of miR-205 and subsequent abnormalities in CHN1 expression promoted the oncogenic potential of human cervical cancer.

目的 探讨95％乙醇不同作用时间对大鼠子宫内膜损伤程度的影响. 方法 在大鼠宫腔内给予95％乙醇,作用时间分别为15s、30 s、60 s和120 s;在处理后7d,观察大鼠子宫的大体形态,并采用组织形态学的方法观察大鼠子宫内膜修复情况以及子宫内膜的厚度和腺体数量分析. 结果 95％乙醇作用15s组子宫腺体数量明显减少,出现纤维化;作用30 s组子宫出现点状淤血,外观较光滑,宫腔狭小,纤维化面积增大;作用60 s和120 s组子宫管表面出现皱痕,有明显淤血,并且子宫内膜明显变薄. 结论 95％乙醇处理时间15～30 s对子宫内膜的损伤可能更贴近临床刮宫的损伤程度.

Magnesium and its alloys were widely investigated in many body fluid microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine microenvironment. In this study, the degradation behaviors of HP-Mg, Mg-1Ca, and Mg-2Zn alloys in simulated uterine fluid (SUF) were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the gluteal muscle of rat was used as the implantation position to study the in vivo biocompatibility as a mimic of the intrauterine device (IUD) fixation part. The 120-day immersion test indicated that the Mg-1Ca alloy had a faster degradation rate than the Mg-2Zn alloy and HP-Mg and dissolved entirely in the SUF. Indirect cytotoxicity assay showed that the extracts of HP-Mg, Mg-1Ca, and Mg-2Zn alloys have positive effects on human uterine smooth muscle cells (HUSMC), human endometrial epithelial cells (HEEC), and human endometrial stromal cells (HESC), especially for the Mg-1Ca alloy group. Furthermore, the in vivo experiment showed that HP-Mg, Mg-1Ca, and Mg-2Zn alloy implants cause a light inflammatory response in the initial 3 days, but they were surrounded mainly by connective tissue, and lymphocytes were rarely observed at 4 weeks. Based on the above facts, we believed that it is feasible for using biomedical Mg alloys in obstetrics and gynecology and proposed three kinds of medical device candidates for future R&D. Statement of Significance Magnesium alloys were widely investigated in various body microenvironments including bone, blood, bile, saliva, and urine; however, no study has been conducted in the intrauterine environment. In this work, the degradation behaviors of Mg alloys in simulated uterine fluid were systematically investigated, and then the biological response of four kinds of uterine cells to these materials was observed. For this purpose, the tibialis anterior of a rat model was used as the implantation position to study the in vivo biocompatibility. The comprehensive in vitro and in vivo testing results indicated that biomedical Mg alloys are feasible for use in obstetrics and gynecology. Further, three kinds of medical device candidates were proposed. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Objective To establish an efficient method for isolating primary human endometrium stromal and epithelial cells in vitro.Methods Health endometrial tissue of hysterectomy patient was obtained,and was cut into a small piece.Firstly,the human endometrial stromal cells (HUSC) and human endometrial epithelial cells (HUEC) were isolated by the twice enzymatic digestion,twice separation and different adherent time of the two types of cells.And then HUSC and HUEC were identified and the percentage of vimentin (Vim)-positive and cytokeratin (CK)-positive ones were determined by flow cytometry.After that,primary HUSC were stimulated by cyclic adenosine monophosphate (cAMP)+medroxyprogesterone acetate (MPA) for 4 d and 7 d.Results The HUSC purity was (97.0 ± 2.5)％ and the HUEC purity was (90.0 ± 4.1)％ determined by flow cytometry,indicating that we had highly purified cultures of HUSC and HUEC in vitro.After cAMP+MPA induction for 4 d and 7 d,the HUSC showed more obvious changes in cell morphology and prolactin (PRL) level.Conclusion We successfully established an efficient method of isolation and characterization of primary human endometrium stromal and epithelial cells in vitro.

Objective: To investigate the protein and mRNA expression of HIF1A and VEGF in mouse menstrual-like model,and explore the possible regulatory relationship between HIF1A and VEGF during menstruation.Methods: Mouse menstrual-like model were manipulated by pseudo-pregnancy mice,and the endometrial decidualization was induced by injecting peanut oil into uterine cavity.Progesterone(P4) was withdrawn to induce mimic menstruation.Mouse uteri were collected 0,8,12,16 and 24 hours after P4 withdrawal.HIF1A and VEGF protein expression and location were investigated by immunohistochemical staining and Western blot,while the mRNA expression was quantified by real-time PCR.The expression pattern of HIF1A and VEGF and their correlation were further analyzed.Results: After P4 was withdrawn,the decidual-endometrium was disintegrated and bled,and the mimic menstruation occurred in mice.The results of immunohistochemical showed that the protein expression of HIF1A was increased in nuclear 12 and 16 hours after P4 withdrawal.The protein expressions of HIF1A and VEGF in nucleus were both concentrated in the peripheral region of endometrial decidualization area,i.e.the junction between the disintegration tissues and basal layer.The results of quantification of protein by Western blot indicated that the HIF1A protein levels in nucleus were significantly increased 8,12 and 16 hours after P4 withdrawal,while the protein levels of VEGF in cytoplasm were relatively higher at 0,8 and 12 hours.The trend of expression of HIF1A and VEGF mRNA was similar,and both expressions were significantly increased after P4 withdrawal and reached the highest at 12 hours,and then decreased subsequently.Conclusions: The transcription factor function of HIF1A is activated,which regulates the expression of VEGF mRNA during endometrial disintegration in menstruation.