Search

We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1β, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV1, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1β, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.

Critical cytotoxicity evaluation of pharmaceuticals is necessary for the clinical practice of chemotherapy. To quantitatively evaluate cell viability, currently there are two main types of sensitive methods including real-time cell analysis (RTCA) and CCK-8 assay, in which RTCA records electrochemical signal changes around an incubated cell, whereas CCK-8 is based on the colorimetric method. Despite the different detection principles adopted for the cytotoxicity assessment, the comparison of the two methods in terms of the application scope is lacking. In this study, comparison studies were conducted between the RTCA and CCK-8 assays using anticancer drugs including doxorubicin hydrochloride, curcumin, irinotecan (CPT-11), taxol, and oxaliplatin, which are classified into two groups of drug molecules in the absence and presence of additives. The cytotoxicity evaluation of these drugs on cancer cells revealed that the physicochemical properties of drug formulations such as optical and electrochemical properties are closely linked with the readout of cytotoxic methods. The experimental results suggested that the preselection of cytotoxic assay is critical for the quantitative measurement of cytotoxicity of anticancer drugs, which is of clinical importance for their therapeutic usage.

Background: Increasing evidence shows that GSDME is involved in tumor chemotherapy. Lobaplatin is an important chemotherapy drug for the treatment of cervical cancer. However, the exact mechanism of lobaplatin in the treatment of cervical cancer remains unclear. Objective: In this study, whether GSDME is a new mechanism of lobaplatin in the treatment of cervical cancer has been explored. Methods: Cell pyroptosis was measured by Cell Counting Kit-8 and flow cytometry analyses. Western blot analysis was used to check proteins expression. Results: The cell viability was significantly decreased by lobaplatin treatment. Compared with the control group, the percentage of pyroptosis (PI and Annexin-V double-positive cells) increased after lobaplatin treatment. In addition, lobaplatin induced caspase-3 activation and GSDME cleavage. z-DEVD, a specific inhibitor of caspase-3, reduced lobaplatin-mediated GSDME cleavage and concurrently inhibited pyroptosis. More importantly, GSDME deficiency obviously reduced lobaplatin-induced pyroptosis. Conclusion: These data demonstrate that caspase-3/GSDME axis contributed to the lobaplatin-mediated pyroptosis in cervical cancer cells. This finding indicates that GSDME-mediated pyroptosis is a new mechanism for lobaplatin to kill tumor cells and suggests that the caspase-3/GSDME pathway offers new insights into cancer chemotherapy.

Background: The protective effect of air purifiers on the respiratory system of healthy children remains unclear so far. Method: We designed an air purifier intervention crossover study among 125 schoolchildren aged 9–12 years in a boarding school in Beijing, China. The indoor and outdoor PM10, PM2.5, and PM1 concentrations were monitored, and a total of 30 indices, including respiratory symptoms, pulmonary functions, inflammation, and oxidative stress indicators, were analyzed. We used the logistic mixed-effects model and the linear mixed-effects model to evaluate the correlation between exposure (intervention and time-weighted PM concentration) and effects (indicators). Findings: The findings showed that the air purifier intervention was associated with a 13.29% decrease in runny nose, 11.05% decrease in FeNO, 12.03% decrease in EBC IL-1β, and 4.2% decrease in IL-6. The patterns of associations with each 10 µg/m3 decrease in the PM10, PM2.5, and PM1 concentrations were consistent with those for filter intervention. Moreover, lower PM2.5 and PM1 were associated with lower EBC MCP-1, 5.47% and 13.56%, respectively. The pulmonary function indices were negatively associated with the intervention and PM. Interpretation: We screened out some sensitive indices (FeNO, IL-6, IL-1β, MCP-1) related to respiratory symptoms and inflammation, which could reflect the early abnormal response of the respiratory system under short-term PM exposure. Our findings suggested that air purifiers have a protective effect on children’s respiratory system. Funding: This work was supported by the National research program for key issues in air pollution control, China (Grant No. DQGG0405). Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Ethics Review Committee of National Institute of Environmental Health, Chinese Center for Disease Control and Prevention (No. 201803) and the Biomedical Ethics Committee of Peking University (No. IRB00001052-18089). Parents and schoolchildren were informed about the study beforehand, and all the participants and their parents signed the informed consent.

Heading aims LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. Materials and methods Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. Key findings HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. Significance To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.

Previous studies have shown that retinoblastoma binding protein 6 (RBBP6) was overexpressed in malignant tumors and was correlated with poorer prognosis in various cancers. However, its role in cervical carcinoma has not been elucidated. This study was to investigate the relationship between RBBP6 and cervical carcinoma. Cervical carcinoma cell lines SiHa and C33a were used to assess the effect of RBBP6 on cell viability, migration, and proliferation. RBBP6 mRNA and protein levels in cervical cancer tissues increased at least three times as that in the adjacent non-cancerous tissues. Overexpression of RBBP6 in SiHa and C33a cell lines resulted in increased phosphorylated c-Jun NH2-terminal kinase (p-JNK) as well as increased cell viability, migration, and proliferation. Moreover, this effect was suppressed by specific JNK inhibitor SP600125. RBBP6 might potentiate cervical carcinoma cell viability, migration and proliferation through JNK signaling pathway. RBBP6 and JNK inhibitor may be beneficial as a novel preventive and therapeutic target for cervical cancer.

Recurrent spontaneous abortion (RSA) is an unknown aetiology common disease troubled women all over the world. Recent studies of circular RNAs (circRNAs) in gynecology and obstetrics area have sprung up. Our purpose in this study was to investigate the expression of circRNAs in chorionic villi from patients with RSA versus corresponding healthy gravidas, and to infer the potential role of these circRNAs in RSA occurrence. We selected 35 pairs of RSA patients and healthy control subjects, and analyzed the aberrant circRNA expression in three pairs of villi samples from each group using circRNA microarray. Altogether, including 335 up-regulated and 259 down-regulated circRNAs, 594 aberrant expressed circRNAs (FC ≥ 2.0, P ≤ 0.05) were found. Considering the raw content of each circRNAs, fold change differences and the restriction of the divergent primers, four down-regulated circRNAs (hsa_circRNA_104948, 104547, 101319 and 104938) and four up-regulated (hsa_circRNA_102116, 100709, 102424 and 103102) were selected as validation genes, using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Paired t-test and receiver operating characteristic (ROC) curves were also established. The result of content verification was accordant exactly with the microarray chip outcome (P ≤ 0.05 in all validation circRNAs). The area under the ROC curves (AUCs) of these eight circRNAs were all greater than 0.5. Further function analysis of circRNAs in RSA patients was performed by paper comparison. Taken together, aberrant villi circRNA expression in RSA played a vital role in its nosogenesis possibly via miRNA sponge function of circRNAs. Deeper analysis of the detailed mechanisms will be worthwhile.

Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in many types of human malignant cancers. However, the function of lncRNAs in benign tumors remains poorly understood. In the present study, to explored the potential roles of lncRNAs in benign epithelial ovarian cysts (BEOCs) which commonly occur in young women and possess malignant potential, we described the expression profile of the lncRNAs between BEOC and normal ovarian tissues using lncRNA microarray techniques. The results showed that 1,325 transcripts of lncRNAs (1,014 upregulated and 311 downregulated) were differentially expressed in the BEOCs compared with the normal controls [absolute fold-change ≥2, false discovery rate (FDR)

Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Endometrial carcinoma (EC) is the most common malignancy in women. Dispite its prevalence, the prognosis of endometrial carcinoma still relies on conventional histological type, grade and invasion information. Its morbidity is still increasing and the outcome is very poor. To the best of our knowledge, hormonal imbalance and/or molecular genetic alterations are the main cause of EC. However, the alterations of lncRNAs which accounts for approximately 4/5 of human transcripts are still poorly understood. In the present study, using the RiboArray™ Custom Array, we studied the expression profiles of lncRNA in EC as compared to normal endometrium (NE) to find potential core lncRNAs for the diagnosis of EC. We found the potential core lncRNA by GO, KEGG, lncRNA and mRNA co-expression network. The potential functional lncRNAs were further detected by qPCR to validate the microarray results. A total of 172 lncRNAs and 188 mRNAs were found to be differentially expressed between type Ⅰ EC and the NE samples (fold change >1.5). qPCR validation showed good consistency with the microarray data. GO, pathway analysis, the lncRNA and mRNA co-expression network as well as the TCGA data revealed that 6 lncRNAs (KIAA0087, RP11-501O2, FAM212B-AS1, LOC102723552, RP11-140I24 and RP11-600K151) may be the core regulators of endometrial carcinogenesis. The potential core lncRNAs revealed by the mRNA and lncRNA co-expression network might be helpful to explore potential early diagnostic and therapeutic targets for EC.