d-type peptides based fluorescent probes for "turn on" sensing of heparin.

Developing "turn on" fluorescent probes was desirable for the detection of the effective anticoagulant agent heparin in clinical applications. Through combining the aggregation induced emission (AIE) fluorogen tetraphenylethene (TPE) and heparin specific binding peptide AG73, the promising "turn on" fluorescent probe TPE-1 has been developed. Nevertheless, although TPE-1 could achieve the sensitive and selective detection of heparin, the low proteolytic stability and undesirable poor solubility may limit its widespread applications. In this study, seven TPE-1 derived fluorescent probes were rationally designed, efficiently synthesized and evaluated. The stability and water solubility were systematically estimated. Especially, to achieve real-time monitoring of proteolytic stability, the novel Abz/Dnp-based "turn on" probes that employ the internally quenched fluorescent (IQF) mechanism were designed and synthesized. Moreover, the detection ability of synthetic fluorescent probes for heparin were systematically evaluated. Importantly, the performance of d-type peptide fluorescent probe XH-6 indicated that d-type amino acid substitutions could significantly improve the proteolytic stability without compromising its ability of heparin sensing, and attaching solubilizing tag 2-(2-aminoethoxy) ethoxy) acid (AEEA) could greatly enhance the solubility. Collectively, this study not only established practical strategies to improve both the water solubility and proteolytic stability of "turn on" fluorescent probes for heparin sensing, but also provided valuable references for the subsequent development of enzymatic hydrolysis-resistant d-type peptides based fluorescent probes.

Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases.

The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self-renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle-aged and elderly patients with stroke or Parkinson's disease (mostly 40-80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 106-108 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow-up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.

LINC00662 contributes to the progression and the radioresistance of cervical cancer by regulating miR-497-5p and CDC25A.

It is reported that long intergenic non-coding RNA 00662 (LINC00662) plays an oncogenic role in tumours. However, the mechanism of LINC00662 in regulating the progression and radiosensitivity of cervical cancer (CC) is not clear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to detect LINC00662 and miR-497-5p expressions in CC tissues and cells. The expression of cell division cycle 25 A (CDC25A) in CC cells was examined by Western blot. CC cell proliferation was determined by cell counting kit-8 (CCK-8) and BrdU assays. The survival rate of CC cells was evaluated by colony formation assay under different doses of X-ray irradiation. CC cell migration and invasion were probed by Transwell assay. Besides, the interactions between miR-497-5p and LINC00662, and miR-497-5p and the 3'UTR of CDC25A were verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down experiments. We demonstrated that, LINC00662 expression was remarkably raised in CC tissues and cell lines. LINC00662 overexpression promoted proliferation, migration, invasion and radioresistance of CC cells, and LINC00662 knockdown inhibited the above malignant phenotypes of CC cells. In terms of mechanism, LINC00662 facilitated CC progression and radioresistance by adsorbing miR-497-5p and indirectly up-regulating CDC25A expression. In a word, the LINC00662/miR-497-5p/CDC25A axis boosts proliferation and metastasis of CC cells and enhances the radioresistance of cancer cells. SIGNIFICANCE OF THE STUDY: CC poses a threat to the health of women all over the world. In this study, we demonstrated for the first time that LINC00662 expression was remarkably raised in CC tissues and cells. Cellular experiments confirmed that LINC00662 facilitated cell proliferation, migration, invasion and radiation resistance through the miR-497-5p/CDC25A axis, which might be a promising target for CC treatments.

Multivariate gene expression-based survival predictor model in esophageal adenocarcinoma.

BACKGROUND: Despite the recent development of molecular-targeted treatment and immunotherapy, survival of patients with esophageal adenocarcinoma (EAC) with poor prognosis is still poor due to lack of an effective biomarker. In this study, we aimed to explore the ceRNA and construct a multivariate gene expression predictor model using data from The Cancer Genome Atlas (TCGA) to predict the prognosis of EAC patients. METHODS: We conducted differential expression analysis using mRNA, miRNA and lncRNA transciptome data from EAC and normal patients as well as corresponding clinical information from TCGA database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of those unique differentially expressed mRNAs using the Integrate Discovery Database (DAVID) database. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network of EAC and used Cox proportional hazard analysis to generate a multivariate gene expression predictor model. We finally performed survival analysis to determine the effect of differentially expressed mRNA on patients' overall survival and discover the hub gene. RESULTS: We identified a total of 488 lncRNAs, 33 miRNAs, and 1207 mRNAs with differentially expressed profiles. Cox proportional hazard analysis and survival analysis using the ceRNA network revealed four genes (IL-11, PDGFD, NPTX1, ITPR1) as potential biomarkers of EAC prognosis in our predictor model, and IL-11 was identified as an independent prognostic factor. CONCLUSIONS: In conclusion, we identified differences in the ceRNA regulatory networks and constructed a four-gene expression-based survival predictor model, which could be referential for future clinical research.

Morphine Postconditioning alleviates autophage in ischemia-reperfusion induced cardiac injury through up-regulating lncRNA UCA1.

BACKGROUND: Cardiac injury that induced by ischemia-reperfusion (I/R) significantly threatens human life, and autophagic cell death plays a pivotal role underlying it. Morphine Postconditioning (MpostC) has been identified to protect hearts against reperfusion injury, while whether MpostC treatment ameliorated cell autophage was still unclear. METHODS: The I/R rats were induced using left anterior descending artery occlusion followed by reperfusion. The H9C2 cells were hypoxia/reoxygenation (H/R) treated to mimic I/R in vitro. Luciferase reporter assay was performed to verify the relationship between miR-128 and HSP70, while RNA immunoprecipitation (RIP) and RNA pull-down were conducted to determine the interaction between UCA1 and miR-128. RESULTS: The expression of UCA1, miR-128 and HSP70 was decreased, increased and decreased, individually, in I/R cardiac tissues, while MpostC treatments significantly reversed it and also ameliorated infarct size and cell autophage. UCA1 regulated the expression of miR-128, while miR-128 regulated HSP70. MpostC alleviated cell autophage and tissue infarct as well as reversed the expression of UCA1, while miR-128 and HSP70 that induced by I/R caused cardiac injury and H/R. CONCLUSION: The present study indicated that MpostC protected against cardiac injury that induced by I/R through regulating UCA1/miR-128/HSP70.

Identification of surgical patients at high risk of OSAS using the Berlin Questionnaire to detect potential high risk of adverse respiratory events in post anesthesia care unit.

Obstructive sleep apnea syndrome (OSAS) increases the risk of post-surgery complications. This study uses Berlin Questionnaire (BQ) to identify Chinese adult surgical patients who are at a high risk of OSAS and to determine if the BQ could be used to detect potential high risk of adverse respiratory events in the post anesthesia care unit (PACU). Results indicated that only 11.4% of the patients were considered at a high risk of OSAS. Age and body mass index are the key factors for the risk of OSAS prevalence in China and also gender specific. Furthermore, the incidence of adverse respiratory events in the PACU was higher in patients with high risk of OSAS than others (6.8% vs. 0.9%, P < 0.001). They also stayed longer than others in the PACU (95 ± 28 min vs. 62 ± 19 min, P < 0.001). Age, high risk for OSAS, and smoking were independent risk factors for the occurrence of adverse respiratory events in the PACU. The BQ may be adopted as a screening tool for anesthesiologists in China to identify patients who are at high risk of OSAS and determine the potential risk of developing postoperative respiratory complications in the PACU.

Nonselective beta-blockers in cirrhotic patients with no or small varices: A meta-analysis.

AIM: To explore effects of nonselective beta-blockers (NSBBs) in cirrhotic patients with no or small varices. METHODS: The PubMed, EMBASE, Science Direct, and Cochrane library databases were searched for relevant papers. A meta-analysis was performed using ORs with 95%CI as the effect sizes. Subgroup analysis was conducted according to the studies including patients without varices and those with small varices. RESULTS: Overall, 784 papers were initially retrieved from the database searches, of which six randomized controlled trials were included in the meta-analysis. The incidences of large varices development (OR = 1.05, 95%CI: 0.25-4.36; P = 0.95), first upper gastrointestinal bleeding (OR = 0.59, 95%CI: 0.24-1.47; P = 0.26), and death (OR = 0.70, 95%CI: 0.45-1.10; P = 0.12) were similar between NSBB and placebo groups. However, the incidence of adverse events was significantly higher in the NSBB group compared with the placebo group (OR = 3.47, 95%CI: 1.45-8.33; P = 0.005). The results of subgroup analyses were similar to those of overall analyses. CONCLUSION: The results of this meta-analysis indicate that NSBBs should not be recommended for cirrhotic patients with no or small varices.

Restrictive vs liberal transfusion for upper gastrointestinal bleeding: a meta-analysis of randomized controlled trials.

AIM: To compare the outcome of upper gastrointestinal bleeding (UGIB) between patients receiving restrictive and liberal transfusion. METHODS: PubMed, EMBASE, and Cochrane Library databases were employed to identify all relevant randomized controlled trials regarding the outcome of UGIB after restrictive or liberal transfusion. Primary outcomes were death and rebleeding. Secondary outcomes were length of hospitalization, amount of blood transfused, and hematocrit and hemoglobin at discharge or after expansion. RESULTS: Overall, 4 papers were included in this meta-analysis. The incidence of death was significantly lower in patients receiving restrictive transfusion than those receiving liberal transfusion (OR: 0.52, 95%CI: 0.31-0.87, P = 0.01). The incidence of rebleeding was lower in patients receiving restrictive transfusion than those receiving liberal transfusion, but this difference did not reach any statistical significance (OR: 0.26, 95%CI: 0.03-2.10, P = 0.21). Compared with those receiving liberal transfusion, patients receiving restrictive transfusion had a significantly shorter length of hospitalization (standard mean difference: -0.17, 95%CI: -0.30--0.04, P = 0.009) and a significantly smaller amount of blood transfused (standard mean difference: -0.74, 95%CI: -1.15--0.32, P = 0.0005) with a lower hematocrit and hemoglobin level at discharge or after expansion. CONCLUSION: Restrictive transfusion should be employed in patients with UGIB.

Clinical significance of ischemia-modified albumin in the diagnosis of doxorubicin-induced myocardial injury in breast cancer patients.

BACKGROUND: Ischemia-modified albumin is an altered serum albumin that forms under conditions of oxidative stress, a state also associated with doxorubicin-induced myocardial injury. OBJECTIVE: The aim of this study was to better assess diagnostic and prognostic significance of ischemia-modified albumin in patients with breast cancer undergoing doxorubicin chemotherapy. METHODS: Blood samples were collected from 152 breast cancer patients before and after each cycle of doxorubicin chemotherapy to measure the serum levels of ischemia-modified albumin, cardiac troponin T and creatine kinase-MB. We also monitored cardiac function during a 12 month follow-up. RESULTS: There was a significant difference in ischemia-modified albumin levels before and after each cycle of chemotherapy and the ischemia-modified albumin concentration positively correlated with the cumulative dose of doxorubicin (r = 0.212, P < 0.05). The combination of ischemia-modified albumin with cardiac troponin T and creatine kinase-MB increased the sensitivity to 0.920 and the specificity to 0.830 in the diagnosis of doxorubicin-induced myocardial injury. The optimal cutoff for ischemia-modified albumin concentration was 112.09 U/ml. The rate of change for ischemia-modified albumin levels correlated negatively with the rate of change for left ventricular ejection fraction at one year (r = -0.221, P < 0.05). CONCLUSION: Ischemia-modified albumin may be a clinically potential new marker for diagnosing doxorubicin-induced myocardial injury, and is helpful to predict long-term impairment of cardiac function.

Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling.

Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway.