SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation.

To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1ß was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor-α (TNF-α) and IL-6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation-specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O-Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL-1ß-induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL-1ß-induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke. Methods: We performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results: A total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 µg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years. Conclusions: Administration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

The correlation between rs2501577 gene polymorphism and biliary atresia: a systematic review and meta-analysis.

IMPORTANCE: Multiple studies indicate a possible correlation between ADD3 rs2501577 and biliary atresia susceptibility; however, a conclusive determination has yet to be made. OBJECTIVE: Investigate the role of ADD3 rs2501577 in biliary atresia susceptibility across diverse populations. DATA SOURCES: The study protocol has been registered on PROSPERO, an international platform for systematic review registration (PROSPERO ID: CRD42023384641). The following databases will be searched until February 1, 2023: PubMed, Embase, Cochrane, CBM, Web of Science, and CNKI. STUDY SELECTION: Eight studies were selected from seven papers to assess the data. A total of 7651 participants were included, consisting of 1662 in the BA group and 5989 in the NC group. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed while conducting the systematic reviews and meta-analyses. Two authors independently assessed the quality of the included studies using the Newcastle-Ottawa Quality Assessment Scale. The significance of the pooled odds ratio (OR) was evaluated with a Z test, and statistical heterogeneity across studies was assessed using the I2 and Q statistics. Publication bias was assessed using Egger's and Begg's tests. MAIN OUTCOME(S) AND MEASURE(S): The primary study outcome was the development of biliary atresia. Subgroup analysis was performed based on race, region, and assessment of Hardy-Weinberg equilibrium (HWE). RESULTS: The studies indicate that the ADD3 rs2501577 susceptibility locus increases the risk of developing biliary atresia, regardless of allelic, homozygote, dominant, and recessive gene inheritance models. Furthermore, ADD3 has been found to be associated with apoptosis, cell cycle, and cell damage repair based on functional analysis. CONCLUSIONS AND RELEVANCE: The ADD3 rs2501577 polymorphic locus is associated with an increased risk of biliary atresia, particularly in Asian populations. This study recommends further investigation of the ADD3 rs2501577 locus in Asian populations to validate its role in the diagnosis of biliary atresia.

Bistable Optoelectronic Properties Originated from the Scissoring Motion of the TEMPO Skeleton in Supramolecular Radical Ferroelectrics.

Bistable materials with multiphysical channels, such as optical, electrical, and magnetic properties, have been paid dramatic attention due to their alternativity of the signal status in electronic devices. Herein, three stable supramolecular radicals ([(NH3-TEMPO)(18-crown-6)][XF6] (1, X = P; 2, X = As; 3, X = Sb)) were synthesized and characterized. The former two molecules present ferroelectric phase transitions around 381.7 and 382.7 K, respectively, with bistability in dielectric property and second-harmonic generation (SHG) effect, which are first found in supramolecular radicals. Their ferroelectric transition and bistable properties are generated from a net polar crystal structure owing to the static ordered packing of NH3-TEMPO radical cations in the low-temperature phase (LTP) to a nonpolar structure owing to a distinctive symmetric scissoring motion of NH3-TEMPO radical cations between two 18-crown-6 molecules in the high-temperature phase (HTP). Both of them exhibit paramagnetic properties in HTP and LTP states since no intermolecular spin-spin interaction occurs due to the long distances among the radicals in their crystals. These results make us possible to design bistable optoelectronic radical materials with bistability in magnetic property in the future.

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer.

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Plastid Phylogenomics of Paeonia and the Evolution of Ten Flower Types in Tree Peony.

Paeonia suffruticosa Andr., a member of Paeoniaceae, is native to China. In its 1600 years' cultivation, more than 2000 cultivars for different purposes (ornamental, medicinal and oil use) have been inbred. However, there are still some controversies regarding the provenance of tree peony cultivars and the phylogenetic relationships between and within different cultivar groups. In this study, plastid genome sequencing was performed on 10 representative tree peony cultivars corresponding to 10 different flower types. Structure and comparative analyses of the plastid genomes showed that the total lengths of the chloroplast genome of the 10 cultivars ranged from 152,153 to 152,385 bp and encoded 84-88 protein-coding genes, 8 rRNAs and 31-40 tRNAs. The number of simple sequence repeats and interspersed repeat sequences of the 10 cultivars ranged from 65-68 and 40-42, respectively. Plastid phylogenetic relationships of Paeonia species/cultivars were reconstructed incorporating data from our newly sequenced plastid genomes and 15 published species, and results showed that subsect. Vaginatae was the closest relative to the central plains cultivar group with robust support, and that it may be involved in the formation of the group. Paeonia ostii was recovered as a successive sister group to this lineage. Additionally, eleven morphological characteristics of flowers were mapped to the phylogenetic skeleton to reconstruct the evolutionary trajectory of flower architecture in Paeoniaceae.

Osteopontin and its downstream carcinogenic molecules: regulatory mechanisms and prognostic value in cancer progression.

Osteopontin (OPN) is a multifunctional phosphorylated glycoprotein that is expressed at significantly elevated levels in various cancers. OPN overexpression is closely associated with the development of cancer progression such as proliferation, metastasis, angiogenesis, apoptosis resistance, drug resistance, and immunosuppression, and may also be an independent prognostic biomarker for a variety of cancers. This review broadly summarizes the mechanisms that regulate the expression of downstream oncogenic molecules after OPN binds to integrin receptors or CD44 receptors, which involve a complex intracellular "signaling traffic network" (including key kinases, signaling pathways, and transcription factors). In addition, we review the prognostic value of OPN, OPN synergistic downstream oncogenic molecules in the female breast, non-small cell lung, prostate, colorectal, gastric, and hepatocellular carcinomas. The prognostic value of OPN in tissues or blood may vary due to differences in study subjects or detection methods, and this aspect of the study requires further systematization with a view to applying the detection of OPN to clinical applications. Importantly, based on the fact that the oncogenic effect of OPN correlates with the expression of the above-mentioned oncogenic molecules, this work may provide some help in the study of combination therapy targeting OPN and the above-mentioned oncogenic molecules.

Clinical evaluation of high-resolution cone-beam computed tomography for the implantation of flow-diverter stents in intracranial aneurysms.

It is well-established that complete expansion and proper apposition to the vessel wall of flow-diverter stents are critical for optimizing endovascular aneurysm outcomes by using flow diversion techniques. We aimed to evaluate the clinical value of high-resolution cone-beam CT (HR-CBCT) upon flow-diverter stent implantation in intracranial aneurysms. In this study, we retrospectively analyzed the clinical data of eighty-one patients (101 intracranial aneurysms) who underwent flow-diverter stent implantation (Pipeline™ or Tubridge™). Images were reconstructed using conventional cone-beam CT (CBCT)(voxel size 0.43 mm isotropic) and HR-CBCT(voxel size 0.15 mm isotropic). Immediately after stent deployment, dual volume 3D fusion images were obtained from 3D-digital subtraction angiography (DSA) and HR-CBCT. The image quality for stent visualization was graded from 0 to 2 (0:not able to assess, 1:limited, but able to assess; 2:clear visualization), and the stent expansion status (full, under-expanded or poor apposition) was also recorded. Finally, patients were treated using flow-diverter stents (n = 92: 17 Pipeline and 75 Tubridge). Compared to CBCT, HR-CBCT led to improved visualization of the structures of the stents and significantly improved the image quality (mean score: 0.59 ± 0.67 vs. 1.6 ± 0.63, P < 0.001). For 28 stents (seven Pipeline and 21 Tubridge), partially incomplete apposition was observed by HR-CBCT but not by conventional CBCT and resolved by microguidewire looping dilation or balloon dilation. High-resolution cone-beam CT could better display flow-diverter stent details and yielded an improved image quality, which facilitated the assessment of stent deployment, potentially reducing the incidence of complications.

Clinical Study of High-Resolution C-Arm CT in Mechanical Recanalization and Stent Implantation for Chronic Cerebral Artery Occlusion.

Background: In recent years, among patients with chronic cerebral artery occlusion, recanalization can be achieved by an endovascular operation. However, complications and restenosis rates remain high. Objective: To evaluate the utility of high-resolution C-arm CT (Dyna micro-CT) for stent placement in patients with chronic cerebral artery occlusion. Methods and Materials: We retrospectively reviewed the clinical data of 27 patients with chronic cerebral artery occlusion who underwent mechanical recanalization and stent implantation. Images were reconstructed using conventional C-arm CT (Dyna CT) and Dyna micro-CT. Whether the stent was fully expanded and image quality was evaluated. Follow-up assessments included clinical and angiographic outcomes and complications. Results: Twenty-two patients successfully underwent stenting (22 stents; 14 cases: Neuroform EZ; eight cases: Enterprise); stenting failed in five patients. Compared to Dyna CT, Dyna micro-CT afforded improved visualization of the stent structure, providing significantly improved image quality (P < 0.05). In seven patients, the stent under-expanded and dilatation was performed; thereafter, stent malapposition improved. One patient experienced sudden headache 22 hours after the procedure; CT showed intraparenchymal hemorrhage. The remaining 21 patients did not have acute thrombosis or bleeding complications and were followed up by imaging for 3-6 months. In three patients, digital subtraction angiography showed mild in-stent stenosis. Conclusions: High-resolution C-arm CT can improve visualization of stent structures in chronic cerebral artery occlusion, making it easy to determine the extent of stent deployment and potentially reduce complications and stent restenosis.

C2-C3 Anterior Cervical Diskectomy and Fusion for Hangman's Fractures with C2 Posterior Dislocation: Technical Notes.

BACKGROUND: The overwhelming majority of hangman's fractures cause anterior dislocation of C2. Hangman's fracture with C2 posterior dislocation is extremely rare; only 1 pediatric case was reported in 2018 to date. This kind of injury cannot be cataloged using current classification schemes, and no established treatment recommendations exist. The purpose of this article is to report a rare case of a hangman's fracture with C2 posterior dislocation, which does not fit into existing classification systems and discuss management technical notes to avoid pitfalls. METHODS: We describe this case, review relevant literature, and share our experience. RESULTS: A 31-year-old male sustained a hangman's fracture with C2 posterior dislocation after he fell into a 50-cm deep roadside ditch when riding a motorcycle. Radiograph and computed tomography on admission showed fractures through both pars of C2 and C2 posterior dislocation. Magnetic resonance imaging on admission showed high T2-weighted signal intensity of cervical spinal cord and compression of the cervical spinal cord by posterior dislocation of the C2 vertebral body. A C2-3 anterior cervical diskectomy and fusion was performed. At 6 months after operation, bony fusion was achieved and magnetic resonance imaging showed the T2-weighted signal hyperintensity of cervical spinal cord before surgery disappeared. CONCLUSIONS: C2-C3 anterior cervical diskectomy and fusion is recommended for hangman's fractures with C2 posterior dislocation. Traction before surgery is not recommended.

Magnetically active terahertz wavefront control and superchiral field in a magneto-optical Pancharatnam-Berry metasurface.

Nowadays, the manipulation of the chiral light field is highly desired to characterize chiral substances more effectively, since the chiral responses of most molecules are generally weak. Terahertz (THz) waves are related to the vibration-rotational energy levels of chiral molecules, so it is significant to actively control and enhance the chirality of THz field. Here, we propose a metal/magneto-optical (MO) hybrid Pancharatnam-Berry (PB) phase structure, which can serve as tunable broadband half-wave plate and control the conversion of THz chiral states with the highest efficiency of over 80%. Based on this active PB element, MO PB metasurfaces are proposed to manipulate THz chiral states as different behaviors: beam deflector and scanning, Bessel beam, and vortex beam. Due to the magnetic-tunablibity, these proposed MO PB metasurfaces can be turned from an "OFF" to "ON" state by changing the external magnetic field. We further investigate the near-field optical chirality and the chirality enhancement factors in far field of the chiral Bessel beam and vortex beam, achieving the superchiral field with the highest chiral enhancement factor of 40 for 0th Bessel beam. These active, high efficiency and broadband chiral PB metasurfaces have promising applications for manipulation the THz chiral light and chiroptical spectroscopic techniques.

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.

Barcode signal amplifying strategy for sensitive and accurate protein detection on LC-MS/MS.

Protein drugs showing strong pharmaceutical activity, high specificity, and low toxicity and side effects have drawn extensive attention in the field of life sciences and medicine. Precise evaluation of the function of these drugs requires accurate and sensitive detection methods. Here, we report a novel chromatography-tandem mass spectrometry (LC-MS/MS) method for sensitive and selective detection of protein drugs. Magnetic nanoparticles (Apt29@MNPs) were functionalized by thrombin aptamers, and quantum dots (Apt15@ss@QDs) were dual-functionalized with quantitative thrombin aptamers and small molecules with high ionization efficiency as the mass barcode. After Apt29@MNPs specifically purify and enrich thrombin from biological samples, they can form a nano "sandwich structure" when Apt15@ss@QDs are added, resulting in the release of the mass barcode for LC-MS/MS analysis via the cutting of the disulfide bond. Since there is a higher quantitative molecular ratio of mass barcode to thrombin in the nano-"sandwich structure", quantitative detection of thrombin with high sensitivity and selectivity can be achieved via the LC-MS/MS detection of the mass barcode with high ionization efficiency rather than thrombin, which effectively avoids the disadvantages of direct protein detection by mass spectrometry. The established method for thrombin detection shows a good linear relationship in a concentration range of 0.00115-1.15 nM with a limit of detection (LOD) of 0.0007 nM. The present work provides a new approach for the effective and sensitive quantitative analysis of protein drugs and would be of great significance in promoting the development of protein drugs and clinical applications.

Repeated balloon dilatation with long-term biliary drainage for treatment of benign biliary-enteric anastomosis strictures: A STROBE-compliant article.

Percutaneous balloon dilatation for benign biliary-enteric anastomosis stricture has been the most widely used alternative to endoscopic treatment. However, patency results from the precedent literature are inconsistent.The objective of this study was to evaluate the safety and feasibility of repeated balloon dilatation with long-term biliary drainage for the treatment of benign biliary-enteric anastomosis strictures.Data from patients with benign biliary-enteric anastomosis strictures who underwent percutaneous transhepatic cholangiography (PTC), repeated balloon dilatation with long-term biliary drainage (repeated-dilatation group; n = 23), or PTC and single balloon dilatation with long-term biliary drainage (single-dilatation group; n = 26) were reviewed. Postoperative complications, jaundice remission, and sustained anastomosis patency were compared between the groups.All procedures were successful. No severe intraoperative complications, such as biliary bleeding and perforation, were observed. The jaundice remission rate in the first week was similar in the 2 groups. During the 26-month follow-up period, 3 patients in the repeated-dilatation group had recurrences (mean time to recurrence: 22.84 ±â€Š0.67 months, range: 18-26 months). In the single-dilatation group, 15 patients had recurrences (mean time to recurrence = 15.28 ±â€Š1.63 months, range: 3-18 months). The duration of patency after dilatation was significantly better in the repeated-dilatation group (P = .01). All patients with recurrence underwent repeat PTC followed by balloon dilatation and biliary drainage.Repeated balloon dilatation and biliary drainage is an effective, minimally invasive, and safe procedure for treating benign biliary-enteric anastomosis strictures, and provides significantly higher patency rates than single dilatation.

Terahertz magneto-optical effect of wafer-scale La: yttrium iron garnet single-crystal film with low loss and high permittivity.

The wafer-scale La:YIG single crystal thick films were fabricated on a three-inch gadolinium gallium garnet (GGG) substrate by liquid phase epitaxy method. The terahertz (THz) optical and magneto-optical properties of La:YIG film were demonstrated by THz time domain spectroscopy (THz-TDS). The results show that a high refractive index of approximately 4.09 and a low absorption coefficient of 10-50 cm-1 from 0.1 to 1.6 THz for this La:YIG film. Moreover, the THz Faraday rotation effect of La:YIG film was measured by the orthogonal polarization detection method in THz-TDS system, which can be actively manipulated by a weak longitudinal magnetic field of up to 0.155 T. With 5 samples stacked together, the Faraday rotation angle varies linearly from -15° to 15°, and the Verdet constant of La:YIG is about 100 °/mm/T within the saturation magnetization. This magneto-optical single crystal thick film with large area shows low loss, high permittivity and strong magneto-optical effect in the THz regime, which will be widely used in magneto-optical polarization conversion, nonreciprocal phase shifter and isolator for THz waves.

Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway.

In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTOR pathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1ß in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.

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.

Stereoselective pharmacokinetics of (R)-(+)- and (S)-(-)-rabeprazole in human using chiral LC-MS/MS after administration of rabeprazole sodium enteric-coated tablet.

Rabeprazole is an effective proton pump inhibitor to treat acid-related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC-MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 µm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid-acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 â†’ 242.2 and 346.1 â†’ 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL-1 , the intra-run precisions were below 5.4%, the inter-run precisions were below 9.9%, and the accuracy was between -9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)-(+)- and (S)-(-)-rabeprazole after oral administration of 10-mg rabeprazole sodium enteric-coated tablet in healthy Chinese subjects.