CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer and is highly malignant with high chemoresistance. CACNA1H is pivotal in tumor development. However, the role of CACNA1H in the acquisition process of chemotherapeutic resistance in OCCC cells is rarely reported. Therefore, this study aimed to explore the role of CACNA1H in chemotherapy resistance of OCCC cells and its related mechanism. Based on bioinformatics analysis, we found that CACNA1H was downregulated in chemoresistant OCCC patients compared to chemosensitive OCCC patients. Comparing DDP-resistant and sensitive OCCC cell lines, the resistant strain showed lower CACNA1H mRNA expression. CACNA1H expression was associated with calcium signaling pathways in chemoresistant OCCC patients. CACNA1H mRNA expression was significantly downregulated in OCCC cells compared to normal ovarian epithelial cells. When CACNA1H was overexpressed, intracellular Ca2+ concentration and protein levels of p-CaMKII and p-Akt were significantly upregulated, while protein levels of LC3-II/LC3-I and Beclin1 were downregulated, indicating a repression of autophagy. The rescue experiment revealed that CACNA1H overexpression in drug-resistant OCCC cells reduced autophagy-induced DDP resistance via CaMKII/Akt signaling. Overall, CACNA1H increased intracellular Ca2+ concentration and activated CaMKII/Akt signaling pathway in OCCC, thereby repressing autophagy to maintain the sensitivity of OCCC cells to DDP.

Regulating the Active Sites of Cs2 AgBiCl6 by Doping for Efficient Coupling of Photocatalytic CO2 Reduction and Benzyl Alcohol Oxidation.

Halide perovskites exhibit outstanding optoelectronic properties, which make them an ideal choice for photocatalytic CO2 reduction and benzyl alcohol (BA) oxidation. Nevertheless, the simultaneous realization of the above redox coupling reactions on halide perovskites remains a great challenge, as it requires distinct catalytic sites for different target reactions. Herein, the catalytic sites of Cs2 AgBiCl6 (CABC) are regulated by doping Fe for efficient coupling of photocatalytic CO2 reduction and BA oxidation. The Fe-doped CABC (Fe: CABC) exhibits an enhanced visible-light response and effective charge separation. Experimental results and theoretical calculations reveal a synergistic interplay between Bi and Fe sites, where the Bi and Fe sites have lower activation energies toward CO2 reduction and BA oxidation. Further investigations demonstrate that electrons and holes prefer to accumulate at the Bi site and Fe site under light irradiation, respectively, which creates favorable conditions for facilitating CO2 reduction and BA oxidation. The resultant Fe: CABC achieves a high photocatalytic performance toward CO (18.5 µmol g-1  h-1 ) and BD (1.1 mmol g-1  h-1 ) generation, which surpasses most of the state-of-the-art halide photocatalysts. This work demonstrates a facile strategy for regulating the catalytic site for redox coupling reactions, which will pave a new way for designing halide perovskites for photocatalysis.

Rubidium Doped Cs2AgBiBr6 Hierarchical Microsphere for Enhanced Photocatalytic CO2 Reduction.

Halide perovskites have garnered significant attention for their unique optoelectronic properties in solar-to-fuel conversions. However, the efficiency of halide perovskites in the field of photocatalytic CO2 reduction is largely limited by serious charge recombination and a lack of efficient active sites. In this work, a rubidium (Rb) doped Cs2AgBiBr6 (Rb:CABB) hierarchical microsphere is developed for photocatalytic CO2 reduction. Experimental and theoretical analysis discloses that partially substituting Rb+ for Ag+ can effectively modulate the electronic structure of CABB, favoring charge separation and making adjacent Bi atoms an electron-rich active site. Further investigations indicated that Rb doping also reduces the energy barriers of the rate-determining step in CO2 reduction. As a result, Rb:CABB demonstrated an enhanced CO yield compared to its undoped counterpart. This work presents a promising approach to optimizing the electronic structures of photocatalysts and paving a new way for exploring halide perovskites for photocatalytic CO2 reduction.

Efficient thermally activated delayed fluorescence organic light-emitting device based on an exciplex.

An exciplex with significant thermally activated delayed fluorescence properties was realized, comprising diphenyl-[3'-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)-biphenyl-4-yl]-amine as a donor and 2,4,6-tris[3-(diphenylphosphinyl)phenyl]-1,3,5-triazine as an acceptor. A very small energy difference between the singlet and triplet levels and a large rate constant of the reverse intersystem crossing were attained simultaneously, contributing to the efficient upconversion of triplet excitons from the triplet state to the singlet state and thermally activated delayed fluorescence emission. A high-efficiency organic light-emitting device based on the exciplex was fabricated, which exhibited a maximum current efficiency, power efficiency, external quantum efficiency, and exciton utilization efficiency of 23.1 cd/A, 24.2 lm/W, 7.32%, and 54%, respectively. The efficiency roll-off of the exciplex-based device was slight, as illustrated by a large critical current density of 34.1 mA/cm2. This efficiency roll-off was ascribed to triplet-triplet annihilation, as confirmed by the triplet-triplet annihilation model. We proved the high binding energy of the excitons and excellent charge confinement within the exciplex by performing transient electroluminescence measurements.

Study on the difference in exciton generation processes for a single host and exciplex-type co-host.

We distinctly reveal the difference in the exciton generation processes in phosphorescent organic light-emitting devices with an exciplex-type co-host and a single host. Excitons in the co-host consisting of 4,4,4-tris(N-carbazolyl)-triphenylamine and 1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene are created via efficient energy transfer from the exciplex to the phosphorescent dopant. In contrast, excitons in the single host of 4,4,4-tris(N-carbazolyl)-triphenylamine are formed by the combination of holes and electrons trapped by the phosphorescent dopants. The optimized device utilizing the co-host system exhibits highly superior performance relative to the single-host device. The maximum external quantum efficiency and maximum luminance are 14.88% and 90,700cd/m2 for the co-host device, being 1.6 times and 3.6 times the maximum external efficiency and maximum luminance for the single-host device, respectively. Significantly, the critical current density, evaluating the device efficiency roll-off characteristic, is as high as 327.8mA/cm2, which is highly superior to 120.8mA/cm2 for the single-host device, indicating the notable alleviation in efficiency roll-off for the co-host device. The significant improvement in device performance is attributed to eliminating the exciton quenching resulting from the captured holes and the efficient energy transfer from the exciplex-type co-host to the phosphorescent emitter incurred by the reverse intersystem crossing process.

Comparison of ground reaction forces as running speed increases between male and female runners.

Introduction: The biomechanics associated with human running are affected by gender and speed. Knowledge regarding ground reaction force (GRF) at various running speeds is pivotal for the prevention of injuries related to running. This study aimed to investigate the gait pattern differences between males and females while running at different speeds, and to verify the relationship between GRFs and running speed among both males and females. Methods: GRF data were collected from forty-eight participants (thirty male runners and eighteen female runners) while running on an overground runway at seven discrete speeds: 10, 11, 12, 13, 14, 15 and 16 km/h. Results: The ANOVA results showed that running speed had a significant effect (p < 0.05) on GRFs, propulsive and vertical forces increased with increasing speed. An independent t-test also showed significant differences (p < 0.05) in vertical and anterior-posterior GRFs at all running speeds, specifically, female runners demonstrated higher propulsive and vertical forces than males during the late stance phase of running. Pearson correlation and stepwise multiple linear regression showed significant correlations between running speed and the GRF variables. Discussion: These findings suggest that female runners require more effort to keep the same speed as male runners. This study may provide valuable insights into the underlying biomechanical factors of the movement patterns at GRFs during running.

A new method proposed for realizing human gait pattern recognition: Inspirations for the application of sports and clinical gait analysis.

BACKGROUND: Finding the best subset of gait features among biomechanical variables is considered very important because of its ability to identify relevant sports and clinical gait pattern differences to be explored under specific study conditions. This study proposes a new method of metaheuristic optimization-based selection of optimal gait features, and then investigates how much contribution the selected gait features can achieve in gait pattern recognition. METHODS: Firstly, 800 group gait datasets performed feature extraction to initially eliminate redundant variables. Then, the metaheuristic optimization algorithm model was performed to select the optimal gait feature, and four classification algorithm models were used to recognize the selected gait feature. Meanwhile, the accuracy results were compared with two widely used feature selection methods and previous studies to verify the validity of the new method. Finally, the final selected features were used to reconstruct the data waveform to interpret the biomechanical meaning of the gait feature. RESULTS: The new method finalized 10 optimal gait features (6 ankle-related and 4-related knee features) based on the extracted 36 gait features (85 % variable explanation) by feature extraction. The accuracy in gait pattern recognition among the optimal gait features selected by the new method (99.81 % ± 0.53 %) was significantly higher than that of the feature-based sorting of effect size (94.69 % ± 2.68 %), the sequential forward selection (95.59 % ± 2.38 %), and the results of previous study. The interval between reconstructed waveform-high and reconstructed waveform-low curves based on the selected feature was larger during the whole stance phase. SIGNIFICANCE: The selected gait feature based on the proposed new method (metaheuristic optimization-based selection) has a great contribution to gait pattern recognition. Sports and clinical gait pattern recognition can benefit from population-based metaheuristic optimization techniques. The metaheuristic optimization algorithms are expected to provide a practical and elegant solution for sports and clinical biomechanical feature selection with better economy and accuracy.

General Post-Regulation Strategy of AIEgens' Photophysical Properties for Intravital Two-Photon Fluorescence Imaging.

Fluorogens with aggregation-induced emission (AIEgens) are promising agents for two-photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post-regulation strategy to optimize AIEgens' photophysical properties. Herein, a general and efficient post-regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two-photon absorption cross-section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single-cell resolution. Furthermore, the TPF imaging quality is improved by the self-supervised denoising algorithm. The proposed binary molecular post-regulation strategy opened a new avenue to efficiently boost the AIEgens' photophysical properties and consequently TPF imaging quality.

Down-regulation of miR-424 inhibited the metastasis of endometrial carcinoma via targeting PTEN/PI3K/AKT signaling pathway.

Background: The incidence of endometrial carcinoma (EC) has been increasing annually, and treatment of advanced cases remains challenging. MicroRNA-424 (miR-424) was reported to affect several types of tumors, but its role in EC has not been studied. Methods: We generated transient knockdown models of miR-424 and PTEN in EC cells. We measured mRNA and protein expression using RT-PCR and western blotting. We evaluated cell proliferation, invasion, migration, and apoptosis using CCK8, Transwell, wound healing, and flow cytometry assays. We also investigated the effect of miR-424 and PTEN on tumor growth using a metastatic tumor model in nude mice. Results: The expression of miR-424 was significantly elevated in EC tissues and cell lines. MiR-424 inhibitor significantly restrained PTEN/PI3K/AKT signaling, while miR-424 mimic activated this pathway. Knockdown of PTEN significantly reversed the effects of miR-424 inhibitor on cell proliferation, invasion, migration, and apoptosis in EC cells. The significant inhibition of tumor growth and ki67 expression caused by miR-424 inhibitor were markedly promoted by sh-PTEN. Conclusions: Our findings suggest that miR-424 inhibitor could inhibit cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) process, and tumor growth, while promoting apoptosis in EC. However, the effects of miR-424 inhibitor were markedly reversed by sh-PTEN. This study provides a potential novel therapeutic strategy for the prevention and treatment of EC by targeting miR-424.

Structural and Physicochemical Properties of a Chinese Yam Starch-Tea Polyphenol Complex Prepared Using Autoclave-Assisted Pullulanase Treatment.

Interactions between food components have a positive impact in the field of food science. In this study, the effects of tea polyphenol on the structural and physicochemical properties of Chinese yam starch using autoclave-assisted pullulanase treatment were investigated. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, rapid visco analysis, differential scanning calorimetry, and the 3,5-dinitrosalicylic acid method were applied in this study. The results showed that the Chinese yam starch-tea polyphenol complex formed a structural domain with higher thermal stability along with lower pasting viscosities than native starch. The in vitro digestibility of Chinese yam starch decreased with the addition of the tea polyphenol, and the amount of resistant starch content in the complex was 56.25 ± 1.37%, significantly higher than that of native starch (p < 0.05). In addition, the complex showed a B+V-type crystalline structure, which confirmed that the interaction modes between the starch and tea polyphenol include hydrogen bonding and hydrophobic interactions. Moreover, the appearance of an irregular sponge network structure of the complex further supported the interactions between the starch and tea polyphenol. This study provides a theoretical basis for the development of functional foods using Chinese yam starch.

PCA of Running Biomechanics after 5 km between Novice and Experienced Runners.

Increased running experience appears to lower the risk of running-related injuries, but the mechanisms underlying this are unknown. Studying the biomechanics of runners with different running experiences before and after long-distance running can improve our understanding of the relationship between faulty running mechanics and injury. The purpose of the present study was to investigate if there were any differences in lower-limb biomechanics between runners after a 5 km run. Biomechanical data were collected from 15 novice and 15 experienced runners. Principal component analysis (PCA) with single-component reconstruction was used to identify variations in running biomechanics across the gait waveforms. A two-way repeated-measures ANOVA was conducted to explore the effects of runner and a 5 km run. Significant runner group differences were found for the kinematics and kinetics of lower-limb joints and ground reaction force (GRF) with respect to the magnitude across the stance phase. We found that novice runners exhibited greater changes in joint angles, joint moments, and GRFs than experienced runners regardless of the prolonged running session, and those patterns may relate to lower-limb injuries. The results of this study suggest that the PCA approach can provide unique insight into running biomechanics and injury mechanisms. The findings from the study could potentially guide training program developments and injury prevention protocols for runners with different running experiences.

Knockdown of lncRNA MALAT1 induces pyroptosis by regulating the miR­124/SIRT1 axis in cervical cancer cells.

The aim of the present study was to elucidate the role and downstream mechanism of long non­coding RNA (lncRNA) metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) in the process of cervical cancer cell pyroptosis. The effect of inhibiting lncRNA MALAT1 on cervical cancer cells was determined using primary cells isolated from patients and U14 cervical tumor­bearing nude mice. The level of lncRNA MALAT1 expression and cell viability were determined for relationship analysis. Pyroptosis was then investigated in HeLa cells with lncRNA MALAT1 knockdown or overexpression with or without lipopolysaccharide (LPS) treatment. Bioinformatics tools were used to identify downstream factors of lncRNA MALAT1, which were subsequently verified by gain­ or loss­of­function analyses in the process of cervical cancer cell pyroptosis. It was observed that the level of lncRNA MALAT1 was markedly higher in cervical carcinoma cells compared with expression in paracarcinoma cells, and knockdown of lncRNA MALAT1 induced cervical cancer cell death through pyroptosis. By contrast, overexpression of lncRNA MALAT1 blocked LPS­induced pyroptosis. These results, combined with bioinformatics statistical tools, demonstrated that the microRNA (miR)­124/sirtuin 1 (SIRT1) axis may affect the progression of cervical cancer at least partly by mediating the effect of lncRNA MALAT1 on the pyroptosis of cervical cancer cells. In conclusion, the lncRNA MALAT1/miR­124/SIRT1 regulatory axis in cervical cancer cells may mediate pyroptosis and may provide potential targets against the progression of cervical cancer.

A fuzzy control algorithm for tracing air pollution based on unmanned aerial vehicles.

The process of atmospheric pollutants traceability based on unmanned aerial vehicles (UAVs) is affected by many factors that can impact and increase the complexity of the traceability of atmospheric pollutants. In this study, we proposed a new algorithm called the fuzzy control traceability (FCT) to track odor plumes. Our proposed algorithm combined the characteristics and fuzzy control of the UAV and designed a controller based on the actual environment of the UAV. The fuzzy controller fuzzed the input gas concentration information, established fuzzy control rules by imitating human brain thinking, and outputted the turning angle and the move length according to rules, thus realizing intelligent tracking of the odor plume by the UAV. We compared the FCT algorithm with the bio-inspired "ZigZag" algorithm to validate its performance. Various concentration fields were constructed, and ten sets of experiments are performed using the two algorithms in different concentration fields. The average success rate of the FCT algorithm under different concentration fields was 95.4% higher than that of the ZigZag algorithm.Implications: Fuzzy control logic is applied to the field of air pollutant traceability of drones, and a single drone traceability algorithm based on fuzzy control is proposed; and in view of the shortcomings of a single traceability subject in the traceability, multiple traceability subjects are introduced to optimize fuzzy control.

Dye-Sensitized Fe-MOF nanosheets as Visible-Light driven photocatalyst for high efficient photocatalytic CO2 reduction.

Dye-sensitized system holds great potential for the development of visible-light-responsive photocatalysts not only because it can enhance the light absorption and charge separation efficiency of the systems but also because it can tune the band structure of catalysts. Herein, two-dimensional (2D) Fe-MOF nanosheets (Fe-MNS) with a LUMO potential of 0.11 V (vs. RHE) was prepared. Interestingly, it has been found that when the 2D Fe-MNS catalyst was functionalized with visible-light-responsive [Ru(bpy)]32+ as a dye-sensitizer, the electrons from the [Ru(bpy)]32+ can effectively inject into the 2D Fe-MNS, which resulted in a negative shift of the LUMO potential of the 2D Fe-MNS to -0.15 V (vs. RHE). Consequently, the [Ru(bpy)]32+/Fe-MNS catalytic system exhibits a sound photocatalytic CO2-to-CO activity of 1120 µmol g-1h-1 under visible-light-irradiation. The photocatalytic CO production was further ameliorated by regulating the electronic structure of the 2D Fe-MNS by doping Co ions, achieving a remarkable photocatalytic activity of 1637 µmol g-1h-1. This work further supports that the dye-sensitized system is an auspicious strategy worth exploring with different catalysts for the development of visible-light-responsive photocatalytic systems.

Identification of potential differentially methylated gene-related biomarkers in endometriosis.

Aim: To identify epigenetic alterations of differentially expressed genes and screen out targeted therapeutic drugs in endometriosis. Methods: Based on the Gene Expression Omnibus database and a series of biological information analysis tools, supplemented by validation of clinical samples, aberrant DNA methylation-driven genes and their functions were explored, as well as possible targeted drugs. Results: This study screened out a range of DNA methylation-driven genes that were associated with powerful properties and corresponding pathways. Among them, BDNF and CCL2 were key genes in the development of endometriosis. Four chemical agents have been flagged as potential treatments for endometriosis. Conclusion: These candidate genes and small-molecule agents may be further explored as potential targets and drugs for endometriosis diagnosis and therapy, respectively.

What is the significance of studying endometriosis? Endometriosis is a common gynecological benign disease affecting an estimated 5­10% of women in their reproductive years. Women with endometriosis suffer from chronic pelvic pain, dyspareunia and dysmenorrhea, and some patients face the possibility of infertility. What were the results of this study? The authors explored a number of key genes that may contribute to the etiology and pathogenesis of endometriosis, discussed the reasons for the changes in the expression levels of these hub genes and then screened for a number of effective small-molecule chemical drugs that may act on endometriosis. What do the results of this study mean? The authors carried out research from the three aspects of etiology, diagnosis and treatment of endometriosis. First, it demonstrated that endometriosis patients did have some differentially expressed genes compared with controls, and then in the analysis of these abnormally expressed genes, it was found that DNA methylation may play an essential role. This is a more meaningful hint, whether the occurrence of endometriosis can be suppressed by targeting methylation modification and then affecting the expression of key genes. In addition, the different severity of endometriosis will also have varying degrees of impact on patients' quality of life. These results are also a good indicator of the severity of endometriosis. Therefore, early detection and timely treatment are guidelines for the treatment of endometriosis. Finally, some of the chemical agents identified to target the cause of endometriosis are expected to become new treatments for endometriosis, supported by the results of follow-up studies, which will lead to more accurate treatments for patients with fewer side effects than existing treatments.

New Insights for the Design of Bionic Robots: Adaptive Motion Adjustment Strategies During Feline Landings.

Felines have significant advantages in terms of sports energy efficiency and flexibility compared with other animals, especially in terms of jumping and landing. The biomechanical characteristics of a feline (cat) landing from different heights can provide new insights into bionic robot design based on research results and the needs of bionic engineering. The purpose of this work was to investigate the adaptive motion adjustment strategy of the cat landing using a machine learning algorithm and finite element analysis (FEA). In a bionic robot, there are considerations in the design of the mechanical legs. (1) The coordination mechanism of each joint should be adjusted intelligently according to the force at the bottom of each mechanical leg. Specifically, with the increase in force at the bottom of the mechanical leg, the main joint bearing the impact load gradually shifts from the distal joint to the proximal joint; (2) the hardness of the materials located around the center of each joint of the bionic mechanical leg should be strengthened to increase service life; (3) the center of gravity of the robot should be lowered and the robot posture should be kept forward as far as possible to reduce machine wear and improve robot operational accuracy.

Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy.

Photodynamic therapy (PDT), which utilizes light excite photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. However, the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment (TME). It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes. Herein, we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles (P-CHNPs) via a facile synthesis procedure for boosting photodynamic anticancer therapy. Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME, which could be further amplified under light irradiation. Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS (hydroxyl radicals and singlet oxygen) generation efficiency, hypoxia relief, and glutathione depletion. Moreover, the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.

In-Situ Generated CsPbBr3 Nanocrystals on O-Defective WO3 for Photocatalytic CO2 Reduction.

Metal halide perovskite (MHP) nanocrystals (NCs) have shown promising application in photocatalytic CO2 reduction, but their activities are still largely restrained by severe charge recombination and narrow solar spectrum response. Assembly of heterojunctions can be beneficial to the charge separation in MHPs while the assembly process usually brings native interfacial defects, impeding efficient charge separation between two materials. Herein, an in-situ generation strategy was developed to prepare CsPbBr3 /WO3 heterojunction, using WO3 nanosheets (NSs) as growing substrate for the growth of CsPbBr3 NCs. The developed CsPbBr3 /WO3 heterojunction exhibited a high-quality interface, greatly facilitating charge transfer between two semiconductors. The hybrid photocatalyst displayed an excellent activity toward CO2 reduction, which was about 7-fold higher than pristine CsPbBr3 NCs and 3.5-fold higher than their assembled counterparts. The experimental results and theoretical simulations revealed that a Z-scheme mechanism with a favorable internal electric field was responsible for the good performance of CsPbBr3 /WO3 heterojunction. By using O-defective WO3 NSs as a near-infrared (NIR) light absorber, the CsPbBr3 /WO3 heterojunction could harvest NIR light and showed an impressive activity toward CO2 reduction. This work demonstrates a new strategy to design MHP-based heterojunctions by synergistically considering the interface quality, charge transfer mode, interfacial electric field, and light response range between two semiconductors.

CPEB3, an RNA-Binding Protein, Modulates the Behavior of Endometriosis-Derived Stromal Cells via Regulating CXCL12.

Endometriosis is a benign gynecological disease sharing several features with malignant tumor. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a potential target of miR-21-5p, is downregulated in endometriotic specimens. However, the function of CPEB3 in endometriosis is elusive. In this study, in cultured primary human endometrial stromal cells (ESCs), the overexpression and inhibition of CPEB3 were achieved by transduction of adenovirus-mediated CPEB3 overexpressed plasmid and shRNA, respectively. Functional analysis uncovered that upregulated CPEB3 reduced cell viability and arrested cell cycle entry. The expression of cyclin D1 and c-Myc was decreased after CPEB3 overexpression. Overexpression of CPEB3 facilitated ESC apoptotic potential, accompanied by increased Bax, cleaved-caspase 3 and cleaved-caspase 9, and reduced Bcl2. Moreover, elevated CPEB3 weakened migration and invasion abilities of ESCs. CPEB3 overexpression also reduced the expression of fibronectin and vimentin and the activities of matrix metalloproteinase (MMP)-9 and MMP-2. Interestingly, these effects were counteracted by CPEB3 inhibition. Furthermore, CPEB3 controlled the protein level of CXCL12, a homeostatic chemokine. CXCL12 elevation partially reversed the effects of CPEB3 on inhibiting ESC proliferation, migration and invasion, and promoting apoptosis. Based on these findings, it seems possible that CPEB3, as a critical player, attenuated the progression of endometriosis through repressing CXCL12 expression.

Effects of an inhibitor of the SHH signaling pathway on endometrial cells of patients with endometriosis.

BACKGROUND: Endometriosis is one of the most common gynecological diseases, and seriously reduces the quality of life of patients. However, the pathogenesis of this disease is unclear. Therefore, more studies are needed to elucidate its pathogenesis. Our previous publication found that the Sonic Hedgehog (SHH) signaling pathway was activated in endometriosis. This study tested whether SHH signaling in endometrial stromal cells (ESCs) was critical for the pathogenesis of endometriosis. METHODS: To examine the effect of inhibiting the SHH signaling pathway on endometriosis, we first isolated ESCs from eutopic endometrial tissues of patients with or without endometriosis and identified the extracted cells by morphological observation and immunofluorescence. Then, we treated ESCs with the GLI inhibitor GANT61 and used CCK-8, wound healing and invasion assays to detect cell activities, such as proliferation, invasion and metastasis. Furthermore, we detected the expression of key proteins and proliferation markers of the SHH signaling pathway in the lesions of nude mice using immunochemistry. RESULTS: We demonstrated that higher concentrations of GANT61 decreased the proliferation rate and migration distance of ESCs. We observed that GANT61 inhibited the invasion of ESCs. In addition, blockage of the SHH signaling pathway significantly reduced cell proliferation in vitro. CONCLUSIONS: Our study suggested that inhibition of the SHH pathway is involved in cell proliferation and invasive growth in the pathogenesis of endometriosis.