IQMNMR: Open source software using time-domain NMR data for automated identification and quantification of metabolites in batches

<p>Abstract</p> <p>Background</p> <p>One of the most promising aspects of metabolomics is metabolic modeling and simulation. Central to such applications is automated high-throughput identification and quantification of metabolites. NMR spectroscopy is a reproducible, nondestructive, and nonselective method that has served as the foundation of metabolomics studies. However, the automated high-throughput identification and quantification of metabolites in NMR spectroscopy is limited by severe spectral overlap. Although numerous software programs have been developed for resolving overlapping resonances, as well as for identifying and quantifying metabolites, most of these programs are frequency-domain methods, considerably influenced by phase shifts and baseline distortions, and effective only in small-scale studies. Almost all these programs require multiple spectra for each application, and do not automatically identify and quantify metabolites in batches.</p> <p>Results</p> <p>We created IQMNMR, an R package that integrates a relaxation algorithm, digital filter, and similarity search algorithm. It differs from existing software in that it is a time-domain method; it uses not only frequency to resolve overlapping resonances but also relaxation time constants; it requires only one NMR spectrum per application; is uninfluenced by phase shifts and baseline distortions; and most important, yields a batch of quantified metabolites.</p> <p>Conclusions</p> <p>IQMNMR provides a solution that can automatically identify and quantify metabolites by one-dimensional proton NMR spectroscopy. Its time-domain nature, stability against phase shifts and baseline distortions, requirement for only one NMR spectrum, and capability to output a batch of quantified metabolites are of considerable significance to metabolic modeling and simulation.</p> <p>IQMNMR is available at <url>http://cran.r-project.org/web/packages/IQMNMR/</url>.</p

Influence of different processing times on the quality of Polygoni Multiflora Radix by metabolomics based on ultra high performance liquid chromatography with quadrupole timeâ ofâ flight mass spectrometry

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136757/1/jssc5378_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136757/2/jssc5378.pd

Invasive reperfusion after 12 hours of the symptom onset remains beneficial in patients with ST-segment elevation myocardial infarction: Evidence from a meta-analysis of published data

Background: Early myocardial reperfusion therapy (&lt; 12 h) in patients with acute myocardial infarc­tion (AMI) can significantly improve their prognosis. However, the effect of late reperfusion (&gt; 12 h) remains controversial. In this study, the effects of late reperfusion versus standard drug therapy on the outcomes of patients with AMI were evaluated by systematic review and meta-analysis. Methods: PubMed, Embase, Medline, Cochrane, Wanfang, and CNKI databases were searched for eligible studies for the present study. Meta-analysis was performed using RevMan 5.3.3 software. Rela­tive risk (RR) and the 95% confidence interval (CI) were used to compare the outcomes between the two groups. The main outcome measures were major adverse cardiac events (MACEs), all-cause mortality, recurrent myocardial infarction (MI), and heart failure. Results: Eighteen studies were identified including 14,677 patients, of whom 5157 received late reperfusion with percutaneous coronary intervention (PCI) and 9520 received medication therapy (MT). Compared to MT, late PCI was associated with decreased all-cause mortality (RR 0.60, 95% CI 0.44–0.83; p = 0.002), MACEs (RR 0.67; 95% CI 0.50–0.89; p &lt; 0.001), and heart failure (RR 0.76; 95% CI 0.60–0.97; p = 0.03), while there was also a trend toward decreased recurrent MI (RR 0.70; 95% CI 0.47–1.05; p = 0.08). However, subgroup analysis according to time to PCI showed that the clinical benefit was only from PCI after 12 h but not from 2 to 60 days of the onset of symptoms. Conclusions: The present meta-analysis suggested that PCI performed &gt; 12 h but not 2–60 days after AMI is associated with significant improvement in clinical outcomes. However, these results need further rigorously designed large sample size clinical trials to be validated

Identification of subtype-specific metastasis-related genetic signatures in sarcoma

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma

Erzhi Pill® Repairs Experimental Liver Injury via TSC/mTOR Signaling Pathway Inhibiting Excessive Apoptosis

The present study aimed to investigate the mechanism of hepatoprotective effect of Erzhi Pill (EZP) on the liver injury via observing TSC/mTOR signaling pathway activation. The experimental liver injury was induced by 2-acetylaminofluorene (2-AAF) treatment combined with partial hepatectomy (PH). EZP treated 2-AAF/PH-induced liver injury by the therapeutic and prophylactic administration. After the administration of EZP, the activities of aspartic transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and gamma-glutamyl transpeptidase (γ-GT) were decreased, followed by the decreased levels of hepatocyte apoptosis and caspase-3 expression. However, the secretion of albumin, liver weight, and index of liver weight were elevated. Microscopic examination showed that EZP restored pathological liver injury. Meanwhile, Rheb and mammalian target of rapamycin (mTOR) activation were suppressed, and tuberous sclerosis complex (TSC) expression was elevated in liver tissues induced by 2-AAF/PHx and accompanied with lower-expression of Bax, Notch1, p70S6K, and 4E-EIF and upregulated levels of Bcl-2 and Cyclin D. Hepatoprotective effect of EZP was possibly realized via inhibiting TSC/mTOR signaling pathway to suppress excessive apoptosis of hepatocyte

Isolation, identification, and complete genome sequence of a bovine adenovirus type 3 from cattle in China

<p>Abstract</p> <p>Background</p> <p>Bovine adenovirus type 3 (BAV-3) belongs to the <it>Mastadenovirus </it>genus of the family <it>Adenoviridae </it>and is involved in respiratory and enteric infections of calves. The isolation of BAV-3 has not been reported prior to this study in China. In 2009, there were many cases in cattle showing similar clinical signs to BAV-3 infection and a virus strain, showing cytopathic effect in Madin-Darby bovine kidney cells, was isolated from a bovine nasal swab collected from feedlot cattle in Heilongjiang Province, China. The isolate was confirmed as a bovine adenovirus type 3 by PCR and immunofluorescence assay, and named as HLJ0955. So far only the complete genome sequence of prototype of BAV-3 WBR-1 strain has been reported. In order to further characterize the Chinese isolate HLJ0955, the complete genome sequence of HLJ0955 was determined.</p> <p>Results</p> <p>The size of the genome of the Chinese isolate HLJ0955 is 34,132 nucleotides in length with a G+C content of 53.6%. The coding sequences for gene regions of HLJ0955 isolate were similar to the prototype of BAV-3 WBR-1 strain, with 80.0-98.6% nucleotide and 87.5-98.8% amino acid identities. The genome of HLJ0955 strain contains 16 regions and four deletions in inverted terminal repeats, E1B region and E4 region, respectively. The complete genome and DNA binding protein gene based phylogenetic analysis with other adenoviruses were performed and the results showed that HLJ0955 isolate belonged to BAV-3 and clustered within the <it>Mastadenovirus </it>genus of the family <it>Adenoviridae</it>.</p> <p>Conclusions</p> <p>This is the first study to report the isolation and molecular characterization of BAV-3 from cattle in China. The phylogenetic analysis performed in this study supported the use of the DNA binding protein gene of adenovirus as an appropriate subgenomic target for the classification of different genuses of the family <it>Adenoviridae </it>on the molecular basis. Meanwhile, a large-scale pathogen and serological epidemiological investigations for BVA-3 infection might be carried out in cattle in China. This report will be a good beginning for further studies on BAV-3 in China.</p

Baicalein inhibits acinar-to-ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC

Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders

ObjectiveThis study is to investigate the diagnostic yield of the combination of trio whole exome sequencing (Trio-WES) and copy number variation sequencing (CNVseq) for rare neurodevelopmental disorders (NDDs).MethodsClinical data from consecutive pediatric patients who were diagnosed with rare NDDs that were suspected to be monogenic disorders, who were admitted to our hospital from April 2017 to March 2019, and who underwent next generation sequencing (NGS) were extracted from the medical records. Patients for whom Trio-WES and CNVseq data were available were enrolled in this study. Sanger sequencing was applied for the validation of the variants identified by Trio-WES. Sequence alignment and structural modeling were conducted for analyzing the possibility of the variants in the onset of the NDDs.ResultsIn total, 54 patients were enrolled in this study, with the median age of 15 (8–26) months. A total of 242 phenotypic abnormalities belonging to 20 different systems were identified in the cohort. Twenty-four patients were diagnosed by Trio-WES, eight patients were diagnosed by CNVseq, and one case was identified by both WES and CNVseq. Compared with Trio-WES, the diagnosis rate of Trio-WES accompanied by CNVseq was significantly higher (P = 0.016). Trio-WES identified 36 variants in 26 different genes, among which 27 variants were novel. CNVseq detected four duplications and eight deletions, ranging from 310 kb to 23.27 Mb. Our case examples demonstrated the high heterogeneity of NDDs and showed the challenges of rare NDDs for physicians.ConclusionThe significantly higher diagnosis rate of Trio-WES accompanied by CNVseq makes this strategy a potential alternative to the most widely used approaches for pediatric children with rare and undiagnosed NDDs