Circulating inflammatory cytokines and hypertensive disorders of pregnancy: a two-sample Mendelian randomization study.

Background: Hypertensive disorders of pregnancy (HDP) pose a significant risk to maternal and fetal well-being; however, the etiology and pathogenesis of HDP remain ambiguous. It is now widely acknowledged that inflammatory response and the immune system are closely related to HDP. Previous research has identified several inflammatory cytokines are associated with HDP. This study applied Mendelian randomization (MR) analysis to further assess causality. Methods: Patients with HDP who participated in the MR analysis presented with four types of HDP: pre-eclampsia or eclampsia (PE); gestational hypertension (GH); pre-existing hypertension complicating pregnancy, childbirth and the puerperium (EH); and pre-eclampsia or poor fetal growth (PF). A two-sample MR analysis was used to analyze the data in the study. The causal relationship between exposure and outcome was analyzed with inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode methods, where IVW was the primary method employed. Results: Our MR analysis demonstrated a reliable causative effect of Interleukin-9 (IL-9) and macrophage migration inhibitory factor (MIF) on reducing HDP risk, while macrophage inflammatory protein 1-beta (MIP1b), Interleukin-13 (IL-13), and Interleukin-16 (IL-16) were associated with promoting HDP risk. Conclusions: This study demonstrated that IL-9, MIF, MIP1b, IL-13, and IL-16 may be cytokines associated with the etiology of HDP, and that a number of inflammatory cytokines are probably involved in the progression of HDP. Additionally, our study revealed that these inflammatory cytokines have causal associations with HDP and may likely be potential therapeutic targets for HDP.

Calycosin Ameliorates Bleomycin-Induced Pulmonary Fibrosis via Suppressing Oxidative Stress, Apoptosis, and Enhancing Autophagy.

Calycosin (CA) is a flavonoid extracted from the root of Astragalus membranaceus and has antioxidant, anti-inflammation, and antiapoptosis properties. The objective of this study was to investigate the efficacy of CA in protecting against pulmonary fibrosis. CA (14 mg/kg) and SB216763 (20 mg/kg) were administrated to bleomycin-induced pulmonary fibrosis mice for 3 weeks. The results concluded that CA alleviated the inflammation and collagen deposition in pulmonary fibrosis. In addition, CA reduced MDA level, enhanced SOD and TAC activities, and increased the activity of the Nrf2/HO-1 pathway. CA also regulated the expressions of apoptosis-related proteins. Moreover, CA enhanced autophagy via upregulating LC3, beclin1, PINK1, and reducing p62. CA also increased expression of LAMP1 and TFEB, and inhibited the release of lysosome enzymes from ruptured lysosomes. These results provide new evidence that CA protects against pulmonary fibrosis through inhibiting oxidative stress and apoptosis. In addition, autophagy abnormality and lysosome dysfunction are restored by CA.

Barriers and Facilitators for Smoking Cessation in Chinese Smokers with Chronic Obstructive Pulmonary Disease: A Qualitative Study.

Background: Smoking cessation is recommended as a key intervention for chronic obstructive pulmonary disease (COPD) smokers. However, in China, few COPD smokers quit successfully. The aim of this study was to explore in depth the barriers and facilitators for smoking cessation among smokers with COPD in China. Methods: A purposive sample of 32 hospitalized smokers with COPD were included, 17 ex-smokers and 15 current smokers, participated in the semi-structured interviews. Interviews were analyzed thematically and using a deductive approach guided by Capability, Opportunity, Motivation-Behavior (COM-B) framework. Results: Three inter-related themes were generated: smokers' motivation was a prerequisite for quitting, maintaining capability to quit smoking, and opportunities that facilitated smokers to quit. Motivation to quit for most participants was activated by COPD-related symptoms, although they had a limited knowledge of COPD. Physical benefits from quitting and strong willpower were facilitators for maintaining quitting, while exposure to smoking environment and strong addiction to nicotine were frequent reasons for relapse. Most ex-smokers quit smoking by their own willpower rather than professionally delivered smoking cessation interventions. Smokers' attitudes toward these interventions depended on their effectiveness and convenience. Very few participants had experienced pharmacotherapy or behavioral support from physicians. However, interviewees preferred auricular acupressure to pharmacotherapy. Conclusion: Motivation to quit among smokers with COPD was usually initiated by COPD-related symptoms. Physical benefits observed by quitting and strong willpower facilitated smoking cessation, while exposure to smoking environment and strong addiction to nicotine led to relapse. COPD smokers in China preferred auricular acupressure to pharmacotherapy.

Long non-coding RNA LINC01215 promotes epithelial-mesenchymal transition and lymph node metastasis in epithelial ovarian cancer through RUNX3 promoter methylation.

Epithelial ovarian cancer (EOC) still remains the most lethal gynaecological malignancy in women, despite the recent progress in the management, including surgery and chemotherapy. According to the microarray data of the GSE18520 and GSE54388 datasets, LINC01215 was identified as an upregulated long noncoding RNA (lncRNA) in EOC. Therefore, this study aimed to figure out the involvement of LINC01215 in the progression of EOC. RT-qPCR was conducted to select the EOC cell line with the highest expression of LINC01215. Methylation of RUNX3 was then examined in EOC cells by MS-PCR. Furthermore, the interaction between LINC01215 and methylation-related proteins was revealed according to the results of RIP and RNA pull down assays. Subsequently, the involvement of LINC01215 and RUNX3 in regulating biological behaviors of EOC cells was investigated. Finally, the effects of the ectopic expression of LINC01215 and RUNX3 on the tumor formation and lymph node metastasis (LNM) of EOC cells were assessed in the xenograft tumors of nude mice. Overexpressing LINC01215 contributed to downregulated levels of RUNX3, as demonstrated by the recruitment of methylation-related proteins. Silencing of LINC01215 elevated the expression of RUNX3, thus suppressing cell proliferation, migration, invasion and EMT and decreasing the expressions of MMP-2, MMP-9 and Vimentin, but increased the expression of E-cadherin. The tumor growth and LNM were suppressed by downregulated levels of LINC01215 through inducing the expression of RUNX3. Collectively, the down-regulating LINC01215 could upregulate the expression of RUNX3 by promoting its methylation, thus suppressing EOC cell proliferation, migration and invasion, EMT, tumor growth and LNM.

Long non-coding RNA ASB16-AS1 enhances cell proliferation, migration and invasion via functioning as a ceRNA through miR-1305/Wnt/ß-catenin axis in cervical cancer.

BACKGROUND: Cervical cancer (CC) is one of the most common cancers in women. Long non-coding RNAs (lncRNAs) have been proposed as therapeutic targets in CC. Hence, the present study evaluated the effect of ASB16-AS1 on CC via regulating miR-1305. METHODS: Differentially expressed lncRNAs associated with CC were screened using bioinformatics database. The expression of ASB16-AS1 and miR-1305 were measured by qRT-PCR in CC tissues and CC cells. Cell proliferation was assessed by CCK-8 and colon formation assays. Cell abilities of migration and invasion were detected by Transwell migration and invasion assays. Luciferase report assays were used to explore the correction between ASB16-AS1, miR-1305 and Wnt2 in CC. Western blot assay detect the activity of Wnt/ß-catenin pathway. The xenograft tumor in nude mice was observed to evaluate tumor formation in vivo. RESULTS: In our study, we showed that the expression of ASB16-AS1 was increased while miR-1305 reduced was re in CC. Clinically, ASB16-AS1 and miR-1305 were correlated with poor-associated clinicopathological features of CC patients. Knockdown of ASB16-AS1 reduced CC cells proliferation, migration and invasion abilities by regulating miR-1305 in vitro and in vivo. Moreover, miR-1305 was directly bound to ASB16-AS1 and Wnt2, regulated their expression negatively. Western blot assays showed that ASB16-AS1 functioned as an oncogene by Wnt/ß-catenin pathway. CONCLUSIONS: This study reveals that ASB16-AS1 promotes cell proliferation, migration, invasion via binding miR-1305 with Wnt2, and enhancing the Wnt/ß-catenin pathway. ASB16-AS1 may play a new therapeutic target for CC.

Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer.

Ovarian cancer (OC) is a fatal cancer in women, mainly due to its aggressive nature and poor survival rate. The lncRNA-miRNA-mRNA (long noncoding RNA-microRNA-messenger RNA) interaction is promising biomarkers for the improving prognosis of OC. Therefore, we explored the regulatory mechanism of WDFY3-AS2/miR-18a/RORA axis involved in the biological activities of OC cells. Microarray analysis predicted differentially expressed lncRNA, miRNA, and mRNA related to OC, followed by investigating the relationship among them. The expression patterns of the identified lncRNA WDFY3-AS2, miR-18a, and RORA were measured in OC tissue and cells. Gain- and loss-of-function experiments were performed to characterize the effect of lncRNA WDFY3-AS2 on OC cells, as well as the involvement of miR-18a and RAR related orphan receptor A (RORA). The in vitro assays were validated by in vivo experiments. According to bioinformatics analysis, WDFY3-AS2 was speculated to affect OC by sponging miR-18a and modulating RORA. WDFY3-AS2 and RORA were underexpressed in OC, while miR-18a was highly expressed. Notably, WDFY3-AS2 acts as a competing endogenous RNA to sponge miR-18a and upregulate RORA. Upon overexpressing WDFY3-AS2 or inhibiting miR-18a, RORA expression was increased, thereby the OC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were suppressed, accompanied by enhanced apoptosis. In vivo experiments confirmed that the tumor growth was reduced in response to overexpressed WDFY3-AS2 or inhibited miR-18a. Taken together, the lncRNA WDFY3-AS2/miR-18a axis regulates the tumor progression of OC by targeting RORA, providing new insights for prevention and control of OC.

LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer.

Cervical carcinoma (CC) is the second most common cancer in females. In order to improve current anti-metastasis strategies for CC, it is important to improve our understanding of the mechanisms involved in epithelial-to-mesenchymal transition (EMT). This study aimed to elucidate the potential role of a novel long non-coding RNA (lncRNA)-CTS and the mechanisms underlying EMT in CC. The expression levels of lncRNA-CTS and miR-505 were detected using quantitative reverse transcriptase polymerase chain reaction in CC specimens and cells (HeLa, SiHa, Ca-Ski, C-33A, and HT-3). Further experiments including wound scratch and transwell invasion assays, Western blotting, immunofluorescence, and luciferase assays were used to investigate the function of lncRNA-CTS/miR-505/ZEB2 in vitro. In addition, a tumor xenograft model was used to assess the effect of lncRNA-CTS in vivo. The expression levels of lncRNA-CTS and miR-505 were correlated with the metastasis-associated clinicopathological features of CC patients. Moreover, lncRNA-CTS was associated with a poor prognosis in CC patients. In vitro and in vivo experiments, along with gain- and loss-of-function studies, showed that lncRNA-CTS enhanced cell migration, invasion, and the transforming growth factor (TGF)-ß1-induced-EMT process. Data also showed that lncRNA-CTS could function as a competing endogenous RNA for miR-505 in CC cells. Further investigations disclosed that ZEB2 was demonstrated as a downstream target of miR-505, and subsequently exerted its metastatic effects via the lncRNA-CTS/miR-505/ZEB2 axis in CC cells. Finally, lncRNA-CTS activated the SMAD/TGF pathway via miR-505 in CC cells. Collectively, our results demonstrate the importance of the lncRNA-CTS/miR-505/ZEB2 axis in CC. LncRNA-CTS can predispose CC patients to metastases and may represent a promising therapeutic target for CC.

MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2.

Ovarian cancer (OC) is xenogeneic that is influenced by many generated factors related to epigenetic factors to accelerate tumor metastasis. This study was conducted with the objective of investigating the effect of microRNA-23a-3p (miR-23a) on the biological characteristics of OC stem cells by targeting discs large homolog 2 (DLG2). OC-related differentially expressed genes were screened by microarray-based gene expression analysis, after which a list of miRNAs that regulate the genes was predicted. In total, 50 patients diagnosed with OC were enrolled in this study. DLG2 positive protein expression was measured in OC tissues. The interaction between DLG2 and miR-23a was predicted and analyzed through luciferase activity measurement. With the intervention of miR-23a and/or DLG2 expression in OC stem cells, the expression of miR-23a, DLG2, Bax, Bcl-2, Oct-4, and Nanog was determined. Afterward, different cell experiments were conducted to examine the regulation effect of miR-23a in OC stem cells. Tumor formation in vivo was also evaluated in nude mice. DLG2 had low expression in OC. The results showed that there was a decrease in the expression of Bcl-2, Oct-4, and Nanog, while DLG2 and Bax were increased as a result of miR-23a depletion. In addition, when miR-23a was suppressed, cell viability, migration, invasion, cloning, and renewal abilities of OC stem cells were decreased, while apoptosis ability was enhanced. As a target gene of miR-23a, DLG2 downregulation reversed the suppressive function of miR-23a in the inhibition of OC development. Finally, in vivo experiment verified that miR-23a downregulation restrained the tumor growth in OC stem cells. In conclusion, our findings suggested that the inhibition of miR-23a results in the suppression of OC progression by releasing DLG2, which provides new understanding on the potential therapeutic effect of miR-23a inhibition in OC patients.

The Hazard Perception for the Surrounding Shape of Warning Signs: Evidence From an Event-Related Potentials Study.

Surrounding shape is a very important component of warning signs. Unlike colors, signal words, and pictorials that can directly convey the surface meaning, the surrounding shapes of warning signs convey warning information somewhat obscurely. Most of the researchers who studied this topic investigated the individuals' hazard perception of the surrounding shapes of warning signs by using questionnaires. In addition, the scholars' points about the role of the surrounding shapes are inconsistent. This study, therefore, decided to use Event-Related Potentials (ERP) technology to explore the impact of the shapes on the perception of warning signs to find the evidences of the hazard perception of the shapes from the electrophysiological perspective. Using the Oddball paradigm, we found four components caused by different shapes of warning signs. Specifically, P200 amplitude characterizes the attraction to attention of surrounding shapes in the early automatic perception stage, the N300 components represented the emotional valance and arousal level, the P300 and the LPP connoted uneasy/unsafe information and reflected the inhibition strength on the uneasy/unsafe information. Experimental data indicated that the shape of UPRIGHT TRIANGLE had larger arousal strength and more negative valence than the shape of CIRCLE. People get stronger negative information from the UPRIGHT TRIANGLE shapes than from the CIRCLE. This finding might be helpful for designing the surrounding shapes of warning signs.

Metabotropic glutamate receptor 5 mediates the suppressive effect of 6-OHDA-induced model of Parkinson's disease on liver cancer.

Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson's disease (PD). However, the underlying mechanisms remain unclear. In the present study, the role of metabotropic glutamate receptor 5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD combined with liver cancer both in vitro and in vivo. We found that PD cellular model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt pathway. The application of 2-methyl-6-(phenylethyl)-pyridine and knockdown of mGluR5 further decreased the effect on Hepa-1-6 cells when co-cultured with conditioned media. The effect was increased by (S)-3,5-dihydroxyphenylglycine and overexpression of mGluR5. Moreover, more release of glutamate from 6-OHDA-lesioned MN9D cells suppressed mGluR5-mediated effect of Hepa1-6 cells. Application of riluzole eliminated the increased glutamate release induced by 6-OHDA in MN9D cells and aggravated the suppressive effect on Hepa-1-6 cells. In addition, the growth of implanted liver cancer was inhibited in 6-OHDA induced PD-like rats, and was associated with increased glutamate release in the serum and down-regulation of mGluR5 in tumor tissue. Collectively, these results indicate that selective antagonism of glutamate and mGluR5 has a potentially beneficial effect in both liver cancer and PD, and thus may provide more understanding for the clinical investigation and further an additional therapeutic target for these two diseases.

[Bacterial community structure and diversity in soils of different forest ages and types in Bao- tianman forest, Henan Province, China].

To compare the microbial compositions and diversities in soils of different forest ages and types in Baotianman forest, Henan Province, China, genomic DNA of forest soils was extracted for amplifying the 16S rRNA V4 hyper variable region by PCR and sequencing by Illumina MiSeq. The BIPES, UCHIME and QIIME were employed to analyze the soil bacterial community. It was shown that 60 phyla were identified, with Proteobacteria, Acidobacteria, and Verrucomicrobia representing the most dominant lineages and accounting for 29%, 18.5% and 10% of all sequences, respectively. At the genus level, 1209 genera were identified, the most abundant phylotypes were DA101 (6.3%), Acidobacteria-2 (5.9%), Candidatus Solibacter (2.9%) and Candidatus Nitrososphaera (2.6%). Different forest age and type soil samples had unique compositions and specific high and rare genus. Forest type and age both impacted the soil microbial community structure, and the influence of the former was stronger than the latter. The soil microbial diversity of the 80-year-old Quercus aliena forest was the lowest among all age and type forest soil samples. Soil pH, soil nitrogen and organic carbon contents were the most important factors affecting soil bacterial community structure.