Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

Aliikangiella coralliicola sp. nov., a bacterium isolated from coral Porites lutea, and proposal of Pleioneaceae fam. nov. to accommodate Pleionea and Aliikangiella.

A novel Gram-stain-negative, non-endospore-forming, motile, and aerobic bacterial strain, M105T, was isolated from coral Porites lutea, and was subjected to a polyphasic taxonomic study. Global alignment based on 16S rRNA gene sequences indicated that M105T shares the highest sequence identity of 94.5 % with Aliikangiella marina GYP-15T. The average nucleotide identity (ANI) and average amino acid identity (AAI) between M105T and A. marina GYP-15T was 69.8 and 71.6 %, respectively. On the basis of the results of phenotypic, chemotaxonomic, phylogenetic, phylogenomic, and comparative genomic analyses, it is concluded that M105T should represent a novel species in the genus Aliikangiella, for which the name Aliikangiella coralliicola sp. nov. is proposed. The type strain is M105T (=MCCC 1K03773T= KCTC 72442T). Furthermore, the family Kangiellaceae was classified into two families on the basis of phylogenetic, phylogenomic, polar lipid profile and motility variations. The novel family Pleioneaceae fam. nov. is proposed to accommodate the genera Aliikangiella and Pleionea.

Denitrobaculum tricleocarpae gen. nov., sp. nov., a marine bacterium from coralline algae Tricleocarpa sp.

A Gram-stain-negative, non-spore-forming, aerobic, motile, curved rod-shaped bacterium, designed strain R148T was isolated from a coralline algae Tricleocarpa sp. collected from Weizhou island, PR China. The optimal growth of R148T occurred at 25 °C, pH 8-9 in the presence of 0.5 % (w/v) NaCl on the basis of amended marine broth 2216. The genomic DNA G+C content was 59.5 mol%. The only detected respiratory quinone was Q-10. The major polar lipids were phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, and three unidentified ninhydrin-positive lipids. The major cellular fatty acids were C18 : 1ω7c, C16 : 1ω7c, C19 : 0cyclo 9, 10 DMA and C18 : 0. The results of 16S rRNA gene-based global alignment indicated that the closest neighbour of strain R148T was Pelagibius litoralis DSM 21314T (93.1 % similarity), the second is Limibacillus halophilus KCTC 42420T (92.2 %). The results of phylogenetic analysis indicated that R148T forms a distinct branch in the robust clade of R148T and P. litoralis DSM 21314T, while the taxonomic position of this clade in the family Rhodospirillaceae is ambiguous among phylogenetic approaches. The low 16S rRNA gene similarity and distinct polar lipid and cellular fatty acid profile could readily distinguish R148T from closely related type strains. So R148T is suggested to represent a novel species in a novel genus, for which the name Denitrobaculum tricleocarpae gen. nov., sp. nov. is proposed. The type strain is R148T (=MCCC 1K03781T=KCTC 72137T).

Exilibacterium tricleocarpae gen. nov., sp. nov., a marine bacterium from coralline algae Tricleocarpa sp.

A Gram-stain-negative, non-spore-forming, aerobic, curved rod-shaped bacterium, designed strain R142T, was isolated from a coralline algae Tricleocarpa sp. in the Beibu Gulf, China. Optimal growth occurred with 0-0.5 % (w/v) NaCl, at 25 °C and at pH 8. Global alignment based on 16S rRNA gene sequences indicated that strain R142T shared 93.8 % similarity with its closest type strain, Pseudomaricurvus alkylphenolicus KU14GT. Phylogenetic analyses showed that strain R142T forms a distinct branch alongside Maricurvus nonylphenolicus KU41ET, Pseudoteredinibacter isoporae SW-11T, Pseudomaricurvus alkylphenolicus KU14GT, Pseudomaricurvus alcaniphilus MEBiC06469T and Aestuariicella hydrocarbonica SM-6T. The major polar lipids of strain R142T were phosphatidylethanolamine and phosphatidylglycerol. The primary cellular fatty acids were C16 : 0, C16 : 1ω7c, C18 : 1ω7c, C18 : 0 and C14 : 0. The genome DNA G+C ratio was 56.4 mol%. The only detected respiratory quinone was ubiquinone 8. The low 16S rRNA gene sequence similarity and differences in cellular fatty acids readily distinguished strain R142T from all validly published type strains. Strain R142T is therefore suggested to represent a novel species of a new genus, for which the name Exilibacterium tricleocarpae gen. nov., sp. nov. is proposed. The type strain of Exilibacterium tricleocarpae is R142T (=MCCC 1K03816T=KCTC 72138T).

Poritiphilus flavus gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from coral Porites lutea.

A novel Gram-stain-negative, non-endospore-forming, non-motile, aerobic bacterium (strain R33T) was isolated from coral Porites lutea and subjected to a polyphasic taxonomic study. The G+C content was 44.5 mol%. The only detected respiratory quinone was menaquinone 6 (MK-6). The major cellular fatty acids were iso-C15 : 0 and iso-C15 : 1 ω6c. The major polar lipids were phosphatidylethanolamine and two unidentified lipids. Global alignment based on 16S rRNA gene sequences indicated that strain R33T shares the highest sequence identity of 93.2 % with Muriicola marianensis A6B8T in the family Flavobacteriaceae. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain R33T forms a distinct branch in a stable clade comprising strain R33T and members of the genera Muriicola, Robiginitalea, Eudoraea and Zeaxanthinibacter. The phylogenomic analysis also supported this 16S rRNA gene-based phylogenetic result. Comparative genomic analysis indicated that strain R33T is rich in AraC-type DNA-binding domain-containing protein-coding genes, which means the regulation of carbon utilization is very complex. Low 16S rRNA gene identity, different polar lipids and/or cellular fatty acid profiles could readily distinguish strain R33T from any validly published type strains. Therefore, strain R33T is suggested to represent a new species in a new genus, for which the name Poritiphilus flavus gen. nov., sp. nov. is proposed. The type strain is R33T (=MCCC 1K03853T=KCTC 72443T).

Intercalation of modified zanthoxylum bungeanum maxin seed oil/ stearate in layered double hydroxide: Toward flame retardant nanocomposites.

Zanthoxylum bungeanum Maxim Seed Oil (ZBMSO) is widely distributed in most parts of China, which cannot be edible and extensively consumed due to its high free fatty acids. This paper reports a rational route to utilization of ZBMSO in preparation of nanocomposites which can enhance leather flame retardancy and thermal stability. ZBMSO was synthesized through three-stage process, decoloration, acid reduction and sulfitation to prepare the modified ZBMSO fatliquoring agent (MZBMSO). Then nanocomposites based on MZBMSO and stearate-layered double hydroxide (s-LDH) were prepared via in-situ method. XRD and TEM results indicated that the MZBMSO intercalate into the galleries of s-LDH with uniform dispersion. Compared with MZBMSO, the leather treated by MZBMSO/s-LDH had a remarkable improvement on flame retardancy and superior softness which limiting oxygen index (LOI) increased from 23.6% to 28.0% and smoke density index decreased from 25 to 6.

Association between socioeconomic status and post-stroke functional outcome in deprived rural southern China: a population-based study.

BACKGROUND: Data on the association between socioeconomic status and post-stroke functional outcome in developing countries is lacking. We aimed to evaluate the association in stroke survivors in deprived rural Southern China. METHODS: We conducted door-to-door interviews and collected data using a structured questionnaire in stroke survivors from five fourth-class rural areas of Guangdong Province through a non-government initiated registry from August 2014 to March 2015. Descriptive statistics were used to provide information on the demographic, socioeconomic and clinical characteristics of the selected population. Univariate and multivariate logistic regression were used to examine the relationship of socioeconomic status indexed by self-reported average family income and functional impairment defined as a modified Rankin Scale of 3 to 5. RESULTS: Among the 425 stroke survivors, 52.7% lived below the poverty line set by the local government. About 50% of patients suffered from functional impairment and required assistance in their daily life. Compared with their wealthier counterpart, stroke survivors with lower income were more likely to have functional impairment (OR 2.85, 95% CI 1.93-4.23). The effect size increased and remained significant after adjusting for possible confounding factors (OR 3.17, 95% CI 2.04-4.91). CONCLUSIONS: Poorer patients tend to have poorer post-stroke functional outcome. Primary and secondary strategies targeting underprivileged populations in less-developed areas are thus urgently needed in China.

Smart nanoparticles improve therapy for drug-resistant tumors by overcoming pathophysiological barriers.

The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have several advantages over the free drug forms, including reduced cytotoxicity, prolonged circulation in the blood and increased accumulation in tumors. Currently, however, nanoparticulate drugs have only marginally improved the overall survival rate in clinical trials because of the various pathophysiological barriers that exist in the tumor microenvironment, such as intratumoral distribution, penetration and intracellular trafficking, etc. Smart NPs with stimulus-adaptable physico-chemical properties have been extensively developed to improve the therapeutic efficacy of nanomedicine. In this review, we summarize the recent advances of employing smart NPs to treat the drug-resistant tumors by overcoming the pathophysiological barriers in the tumor microenvironment.

Predicting response to repetitive transcranial magnetic stimulation in patients with chronic insomnia disorder using electroencephalography: A pilot study.

Predicting responsvienss to repetitive transcranial magnetic stimulation (rTMS) can facilitate personalized treatments with improved efficacy; however, predictive features related to this response are still lacking. We explored whether resting-state electroencephalography (rsEEG) functional connectivity measured at baseline or during treatment could predict the response to 10-day rTMS targeted to the right dorsolateral prefrontal cortex (DLPFC) in 36 patients with chronic insomnia disorder (CID). Pre- and post-treatment rsEEG scans and the Pittsburgh Sleep Quality Index (PSQI) were evaluated, with an additional rsEEG scan conducted after four rTMS sessions. Machine-learning approaches were employed to assess the ability of each connectivity measure to distinguish between responders (PSQI improvement > 25%) and non-responders (PSQI improvement ≤ 25%). Furthermore, we analyzed the connectivity trends of the two subgroups throughout the treatment. Our results revealed that the machine learning model based on baseline theta connectivity achieved the highest accuracy (AUC = 0.843) in predicting treatment response. Decreased baseline connectivity at the stimulated site was associated with higher responsiveness to TMS, emphasizing the significance of functional connectivity characteristics in rTMS treatment. These findings enhance the clinical application of EEG functional connectivity markers in predicting treatment outcomes.

Neuromyelitis optica spectrum disorder mimicking stroke: A case report and literature review.

Hemiparesis is a frequently observed manifestation of stroke but exceptionally rare in the context of neuromyelitis optica spectrum disorder (NMOSD). In this case, a 68-year-old woman initially presented with acute right-sided weakness, leading to suspicion of ischemic stroke. However, her symptoms worsened despite treatment with aspirin and statins. Subsequent spinal MRI and aquaporin 4 antibody testing confirmed the diagnosis of NMOSD. The administration of methylprednisolone and immunoglobulin resulted in improved clinical outcomes. This case serves as an illustrative example of the diverse manifestations encountered in NMOSD and underscores the significance of considering this potential etiology in elderly patients to facilitate prompt diagnosis and therapeutic intervention.

Functional connectivity changes are correlated with sleep improvement in chronic insomnia patients after rTMS treatment.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited. Objective: This study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS. Methods: Thirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI). Results: After treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8-10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment. Conclusion: Based on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

Neuro-11: a new questionnaire for the assessment of somatic symptom disorder in general hospitals.

Background: Somatic symptom disorder (SSD) commonly presents in general hospital settings, posing challenges for healthcare professionals lacking specialised psychiatric training. The Neuro-11 Neurosis Scale (Neuro-11) offers promise in screening and evaluating psychosomatic symptoms, comprising 11 concise items across three dimensions: somatic symptoms, negative emotions and adverse events. Prior research has validated the scale's reliability, validity and theoretical framework in somatoform disorders, indicating its potential as a valuable tool for SSD screening in general hospitals. Aims: This study aimed to establish the reliability, validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD. Through this comparative analysis, we aimed to validate the effectiveness and precision of the Neuro-11, enhancing its utility in clinical settings. Methods: Between November 2020 and December 2021, data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People's Hospital in China for various physical discomforts. The patients completed multiple questionnaires, including the Neuro-11, Short Form 36 Health Survey, Patient Health Questionnaire 15 items, Hamilton Anxiety Scale and Hamilton Depression Scale. Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD. Results: The Neuro-11 demonstrated strong content reliability and structural consistency, correlating significantly with internationally recognised and widely used questionnaires. Despite its brevity, the Neuro-11 exhibited significant correlations with other questionnaires. A test-retest analysis yielded a correlation coefficient of 1.00, Spearman-Brown coefficient of 0.64 and Cronbach's α coefficient of 0.72, indicating robust content reliability and internal consistency. Confirmatory factor analysis confirmed the validity of the three-dimensional structure (p<0.001, comparative fit index=0.94, Tucker-Lewis index=0.92, root mean square error of approximation=0.06, standardised root mean square residual=0.04). The threshold of the Neuro-11 is set at 10 points based on the maximum Youden's index from the receiver operating characteristic curve analysis. In terms of diagnostic efficacy, the Neuro-11 has an area under the curve of 0.67. Conclusions: (1) The Neuro-11 demonstrates robust associations with standard questionnaires, supporting its validity. It is applicable in general hospital settings, assessing somatic symptoms, negative emotions and adverse events. (2) The Neuro-11 exhibits strong content reliability and validity, accurately capturing the intended constructs. The three-dimensional structure demonstrates robust construct validity. (3) The threshold of the Neuro-11 is set at 10 points.

MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1.

[This retracts the article DOI: 10.3892/etm.2018.6223.].

Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Modulates Electroencephalographic Functional Connectivity in Alzheimer's Disease.

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer's disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear. Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment. Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared. Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group. Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.

Electroencephalographic connectivity predicts clinical response to repetitive transcranial magnetic stimulation in patients with insomnia disorder.

BACKGROUND: Accumulating evidence suggests that low frequency repetitive transcranial magnetic stimulation (rTMS), which generally decreases cortical excitability and remodels plastic connectivity, improves sleep quality in patients with insomnia disorder. However, the effects of rTMS vary substantially across individuals and treatment is sometimes unsatisfactory, calling for biomarkers for predicting clinical outcomes. OBJECTIVE: This study aimed to investigate whether functional connectivity of the target network in electroencephalography is associated with the clinical response to low frequency rTMS in patients with insomnia disorder. METHODS: Twenty-five patients with insomnia disorder were subjected to 10 sessions of treatment with 1 Hz rTMS over the right dorsolateral prefrontal cortex. Resting-state electroencephalography was collected before rTMS. Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Mini-Mental State Exam were performed before and after rTMS treatment, with a follow-up after one month. Electroencephalographic connectivity was measured by the power envelope connectivity at the source level. Partial least squares regression identified models of connectivity that maximally accounted for the rTMS response. RESULTS: Scores of Pittsburgh Sleep Quality Index, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale were decreased after rTMS and one-month later. Baseline weaker connectivity of a network in the beta and alpha bands between a brain region approximating the stimulated right dorsolateral prefrontal cortex and areas located in the frontal, insular, and limbic cortices was associated with a greater change in Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale following rTMS. CONCLUSIONS: Low frequency rTMS could improve sleep quality and depressive moods in patients with insomnia disorder. Moreover, electroencephalographic functional connectivity would potentially be a robust biomarker for predicting the therapeutic effects.

Identifying Mild Cognitive Impairment in Parkinson's Disease With Electroencephalogram Functional Connectivity.

OBJECTIVE: Cognitive impairment occurs frequently in Parkinson's disease (PD) and negatively impacts the patient's quality of life. However, its pathophysiological mechanism remains unclear, hindering the development of new therapies. Changes in brain connectivity are related to cognitive impairment in patients with PD, with the dorsolateral prefrontal cortex (DLPFC) being considered the essential region related to PD cognitive impairment. Nevertheless, few studies have focused on the global connectivity responsible for communication with the DLPFC node, the posterior division of the middle frontal gyrus (PMFG) in patients with PD; this was the focus of this study. METHODS: We applied resting-state electroencephalography (EEG) and calculated a reliable functional connectivity measurement, the debiased weighted phase lag index (dWPLI), to examine inter-regional functional connectivity in 68 patients with PD who were classified into two groups according to their cognitive condition. RESULTS: We observed that altered left and right PMFG-based functional connectivity associated with cognitive impairment in patients with PD in the theta frequency bands under the eyes closed condition (r = -0.426, p < 0.001 and r = -0.437, p < 0.001, respectively). Exploratory results based on the MoCA subdomains indicated that poorer visuospatial function was associated with higher right PMFG-based functional connectivity (r = -0.335, p = 0.005), and poorer attention function was associated with higher left and right PMFG-based functional connectivity (r = -0.380, p = 0.001 and r = -0.256, p = 0.035, respectively). Further analysis using logistic regression and receiver operating characteristic (ROC) curves found that this abnormal functional connectivity was an independent risk factor for cognitive impairment [odds ratio (OR): 2.949, 95% confidence interval (CI): 1.294-6.725, p = 0.01 for left PMFG; OR: 11.278, 95% CI: 2.578-49.335, p = 0.001 for right PMFG, per 0.1 U], and provided moderate classification power to discriminate between cognitive abilities in patients with PD [area under the ROC curve (AUC) = 0.770 for left PMFG; AUC = 0.809 for right PMFG]. CONCLUSION: These preliminary findings indicate that abnormal PMFG-based functional connectivity patterns associated with cognitive impairment in the theta frequency bands under the eyes closed condition and altered functional connectivity patterns have the potential to act as reliable biomarkers for identifying cognitive impairment in patients with PD.

Classification of Cognitive Impairment and Healthy Controls Based on Transcranial Magnetic Stimulation Evoked Potentials.

Backgrounds: Nowadays, risks of Cognitive Impairment (CI) [highly suspected Alzheimer's disease (AD) in this study] threaten the quality of life for more older adults as the population ages. The emergence of Transcranial Magnetic Stimulation-Electroencephalogram (TMS-EEG) enables noninvasive neurophysiological investi-gation of the human cortex, which might be potentially used for CI detection. Objectives: The aim of this study is to explore whether the spatiotemporal features of TMS Evoked Potentials (TEPs) could classify CI from healthy controls (HC). Methods: Twenty-one patients with CI and 22 HC underwent a single-pulse TMS-EEG stimulus in which the pulses were delivered to the left dorsolateral prefrontal cortex (left DLPFC). After preprocessing, seven regions of interest (ROIs) and two most reliable TEPs' components: N100 and P200 were selected. Next, seven simple and interpretable linear features of TEPs were extracted for each region, three common machine learning algorithms including Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbor (KNN) were used to detect CI. Meanwhile, data augmentation and voting strategy were used for a more robust model. Finally, the performance differences of features in classifiers and their contributions were investigated. Results: 1. In the time domain, the features of N100 had the best performance in the SVM classifier, with an accuracy of 88.37%. 2. In the aspect of spatiality, the features of the right frontal region and left parietal region had the best performance in the SVM classifier, with an accuracy of 83.72%. 3. The Local Mean Field Power (LMFP), Average Value (AVG), Latency and Amplitude contributed most in classification. Conclusions: The TEPs induced by TMS over the left DLPFC has significant differences spatially and temporally between CI and HC. Machine learning based on the spatiotemporal features of TEPs have the ability to separate the CI and HC which suggest that TEPs has potential as non-invasive biomarkers for CI diagnosis.

Coagulation factor 2 thrombin receptor promotes malignancy in glioma under SOX2 regulation.

Glioma is the most common human primary brain cancer with high mortality and unfavorable clinical outcome. Coagulation factor 2 thrombin receptor (F2R), is a key component in the thrombosis process and has been demonstrated upregulated in various cancers. However, the effect and molecular mechanisms of F2R in glioma remains unclear. In our study, we confirmed that the expression of F2R was upregulated in glioma and predicted poor prognosis. Gene Set Enrichment Analysis (GSEA) and function assays demonstrated that F2R overexpression promoted glioma cell proliferation, metastasis and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Then, we identified and validated F2R was the target gene of SRY-box 2 (SOX2) by dual luciferase reporter assay and chromatin immunoprecipitation assay. Besides, High expression of F2R in malignant glioma was associated with ß-catenint signaling pathway activation. Our findings conclude that F2R promotes glioma cell proliferation and metastasis under SOX2 and actives WNT/ß-catenin Signaling pathway, which provides novel insight to the therapeutic regimen in glioma.

Interference of the long noncoding RNA CDKN2B-AS1 upregulates miR-181a-5p/TGFßI axis to restrain the metastasis and promote apoptosis and senescence of cervical cancer cells.

Long noncoding RNA (lncRNA) CDKN2B-AS1 has been shown to play a crucial role in the development as well as in the prognosis of various human cancers, including cervical cancer. However, the underlying mechanisms need to be further explored between CDKN2B-AS1 and cervical cancer. In the present study, RT-PCR showed that the mRNA level of CDKN2B-AS1 was significantly upregulated while the miR-181a-5p was downregulated in cervical cancer cell lines. In addition, the interference of CDKN2B-AS1 by shRNA resulted in the suppression of cell proliferation, invasion, migration and promotion of apoptosis and senescence, and either CDKN2B-AS1 overexpression or miR-181a-5p showed reversed results. Further studies demonstrated that CDKN2B-AS1 could directly interact with miR-181a-5p, and that there was an inverse correlation between miR-181a-5p and CDKN2B-AS1. In addition, we found that TGFßI was a target of miR-181a-5p and could be downregulated by CDKN2B-AS1 knockdown. Moreover, the in vivo experiments further demonstrated the contribution of CDKN2B-AS1 in cervical cancer including tumor growth, apoptosis inhibition and senescence inhibition, and CDKN2B-AS1 knockdown could inhibit the aforementioned activities. In summary, our study demonstrated that the CDKN2B-AS1/miR-181a-5p/TGFßI axis might play a vital role in cervical cancer development.

MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1.

MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367 cluster has been reported to suppress the proliferation of cervical carcinoma cells through the novel target AKT1; however, the molecular mechanism of miR-302 in cervical cancer metastasis remains unclear. The present study aimed to investigate the clinical significance of miR-302-3p expression in cervical cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant phenotypes of cervical cancer cells. The present data indicated that miR-302-3p was significantly downregulated in cervical cancer tissues compared with the level in adjacent non-tumor tissues, and low expression of miR-302-3p was significantly associated with node metastasis, advanced clinical stage, and poor prognosis in patients with cervical cancer. Restoration of miR-302-3p expression caused a significant reduction in cervical cancer cell migration and invasion. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally, overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in cervical cancer tissues compared with the levels in adjacent tissues, and its high expression was associated with node metastasis, advanced clinical stage, and shorter survival time in patients with cervical cancer. Notably, a negative correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues was observed. Taken together, the present study suggests that miR-302-3p serves a suppressive role in cervical cancer metastasis, partly at least, via directly targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic target for cervical cancer treatment.