Knowledge, attitudes, and practices of human papillomavirus and self-sampling among adult women: a cross-sectional study.

Background: This study aimed to investigate the knowledge, attitude, and practice (KAP) of human papillomavirus (HPV) and self-sampling among adult women. Methods: The cross-sectional, questionnaire-based study included adult women at Shanghai Pudong Hospital from October 14, 2022, to March 31, 2023. The questionnaire contained demographic information, knowledge, attitude and practice dimensions. Factors associated with KAP and self-sampling were identified by multivariate logistic regression. Results: A total of 1843 valid questionnaires were collected. The average knowledge, attitude, and practice score was 10.09 ± 5.60, 26.76 ± 3.80, and 6.24 ± 2.20, respectively. Urban residents (estimate = 0.705, p < 0.001), suburban residents (estimate = 0.512, p < 0.001), as well as individuals with undergraduate degrees and higher (estimate = 0.535, p < 0.001), were associated with good knowledge, while individuals lacking a history of HPV infection (estimate = -0.461, p < 0.001) and married individuals (estimate = -0.185, p < 0.001) were less likely to have good knowledge. Higher knowledge scores (estimate = 0.087, p < 0.001) and individuals with undergraduate education and above (estimate = 1.570, p < 0.001) were associated with a positive attitude. Being married (estimate = 0.291, p = 0.049) was associated with good practice, whereas not engaging in sexual activity (estimate = -0.959, p < 0.001) or lacking a history of HPV infection (estimate = -0.499, p = 0.011) were associated with unfavorable practices. Minorities (OR = 2.787, p = 0.038) and individuals with multiple sexual partners (OR = 2.297 for two partners, OR = 2.767 for three or more partners, p = 0.020 and p = 0.022) were positively associated with self-sampling. However, higher knowledge (OR = 0.952, p = 0.026) and attitude scores (OR = 0.929, p = 0.015) were negatively associated with self-sampling. Conclusion: Demographic and behavioral factors significantly influenced KAP scores and self-sampling behaviors regarding HPV. Urban residency, higher education levels, positive attitudes, and minority status correlated with favorable outcomes, while factors like marriage and lack of sexual activity were associated with less favorable practices.

SLC38A2 promotes cell proliferation and invasion by promoting glutamine metabolism in adenomyosis.

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.

SMAD4 inhibits glycolysis in ovarian cancer through PI3K/AKT/HK2 signaling pathway by activating ARHGAP10.

BACKGROUND: ARHGAP10 is a tumor-suppressor gene related to ovarian cancer (OC) progression; however, its specific mechanism is unclear. AIMS: To investigate the effect of ARHGAP10 on OC cell migration, invasion, and glycolysis. METHODS AND RESULTS: Quantitative real-time PCR (qRT-PCR) quantified mRNA and protein expressions of AKT, p-AKT, HK2, and SMAD4 were tested by Western blot. EdU, Wound healing, and Transwell assay were utilized to evaluate OC cell proliferation, migration, and invasion. We used a Seahorse XF24 Extracellular Flux Analyzer to monitor cellular oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Chromatin immunoprecipitation (ChIP) was used to analyze the transcriptional regulation of ARHGAP10 by SMAD4. ARHGAP10 expression in OC tissues was detected by immunohistochemistry. Our results showed that ARHGAP10 expression was negatively related to lactate levels in human OC tissues. ARHGAP10 overexpression can inhibit the migration, proliferation, and invasion of OC cells, and this function can be blocked by 2-Deoxy-D-glucose. Moreover, we found that ARHGAP10 expression can be rescued with the AKT inhibitor LY294002. CONCLUSIONS: This study revealed that the antitumor effects of ARHGAP10 in vivo and in vitro possibly suppress oncogenic glycolysis through the PI3K/AKT/HK2-regulated glycolysis metabolism pathway.

m6A-related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma.

BACKGROUND: N6-methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional modification. Long noncoding RNAs (lncRNAs) are noncoding RNAs consisting of more than 200 nucleotides, and the expression of various lncRNAs may affect cancer prognosis. The impact of m6A-associated lncRNAs on uterine corpus endometrial carcinoma (UCEC) prognosis is unknown. METHODS: In this study, UCEC prognosis-related m6A lncRNAs were screened, bioinformatics analysis was performed, and experimental validation was conducted. Endometrial carcinoma (EC) and normal tissue samples were obtained from The Cancer Genome Atlas. The prognosis-related m6A lncRNAs screened by the least absolute shrinkage and selection operator method were used for multivariate Cox proportional risk regression modeling. Principal component analysis and Gene Ontology, immune function difference, and drug sensitivity analyses of the prognostic models were performed. Prognostic analysis was conducted for m6A-associated lncRNAs. The immune infiltration relationship of m6A-associated lncRNAs in EC was identified using the ssGSEA immune infiltration algorithm. A competing endogenouse RNA network was constructed using the LncACTdb database. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) assays were used to validate the differences in m6A-related lncRNA expression in normal and EC cells. RESULTS: CDKN2B-AS1 and MIR924HG were found to be risk factors for EC. RAB11B-AS1 was a protective factor in EC patients. MIR924HG expression was upregulated in KLE and RL95-2 endometrial cancer cell lines. Prognostic models involved RAB11B-AS1, LINC01812, HM13-IT1, TPM1-AS, SLC16A1-AS1, LINC01936, and CDKN2B-AS1. The high-risk group was more sensitive to five compounds (ABT.263, ABT.888, AP.24534, ATRA, and AZD.0530) than the low-risk group. CONCLUSION: These findings contribute to understanding of the function of m6A-related lncRNAs in UCEC and provide promising therapeutic strategies for UCEC.

An electrochemical sensor based on electrospun MoS2 @SnO2 modified carbon nanofiber composite materials for simultaneously detection of phenacetin and indomethacin.

SnO2 -CNF was prepared by coaxial blending technology, and MoS2 was grown uniformly on SnO2 -CNF composite by adding a hydrothermal post-treatment step. The uniform distribution of MoS2 on one-dimensional SnO2 -CNF can effectively establish a layered three-dimensional structure. Accordingly, the prepared MoS2 -coated SnO2 -CNF composite material has higher surface area and more active sites to obtain better electrochemical performance. We constructed an electrochemical sensor within the composite material with enhanced performance to realize the simultaneous and highly sensitive detection of phenacetin and indomethacin. The sensor has linear ranges of 0.050-7200 µM and 0.05-500 µM, respectively, and the detection limits were 0.016 µM and 0.013 µM. Furthermore, the sensor has good anti-interference ability and stability, which also achieves good recovery rate in the actual sample detection.

Lanatoside C inhibits human cervical cancer cell proliferation and induces cell apoptosis by a reduction of the JAK2/STAT6/SOCS2 signaling pathway.

Cervical cancer is one of the leading causes of cancer-associated mortality in gynecological diseases and ranks third among female cancers worldwide. Although early detection and vaccination have reduced incidence rates, cancer recurrence and metastasis lead to high mortality due to the lack of effective medicines. The present study aimed to identify novel drug candidates to treat cervical cancer. In the present study, lanatoside C, an FDA-approved cardiac glycoside used for the treatment of heart failure, was demonstrated to have anti-proliferative and cytotoxic effects on cervical cancer cells, with abrogation of cell migration in a dose-dependent manner. Lanatoside C also triggered cell apoptosis by enhancing reactive oxygen species production and reducing the mitochondrial membrane potential, which induced cell cycle arrest at the S and G2/M phases. Furthermore, lanatoside C inhibited the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 6 (STAT6), while inducing the expression of suppressor of cytokine signaling 2, a negative regulator of JAK2-STAT6 signaling. Taken together, the results of the present study suggest that lanatoside C suppresses cell proliferation and induces cell apoptosis by inhibiting JAK2-STAT6 signaling, indicating that lanatoside C is a promising agent for the treatment of cervical cancer.

A sensitive molecularly imprinted electrochemical aptasensor for highly specific determination of melamine.

An electrochemical aptamer sensor based on gold nanoparticles (AuNPs) was developed for highly specific sensing of melamine (MEL), which combines molecularly imprinted polymers (MIPs) and aptamers. AuNPs were synthesized by simple reduction of sodium citrate and characterized by transmission electron microscopy. The MIP membranes with particular recognition sites were formed by electropolymerization of dopamine (DA) with polythymine (poly T) aptamers as functional monomers and melamine as template molecules. Under optimal experimental conditions, this molecularly imprinted electrochemical aptamer sensor (MIEAS) exhibits a linear relationship between 10-12 M and 10-4 M for detecting MEL with the detection limit of 6.7 × 10-13 M. Moreover, this sensor displays excellent selectivity, reproducibility and stability. The milk samples analysis has confirmed the potential application of this MIEAS to quantitative detection of melamine.

Fabrication of poly-sulfosalicylic acid film decorated pure carbon fiber as electrochemical sensing platform for detection of theophylline.

In this work, we integrated the superiority of good conductivity, large surface area of carbon fibers and the catalytic property, good biocompatibility of polymer sulfosalicylic acid to construct a novel electrochemical sensor to detect theophylline in drug analysis. The morphology of nanocomposite was characterized by scanning electron microscopy (SEM). The polymerization between monomers was observed by Fourier transform infrared spectroscopy (FTIR). The composite between carbon material and polymer was verified by Raman spectrum. Under the optimal experimental conditions, the concentration of theophylline (0.6∼137 µM) and the peak current value revealed a good linear relationship and the limit of detection as low as 0.2 µM. In addition, the proposed sensor exhibits repeatability, stability and ease of selectivity.

A Fluorescent "Turn-off" Probe for the Determination of Curcumin Using Upconvert Luminescent Carbon Dots.

This work established a novel and simple method for quantitative determination of curcumin by developing a "turn-off" fluorescence probe based on upconvert luminescent carbon dots (p-CDs). The carbon dots were synthesized with p-aminobenzoic acid (PABA) and ethanol by solvothermal method and had specific up-conversion luminescence properties which could be applied in other sensing fields. The sensing mechanism of this fluorescent probe was based on the inter filter effect (IFE) between p-CDs and curcumin. As the concentration of curcumin increased, the fluorescence of p-CDs could be selectively quenched. Under the optimal conditions, the fluorescence quenching intensity of p-CDs had a good linear relationship with curcumin in the range of 0.4-45 µΜ and the detection limit was 0.133 µM. In addition, the fluorescent "turn-off" probe constructed with p-CDs exhibited high accuracy and recovery in the analysis of real sample curry powder, indicating that the fluorescence "turn-off" probe had potential application for the detection of curcumin in the complex matrixes.

HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions.

BACKGROUND: Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia. METHODS: The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively. RESULTS: The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects. CONCLUSION: These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.

Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation.

δ­Like ligand 4 (DLL4) has recently been reported to be involved in the process of cancer angiogenesis and considered to play a vital role in vascular endothelial growth factor (VEGF) signaling, while the role of DLL4 in cancer metastasis and growth has not been systematically studied. In the present study, the esophagus cancer cell line Eca109 was infected in vitro with a lentiviral vector loaded with dll4­shRNA to obtain a stable cell line of DLL4 expression which was downregulated through puromycin screening. The migration and invasion ability of the Eca109 dll4­shRNA cells were evaluated by scratch and Transwell assays, respectively. The underlying signaling pathway was further explored by western blotting. Subsequently, to explore the role of dll4 in the development of esophagus cancer cells in vivo, a xenograft model was established by intraperitoneal injection with Eca109 dll4­shRNA cells containing luciferase activity in nude mice. Then, small animal imaging system was used to evaluate the volume and metastatic potential of the tumors. Additionally, the overall survival rate of the nude mice was also recorded. Following infection with lentivirus, the expression of DLL4 in the Eca109 cells could be stably silenced through screening with puromycin, which was confirmed by western blotting. The scratch and Transwell assays demonstrated that downregulated DLL4 significantly diminished the aggressive invasion and migration properties of the Eca109 cells. The underlying mechanisms may be attributed to the inactivation of the PI3K/Akt/E­cadherin pathway by western blotting. Finally, the results from the in vivo study indicated that the tumor growth rate in the Eca109 dll4­shRNA group, as displayed by the tumor volume and the weak staining of the proliferating cell nuclear antigen (PCNA), was significantly slower than the control group, and the metastasis ability of the Eca109 dll4­shRNA cells was also dramatically abolished in vivo. It was also observed that downregulated DLL4 led to the formation of less pulmonary nodules in mice lungs and to a prolonged survival rate of nude mice. In summary, this study revealed that DLL4 has pathophysiological roles on the progression of esophagus cancer cells, including migration, invasion and apoptosis, which indicated that DLL4 may be considered as a potent therapeutic target for the treatment of malignant esophageal cancer.

SalA attenuates hypoxia-induced endothelial endoplasmic reticulum stress and apoptosis via down-regulation of VLDL receptor expression.

BACKGROUND: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. METHODS: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. RESULTS: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. CONCLUSION: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression.