Implications of depressive mood in OSAHS patients: insights from event-related potential.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic breathing disorder characterized by recurrent upper airway obstruction during sleep. Although previous studies have shown a link between OSAHS and depressive mood, the neurobiological mechanisms underlying mood disorders in OSAHS patients remain poorly understood. This study aims to investigate the emotion processing mechanism in OSAHS patients with depressive mood using event-related potentials (ERPs). METHODS: Seventy-four OSAHS patients were divided into the depressive mood and non-depressive mood groups according to their Self-rating Depression Scale (SDS) scores. Patients underwent overnight polysomnography and completed various cognitive and emotional questionnaires. The patients were shown facial images displaying positive, neutral, and negative emotions and tasked to identify the emotion category, while their visual evoked potential was simultaneously recorded. RESULTS: The two groups did not differ significantly in age, BMI, and years of education, but showed significant differences in their slow wave sleep ratio (P = 0.039), ESS (P = 0.006), MMSE (P < 0.001), and MOCA scores (P = 0.043). No significant difference was found in accuracy and response time on emotional face recognition between the two groups. N170 latency in the depressive group was significantly longer than the non-depressive group (P = 0.014 and 0.007) at the bilateral parieto-occipital lobe, while no significant difference in N170 amplitude was found. No significant difference in P300 amplitude or latency between the two groups. Furthermore, N170 amplitude at PO7 was positively correlated with the arousal index and negatively with MOCA scores (both P < 0.01). CONCLUSION: OSAHS patients with depressive mood exhibit increased N170 latency and impaired facial emotion recognition ability. Special attention towards the depressive mood among OSAHS patients is warranted for its implications for patient care.

Daytime Hypercapnia Impairs Working Memory in Young and Middle-Aged Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS. Patients and Methods: This prospective study screened 218 patients and eventually recruited 131 patients (aged 25-60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery. Results: Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance. Conclusion: Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.

Cortical thinning in male obstructive sleep apnoea patients with excessive daytime sleepiness.

Background and purpose: Obstructive sleep apnoea is associated with excessive daytime sleepiness due to sleep fragmentation and hypoxemia, both of which can lead to abnormal brain morphology. However, the pattern of brain structural changes associated with excessive daytime sleepiness is still unclear. This study aims to investigate the effects of excessive daytime sleepiness on cortical thickness in patients with obstructive sleep apnoea. Materials and methods: 61 male patients with newly diagnosed obstructive sleep apnoea were included in the present study. Polysomnography and structural MRI were performed for each participant. Subjective daytime sleepiness was assessed using the Epworth Sleepiness Scale score. Surface-based morphometric analysis was performed using Statistical Parametric Mapping 12 and Computational Anatomy 12 toolboxes to extract cortical thickness. Results: Using the median Epworth Sleepiness Scale score, patients were divided into the non-sleepiness group and the sleepiness group. The cortical thickness was markedly thinner in the sleepiness group in the left temporal, frontal, and parietal lobe and bilateral pre- and postcentral gyri (pFWE < 0.05). There was a significant negative correlation between the cortical thickness and the Epworth Sleepiness Scale score. After adjusting for age, body mass index, and obstructive sleep apnoea severity, the Epworth Sleepiness Scale score remained an independent factor affecting the cortical thickness of the left middle temporal lobe, transverse temporal and temporal pole. Conclusion: Subjective daytime sleepiness is associated with decreased cortical thickness, and the Epworth Sleepiness Scale score may be of utility as a clinical marker of brain injury in patients with obstructive sleep apnoea.

The complex interplay of hypoxia and sleep disturbance in gray matter structure alterations in obstructive sleep apnea patients.

Background: Obstructive Sleep Apnea (OSA) characteristically leads to nocturnal hypoxia and sleep disturbance. Despite clear evidence of OSA-induced cognitive impairments, the literature offers no consensus on the relationship between these pathophysiological processes and brain structure alterations in patients. Objective: This study leverages the robust technique of structural equation modeling to investigate how hypoxia and sleep disturbance exert differential effects on gray matter structures. Methods: Seventy-four Male participants were recruited to undergo overnight polysomnography and T1-weighted Magnetic Resonance Imaging. Four structural outcome parameters were extracted, namely, gray matter volume, cortical thickness, sulcal depth, and fractal dimension. Structural equation models were constructed with two latent variables (hypoxia, and sleep disturbance) and three covariates (age, body mass index, and education) to examine the association between gray matter structural changes in OSA and the two latent variables, hypoxia and sleep disturbance. Results: The structural equation models revealed hypoxia-associated changes in diverse regions, most significantly in increased gray matter volume, cortical thickness and sulcal depth. In contrast, sleep disturbance. Was shown to be largely associated with reduce gray matter volume and sulcal depth. Conclusion: This study provides new evidence showing significant effects of OSA-induced hypoxia and sleep disturbance on gray matter volume and morphology in male patients with obstructive sleep apnea. It also demonstrates the utility of robust structural equation models in examining obstructive sleep apnea pathophysiology.

A nanotherapeutic system for gastric cancer suppression by synergistic chemotherapy and immunotherapy based on iPSCs and DCs exosomes.

BACKGROUND: Chemotherapeutic drugs, the indispensable therapy in the treatment of gastric cancer, contain many problems such as high organ toxicity and insufficient therapeutic effect. The development of nanodrug delivery carriers with both tumor targeting function and immune stimulation ability possesses the potential to remedy these practical defects. METHODS AND RESULTS: In this study, a tumor targeting nanosystem that combines chemotherapy with immunotherapy was applied to the treatment and prognosis of gastric cancer. The fusion vector of iPSCs and DCs exosomes, which simultaneously possess the ability of tumor targeting and immune factor recruitment, effectively improved the in vivo efficacy of chemotherapy drugs and released the suppressed T lymphocytes under the action of modified PD-1 antibody to dredge the immunotherapy process. In addition, extensive recruitment of immune cells to clean the environment while exposing vast tumor antigens efficiently amplified the anti-tumor immune effect and ensured the good prognosis. CONCLUSIONS: Nanodrug delivery system DOX@aiPS-DCexo could effectively inhibit the expansion process of gastric cancer MFC through synergistic chemotherapy and immunotherapy and demonstrated the capacity of improving prognosis. Scheme: schematic illustration of the nanostructure DOX@aiPS-DCexo and the mechanism of action.

Knockdown of OLR1 weakens glycolytic metabolism to repress colon cancer cell proliferation and chemoresistance by downregulating SULT2B1 via c-MYC.

Chemoresistance is one of the major problems of colon cancer treatment. In tumors, glycolytic metabolism has been identified to promote cell proliferation and chemoresistance. However, the molecular mechanisms underlying glycolytic metabolism and chemoresistance in colon cancer remains enigmatic. Hence, this research was designed to explore the mechanism underlying the OLR1/c-MYC/SULT2B1 axis in the regulation of glycolytic metabolism, to affect colon cancer cell proliferation and chemoresistance. Colon cancer tissues and LoVo cells were attained, where OLR1, c-MYC, and SULT2B1 expression was detected by immunohistochemistry, RT-qPCR, and western blot analysis. Next, ectopic expression and knockdown assays were implemented in LoVo cells. Cell proliferation was detected by MTS assay and clone formation. Extracellular acidification, glucose uptake, lactate production, ATP/ADP ratio, and GLUT1 and LDHA expression were measured to evaluate glycolytic metabolism. Then, the transfected cells were treated with chemotherapeutic agents to assess drug resistance by MTS experiments and P-gp and SMAD4 expression by RT-qPCR. A nude mouse model of colon cancer transplantation was constructed for in vivo verification. The levels of OLR1, c-MYC, and SULT2B1 were upregulated in colon cancer tissues and cells. Mechanistically, OLR1 increased c-MYC expression to upregulate SULT2B1 in colon cancer cells. Moreover, knockdown of OLR1, c-MYC, or SULT2B1 weakened glycolytic metabolism, proliferation, and chemoresistance of colon cancer cells. In vivo experiments authenticated that OLR1 knockdown repressed the tumorigenesis and chemoresistance in nude mice by downregulating c-MYC and SULT2B1. Conclusively, knockdown of OLR1 might diminish SULT2B1 expression by downregulating c-MYC, thereby restraining glycolytic metabolism to inhibit colon cancer cell proliferation and chemoresistance.

miR­200b upregulation promotes migration of BEAS­2B cells following long­term exposure to cigarette smoke by targeting ETS1.

Cigarette smoking is the leading cause of all histological types of lung cancer, and the role that microRNAs (miRNAs) serve in its pathogenesis is being increasingly recognized. The aim of the present study was to investigate the role of miR­200b on migration in cigarette smoke­induced malignant transformed cells. In the present study, miR­200b expression was found to be increased in cigarette smoke (CS)­exposed BEAS­2B cells, lung cancer cell lines and tumor tissue samples. Using wound healing and Transwell migration assays, the migratory ability was shown to be increased in miR­200b­overexpressing cells, whereas miR­200b knockdown resulted in reduced migration. Additionally, the expression of E­Cadherin was downregulated, whereas that of N­Cadherin was upregulated in miR­200b mimic­transfected cells, suggesting an increase in epithelial­mesenchymal transition. Downstream, using four target gene prediction tools, six target genes of miR­200b were predicted, amongst which, ETS proto­oncogene 1 transcription factor (ETS1) was shown to be significantly associated with tumor invasion depth and negatively associated with miR­200b expression. The interaction between miR­200b and ETS1 was confirmed using a dual­luciferase reporter assay. Using rescue experiments, the increased migratory ability of the miR­200b­overexpressing cells was reversed by ETS1 overexpression. In summary, this study showed that miR­200b overexpression serves a carcinogenic role and promotes the migration of BEAS­2B cells following long­term exposure to CS by targeting ETS1.

EEG Power Spectral Analysis of Abnormal Cortical Activations During REM/NREM Sleep in Obstructive Sleep Apnea.

Objective: To characterize electroencephalogram (EEG) power in different frequency bands during rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with obstructive sleep apnea (OSA). Methods: Retrospective data on 151 patients were collected and divided into three groups: primary snoring group (AHI < 5/h), mild-moderate OSA group (6 ≤ AHI < 30/h), and severe OSA group (AHI ≥ 30/h). EEG recordings in the frontal, central, and occipital regions were extracted from both REM and NREM sleep, to compute the normalized spectral power densities in the delta, theta, alpha, sigma, beta, and gamma frequency bands, using Fast Fourier Transform. Correlations between the computed EEG power and PSG parameters were analyzed. Results: In NREM sleep, elevated normalized power spectral density (PSD) in the delta band was observed in the severe OSA group compared to the other two groups. In contrast, the PSD of the other frequency bands showed a corresponding decrease in the severe OSA group. In REM sleep, similar changes were observed in the frontal region. Delta band PSD was positively correlated with Apnea Hypopnea Index (AHI) (r = 0.33), longest time of apnea, oxygen desaturation index (ODI) (r = 0.34), percent sleep time below 90% SaO2 (T90%) (r = 0.30), Arousal Index (ArI) (r = 0.29), and negatively correlated with N3%, minimum oxygen saturation (minSaO2). Conclusion: Our findings provide neurophysiological evidence for pathological cortical activation during REM/NREM sleep, which may be associated with the arousals and cognitive impairments in OSA. The technique of power spectral analysis could prove a potentially useful tool in complementing traditional PSG parameters in assessing disease burden to guide therapeutic decisions.

Low Arousal Threshold: A Potential Bridge Between OSA and Periodic Limb Movements of Sleep.

OBJECTIVE: Periodic Limb Movements of Sleep (PLMS) is a poorly understood comorbidity with close association to Obstructive Sleep Apnea (OSA). The mechanistic link between the two is unclear. Recent studies on the latter have uncovered low respiratory arousal threshold as an important non-anatomical cause of the disorder. This study sought to investigate whether periodic limb movements are associated with the low respiratory arousal threshold (ArTH) in OSA. METHODS: Retrospective data on 720 OSA patients (mean age = 47.0) who underwent Polysomnography (PSG) were collected. Using PLMS diagnostic criteria of PLMS index ≥ 15, patients were divided into the OSA-PLMS group (n=95) and the OSA-only group (n=625). Binary logistic regression analysis was used to examine the correlation between PLMS and the presence of low ArTH, classified using a predicted tool (developed by Edward et al) requiring meeting at least two of the three criteria: apnea-hypopnea index (AHI) < 30/h, nadir oxygen saturation (SaO2) > 82.5%, and fraction of hypopneas > 58.3%. The resulting model was validated in the external MrOS database. RESULTS: The patients in the OSA-PLMS group tend to be older, with a higher prevalence of hypertension, diabetes, and stroke. PLMS was associated with age, diabetes, oxygen desaturation index, and low respiratory arousal threshold (OR=8.78 (4.73-16.30), p<0.001). When validated against the MrOS database, low ArTH remained a significant predictor of PLMS with an odds ratio of 1.33 (1.08-1.64, p = 0.009). CONCLUSION: This is the first study that demonstrated a strong correlation between PLMS and low respiratory arousal threshold. This suggests a possible mechanistic link between the physical manifestation of PLMS and the non-anatomical low arousal threshold phenotype in OSA.

Relationship between total plasma homocysteine and the risk of aneurysms - a meta-analysis.

Our meta-analysis focused on the relationship between homocysteine (Hcy) level and the incidence of aneurysms and looked at the relationship between smoking, hypertension and aneurysms. A systematic literature search of Pubmed, Web of Science, and Embase databases (up to March 31, 2020) resulted in the identification of 19 studies, including 2,629 aneurysm patients and 6,497 healthy participants. Combined analysis of the included studies showed that number of smoking, hypertension and hyperhomocysteinemia (HHcy) in aneurysm patients was higher than that in the control groups, and the total plasma Hcy level in aneurysm patients was also higher. These findings suggest that smoking, hypertension and HHcy may be risk factors for the development and progression of aneurysms. Although the heterogeneity of meta-analysis was significant, it was found that the heterogeneity might come from the difference between race and disease species through subgroup analysis. Large-scale randomized controlled studies of single species and single disease species are needed in the future to supplement the accuracy of the results.

Drug Response Associated With and Prognostic lncRNAs Mediated by DNA Methylation and Transcription Factors in Colon Cancer.

Colon cancer is the most commonly diagnosed malignancy and the leading cause of cancer deaths worldwide. As well as lifestyle, genetic and epigenetic changes are key factors that influence the risk of colon cancer. However, the impact of epigenetic alterations in non-coding RNAs and their consequences in colon cancer have not been fully characterized. We detected differential methylation sites (DMSs) in long non-coding RNA (lncRNA) promoters and identified lncRNA expression quantitative trait methylations (lncQTMs) by association tests. To investigate how transcription factor (TF) binding was affected by DNA methylation, we characterized the occurrence of known TFs among DMSs collected from the MEME suite. We further combined methylome and transcriptome data to construct TF-methylation-lncRNA relationships. To study the role of lncRNAs in drug response, we used pharmacological and lncRNA profiles from the Cancer Cell Line Encyclopedia (CCLE) and investigated the association between lncRNAs and drug activity. We also used combinations of TF-methylation-lncRNA relationships to stratify patient survival using a risk model. DNA methylation sites displayed global hyper-methylation in lncRNA promoters and tended to have negative relationships with the corresponding lncRNAs. Negative lncQTMs located near transcription start sites (TSSs) had more significant correlations with the corresponding lncRNAs. Some lncRNAs found to be mediated by the interplay between DNA methylation and TFs were previously identified as markers for colon cancer. We also found that the ELF1-cg05372727- LINC00460 relationship were prognostic signatures for colon cancer. These findings suggest that lncRNAs mediated by the interplay between DNA methylation and TFs are promising predictors of drug response, and that combined TF-methylation-lncRNA can serve as a prognostic signature for colon cancer.

Identification of intestinal flora-related key genes and therapeutic drugs in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a multifactorial tumor and a leading cause of cancer-specific deaths worldwide. Recent research has shown that the alteration of intestinal flora contributes to the development of CRC. However, the molecular mechanism by which intestinal flora influences the pathogenesis of CRC remains unclear. This study aims to explore the key genes underlying the effect of intestinal flora on CRC and therapeutic drugs for CRC. METHODS: Intestinal flora-related genes were determined using text mining. Based on The Cancer Genome Atlas database, differentially expressed genes (DEGs) between CRC and normal samples were identified with the limma package of the R software. Then, the intersection of the two gene sets was selected for enrichment analyses using the tool Database for Annotation, Visualization and Integrated Discovery. Protein interaction network analysis was performed for identifying the key genes using STRING and Cytoscape. The correlation of the key genes with overall survival of CRC patients was analyzed. Finally, the key genes were queried against the Drug-Gene Interaction database to find drug candidates for treating CRC. RESULTS: 518 genes associated with intestinal flora were determined by text mining. Based on The Cancer Genome Atlas database, we identified 48 DEGs associated with intestinal flora, including 25 up-regulated and 23 down-regulated DEGs in CRC. The enrichment analyses indicated that the selected genes were mainly involved in cell-cell signaling, immune response, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. The protein-protein interaction network was constructed with 13 nodes and 35 edges. Moreover, 8 genes in the significant cluster were considered as the key genes and chemokine (C-X-C motif) ligand 8 (CXCL8) correlated positively with the overall survival of CRC patients. Finally, a total of 24 drugs were predicted as possible drugs for CRC treatment using the Drug-Gene Interaction database. CONCLUSIONS: These findings of this study may provide new insights into CRC pathogenesis and treatments. The prediction of drug-gene interaction is of great practical significance for exploring new drugs or novel targets for existing drugs.

PD-L1 expression increased by IFN-γ via JAK2-STAT1 signaling and predicts a poor survival in colorectal cancer.

PD-L1 inhibitors are widely used in tumor immunotherapy, but their mechanism in colorectal cancer remains unclear. The present study aimed to investigate the mechanisms underlying programmed death ligand 1 (PD-L1) regulation via the interferon-γ (IFN-γ)/janus kinase (JAK)/STAT signaling pathway, and its prognostic value in patients with colorectal cancer (CRC). A cohort of 181 patients were recruited to determine the association between PD-L1 expression and CRC prognosis; the patients were newly diagnosed with colorectal adenocarcinoma and had also undergone a physical tumorectomy. Immunohistochemical staining and survival analysis were used to evaluate the predictive value of PD-L1 protein expression in CRC. Gene set enrichment analysis, RT-qPCR and western blotting, etc were performed to confirm that PD-L1 is regulated by the IFN-γ/JAK/STAT signaling pathway. PD-L1 up-regulation was more frequently observed in patients with larger tumors, positive vascular or lymphatic infiltration and a poorly differentiated stage in addition to being associated with a poor survival in patients with CRC. Following the stimulation with IFN-γ, PD-L1 expression levels were revealed to be increased via the JAK2/STAT1 signaling pathway. In conclusion, the findings of the present study indicated that the expression levels of PD-L1 may be associated with a poor prognosis in patients with CRC. In addition, the results suggested that the IFN-γ-mediated overexpression of PD-L1 in CRC cells may be regulated by the JAK2/STAT1 signaling pathway.

Lnc HAGLR Promotes Colon Cancer Progression Through Sponging miR-185-5p and Activating CDK4 and CDK6 in vitro and in vivo.

BACKGROUND/AIM: LncRNA plays a key role in tumor progression. HAGLR functions as an oncogene in many cancers. However, the molecular mechanism of HAGLR in colon cancer is still unclear. METHODS: qRT-PCR was used to measure the expression of HAGLR, miR-185-5p in colon cancer. The expression of CDK4 and CDK6 was detected by Western blot. CCK-8 assay, EdU staining, transwell and Annexin V-FITC/PI assay were used to analyze the effect of HAGLR and miR-185-5p on cell proliferation, invasion, migration and apoptosis. Bioinformatic analysis and luciferase were used to analyze the target genes of HAGLR and miR-185-5p. Nude mice were used to detect mouse tumor changes. RESULTS: Compared with normal colon cancer tissues and cells, the expression of HAGLR was increased in colon cancer tissues and cells. In addition, the expression of HAGLR down-regulation inhibited the growth, migration, and invasion of colon cancer cells. MiR-185-5p was reduced in colon cancer, and CDK4 and CDK6 acted as target genes of miR-185-5p to regulate the progress of colon cancer. And CDK4 and CDK6 were predicted as downstream targets of miR-185-5p. Finally, it was demonstrated that HAGLR regulated tumor progression in vivo. CONCLUSION: Lnc HAGLR promoted the development of colon cancer by miR-185-5p/CDK4/CDK6 axis, and lnc HAGLR might be potential target for colon cancer.

lncRNA FOXD2-AS1 promotes hemangioma progression through the miR-324-3p/PDRG1 pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) are reported could function as tumor promoter in several cancers. However, its role in hemangioma was not reported to yet. METHODS: Expression level of FOXD2-AS1 in hemangioma tissues and cells was explored using quantitative reverse-time PCR. Cell counting kit-8 (CCK-8) assay, colony formation assay, wound-healing assay, and transwell invasion assay were conducted to measure the roles of FOXD2-AS1. In addition, the levels of markers for proliferation and Epithelial-Mesenchymal Transition were investigated. Connection of FOXD2-AS1 and mcroRNA-324-3p (miR-324-3p) or miR-324-3p and p53 and DNA damage regulated 1 (PDRG1) was analyzed with bioinformatic analysis method and dual-luciferase activity reporter assay. RESULTS: Here, we found that FOXD2-AS1 was highly expressed in proliferating-phase hemangioma tissues compared with the involuting-phase hemangioma tissues. Functionally, FOXD2-AS1 knockdown suppressed cell proliferation, colony formation, migration, and invasion in vitro. Conversely, overexpression of FOXD2-AS1 promoted tumor growth in vitro. Mechanistically, FOXD2-AS1 inversely regulated miR-324-3p abundance in hemangioma cells. We also found FOXD2-AS1 acted as a competing endogenous RNA (ceRNA) by directly sponging miR-324-3p to regulate PDRG1 expression. In addition, the knockdown of PDRG1 reversed the stimulation effects of FOXD2-AS1 overexpression on HA cells. CONCLUSION: To conclude, our study sheds novel light on the biological roles of FOXD2-AS1 in hemangioma, which may help the development of targeted therapy method for cancer.

Evaluation of serum MUC5AC in combination with CA19-9 for the diagnosis of pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive tumor with a poor prognosis that lacks specific diagnostic markers. Mucin 5AC (MUC5AC) is a member of the mucin family, a heterogeneous group of high molecular weight, heavily glycosylated proteins that could be either membrane-bound or secreted. This multi-central study is to evaluate the performance of serum MUC5AC in combination with carbohydrate antigen 19-9 (CA19-9) for the diagnosis of PC in Asian. METHODS: Sixty-one patients with PC (comprised of early pancreatic cancer [n = 30] and late pancreatic cancer [n = 31] patients), 29 benign control, 35 choledocholithiasis, 25 chronic pancreatitis, and 34 healthy controls, were recruited from two hospitals. Serum levels of MUC5AC were evaluated by commercial ELISA kits. CA19-9 was measured by chemiluminescence immunoassay. The cutoff value of MUC5AC was determined based on optimal sensitivity and specificity. RESULTS: Serum MUC5AC in patients with PC (210.1 [100.5-423.8] ng/mL) presented higher levels than those in controls. The combined biomarker panel (MUC5AC and CA19-9) presented better performance and improved specificity to differentiate PC from controls (AUC 0.894; 95% CI (0.844-0.943), sensitivity 0.738, specificity 0.886) than CA19-9 (p = 0.043) or MUC5AC alone (p = 0.010); however, the latter two had no difference (p = 0.824). CONCLUSIONS: Serum MUC5AC is a potential biomarker for PC. The combination with CA19-9 presents improved specificity and better performance.

Defect induced photoluminescence and triboluminescence in layered CaLaAl3O7.

In this work, a layered melilite structure, CaLaAl3O7, was synthesized and observed to have obvious luminescence behaviors under the stimuli of ultraviolet light and rubbing, which were called photoluminescence and triboluminescence, respectively. Considering the wide bandgap of CaLaAl3O7 and its specific crystal structure, the observed luminescence should be attributed to intrinsic defects. Both the photoluminescence and triboluminescence of CaLaAl3O7 show a strong dependence on the synthesis atmosphere, suggesting that they should be related to the oxygen vacancy. It is attractive to find that the triboluminescence of CaLaAl3O7 shows a distinct spectral characteristic compared to its photoluminescence. Further computational results suggest that the applied mechanical stimuli on the CaLaAl3O7 cell could promote the formation of the vacancies of oxygen and calcium, responsible for the spectral differences.

Photothermal and gene therapy combined with immunotherapy to gastric cancer by the gold nanoshell-based system.

BACKGROUND: The gastric cancer is the second most malignant tumor in the world. HER-2 is one of the key targets for the gastric cancer therapy. Anti-HER-2 antibodies like trastuzumab, exhibits the satisfactory therapeutic effect in clinical. However, the drug resistance problem limits its application. METHOD: In this study, we develop a gold nanoshell (Gold Nanoshell) drug carrier for delivery and selective photo-thermal release of genes which target HER-2 and immunologic adjuvant CPG sequence in gastric tumor cells. The drug delivery system generated a multidimensional treatment strategy which includes gene-, immune- and photothermal-therapy. RESULTS: The whole gold nanoshell drug delivery system exhibits the well gene transduction ability and combined treatment effect. Both in vitro and in vivo results demonstrate the multiple therapeutic effects of the drug delivery system is better than the monotherapy. CONCLUSIONS: This study indicates the multiple combined therapy based on the gold nanoshell system would be a promising translational treatment for gastric cancer.

LncRNA OIP5-AS1 Promotes the Proliferation of Hemangioma Vascular Endothelial Cells via Regulating miR-195-5p/NOB1 Axis.

Background: Hemangioma, which is a benign vascular neoplasm, has been demonstrated to be the most common tumor of infancy, resulting from aberrant proliferation of endothelial cells and pericytes. Objective: The aim of this study was to determine the role of lncRNA OIP5-AS1 on the proliferation and metastasis of human hemangioma endothelial cells (HemECs). Methods: In this study, we examined the expression of OIP5-AS1 and miR-195-5p in hemangiomas patients. The effects of knockdown or ectopic expression of OIP5-AS1 on the viability, proliferation and apoptosis of HemECs were explored. Rescue assays were performed to explore the effects of OIP5-AS1/miR-195-5p/NOB1 axis on biological behaviors in the HemECs. Results: It was found that OIP5-AS1 was overexpressed in both hemangioma tissues and HemECs cells. OIP5-AS1 knockdown suppressed the proliferation, migration, and invasion of HemECs cell, while overexpression of OIP5-AS1 had opposite effects LncRNA OIP5-AS1 acted as a ceRNA through binding with miR-195-5p to upregulate NOB1 in HemECs. Conclusion: Taken together, lncRNA OIP5-AS1 acted as a ceRNA to drive proliferation, migration and invasion of HemECs through regulating miR-195-5p/NOB1 axis.

Curcumin ameliorates atherosclerosis through upregulation of miR-126.

The potential usage of curcumin in diverse human diseases has been widely studied, including arteriosclerosis (AS). This study focused on investigating the relationship between curcumin and AS-associated microRNA, which may provide a better understanding of curcumin in a different mechanism. Human microvascular endothelial HMEC-1 cells were treated by curcumin alone or oxidized low-density lipoprotein (ox-LDL) plus curcumin, after which the following parameters were analyzed: cell viability, migration, and the expression of AS-associated factors. The regulatory effects of curcumin on miR-126 and signaling pathways involved in AS were then studied. Further, an animal model of AS was stimulated by feeding rabbits with 1% cholesterol diet. The effects of curcumin on the animal model were explored. We found that curcumin treatment significantly reduced HMEC-1 cells viability, migration, and the protein levels of MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) in the presence or absence of ox-LDL. Meanwhile, the expression of VEGFR1 and VEGFR2 was repressed by curcumin. miR-126 was upregulated by curcumin. The abovementioned effects of curcumin on HMEC-1 cells were all attenuated when miR-126 was silenced. And also, VEGF was a target gene of miR-126, and curcumin could inhibit the activation of PI3K/AKT JAK2/STAT5 signaling pathways via miR-126. The effects of curcumin and its regulation on miR-126 and VEGF were confirmed in the animal model of AS. To sum up, curcumin exerted potent anti-AS property possibly via upregulating miR-126 and thereby inhibiting PI3K/AKT and JAK2/STAT5 signaling pathways.