Novel Copper Nanoparticles Intercalated Polyurethane Heparin/Poly-L-Lysine Chelates Coated Stents: Viability Study for Coronary Vascular Cells and Aneurysms Treatments.

Continuous delayed endothelium regeneration and continues thrombosis development designate a task for coronary artery stent rehabilitation. To progress the direct vascular cell behavior, aneurysms treatments and compatibility of cardiovascular implants novel copper intercalated polyurethane heparin/poly-L-lysine chelates treated stent has established in this report. The functional group modifications, structural characteristics, and stability of the chelates have investigated for polyurethane heparin: poly-L-lysine, copper intercalated polyurethane heparin/poly-L-lysine coated stents. The FTIR results showed the copper intercalation at 446 cmr and the Cu 2s peak at 932 eV from XPS also indicated that the successful coating of copper, polyurethane heparin, poly-L-lysine. The relative surface geomorphology of the chelates displayed the uniform Cu coating consisting of multilayer poly-L-lysine on the substrate. The stability and biocompatibility studies indicated the significantly enhanced performance with clot the APTT and TT periods as clotting and cell proliferation assessments. This type of composite proposes a stage on a stent external area for discerning track of vascular cell performance and aneurysms treatments with low side effects.

Downregulated MEG3 contributes to tumour progression and poor prognosis in oesophagal squamous cell carcinoma by interacting with miR-4261, downregulating DKK2 and activating the Wnt/ß-catenin signalling.

Long noncoding RNA (lncRNA) MEG3 has been widely reported to be decreased in a growing list of primary human tumours and play a key role in tumour suppression. However, there are few reports about MEG3 expression and function in oesophagal squamous cell carcinoma (ESCC). Here, we found that MEG3 expression was significantly downregulated in tumour tissues, and its low expression was associated with large tumour size, lymph node metastasis and advanced clinical stage in ESCC patients. Univariate and multivariate analyses revealed low expression of MEG3 as an independent predictor for disease-free survival and overall survival. Cell experiments showed that MEG3 inhibited ESCC cell proliferation, migration and invasion. Subsequently, miR-4261 was identified and confirmed to be the target of MEG3, and MEG3 functions, at least in part, by targeting miR-4261. Additionally, Dickkopf-2 (DKK2), a Wnt/ß-catenin signalling inhibitor, was identified to be a target of miR-4261. MEG3 interacted with miR-4261, derepressed DKK2 and blocked the Wnt/ß-catenin signalling, thereby inhibiting tumourigenesis and progression in ESCC. In vivo experiments also confirmed this conclusion. Our study for the first time elaborated the critical role of MEG3-miR-4261-DKK2-Wnt/ß-catenin signalling axis in ESCC, and MEG3 could represent a novel diagnostic and prognostic biomarker and therapeutic target in ESCC.

LINC00702/miR-4652-3p/ZEB1 axis promotes the progression of malignant meningioma through activating Wnt/ß-catenin pathway.

Long noncoding RNAs (lncRNAs) have been acknowledged as significant regulators in the progression of various cancers, including malignant meningioma. Being a newly identified lncRNA, long intergenic non-protein coding RNA 702 (LINC00702) has not been comprehensively studied in malignant meningioma. In this study, the role of LINC00702 was identified and explored in malignant meningioma. The LINC00702 expression was determined in malignant meningioma tissues and cell lines by qRT-PCR. Then the association between LINC00702 expression and the prognosis of malignant meningioma patients was analyzed by Kaplan-Meier analysis. The functional role of LINC00702 in malignant meningioma cell proliferation and migration was analyzed by loss-of function assays. Subcellular fractionation assay and FISH assay revealed the cytoplasmic localization of LINC00702. Bioinformatics analysis and mechanism experiments demonstrated that LINC00702 acted as the molecular sponge of miR-4652-3p to upregulate ZEB1 in malignant meningioma. Furthermore, high level of LINC00702 was demonstrated to be associated with the activity of Wnt/ß-catenin signaling. Moreover, miR-4652-3p and ZEB1 involved in LINC00702-mediated Wnt/ß-catenin signaling. At last, rescue assays revealed that miR-4652-3p and ZEB1 attenuated LINC00702-mediated cell proliferation and migration.

RETRACTED: MiR-29b aggravates lipopolysaccharide-induced endothelial cells inflammatory damage by regulation of NF-κB and JNK signaling pathways.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. The authors sent some data to the journal in response to its request but this was inconsistent with the data in the manuscript and therefore the Editor-in-Chief decided to retract the article.

MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1.

Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively. The direct interaction between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of FoxM1, Sirt1 and γH2AX were measured by western blot assay. We found that miR-320 expression was down-regulated and FoxM1 expression was up-regulated in radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression dramatically enhanced radiosensitivity, promoted apoptosis, and improved γH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter assay and western blot assay further validated that miR-320 suppressed FoxM1 expression by directly targeting 3' UTR region of FoxM1. Moreover, miR-320 inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore, overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase of radiosensitivity, apoptosis and γH2AX expression in glioma cells. In conclusion, miR-320 enhanced radiosensitivity of glioma cells through down-regulation of Sirt1 by directly targeting FoxM1.

Knockdown of LncRNA ANRIL suppresses cell proliferation, metastasis, and invasion via regulating miR-122-5p expression in hepatocellular carcinoma.

OBJECTIVE: Previous studies reported that lncRNA antisense non-coding RNA in the INK4 locus (ANRIL) was upregulated in hepatocellular carcinoma (HCC) tissues and decreased expression of ANRIL could suppress cell proliferation, metastasis, and invasion and induce apoptosis of HCC cells. However, the molecular mechanism of ANRIL involved in HCC tumorigenesis is still unknown. METHODS: The expressions of ANRIL and miR-122-5p in HCC tissues and cells were quantified by qRT-PCR. MTT assay, colony formation assay, wound healing assay, and transwell invasion assay were performed to evaluate cell growth, metastasis, and invasion, respectively. RNA immunoprecipitation (RIP) assay and luciferase reporter assay were performed to determine whether ANRIL could directly bind to miR-122-5p in HCC cells. Xenograft tumor experiment was conducted to confirm the biological role and underlying mechanism of ANRIL in vivo. RESULTS: The results showed that ANRIL was upregulated and miR-122-5p was downregulated in HCC tissues and cells. ANRIL was negatively correlated with miR-122-5p expression in HCC tissues. Knockdown of ANRIL or miR-122-5p overexpression suppressed HCC cell viability, colony formation ability, metastasis, and invasion. ANRIL was demonstrated to directly bind to miR-122-5p and inhibit its expression. Forced expression of ANRIL abolished the inhibitory effect of miR-122-5p overexpression on HCC progression. In vivo experiment demonstrated that ANRIL knockdown impeded tumor growth in vivo and increased miR-122-5p expression. CONCLUSION: Our finding suggested that knockdown of ANRIL suppressed cell proliferation, metastasis and invasion via regulating miR-122-5p expression in HCC, illustrating the underlying mechanism of the oncogenic role of ANRIL in HCC.

MicroRNA-29a inhibits proliferation and motility of schwannoma cells by targeting CDK6.

MicroRNA-29 (miR-29) family is involved in various types of cancer regulation. Although miR-29 family was shown to play an inhibitory role in tumorigenesis, the effect of miR-29a expression on schwannoma cells still remains unclear. In this study, we aimed to explore the role of miR-29 family in schwannoma. The expressions of miR-29a, miR-29b, and miR-29c were detected in the Schwann tissues and cell lines using qRT-PCR. The effect of miR-29a, miR-29b, and miR-29c on cell viability, migration, invasion, and apoptosis was tested. Then, the regulatory relationship between miR-29a and CKD6 was detected using qRT-PCR, Western blot, and luciferase assay. Finally, the phosphorylation levels of mainly factors in JNK and p38MAPK/ERK pathways were analyzed by Western blot. The expression of miR-29a, miR-29b, and miR-29c was downregulated in Schwann tissues and cell lines. Cell viability, migration, invasion were decreased, while apoptosis was increased when miR-29a, miR-29b, and miR-29c overexpression. We further found that miR-29a negatively regulated expression of CDK6. Then, knockdown of miR-29a promoted cell viability, migration, invasion, and inhibited apoptosis in schwannoma cells by upregulating CDK6 expression. In addition, the overexpression of miR-29a downregulated CDK6 expression by deactivation of JNK and p38MAPK/ERK pathways. Our data suggested that miR-29a could play an important role in inhibiting proliferation and motility of cancerous Schwann cells, and may suppress tumor growth through upregulation of CDK6.

Discovery and mechanism of action of Novel Baicalein modified derivatives as potent antihepatitis agent.

Anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells by novel Baicalein derivatives. The result showed that compounds 4k and 4h was found to be effective anti-HBV agent. Further, the effect of compounds 4k and 4h showed dose-dependent inhibition of HBV-DNA as compared to control together with significant inhibition of HbeAG and HbsAG expression in the tested dose. Both compounds showed considerable affinity against the HepG2.2.15 cells. Moreover, the docking study of compound 4k was carried out with HLA molecule showing excellent intermolecular interactions with the receptor via creation of numerous bonds with Ser5, Thr27, Asp29 and Phe8. The compound 4k showed significant effect on the HO-1 expression in HepG2.2.15 cells together with excellent anti-HBV activity in transgenic mouse confirmed by biochemical and histopathological parameters. Compound 4k also showed excellent pharmacokinetic profile in experimental animal and thus, provide a novel class of potent anti-HBV agents.

A Case-Control Study of Risk Factors of Abdominal Aortic Aneurysm.

OBJECTIVE: To explore the potential risk factors of abdominal aortic aneurysm (AAA) in the Chinese population. METHODS: A matched case-control study was designed for the study. Patients with AAA administrated in the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2007 were included in the study. Sex and age-matched volunteers were selected for the case-control in the same period. A uniform questionnaire was sent to patients and volunteers to collect demographic data, past medical history, and behavioral factors. General physical examination, ultrasound examination of the abdominal aorta, and serological testing were used to collect clinical data. Environmental risk factors of abdominal aortic aneurysms were analyzed by conditional logistic regression. RESULTS: A total of 465 subjects including 155 patients were enrolled in the study. Multivariate regression analysis found that people with high blood pressure have high risk of AAA (OR = 1.88, 95% CI 1.12-3.18; P = .02). Smoking is a significant independent risk factor for AAA; the morbidity of AAA in smokers is 5.23-fold of non-smokers (95% CI 2.44-11.23). Dyslipidemia (OR = 2.61, 95% CI 1.45-4.70), serum high sensitivity C-reactive protein (OR = 2.43, 95% CI 1.37-4.31), and homocysteine (OR = 2.73, 95% CI 1.61-4.65) were valuable parameters in detecting AAA. CONCLUSION: Hypertension and smoking are risk factors of abdominal aortic aneurysms; dyslipidemia, high-sensitivity C-reactive protein, and homocysteine levels are associated with AAA.

Flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy of small (≤3 cm) pulmonary lesions.

BACKGROUND: Nowadays, flat detector (FD) equipped angiographic C-arm computed tomography (CACT) systems can be used to acquire CT-like cross-sectional images directly within the interventional suite. The CACT systems offer real time visualization of transthoracic needle biopsy (TNB) procedure and more flexibility in the orientation of the detector system around the patient compared to traditional CT systems. PURPOSE: To evaluate the value of a flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy (PTNB) for small (≤3 cm) pulmonary lesions in clinical practice. MATERIAL AND METHODS: A total of 60 patients with solid lung lesions were retrospectively enrolled to undergo PTNB procedures. The mean diameter of lesions was 2.3 ± 0.6 cm (range, 0.6-3 cm). The needle path was carefully planned and calculated on the C-arm CT system, which acquired three-dimensional CT-like cross-sectional images. The PTNB procedures were performed under needle guidance with fluoroscopic feedbacks. RESULTS: Histopathologic tissue was successfully obtained from 59 patients with a puncture success rate of 98.3% (59/60). The diagnostic accuracy rate was found to be 91.5% (54/59). There were only two cases of pneumothorax (3.3%) requiring therapy. The rates of pneumothorax and hemoptysis were low (15.0% [9/60] and 8.3% [5/60], respectively). The overall procedural time was in the range of 12-18 min, resulting in a mean exposure dose of 224.4 ± 4.8 mGy. CONCLUSION: Our study shows that C-arm CT-based needle guidance enables reliable and efficient needle positioning and progression by providing real-time intraoperative guidance for small (≤3 cm) pulmonary lesions in clinical practice.

Flat detector C-arm CT-guided transthoracic needle biopsy of small (≤2.0 cm) pulmonary nodules: diagnostic accuracy and complication in 100 patients.

PURPOSE: This study aimed at assessing the usefulness of flat detector cone-beam CT virtual navigation-guided transthoracic needle biopsy of small (≤2.0 cm) pulmonary nodules in terms of diagnostic accuracy and complications to evaluate the diagnostic performance and complications of small pulmonary nodules under cone-beam CT (CBCT) guidance. MATERIALS AND METHODS: A total of 100 patients with 100 solid lung nodules were retrospectively enrolled to undergo transthoracic needle biopsy (TNB) procedures. The mean diameter of lesions was 1.25 cm ± 0.39 (range 0.50-2.00 cm). The needle path was carefully planned and calculated on the CBCT virtual navigation guidance system, which acquired 3D CT-like cross-sectional images. Diagnostic performance, complication rate, and patient radiation exposure were investigated. RESULTS: The technical success rate of TNB under iGuide CBCT virtual navigation system was 99% (99/100). The sensitivity, specificity, and accuracy of TNB of small nodules under iGuide CBCT virtual navigation guidance were 98.7% (77/78), 90.5% (19/21), and 97.0% (96/99), respectively. The number of pleural passages with coaxial needle, biopsies, and CBCT acquisitions were 1.09 ± 0.32, 1.20 ± 0.47, and 3.06 ± 1.35, respectively. Complications occurred in 22 (22%) cases. The mean total procedure time was 12.84 min ± 3.74, resulting in a mean exposure dose of 7.6 mSv ±3.1. CONCLUSIONS: Flat detector Cone-beam CT-guided TNB is a highly accurate and safe diagnostic method for small (≤2.0 cm) lung nodule.

[Clinical efficacy of malignant obstructive jaundice treated by domestic biliary metallic stent insertion].

OBJECTIVE: To evaluate the clinical efficacy of implanted biliary metallic stents in the management of malignant obstructive jaundice (MOJ). METHODS: Percutaneous transhepatic cholangiography and stent insertion were performed in 241 consecutive patients to treat malignant biliary obstruction between December 1998 and February 2009. The study end point was patient death. All patients were followed-up until death or until February 2010. The therapeutic efficacy was determined by statistical analysis of life span and pre- and post-operative laboratory indices. RESULTS: All 241 patients were successfully stented. The level of bilirubin descended obviously within four weeks of implantation (P less than 0.05), and the early mortality rate was 4.56% (11/241). Two-hundred-and-two patients were followed-up (range: 8-193 weeks post-transplantation) and showed a median survival of 43.55 weeks. The survival rates at 13, 26, 39 and 52 weeks post-transplantation were 87%, 66%, 56%, and 41%, respectively. The stent patency rates at 13, 26, 39 and 52 weeks post-transplantation were 70%, 46%, 36% and 24%, respectively; the mean stent patency was 27.57 weeks. Cox regression analysis identified the strong predictors of improved survival as an initial bilirubin level of less than 221 mumol/L (P = 0.01) and a stent-induced bilirubin reduction of more than 50% (P = 0.002). CONCLUSION: Transhepatic metallic biliary stenting is a safe and effective therapeutic intervention for malignant biliary obstruction. Significant periods of survival and palliation of jaundice can be achieved with this method. Hyperbilirubinemia and a stent-induced bilirubin reduction of less than 50% are independent predictive factors for the survival of MOJ patients.

Norepinephrine regulates arginine vasopressin secretion in hypothalamic paraventricular nucleus relating with pain modulation.

Our previous study has pointed that arginine vasopressin (AVP) and norepinephrine (NA) are two most important bioactive substances that play a role in hypothalamic paraventricular nucleus (PVN) regulating pain process. The communication was designed to investigate the interaction between AVP and NA in the rat PVN during the pain process. We used the potassium iontophoresis inducing tail-flick to test the pain threshold, PVN push-pull perfusion to collect the samples, high performance chromatography (HPLC) to determine the NA concentration and radioimmunoassay (RIA) to measure the AVP concentration. The results showed that (1) pain stimulation increased both NA and AVP concentrations in the PVN perfusion liquid; (2) PVN administration of l-glutamate sodium increased AVP, not NA concentration in the PVN perfusion liquid; (3) AVP or d(CH(2))(5)Tyr(Et)DAVP (AVP-receptor antagonist) neither changed pain threshold, nor influenced NA concentration in the PVN perfusion liquid; (4) Microinjection of NA into PVN could increase pain threshold in a dose-dependent manner, while PVN administration with phentolamine (alpha-receptor antagonist), not propranolol (beta-receptor antagonist) decreased pain threshold; (5) Administration of NA increased AVP concentration, while phentolamine, not propranolol decreased AVP concentration in the PVN perfusion liquid. These data suggested that it is through alpha-receptor rather than beta-receptor, NA induced PVN secretion of AVP that was delivered to the related brain regions to participate in pain modulation.

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the nucleus raphe magnus to participate in pain modulation.

Hypothalamic paraventricular nucleus (PVN) is one of the main sources of arginine vasopressin (AVP) synthesis and secretion. AVP is the most important bioactive substance in PVN regulating pain process. Our previous study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation. The present study was designed to investigate the source of AVP in the rat NRM during pain process using the methods of nucleus push-pull perfusion and radioimmunoassay. The results showed that pain stimulation increased the AVP concentration in the NRM perfusion liquid, PVN cauterization inhibited the role that pain stimulation induced the increase of AVP concentration in the NRM perfusion liquid, and PVN microinjection of L-glutamate sodium, which excited the PVN neurons, could increase the AVP concentration in the NRM perfusion liquid. The data suggested that AVP in the PVN might be transferred to the NRM to participate in pain modulation.

Arginine vasopressin antinociception in the rat nucleus raphe magnus is involved in the endogenous opiate peptide and serotonin system.

Arginine vasopressin (AVP) in the nucleus raphe magnus (NRM) has been implicated in antinociception. This communication was designed to investigate which neuropeptide and neurotransmitter are involved in AVP antinociception in the rat NRM. The results showed that (1) in the NRM perfuse liquid, pain stimulation could increase the concentrations of AVP, leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), beta-endorphin (beta-Ep), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), but not change the concentrations of dynorphinA(1-13) (DynA(1-13)), oxytocin, achetylcholine, choline, gamma-aminobutyric acid, glutamate, dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, norepinephrine and epinephrine; (2) in the NRM perfuse liquid, AVP increased the concentrations of L-Ek, M-Ek, beta-Ep, DynA(1-13), 5-HT and 5-HIAA, but did not change the concentrations of oxytocin and the other studied neurotransmitters; (3) AVP antinociception in the NRM was attenuated by cypoheptadine (a 5-HT-receptor antagonist) or naloxone (an opiate receptor antagonist), but was not influenced by the other studied receptor antagonists. The data suggested that AVP antinociception in the NRM might be involved in endogenous opiate peptide and 5-HT system.