Cisplatin resistance severely limits the efficacy of chemotherapy for cervical cancer (CC), and its molecular mechanisms remain incompletely understood. While epigenetic alterations such as DNA methylation are recognized as important contributors, the upstream regulatory networks, particularly the role of long non-coding RNAs (lncRNAs), are still unclear. This study aimed to explore novel mechanisms influencing cisplatin resistance in cervical cancer. Cisplatin-resistant CC cells (HeLa and SiHa) were established. A comprehensive approach employing mRNA and lncRNA microarrays, RT-qPCR, methylation-specific PCR (MSP-PCR), chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, RNA immunoprecipitation, cellular functional assays, and a mouse subcutaneous xenograft tumor model was utilized. The study found that Kallikrein 10 (KLK10) expression was significantly downregulated in cisplatin-resistant CC cells due to promoter hypermethylation mediated by DNA methyltransferase 1 (DNMT1). LncRNA microarray analysis revealed that TMPO-AS1 was the most significantly upregulated lncRNA in resistant cells. Functional assays confirmed that TMPO-AS1 promoted cisplatin resistance, proliferation, migration, and invasion of CC cells. Mechanistically, TMPO-AS1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-140-5p, thereby relieving its inhibitory effect on DNMT1 mRNA, upregulating DNMT1 expression, enhancing KLK10 promoter methylation, and leading to its silencing. In vivo experiments further demonstrated that silencing TMPO-AS1 inhibited tumor growth. This study unveils a novel TMPO-AS1/miR-140-5p/DNMT1/KLK10 regulatory axis that plays a critical role in cisplatin resistance in CC, providing a potential therapeutic target for overcoming chemoresistance.

Adenomyosis (AM) is traditionally explained by biochemical dysregulation at the endometrial-myometrial interface, leading to passive displacement of endometrial stromal cells (ESCs). However, the uterus is a highly mechanosensitive organ. Aberrant myometrial hypercontractility in AM may expose ESCs to chronic mechanical stimulation. Whether such mechanical cues can modulate ESCs' behavior under in vitro conditions remains incompletely understood. This study hypothesizes that cyclic mechanical strain-independent of biochemical cues-can induce a pro-migratory and pro-invasive ESC phenotype in vitro. Immortalized human ESCs (hESCs) were subjected to cyclic uniaxial stretching (12% strain, 0.2 Hz, 48 h) to model sustained mechanical loading. We evaluated cellular morphology, migration and invasion (wound healing and Transwell assays), cytoskeletal remodeling (F-actin), extracellular matrix (ECM) related proteins, transcriptomic changes (RNA-sequencing), and MAPK pathway activation. The functional involvement of p38 MAPK was tested using the selective inhibitor Adezmapimod. The results indicated that cyclic stretch induced marked cellular elongation without increasing apoptosis. RNA-sequencing revealed 580 differentially expressed genes enriched in migration and ECM remodeling. Functionally, stretched hESCs exhibited enhanced migration and invasion capacity in vitro, accompanied by elevated F-actin, fibronectin, and CTGF. Mechanistically, mechanical strain triggered selective activation of the p38 MAPK pathway, without affecting ERK or JNK. Pharmacological inhibition of p38 attenuated stretch-associated cytoskeletal remodeling, ECM-related protein expression, and cell motility. Together, these findings demonstrate that cyclic mechanical stretch, as an underexplored non-biochemical factor, can promote a motile and invasive stromal cell phenotype in vitro via a p38 MAPK/F-actin-associated mechanism. While these results do not establish causality for AM development in vivo, they suggest a potential mechanotransduction pathway through which abnormal uterine mechanics may influence stromal cell behavior. Targeting mechanotransduction-such as p38 inhibition-may represent novel mechano-therapeutics for AM. This warrants further investigation using more complex and physiologically relevant models.

ABSTRACTProblemEndometriosis (EM) is known as a common estrogen‐dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC‐ESCs).Method of StudyFOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC‐ESCs. Hematoxylin‐eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT‐qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM‐related genes, and epithelial to mesenchymal transition‐related proteins. The proliferation, migration, invasion, and apoptosis of EC‐ESCs were determined by 5‐ethynyl‐2′‐deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.ResultsThe FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER‐α, ER‐ß, and Cyp19a. Additionally, down‐regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC‐ESCs. Besides, FOXL2‐small interfering RNA (FOXL2‐siRNA) treatment resulted in enhanced cleaved‐Caspase3 protein expression and cleaved‐Caspase3/Caspase3 ratio in EC‐ESCs.ConclusionFOXL2 participates in the occurrence and development of EM through promoting epithelial‐mesenchymal transition procession and enhancing the migration and invasion of EC‐ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.

BackgroundEndometriosis (EMs) is a common condition that causes dysmenorrhea, chronic pelvic pain, and infertility, affecting millions of women worldwide. Despite the use of assisted reproductive technology, EMs patients often experience lower embryo implantation rates and recurrent implantation failure (RIF) due to impaired uterine endometrial receptivity. This study aims to identify shared diagnostic genes and underlying mechanisms between EMs and RIF using integrated transcriptomic analysis and machine learning with Gene Expression Omnibus (GEO) datasets.MethodsWe analyzed GSE11691, GSE7305, GSE111974, and GSE103465 as training datasets for EMs and RIF, and GSE25628 and GSE92324 as validation datasets. Differentially expressed genes (DEGs) and Weighted Gene Co-Expression Network Analysis (WGCNA) identified key genes specific to and shared by EMs and RIF. Machine learning algorithms were used to determine the shared diagnostic gene, whose performance was validated in both training and validation datasets. Single-gene Gene Set Enrichment Analysis (GSEA) revealed shared biological processes in EMs and RIF, while CIBERSORT analysis highlighted similarities and differences in immune infiltration between the two conditions. Finally, endometrial samples from healthy controls, EMs, and RIF patients were collected, and qRT-PCR was performed to validate the diagnostic gene.ResultsWe identified 48 shared key genes between EMs and RIF. The diagnostic gene EHF was selected through machine learning algorithms, and its diagnostic performance was validated in both training and validation datasets. ROC curve analysis demonstrated excellent diagnostic accuracy of EHF for both diseases. Gene Set Enrichment Analysis (GSEA) revealed that both conditions shared biological processes, including dysregulated extracellular matrix remodeling and abnormal immune infiltration. Furthermore, we validated the expression of EHF in endometrial samples from healthy controls, EMs, and RIF patients. Additionally, we characterized the immune microenvironment in EMs and RIF, highlighting changes in immune cell components associated with EHF.DiscussionThe diagnostic gene EHF identified in this study may serve as a key link between EMs and RIF. The shared pathological processes in both conditions involve alterations in the extracellular matrix and subsequent changes in the immune microenvironment. These findings provide novel insights into potential therapeutic strategies for improving infertility treatment in patients with EMs.

Background The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated. Results The bioinformatics data revealed a negative correlation between the patient’s survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-β1/Smad2/3 signaling pathway activation. Conclusions CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.

Background: Cervical cancer (CC) is currently the most common malignant tumour in the female reproductive tract, and paclitaxel (PTX) is a commonly used chemotherapeutic agent, but tumour cell resistance will seriously affect the therapeutic efficacy of PTX. Nanoparticle human serum albumin-bound paclitaxel (Nano-HSA-PTX) is a novel drug delivery modality that may have superior effects to PTX alone. Objective: To clarify the effect of Nano-HSA-PTX on cervical carcinoma (CC) cells and the underlying mechanisms. Methods: After the preparation of Nano-HSA-PTX, its morphology was observed by electron transmission microscope (TEM), and its entrapment efficiency (EE%) and drug loading rate (DL%) were detected. Nano-HSA-PTX was compared with conventional PTX for drug metabolism. Additionally, CC HeLa and SiHa cells were purchased and divided into three groups to treat with Nano-HSA-PTX, PTX and normal saline, respectively. MTT, cell cloning, Transwell and cell scratch assays were carried out to determine cell proliferation, invasion and migration, flow cytometry and Western blotting were performed to detect apoptosis rate and apoptosis-related protein expression, and PCR was conducted to quantify oxidative damage indicators. Further, CYP3A4 and CYP2C8 expression patterns in CC cells (HeLa and SiHa) and human normal cervical epithelia (End1/E6E7) and the changes of their levels under the intervention of Nano-HSA-PTX were measured. Subsequently, C57BL/6mice were purchased for subcutaneous tumorigenesis experiment to observe the impact of Nano-HSA-PTX on tumor growth. Results: Under TEM, Nano-HSA-PTX was complete and arranged compactly, with a stable structure and markedly higher EE% and DL% than PTX (P < 0.05). Under Nano-HSA-PTX intervention, the proliferation, invasion, migration and oxidative damage of HeLa and SiHa were significantly decreased compared with the control and PTX groups, while the apoptosis was increased (P < 0.05). Besides, elevated CYP3A4 and CYP2C8 levels were observed in CC cells, which were inhibited by Nano-HSA-PTX and PTX (P < 0.05). Finally, tumorigenesis experiments in nude mice revealed that Nano-HSA-PTX could inhibit tumor growth. Conclusion: Compared with PTX, Nano-HSA-PTX has a superior effect of inhibiting CC activity. And this mechanism of action was carried out by inhibiting the expression of CYP3A4 and CYP2C8.

Intrauterine adhesions (IUA), the main cause of secondary infertility in women, result from irreversible fibrotic repair of the endometrium due to inflammation or human factors, accompanied by disruptions in the repair function of endometrial stem cells. This significantly impacts the physical and mental health of women in their childbearing years. Telocytes (TCs), a distinctive type of interstitial cells found in various tissues and organs, play diverse repair functions due to their unique spatial structure. In this study, we conduct the inaugural exploration of the changes in TCs in IUA disease and their potential impact on the function of stem cells. Our results show that in vivo, through double immunofluorescence staining (CD34+/Vimentin+; CD34+/CD31-), as endometrial fibrosis deepens, the number of TCs gradually decreases, telopodes shorten, and the three-dimensional structure becomes disrupted in the mouse IUA mode. In vitro, TCs can promote the proliferation and cycle of bone mesenchymal stem cells (BMSCs) by promoting the Wnt/β-catenin signaling pathway, which were inhibited using XAV939. TCs can promote the migrated ability of BMSCs and contribute to the repair of stem cells during endometrial injury. In addition, TCs can inhibit the apoptosis of BMSCs through the Bcl-2/Bax pathway. In conclusion, our study demonstrates, for the first time, the resistance role of TCs in IUA disease, shedding light on their potential involvement in endometrial repair through the modulation of stem cell function.

Previous ultrasound studies suggest that patients with adenomyosis (AM) exhibit increased uterine cavity stiffness, although direct evidence regarding extracellular matrix (ECM) content and its specific impact on endometrial stiffness remains limited. This study utilized atomic force microscopy to directly measure endometrial stiffness and collagen morphology, enabling a detailed analysis of the endometrium’s mechanical properties: through this approach, we established direct evidence of increased endometrial stiffness and fibrosis in patients with AM. Endometrial specimens were also stained with Picrosirius red or Masson’s trichrome to quantify fibrosis, and additional analyses assessed α-SMA and Ki-67 expression. Studies indicate that pathological conditions significantly influence the mechanical properties of endometrial tissue. Specifically, adenomyotic endometrial tissue demonstrates increased stiffness, associated with elevated ECM and fibrosis content, whereas normal endometrial samples are softer with lower ECM content. AM appears to alter both the mechanical and histological characteristics of the eutopic endometrium. Higher ECM content may significantly impact endometrial mechanical properties, potentially contributing to AM-associated decidualization defects and fertility challenges.

AimTo evaluate the association between urinary polycyclic aromatic hydrocarbon (PAH) metabolites and the risk of endometriosis.MethodsThis cross-sectional study obtained data on women aged 20–54 years from the National Health and Nutrition Examination Survey (NHANES) 2001–2006. The weighted multivariate logistic regression model was established to assess the association between the eight urinary PAH metabolites and the risk of endometriosis. In this multivariate analysis, the eight urinary PAH metabolites were adjusted with urinary creatinine, and were divided into three groups according to tertiles: Tertile 1, Tertile 2 and Tertile 3. To evaluate the overall association of mixed PAH metabolites with endometriosis, the Bayesian kernel machine regression (BKMR) model was applied.ResultsTotally 1,291 women were included, of which 90 (6.97%) had endometriosis and 1,201 (93.03%) did not have endometriosis. After adjusting for age, race, smoking, age at menarche, hysterectomy, ovary removed, female hormone use, and menopause, compared with the Tertile 1 group, the Tertile 2 and Tertile 3 groups of all PAH metabolites demonstrated no significant risk of endometriosis. A positive tendency was found between mixed PAH metabolites and endometriosis when all the metabolites were at their 60th percentile levels or above compared with their median levels. When all the other metabolites were fixed at their median levels, 1-hydroxynaphthalene was positively correlated with endometriosis. Potential interactions existed between 1-hydroxynaphthalene and 2-hydroxynaphthalene and between 2-hydroxyfluorene and 3-hydroxyfluorene.ConclusionNo significant association was found between individual PAH metabolites and endometriosis. A positive association existed between mixed PAH metabolites and the risk of endometriosis.

Intrauterine adhesions (IUAs) often occurred after common obstetrical and gynecological procedures or infections in women of reproductive age. It was characterized by the formation of endometrial fibrosis and prevention of endometrial regeneration, usually with devastating fertility consequences and poor treatment outcomes so far. Telocytes (TCs), as a novel interstitial cell type, present in female uterus with in vitro therapeutic potential in decidualization-defective gynecologic diseases. This study aims to further investigate the role of TC-derived Wnt ligands carried by exosomes (Exo) in reversal of fibrosis and enhancement of regeneration repair in endometrium. IUA cellular and animal models were established from endometrial stromal cells (ESCs) and mice, followed with treatment of TC-conditioned medium (TCM) or TC-derived Exo. In cellular model, fibrosis markers (collagen type 1 alpha 1 [COL1A1], fibronectin [FN], and α-smooth muscle actin [α-SMA]), angiogenesis (vascular endothelial growth factor [VEGF]), and pathway protein (β-catenin) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting (WB), and immunofluorescence. Results showed that, TCs (either TCM or TC-derived Exo) provide a source of Wnts that inhibit cellular fibrosis, as evidenced by significantly elevated VEGF and β-catenin with decreased fibrotic markers, whereas TCs lost salvage on fibrosis after being blocked with Wnt/β-catenin inhibitors (XAV939 or ETC-159). Further in mouse model, regeneration repair (endometrial thickness, number of glands, and fibrosis area ratio), fibrosis markers (fibronectin [FN]), mesenchymal–epithelial transition (MET) (E-cadherin, N-cadherin), and angiogenesis (VEGF, microvessel density [MVD]) were studied by hematoxylin–eosin (HE), Masson staining, and immunohistochemistry. Results demonstrated that TC-Exo treatment effectively promotes regeneration repair of endometrium by relieving fibrosis, enhancing MET, and angiogenesis. These results confirmed new evidence for therapeutic perspective of TC-derived Exo in IUAs.

In this study, to increase the accumulation of MTX in the tumor site and reduce the toxicity to normal tissues by MA, a novel nano-drug delivery system comprised of hyaluronic acid (HA)-mangiferin (MA)-methotrexate (MTX) (HA-MA-MTX) was developed by a self-assembly strategy. The advantage of the nano-drug delivery system is that MTX can be used as a tumor-targeting ligand of the folate receptor (FA), HA can be used as another tumor-targeting ligand of the CD44 receptor, and MA serves as an anti-inflammatory agent. 1HNMR and FT-IR results confirmed that HA, MA, and MTX were well coupled together by the ester bond. DLS and AFM images revealed that the size of HA-MA-MTX nanoparticles was about ~138 nm. In vitro cell experiments proved that HA-MA-MTX nanoparticles have a positive effect on inhibiting K7 cancer cells while having relatively lower toxicity to normal MC3T3-E1 cells than MTX does. All these results indicated that the prepared HA-MA-MTX nanoparticles can be selectively ingested by K7 tumor cells through FA and CD44 receptor-mediated endocytosis, thus inhibiting the growth of tumor tissues and reducing the nonspecific uptake toxicity caused by chemotherapy. Therefore, these self-assembled HA-MA-MTX NPs could be a potential anti-tumor drug delivery system.

Cervical cancer is a significant global health burden, necessitating a comprehensive understanding of its underlying molecular mechanisms to improve diagnostic and therapeutic strategies. In this study, we conducted an in-depth bioinformatics analysis of cervical cancer using a high-throughput microarray dataset, GSE9750. Through robust screening and selection, we identified 1633 differentially expressed genes (DEGs) associated with cervical cancer. Enrichment analysis revealed crucial pathways and processes, such as DNA replication, cell cycle, and epithelial cell differentiation, implicated in cancer development. Additionally, we discovered key genes, including NEK2, AURKA, FOXM1, CDCA8, and CDC25A, linked to these pathways, which also showed significant differences in expression levels between various clinical characteristics. Our findings shed light on potential molecular targets for therapeutic interventions and contribute to the growing body of knowledge in cervical cancer research. This integrative bioinformatics approach serves as a valuable resource for future studies aiming to unravel the intricate molecular landscape of cervical cancer.

Background: The prognostic significance of miR-107 and miR-17 in patients with acute myeloid leukemia (AML) remains unclear.Methods: A total of 173 patients with de novo AML from the Cancer Genome Atlas database were enrolled in this study and further divided into a chemotherapy group (98 cases) and an allogeneic hematopoietic stem cell transplantation (allo-HSCT) group (75 cases) according to their therapy regimen.Results: In the chemotherapy cohort, high miR-107 or miR-17 expression was associated with poorer overall survival (OS) and event-free survival (EFS). On the other hand, there were no significant differences in OS and EFS between the high- and low-expression subgroups in the allo-HSCT group. Next, we stratified the total number of patients with AML into high- and low-expression groups according to the median expression levels of miR-107 or miR-17. In the high miR-107 or miR-17 expression group, patients treated with allo-HSCT had longer OS than those treated with chemotherapy. In the low miR107 or miR-17 expression group, no significant differences in OS and EFS were observed between the two therapy subgroups. When patients were further clustered into three groups (both low miR-107 and low miR-17, either high miR-107 or high miR-17, and both high miR-107 and high miR-17), patients with both high miR-107 and high miR-17 expression had the worst OS and EFS of the entire group and of the chemotherapy group. On the other hand, there were no significant differences in OS and EFS among the three subgroups in the allo-HSCT group. Cox regression confirmed the concurrence of high expression of miR-107 and miR-17 might act as an independent prognostic factor for EFS and OS in the entire group and the chemotherapy group. Bioinformatics analysis showed differentially expressed genes (DEGs) associated with miR-107 and miR-17 expression were mainly enriched in multiple metabolic processes.Conclusions: The combination of miR-107 and miR-17 provides prognostic significance for patients with AML and should be considered in the clinical selection of the optimal treatment regimen when deciding between chemotherapy and allo-HSCT.

Dysregulated thioredoxin-interacting protein (TXNIP) has been observed in women with gestational diabetes mellitus (GDM), but the specific role of TXNIP in GDM and the underlying mechanism remain unclear. HTR-8/SVneo cells were treated with high glucose to mimic the injured trophoblasts of GDM. In vitro, TXNIP knockdown was performed by siRNA. RTqPCR was performed to determine the expression of the corresponding genes. Cell proliferation and apoptosis were measured using CCK-8, EdU and Annexin V/PI assays. The autophagosome number was assessed using transmission electron microscopy. The expression of the autophagy substrate sequestosome 1 (P62) was evaluated by immunofluorescence. Autophagy-related proteins, including P62, light chain 3 (LC3)-I, and LC3-II, were analysed by Western blotting. HTR-8/Svneo cells treated with high glucose demonstrated reduced proliferation, increased apoptosis, decreased autophagosome formation and overall decreased autophagy. However, knockdown of TXNIP reversed the effects of HG on HTR-8/Svneo cells. However, the effect of TXNIP knockdown on HG-treated HTR-8/Svneo cells was inhibited by 3-methyladenine (3-MA) (widely used as an inhibitor of autophagy). We concluded that knockdown of TXNIP has the potential to enhance the activity of high glucose-treated human trophoblasts through autophagic activation, thereby improving pregnancy outcomes in patients with GDM.

Beta-cypermethrin (β-CYP) is a commonly used insecticide that is potentially toxic and has adverse effects on the health of both animals and humans. Studies have indicated that β-CYP damages organs like the liver, thyroid, intestinal tract, and uterus. However, the underlying mechanisms that β-CYP affects oocyte quality are poorly understood. According to our research, β-CYP exposure led to the aberrant assembly of spindles and alignment of chromosomes, resulting in porcine oocytes' defective nuclear maturation. Concurrently, β-CYP exposure perturbed the cytoplasmic maturation by disturbing the cortical granules (CGs), endoplasmic reticulum (ER), and mitochondrial integrity. It also led to accumulating reactive oxygen species (ROS) and apoptosis. We found that supplementation with glutathione (GSH) mitigated the meiotic defects induced by β-CYP exposure via regulating ROS levels. Our observations illustrate that β-CYP exposure adversely impacts oocyte meiotic maturation, and taking GSH supplementation is an effective strategy.

Purpose: Telocytes (TCs), a novel type of stromal cells found in tissues, induce macrophage differentiation into classically activated macrophages (M1) types and enhance their phagocytic function. The purpose of this study was to investigate the inhibitory effects of TC-induced M1 macrophages on endometriosis (EMs).Methods: mouse uterine primary TCs and endometrial stromal cells (ESCs) were isolated and identified using double immunofluorescence staining. For the in vitro study, ESCs were treated with TC-induced M1 macrophages, and the vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP9), and nuclear factor kappa B (NF-Kb) genes were identified by quantitative real-time PCR (qRT-PCR) or western blotting (WB). For the in vivo study, an EMs mouse model received TC-conditioned medium (TCM) via abdominal administration, and characterized the inhibitory effects on growth (lesion weight, volume, and pathology), tissue-resident macrophages differentiation by immunostaining, angiogenic capacity (CD31 and VEGF), invasive capacity (MMP9), and NF-Kb expression within EMs lesions.Results: immunofluorescent staining showed that uterine TCs expressed CD34+ and vimentin+, whereas ESCs expressed vimentin+ and cytokeratin-. At the cellular level, TC-induced M1 macrophages can significantly inhibit the expression of VEGF and MMP9 in ESCs through WB or qRT-PCR, possibly by suppressing the NF-Kb pathway. The in vivo study showed that macrophages switch from the alternatively activated macrophages (M2) in untreated EMs lesions to the M1 subtype after TCM exposure. Thereby, TC-induced M1 macrophages contributed to the inhibition of EMs lesions. More importantly, this effect may be achieved by suppressing the expression of NF-Kb to inhibit angiogenesis (CD31 and VEGF) and invasion (MMP9) in the tissue.Conclusion: TC-induced M1 macrophages play a prevailing role in suppressing EMs by inhibiting angiogenic and invasive capacity through the NF-Kb pathway, which provides a promising therapeutic approach for EMs.

Scope: High salinity has been reported to induce many human disorders in tissues and organs to interfere with their normal physiological functions. However, it is unknown how salinity affects the development of female germ cells. This study suggests that a high-salt diet (HSD) may weaken oocyte quality to impair female fertility in mice and investigates the underlying mechanisms.Methods and results: C57BL/6 female mice are fed with a regular diet (Control) or a high-salt diet (HSD). Oocyte maturation, fertilization rate, embryonic development, and female fertility are evaluated. In addition, the spindle organization, actin polymerization, and kinetochore-microtubule attachment of oocytes are examined in both groups. Moreover, single-cell transcriptome data are used to demonstrate how HSD alters the transcript levels of genes. The observations confirm that HSD leads to female subfertility due to the deterioration of oocyte and embryo quality. The mechanism underlying reveals HSD compromises the oocytes' autophagy, apoptosis level, and mitochondrial function.Conclusion: The work illustrates that a high concentration of salt diet results in oocyte meiotic arrest, fertilization failure, and early developmental defection that embryos undergo to reduce female fertility in mice by perturbing the level of autophagy and apoptosis, mitochondrial function in oocytes.

Perinatal malnutrition affects vascular functions, and calcium is important in vascular regulations. It is unknown whether and how perinatal maternal high-fat diets (MHF)-mediated vascular dysfunction occurs via the angiotensin-PKC-L-type-calcium-channels (LTCC) axis. This study determined angiotensin II (AII) roles in the PKC-LTCC axis in controlling calcium influx in the arteries of offspring after perinatal MHF. Mesenteric arteries (MA) and smooth muscle cells (SMCs) from 5-month-old offspring rats were studied using physiological, ion channel, molecular, and epigenetic analysis. Pressor responses to AII were significantly increased in the free-moving MHF offspring rats. In cell experiments, MA-SMC proliferation was enhanced, and associated with thicker vascular wall in the obese offspring. Imaging analysis showed increase of fluorescence Ca2+ intensity in the SMCs of the MHF group. Angiotensin II receptor (AT1R)-mediated PKC-LTCC axis in vasoconstrictions was altered by perinatal MHF via reduced DNA methylation at specific CpG sites of Agtr1a and Prkcb gene promoters at the transcription level. Accordingly, mRNA and protein expression of AT1R and PKCβ in the offspring MA were increased, contributing to enhanced Ca2+ currents and vascular tone. The results showed that DNA methylation resulted in perinatal MHF-induced vascular disorders via altered AT1-PKC-LTCC pathway in resistance arteries of the offspring, providing new insights into the pathogenesis and early prevention/treatments for hypertension in developmental origins.

Background The clinical significance of miR-17 in patients with acute myeloid leukemia (AML) remains unknown. Methods Real-time quantitative reverse transcription-polymerase chain reaction (qPCR) was performed to detect the miR-17 expression in 115 de novo AML patients, 31 patients at complete remission (CR) time, 8 patients at relapse time and 30 normal controls. Results MiR-17 was upregulated in de novo AML compared with normal controls. Patients with high expression of miR-17 had less CEBPA double mutation, less favorable ELN-risk and lower CR rate. The level of miR-17 was significantly decreased at CR phase and was returned to primary level even higher when in relapse phase. In addition, Cox regression analysis revealed that miR-17 expression retained independent prognostic significance for overall survival (OS). Moreover, the gene-expression profile analysis of miR-17 in AML obtained from TCGA database was involved in multiple biological functions and signal pathways. Among the differential expressed genes (DEGs), we identified FGL2, PLAUR, SLC2A3, GPR65, CTSS, TLR7, S1PR3, OGFRL1, LILRB1, IL17RA, SIGLEC10, SLAMF7, PLXDC2, HPSE, TCF7 and MYCL as potential direct targets of miR-17 according to in silico analysis. Conclusions High expression of miR-17 in de novo AML patients pointed to dismal clinical outcome and disease recurrence, which could serve as novel prognostic biomarker for AML patients.

Telocytes (TCs), a distinct type of interstitial (stromal) cells, have been discovered in many organs of human and mammal animals. TCs, which have unique morphological characteristics and abundant paracrine substance, construct a three-dimensional (3D) interstitial network within the stromal compartment by homocellular and heterocellular communications which are important for tissue homeostasis and normal development. Fibrosis-related diseases remain a common but challenging problem in the field of medicine with unclear pathogenesis and limited therapeutic options. Recently, increasing evidences suggest that where TCs are morphologically or numerically destructed, many diseases continuously develop, finally lead to irreversible interstitial fibrosis. It is not difficult to find that TCs are associated with chronic inflammation and fibrosis. This review mainly discusses relationship between TCs and the occurrence of fibrosis in various diseases. We analyzed in detail the potential roles and speculated mechanisms of TCs in onset and progression of systemic fibrosis diseases, as well as providing the most up-to-date research on the current therapeutic roles of TCs and involved related pathways. Only through continuous research and exploration in the future can we uncover its magic veil and provide strategies for treatment of fibrosis-related disease.