Gradient high performance liquid chromatography method for simultaneous determination of ilaprazole and its related impurities in commercial tablets

AbstractA methodology (HPLC) proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated. The chromatographic separation was carried out by gradient elution using an Agilent C8 column (4.6 mm × 250 mm, 5 μm) which was maintained at 25 °C. The mobile phase composed of solvent A (methanol) and solvent B (solution consisting 0.02 mmol/l monopotassium phosphate and 0.025 mmol/l sodium hydroxide) was at a flow rate of 1.0 ml/min. The samples were detected and quantified at 237 nm using an ultraviolet absorbance detector. Calibration curves of all analytes from 0.5 to 3.5 μg/ml were good linearity (r ≥ 0.9990) and recovery was greater than 99.5% for each analyte. The lower limit of detection (LLOD) and quantification (LOQ) of this analytical method were 10 ng/ml and 25 ng/ml for all impurities, respectively. The stress studies indicated that the degradation products could not interfere with the detection of ilaprazole and its related impurities and the assay can thus be considered stability-indicating. The method precisions were in the range of 0.41–1.21 while the instrument precisions were in the range of 0.38–0.95 in terms of peak area RSD% for all impurities, respectively. This method is considered stability-indicating and is applicable for accurate and simultaneous measuring of the ilaprazole and its related impurities in commercial enteric-coated tablets

The Improvement of Hyperglycemia after RYGB Surgery in Diabetic Rats Is Related to Elevated Hypothalamus GLP-1 Receptor Expression

Objectives. This study aimed to explore the expression of GLP-1 receptor in hypothalamus and gastrointestinal tissues after Roux-en-Y gastric bypass (RYGB) surgery in diabetic rats. Methods. Male 12-week-old Wistar rats (control) and Goto-Kakizaki rats (diabetic) were randomly divided into two groups, respectively: control sham surgery group (C), control RYGB group (C + R), diabetic sham surgery group (D), and diabetic RYGB group (D + R). Body weight and blood glucose were monitored before and after surgery every week. Eight weeks after surgery, all rats were sacrificed and the serum fasting GLP-1 concentrations were measured by ELISA. GLP-1R and DPP-4 expression in hypothalamus and ileum were measured by RT-PCR. Results. The body weight and fasting/random blood glucose in the D + R group decreased significantly compared with the D group (P<0.05). Serum GLP-1 levels in diabetic rats treated with RYGB were higher than the corresponding sham surgery rats. The expression of GLP-1R of hypothalamus in RYGB-treated diabetic rats was significantly higher than those of the sham surgery diabetic rats and both control group rats (P<0.05). We found a negative correlation between hypothalamus GLP-1R mRNA and blood glucose level. No significant difference was seen in ileum GLP-1R and DPP-4 expression among all groups. Conclusions. RYGB efficiently promoted serum GLP-1 levels and the expression of GLP-1 receptor in the hypothalamus in diabetic rats. These data suggest that the hypothalamus GLP-1R may play an important role in the GLP-1 system for improving glucose homeostasis after reconstruction of the gastrointestinal tract

A novel predictive model for the recurrence of pediatric alopecia areata by bioinformatics analysis and a single-center prospective study

BackgroundAlopecia areata (AA) is a disease featured by recurrent, non-scarring hair loss with a variety of clinical manifestations. The outcome of AA patients varies greatly. When they progress to the subtypes of alopecia totalis (AT) or alopecia universalis (AU), the outcome is unfavorable. Therefore, identifying clinically available biomarkers that predict the risk of AA recurrence could improve the prognosis for AA patients.MethodsIn this study, we conducted weighted gene co-expression network analysis (WGCNA) and functional annotation analysis to identify key genes that correlated to the severity of AA. Then, 80 AA children were enrolled at the Department of Dermatology, Wuhan Children’s Hospital between January 2020 to December 2020. Clinical information and serum samples were collected before and after treatment. And the serum level of proteins coded by key genes were quantitatively detected by ELISA. Moreover, 40 serum samples of healthy children from the Department of Health Care, Wuhan Children’s Hospital were used for healthy control.ResultsWe identified four key genes that significantly increased (CD8A, PRF1, and XCL1) or decreased (BMP2) in AA tissues, especially in the subtypes of AT and AU. Then, the serum levels of these markers in different groups of AA patients were detected to validate the results of bioinformatics analysis. Similarly, the serum levels of these markers were found remarkedly correlated with the Severity of Alopecia Tool (SALT) score. Finally, a prediction model that combined multiple markers was established by conducting a logistic regression analysis.ConclusionIn the present study, we construct a novel model based on serum levels of BMP2, CD8A, PRF1, and XCL1, which served as a potential non-invasive prognostic biomarker for forecasting the recurrence of AA patients with high accuracy

Albumin Binding Function: The Potential Earliest Indicator for Liver Function Damage

Background. Currently there is no indicator that can evaluate actual liver lesion for early stages of viral hepatitis, nonalcoholic fatty liver disease (NAFLD), and cirrhosis. Aim of this study was to investigate if albumin binding function could better reflect liver function in these liver diseases. Methods. An observational study was performed on 193 patients with early NAFLD, viral hepatitis, and cirrhosis. Cirrhosis patients were separated according to Child-Pugh score into A, B, and C subgroup. Albumin metal ion binding capacity (Ischemia-modified albumin transformed, IMAT) and fatty acid binding capacity (total binding sites, TBS) were detected. Results. Both IMAT and TBS were significantly decreased in patients with NAFLD and early hepatitis. In hepatitis group, they declined prior to changes of liver enzymes. IMAT was significantly higher in cirrhosis Child-Pugh class A group than hepatitis patients and decreased in Child-Pugh class B and class C patients. Both IMAT/albumin and TBS/albumin decreased significantly in hepatitis and NAFLD group patients. Conclusions. This is the first study to discover changes of albumin metal ion and fatty acid binding capacities prior to conventional biomarkers for liver damage in early stage of liver diseases. They may become potential earliest sensitive indicators for liver function evaluation

Anti-tat Hutat2:Fc mediated protection against tat-induced neurotoxicity and HIV-1 replication in human monocyte-derived macrophages

Background: HIV-1 Tat is essential for HIV replication and is also a well-known neurotoxic factor causing HIV-associated neurocognitive disorder (HAND). Currently, combined antiretroviral therapy targeting HIV reverse transcriptase or protease cannot prevent the production of early viral proteins, especially Tat, once HIV infection has been established. HIV-infected macrophages and glial cells in the brain still release Tat into the extracellular space where it can exert direct and indirect neurotoxicity. Therefore, stable production of anti-Tat antibodies in the brain would neutralize HIV-1 Tat and thus provide an effective approach to protect neurons. Methods: We constructed a humanized anti-Tat Hutat2:Fc fusion protein with the goal of antagonizing HIV-1 Tat and delivered the gene into cell lines and primary human monocyte-derived macrophages (hMDM) by an HIV-based lentiviral vector. The function of the anti-Tat Hutat2:Fc fusion protein and the potential side effects of lentiviral vector-mediated gene transfer were evaluated in vitro. Results: Our study demonstrated that HIV-1-based lentiviral vector-mediated gene transduction resulted in a high-level, stable expression of anti-HIV-1 Tat Hutat2:Fc in human neuronal and monocytic cell lines, as well as in primary hMDM. Hutat2:Fc was detectable in both cells and supernatants and continued to accumulate to high levels within the supernatant. Hutat2:Fc protected mouse cortical neurons against HIV-1 Tat86-induced neurotoxicity. In addition, both secreted Hutat2:Fc and transduced hMDM led to reducing HIV-1BaL viral replication in human macrophages. Moreover, lentiviral vector-based gene introduction did not result in any significant changes in cytomorphology and cell viability. Although the expression of IL8, STAT1, and IDO1 genes was up-regulated in transduced hMDM, such alternation in gene expression did not affect the neuroprotective effect of Hutat2:Fc. Conclusions: Our study demonstrated that lentivirus-mediated gene transfer could efficiently deliver the Hutat2:Fc gene into primary hMDM and does not lead to any significant changes in hMDM immune-activation. The neuroprotective and HIV-1 suppressive effects produced by Hutat2:Fc were comparable to that of a full-length anti-Tat antibody. This study provides the foundation and insights for future research on the potential use of Hutat2:Fc as a novel gene therapy approach for HAND through utilizing monocytes/macrophages, which naturally cross the blood-brain barrier, for gene delivery. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0195-2) contains supplementary material, which is available to authorized users

Discovery and biosynthetic investigation of a new antibacterial dehydrated non‐ribosomal tripeptide

Acknowledgement: QF and HD are grateful to the University of Aberdeen Elphinstone Scholarship and Scottish Funding Council/ScotCHEM (PEER/PERCE) for financial support. HD, ZL and SW thank the financial supports of Biotechnology and Biological Sciences Research Council UK (BBSRC, BB/P00380X/1) and the Royal Society-NSFC Newton Mobility Grant Award (IEC\NSFC\170617 to HD). HD, SAM and CP thank Business Interaction Vouchers (BIV009) from BBSRC funded Natural Products discovery and bioengineering Network (NPRONET). Y.G. thanks NSFC oversea scholarship, Natural Science Foundation of Jiangsu Province (BK20170450), and the Open Research fund of Jiangsu Key Laboratory of Marine Biotechnology (HS2017003).Peer reviewedPostprin

Enhancement of two photon processes in quantum dots embedded in subwavelength metallic gratings

We show a large enhancement of two-photon absorption processes in nanocrystal quantum dots and of light upconversion efficiency from the IR to the near-IR spectral regime, using a hybrid optical device in which near-IR emitting InAs quantum dots were embedded on top a metallic nanoslit array. The resonant enhancement of these nonlinear optical processes is due to the strong local electromagnetic field enhancements inside the nanoslit array structure at the extraordinary transmission resonances. A maximal two-photon absorption enhancement of more than 20 was inferred. Different high field regions were identified for different polarizations, which can be used for designing and optimizing efficient nonlinear processes in such hybrid structures. Combining nanocrystal quantum dots with subwavelength metallic nanostructures is therfore a promising way for a range of possible nonlinear optical devices.Comment: 14 pages, 7 figure

Phylogenetic analysis of porcine parvoviruses from swine samples in China

<p>Abstract</p> <p>Background</p> <p>Porcine parvovirus (PPV) usually causes reproductive failure in sows. The objective of the present study was to analyze the phylogenetic distribution and perform molecular characterization of PPVs isolated in China, as well as to identify two field strains, LZ and JY. The data used in this study contained the available sequences for NS1 and VP2 from GenBank, as well as the two aforementioned Chinese strains.</p> <p>Results</p> <p>Phylogenetic analysis shows that the PPV sequences are divided into four groups. The early Chinese PPV isolates are Group I viruses, and nearly all of the later Chinese PPV isolates are Group II viruses. LZ belongs to group II, whereas the JY strain is a Group III virus. This is the first report on the isolation of a Group III virus in China. The detection of selective pressures on the PPV genome shows that the NS1 and VP2 genes are under purifying selection and positive selection, respectively. Moreover, the amino acids in the VP2 capsid are highly variable because of the positive selection.</p> <p>Conclusions</p> <p>Our study provides new molecular data on PPV strains in China, and emphasizes the importance of etiological studies of PPV in pigs.</p