Publications by authors named "Xiang Shu"

55 Publications

Kinetic Characterization and Inhibitor Screening of Pyruvate Kinase I From .

Front Microbiol 2021 16;12:710678. Epub 2021 Sep 16.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

The apicomplexan is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC value 0.49 μM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of -cultured with IC values of 0.77, 2.10, 1.73, and 1.15 μM. Overall, the present study provides a theoretical basis for the design and development of new anti- drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.710678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481833PMC
September 2021

Integrating Genome and Methylome Data to Identify Candidate DNA Methylation Biomarkers for Pancreatic Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Sep 8. Epub 2021 Sep 8.

Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.

Background: The role of methylation in pancreatic cancer risk remains unclear. We integrated genome and methylome data to identify CpG sites (CpG) with the genetically predicted methylation to be associated with pancreatic cancer risk. We also studied gene expression to understand the identified associations.

Methods: Using genetic data and white blood cell methylation data from 1,595 subjects of European descent, we built genetic models to predict DNA methylation levels. After internal and external validation, we applied prediction models with satisfactory performance to the genetic data of 8,280 pancreatic cancer cases and 6,728 controls of European ancestry to investigate the associations of predicted methylation with pancreatic cancer risk. For associated CpGs, we compared their measured levels in pancreatic tumor versus benign tissue.

Results: We identified 45 CpGs at nine loci showing an association with pancreatic cancer risk, including 15 CpGs showing an association independent from identified risk variants. We observed significant correlations between predicted methylation of 16 of the 45 CpGs and predicted expression of eight adjacent genes, of which six genes showed associations with pancreatic cancer risk. Of the 45 CpGs, we were able to compare measured methylation of 16 in pancreatic tumor versus benign pancreatic tissue. Of them, six showed differentiated methylation.

Conclusions: We identified methylation biomarker candidates associated with pancreatic cancer using genetic instruments and added additional insights into the role of methylation in regulating gene expression in pancreatic cancer development.

Impact: A comprehensive study using genetic instruments identifies 45 CpG sites at nine genomic loci for pancreatic cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-21-0400DOI Listing
September 2021

Identification of a novel variant erythrocyte surface antigen-1 (VESA1) in Babesia orientalis.

Parasitol Res 2021 Aug 5;120(8):2863-2872. Epub 2021 Jul 5.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Babesia orientalis, belonging to the phylum Apicomplexa, is mainly accountable for water buffalo babesiosis, which adversely affected the livestock industry in China. Variant erythrocyte surface antigen-1 (VESA1), an antigen that helps infected erythrocytes to escape from host immune responses, was first reported in Babesia bovis. Various VESA1 proteins have also been characterized in other Babesia species. Nevertheless, there is no research on the identification and characterization of VESA1 proteins in Babesia orientalis. In this study, the BoVESA1 gene was amplified from both gDNA and cDNA. The results revealed that it is an intronless gene with a full length of 753 bp, encoding a protein of 250 amino acids with a predicted molecular weight of 28 kDa. The coding sequence (CDS) was cloned into the pGEX-6p-1 vector using a homologous recombination kit and expressed as a glutathione-S-transferase (GST)-fusion protein with a molecular weight of 53 kDa. The tertiary structure of BoVESA1 was predicted using the I-TASSER software. The recombinant protein was subjected to western blotting; the immunogenicity of recombinant BoVESA1 (rBoVESA1) was identified by incubating it with B. orientalis-positive serum. The native BoVESA1 was identified using the lysates of B. orientalis-infected water buffalo erythrocytes incubated with the anti-rBoVESA1 mouse serum. The results showed a band of ~ 28 kDa, which is similar to the predicted size. Immunofluorescence assay (IFA) using anti-rBoVESA1 serum probed indicated a strong signal in the infected RBCs, while the negative control showed no signal. In conclusion, the VESA1 protein was first identified in B. orientalis. This study facilitated further investigation of B. orientalis, and the results indicated that BoVESA1 may serve as a potential candidate antigen for diagnosis and detection of B. orientalis infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00436-021-07194-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255115PMC
August 2021

Erythrocyte Adhesion of Merozoite Surface Antigen 2c1 Expressed During Extracellular Stages of .

Front Immunol 2021 17;12:623492. Epub 2021 May 17.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by . However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in . We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.623492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165267PMC
September 2021

Functional Genomic Analyses of the 21q22.3 Locus Identifying Functional Variants and Candidate Gene for Breast Cancer Risk.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Department of Medicine, Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.

We previously identified a locus at 21q22.3, tagged by the single nucleotide polymorphism (SNP) rs35418111, being associated with breast cancer risk at a genome-wide significance level; however, the underlying causal functional variants and gene(s) responsible for this association are unknown. We performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association. Functional annotation for SNPs in high linkage disequilibrium (LD, r > 0.8) with rs35418111 in Asians showed evidence of promoter and/or enhancer activities, including rs35418111, rs2078203, rs8134832, rs57385578, and rs8126917. These five variants were assessed for interactions with nuclear proteins by electrophoretic mobility shift assays. Our results showed that the risk alleles for rs2078203 and rs35418111 altered DNA-protein interaction patterns. Cis-expression quantitative loci (cis-eQTL) analysis, using data from the Genotype-Tissue Expression database (GTEx) European-ancestry female normal breast tissue, indicated that the risk allele of rs35418111 was associated with a decreased expression of the gene, a relatively uncharacterized endoribonuclease in humans. We investigated the biological effects of on breast cancer cell lines by transient knock-down of expression in MCF-7, T47D, and MDA-MB-231 cell lines. Knockdown of mRNA in breast cancer cell lines consistently decreased cell proliferation, colony formation, and migration/invasion, regardless of estrogen receptor status. We performed RNA sequencing in MDA-MB-231 cells transfected with siRNA targeting and subsequent gene set enrichment analysis to identify gene networks associated with knockdown. These data indicated was involved in networks associated with inflammation and metabolism. Finally, we showed trends in expression patterns in breast tissues from The Cancer Genome Atlas (TCGA); early-stage breast cancers had elevated expression compared with normal tissue, but significantly decreased expression in late-stage disease. Our study provides evidence of a significant role for the human gene in breast cancer pathogenesis and the association between the rs35418111/21q22.3 locus and breast cancer risk, which may be mediated through functional SNPs, rs35418111 and rs2078203, that regulate expression of .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122893PMC
April 2021

Recombinase polymerase amplification with lateral flow strip for detecting Babesia microti infections.

Parasitol Int 2021 Aug 16;83:102351. Epub 2021 Apr 16.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei 430070, China. Electronic address:

Babesia microti is one of the most important pathogens causing humans and rodents babesiosis-an emerging tick-borne disease that occurs worldwide. At present, the gold standard for the detection of Babesia is the microscopic examination of blood smears, but this diagnostic test has several limitations. The recombinase polymerase amplification with lateral flow (LF-RPA) assay targeting the mitochondrial cytochrome oxidase subunit I (cox I) gene of B. microti was developed in this study. The LF-RPA can be performed within 10-30 min, at a wide range of temperatures between 25 and 45 °C, which is much faster and easier to perform than conventional PCR. The results showed that the LF-RAP can detect 0.25 parasites/μl blood, which is 40 times more sensitive than the conventional PCR based on the V4 variable region of 18S rRNA. Specificity assay showed no cross-reactions with DNAs of related apicomplexan parasites and their host. The applicability of the LF-RPA method was further evaluated using two clinical human samples and six experimental mice samples, with seven samples were positively detected, while only three of them were defined as positive by conventional PCR. These results present the developed LF-RPA as a new simple, specific, sensitive, rapid and convenient method for diagnosing infection with B. microti. This novel assay was the potential to be used in field applications and large-scale sample screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parint.2021.102351DOI Listing
August 2021

A Prospective Investigation of Circulating Metabolome Identifies Potential Biomarkers for Gastric Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Sep 1;30(9):1634-1642. Epub 2021 Apr 1.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development.

Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women's Health and the Shanghai Men's Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and values.

Results: Eighteen metabolites were associated with gastric cancer risk at < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; = 1.89 × 10). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions.

Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of infection and other major risk factors.

Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419074PMC
September 2021

Celiac plexus block for chronic flank pain: a case series.

Can J Urol 2021 02;28(1):10556-10559

Department of Urology, University of North Carolina Medical Center, Chapel Hill, North Carolina, USA.

Non-obstructive, chronic flank pain in urologic patients can be a challenging problem to manage. In this series, we examined the efficacy of celiac plexus blockade in providing pain relief and reducing opiate use in 14 adult urology patients with non-obstructive flank pain for > 1 year. Demographic, clinical, and procedural variables were collected from the medical record for retrospective analysis. Subjective improvement in pain occurred in 11 individuals (79%), and 5 (50%) were able to reduce their daily morphine equivalent dose (MED). Celiac plexus blockade is a viable option for symptomatic relief in urologic patients with non-obstructive chronic flank pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2021

Genetically predicted circulating protein biomarkers and ovarian cancer risk.

Gynecol Oncol 2021 02 25;160(2):506-513. Epub 2020 Nov 25.

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address:

Objective: Most women with epithelial ovarian cancer (EOC) are diagnosed after the disease has metastasized and survival in this group remains poor. Circulating proteins associated with the risk of developing EOC have the potential to serve as biomarkers for early detection and diagnosis. We integrated large-scale genomic and proteomic data to identify novel plasma proteins associated with EOC risk.

Methods: We used the germline genetic variants most strongly associated (P <1.5 × 10) with plasma levels of 1329 proteins in 3301 healthy individuals from the INTERVAL study to predict circulating levels of these proteins in 22,406 EOC cases and 40,941 controls from the Ovarian Cancer Association Consortium (OCAC). Association testing was performed by weighting the beta coefficients and standard errors for EOC risk from the OCAC study by the inverse of the beta coefficients from INTERVAL.

Results: We identified 26 proteins whose genetically predicted circulating levels were associated with EOC risk at false discovery rate < 0.05. The 26 proteins included MFAP2, SEMG2, DLK1, and NTNG1 and a group of 22 proteins whose plasma levels were predicted by variants at chromosome 9q34.2. All 26 protein association signals identified were driven by association with the high-grade serous histotype that comprised 58% of the EOC cases in OCAC. Regional genomic plots confirmed overlap of the genetic association signal underlying both plasma protein level and EOC risk for the 26 proteins. Pathway analysis identified enrichment of seven biological pathways among the 26 proteins (P <0.05), highlighting roles for Focal Adhesion-PI3K-Akt-mTOR and Notch signaling.

Conclusion: The identified proteins further illuminate the etiology of EOC and represent promising new EOC biomarkers for targeted validation by studies involving direct measurement of plasma proteins in EOC patient cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855757PMC
February 2021

Characterization of the variable merozoite surface antigen (VMSA) gene family of Babesia orientalis.

Parasitol Res 2020 Nov 15;119(11):3639-3648. Epub 2020 Sep 15.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Due to its wide presence in apicomplexan parasites as well as high polymorphism and antigenic diversity, the variable merozoite surface antigen (VMSA) family in Babesia sp. has attracted increasing attention of researchers. Here, all the reported VMSA genes of Babesia spp. were obtained from GenBank, and multiple alignments were performed by using conserved regions to blast the Babesia orientalis genome database (unpublished data). Five MSA genes (named MSA-2a1, MSA-2a2, MSA-2c1, MSA-1, and MSA-2c2, respectively) were identified, sequenced, and cloned from B. orientalis, which were shown to encode proteins with open reading frames ranging in size from 266 (MSA-2c1) to 317 (MSA-1) amino acids. All the five proteins contain an MSA-2c superfamily conserved domain, with an identical signal peptide and glycosyl phosphatidyl inositol (GPI)-anchor for each of them. The five proteins were also predicted to contain B cell epitopes, with only three for BoMSA-2c1, the smallest protein in the BoVMSA family, while at least six for each of the others. Notably, BoMSA-2a1 has 2 identical copies, a specific phenomenon only present in B. orientalis. This research has determined the MSA genes of B. orientalis and provides a genetic basis for further research of functional genes in B. orientalis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00436-020-06877-zDOI Listing
November 2020

Investigating the associations of glycemic load and glycemic index with lung cancer risk in the Southern Community Cohort Study.

Cancer Causes Control 2020 Dec 11;31(12):1069-1077. Epub 2020 Sep 11.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: Diets with a high glycemic load (GL) or glycemic index (GI) may increase cancer risk. Findings from prior studies on the relationship between GL, GI, and lung cancer risk are inconsistent. We investigated this relationship in a large prospective cohort.

Methods: We analyzed data from the Southern Community Cohort Study, a prospective cohort that includes diverse racial groups predominantly low-income adults aged 40-79 in 12 southeastern states of the USA. We estimated dietary GL and GI values using data collected from food frequency questionnaires at baseline. Dietary GL and GI were energy adjusted by residual method and categorized into sex-specific quintiles. Cox proportional hazard regression was used to assess the associations between dietary GL, GI, and lung cancer risk. We further performed stratified analyses by various factors.

Results: Intakes of individual food items or food groups that commonly contribute to GL were similar between blacks and whites in the cohort. After excluding the first two years of follow-up, 947 incident lung cancers were ascertained among 55,068 participants. Neither dietary GL nor GI was significantly associated with incident lung cancer risk in the overall population (GL: Q5 vs. Q1, HR = 0.88, 95% CI 0.72-1.07, p = 0.29; GI: Q5 vs. Q1, HR = 1.06, 95% CI 0.86-1.30, p = 0.71), nor in subgroups of populations (p > 0.05), in multivariable-adjusted analyses.

Conclusion: Dietary GL and GI were not independently associated with incident lung cancer risk in a large understudied population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01344-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572706PMC
December 2020

An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk.

Nat Commun 2020 08 6;11(1):3905. Epub 2020 Aug 6.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17673-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413371PMC
August 2020

A novel 53 kDa protein (BoP53) in Babesia orientalis poses the immunoreactivity using the infection serum.

Parasitol Int 2020 Oct 5;78:102152. Epub 2020 Jun 5.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine, Wuhan, Hubei 430070, China. Electronic address:

Babesia orientalis (B. orientalis) is responsible for water buffalo babesiosis, which caused serious economic losses in the south of China. Although the invasion process has been roughly described, there are still some unknown molecules that have not yet been identified. Recently, an invasion-related protein BOV57 has been identified in the Babesia bovis. However, there is no report available about the gene in B. orientalis. B. orientalis P53 (BoP53) sequence was obtained by blast BOV57 sequence in B. orientalis genome database, and the full length of the BoP53 gene is 1599 bp. BoP53 gene was cloned into a pGEX-6P-1 expression vector and expressed as a GST-tag fusion protein. The tertiary structure of BoP53 was predicted with the I-TASSER software. The native BoP53 was identified from of B. orientalis lysate incubation with mouse antiserum against rBoP53. BoP53 as a novel identified protein promotes the study of B. orientalis, the reaction of rBoP53 with the serum of B. orientalis-infected water buffalo but not with healthy buffalo serum indicated its good antigenicity. It may be a candidate antigen for the diagnosis of B. orientalis infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parint.2020.102152DOI Listing
October 2020

Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2020 07 21;29(7):1501-1508. Epub 2020 May 21.

Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments.

Methods: To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci.

Results: We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by , which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production.

Conclusions: We identified 38 candidates of protein biomarkers for PDAC risk.

Impact: This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334065PMC
July 2020

Identification and characterizations of a rhoptries neck protein 5 (BoRON5) in Babesia orientalis.

Parasitol Int 2020 Aug 14;77:102106. Epub 2020 Mar 14.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei 430070, China; Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:

Babesiosis caused by Babesia orientalis is one of the most serious parasitic diseases of water buffalo in the central and south part of China. Rhoptry neck proteins (RONs) are very important protein components to form a complex moving junction (MJ) which mainly participate in the invasion processes in apicomplexan parasites. Aimed to the further investigation of the function of BoRON proteins in B. orientalis, in this study, BoRON5 was characterized. A truncated 921 bp fragment of BoRON5 with predicted antigenic epitopes was cloned and inserted into pSUMO expression vector. Recombinant protein rSUMO-BoRON5 was purified from Escherichia coli. and used to produce antisera in Kunming mice. rSUMO-BoRON5 showed strong immunosignals when blotted with the positive serum from B. orientalis-infected water buffalo. Antisera raised in Kunming mice against rSUMO-BoRON5 could detect the native BoRON5 in parasite lysates. Immuofluorescence assay showed that mice antisera of rSUMO-BoRON5 could detect merozoite in B. orientalis infected water buffalo erythrocytes. This study provides useful information for the further investigation of the BoRON5 function during B. orientalis invasion of water buffalo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.parint.2020.102106DOI Listing
August 2020

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants.

Nat Commun 2020 03 5;11(1):1217. Epub 2020 Mar 5.

Departments of Health Research and Policy, School of Medicine, Stanford University, California, CA, USA.

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15046-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057957PMC
March 2020

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh.

Nat Commun 2020 01 17;11(1):341. Epub 2020 Jan 17.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223, Kunming, China.

Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14183-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969145PMC
January 2020

Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry.

EBioMedicine 2019 Oct 16;48:203-211. Epub 2019 Oct 16.

Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

Background: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

Methods: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

Findings: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10. The associations for four variants reached P < 5 × 10 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS.

Interpretation: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838373PMC
October 2019

Overall Mortality After Diagnosis of Breast Cancer in Men vs Women.

JAMA Oncol 2019 Nov;5(11):1589-1596

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Survival differences between male and female patients with breast cancer have been reported, but the underlying factors associated with the disparity have not been fully studied. This understanding is fundamental to developing strategies for cancer treatment and survivorship care.

Objective: To compare mortality between male and female patients with breast cancer and quantitatively evaluate the factors associated with sex-based disparity in mortality.

Design, Setting, And Participants: This large, nationwide, registry-based cohort study used the National Cancer Database to identify and obtain data on patients who received a breast cancer diagnosis between January 1, 2004, and December 31, 2014. After exclusions, the final study population comprised 1 816 733 patients. Statistical analyses were conducted from September 1, 2018, to January 15, 2019.

Main Outcomes And Measures: The primary outcome was overall survival. Secondary outcomes were 3-year and 5-year mortality. Mortality differences were evaluated by Kaplan-Meier analysis. The roles of race/ethnicity, clinical characteristics, treatments, and access-to-care factors in the association between sex and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age.

Results: In total, 16 025 male (mean [SD] age, 63.3 [13.0] years) and 1 800 708 female (mean [SD] age, 59.9 [13.3] years) patients with breast cancer were included in the study. Compared with female patients, male patients had higher mortality across all stages. For men, the overall survival rate was 45.8% (95% CI, 49.5-54.0; P < .001), the 3-year rate was 86.4% (95% CI, 85.9-87.0; P < .001), and the 5-year rate was 77.6% (95% CI, 76.8-78.3; P < .001). For women, the overall survival rate was 60.4% (95% CI, 58.7-62.0; P < .001), the 3-year rate was 91.7% (95% CI, 91.7-91.8; P < .001), and the 5-year rate was 86.4% (95% CI, 86.4-86.5; P < .001). Overall, clinical characteristics and undertreatments were associated with a 63.3% excess mortality rate for male patients. A higher proportion of excess deaths in men were explained by these factors in the first 3 years after breast cancer diagnosis (66.0%) and in all patients with early-stage cancer (30.5% for stage I and 13.6% for stage II). However, sex remained a significant factor associated with overall mortality (adjusted hazard ratio [HR], 1.19; 95% CI, 1.16-1.23) as well as mortality at 3-year (adjusted HR, 1.15; 95% CI, 1.10-1.21) and 5-year (adjusted HR, 1.19; 95% CI, 1.14-1.23) analyses, even after adjustment for clinical characteristics, treatment factors, age, race/ethnicity, and access to care.

Conclusions And Relevance: This study found that mortality after cancer diagnosis was higher among male patients with breast cancer compared with their female counterparts. Such disparity appeared to persist after accounting for clinical characteristics, treatment factors, and access to care, suggesting that other factors (particularly additional biological attributes, treatment compliance, and lifestyle factors) should be identified to help in eliminating this disparity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2019.2803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753503PMC
November 2019

Plant and Animal Protein Intake and Risk of Incident Kidney Stones: Results from the Shanghai Men's and Women's Health Studies.

J Urol 2019 12 20;202(6):1217-1223. Epub 2019 Aug 20.

Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee.

Purpose: High animal protein intake is a risk factor for nephrolithiasis. Whether plant based sources of protein are associated with kidney stone risk is not well studied. We examined the association of animal and plant protein intake with the risk of incident kidney stones in Shanghai, China.

Materials And Methods: Dietary intakes were obtained from a validated food frequency questionnaire at baseline. Self-reported stone events were ascertained at baseline and at followup visits. Multivariable Cox regression models were used to evaluate the associations of protein intake with the incident stone risk.

Results: During 319,211 and 696,950 person-years of followup 1,451 men and 1,202 women, respectively, reported incident stones. The average ± SD intake of animal and plant protein standardized to 2,000 kcal was 31.3 ± 13.7 and 48.4 ± 7.2 gm per day in women, and 30.8 ± 13.3 and 51.3 ± 7.6 gm per day, respectively, in men. On multivariable analysis participants in the highest quintiles of animal and nondairy animal protein intake showed an increased risk of incident stones compared to those in the lowest quintiles (HR 1.16, 95% CI 1.01-1.32, p=0.03 vs HR 1.14, 95% CI 1.01-1.30, p=0.04). Compared to the lowest quintile the highest intake quintiles of the animal-to-plant protein ratios and the nondairy animal-to-plant protein ratios were positively associated with stone risk (HR 1.17, 95% CI 1.03-1.33, p=0.02 and HR 1.20, 95% CI 1.06-1.36, p=0.005, respectively). No association was observed with plant protein intake (p=0.14).

Conclusions: In this population with a relatively low animal protein intake and a high plant protein intake, a greater animal protein intake was associated with a kidney stone risk. Increasing the proportion of plant protein relative to animal protein appeared protective against the risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000000493DOI Listing
December 2019

Treatment at Academic Centers Decreases Insurance-Based Survival Disparities in Colon Cancer.

J Surg Res 2020 01 14;245:265-272. Epub 2019 Aug 14.

Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Background: Although insurance and race-based survival disparities in colon cancer are well studied, little is known regarding how these survival disparities are impacted by type of treating facility.

Materials And Methods: This is a retrospective cohort study of 433,997 patients diagnosed with colon adenocarcinoma using the National Cancer Database (NCDB). Using Cox proportional hazard analyses, we assessed overall survival (OS) as a function of race, insurance status, and treating facility, after adjusting for demographic and clinical factors. We also assessed differences in OS according to race and insurance status stratified by treating facility type.

Results: OS was significantly diminished for blacks (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.07-1.10; P < 0.001) and increased for patients of other race (primarily Asians; HR, 0.76; 95% CI, 0.74-0.78) compared with whites. Patients with private insurance had improved OS compared with uninsured (HR, 1.28; 95% CI, 1.25-1.31; P < 0.001), Medicaid (HR, 1.35; 95% CI, 1.33-1.38; P < 0.001) and Medicare (HR, 1.13, 95% CI, 1.12-1.15; P < 0.001) patients. Compared with patients treated at comprehensive community programs, patients treated at academic centers (ACs) had improved OS (HR, 0.86; 95% CI, 0.85-0.88; P < 0.001). When stratified by type of treating facility, racial disparities were not mitigated for patients treated at ACs compared with other facilities (P = 0.266 for interaction). At ACs, patients with Medicaid had persistent OS disparities compared with patients with private insurance (HR, 1.12; 95% CI, 1.09-1.15; P < 0.001), although these disparities were significantly diminished compared with patients treated at other facilities (HR, 1.41; 95% CI, 1.38-1.45; P < 0.001).

Conclusions: Other race, private insurance, and treatment at AC were independently associated with improved OS in patients with colon cancer. Medicaid-based, but not race-based, survival disparities are reduced at ACs compared with other facilities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2019.07.059DOI Listing
January 2020

Analysis of Over 140,000 European Descendants Identifies Genetically Predicted Blood Protein Biomarkers Associated with Prostate Cancer Risk.

Cancer Res 2019 09 23;79(18):4592-4598. Epub 2019 Jul 23.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Several blood protein biomarkers have been associated with prostate cancer risk. However, most studies assessed only a small number of biomarkers and/or included a small sample size. To identify novel protein biomarkers of prostate cancer risk, we studied 79,194 cases and 61,112 controls of European ancestry, included in the PRACTICAL/ELLIPSE consortia, using genetic instruments of protein quantitative trait loci for 1,478 plasma proteins. A total of 31 proteins were associated with prostate cancer risk including proteins encoded by , whose methylation level was shown previously to be associated with prostate cancer risk, and , and , which were previously implicated as potential target genes of prostate cancer risk variants identified in genome-wide association studies. A total of 18 proteins inversely correlated and 13 positively correlated with prostate cancer risk. For 28 of the identified proteins, gene somatic changes of short indels, splice site, nonsense, or missense mutations were detected in patients with prostate cancer in The Cancer Genome Atlas. Pathway enrichment analysis showed that relevant genes were significantly enriched in cancer-related pathways. In conclusion, this study identifies 31 candidates of protein biomarkers for prostate cancer risk and provides new insights into the biology and genetics of prostate tumorigenesis. SIGNIFICANCE: Integration of genomics and proteomics data identifies biomarkers associated with prostate cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-18-3997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744971PMC
September 2019

Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk.

Int J Cancer 2020 04 16;146(8):2130-2138. Epub 2019 Jul 16.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.

A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10 -3.28 × 10 ), are linked to insulin resistance and estrogen receptor signaling pathways. Proteins identified at other loci include those involved in biological processes such as alcohol and lipid metabolism, proteolysis, apoptosis, immune regulation and cell motility and proliferation. Consistent associations were observed for 22 proteins in the UK Biobank data (p < 0.05). The study identifies potential novel biomarkers for breast cancer, but further investigation is needed to replicate our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32542DOI Listing
April 2020

Genetically Predicted Levels of DNA Methylation Biomarkers and Breast Cancer Risk: Data From 228 951 Women of European Descent.

J Natl Cancer Inst 2020 03;112(3):295-304

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.

Background: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk.

Methods: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided.

Results: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes.

Conclusion: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djz109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073907PMC
March 2020

Preparation and in vitro performance evaluation of resveratrol for oral self-microemulsion.

PLoS One 2019 16;14(4):e0214544. Epub 2019 Apr 16.

College of Materials Science and Engineering, Central South University of Forestry & Technology, Changsha, China.

The purpose of this study was to improve the solubility of resveratrol (Res) by a self-microemulsifying drug-delivery system (SMEDDS). Through a solubility experiment, the pseudoternary phase diagram and ternary phase diagram were used to optimize the Res SMEDDS formula. The optimum formulation consisted of 5% IPM, 20% PEG400, and 65% Cremophor RH40. The water solubility, stability, in vitro release and antioxidant activity of the Res SMEDDS were characterized. The Res solubility in the SMEDDS was at least 1,000 times compared to that in water. The average droplet size of the microemulsion was 28.00±1.67 nm and uniform distribution. The Res SMEDDS should be stored at low temperature and in the dark to avoid light conditions. Res SMEDDS was able to improve the in vitro release rate of Res, and the in vitro release of Res from Res SMEDDS was significantly faster that of Res powder and unaffected by pH value of media. Antioxidant assays showed that antioxidant activities of Res in Res SMEDDS were unaffected compared to Res powder. Cytotoxicity study indicated that Res SMEDDS at the concentration of less than 100 μM was safe. These results demonstrated the potential use of Res SMEDDS for oral administration of Res.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467382PMC
December 2019

Upregulation of STC2 in colorectal cancer and its clinicopathological significance.

Onco Targets Ther 2019 15;12:1249-1258. Epub 2019 Feb 15.

Department of Gastrointestinal Surgery and Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratoryof Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuchang District, Wuhan 430071, China,

Background: Stanniocalcin 2 (STC2) is a glycoprotein hormone involved in many biological processes and a secretory protein that regulates malignant tumor progression. The aim of the present study was to further explore the clinicopathological significance and prognostic role of STC2 in colorectal cancer (CRC).

Methods: In this study, STC2 expression was first investigated in Gene Expression Omnibus and The Cancer Genome Atlas, and then validated with the data from our medical center. Univariate and multivariate analyses were performed to assess the association between prognostic factors and survival outcome.

Results: In Gene Expression Omnibus and The Cancer Genome Atlas databases, bioinformatics analysis confirmed that STC2 was significantly increased in CRC compared with that in normal tissues (<0.01), and CRC patients with high STC2 expression had a shorter overall survival. By analyzing data from our medical center, the results also showed that STC2 expression of CRC tissues was higher than that in normal tissues, whether the transcriptional or protein levels. In the CRC tissues, high STC2 expression was significantly correlated with lymph node metastasis (=0.047), distant metastasis (=0.040), and advanced clinical stage (=0.047). Moreover, Kaplan-Meier analyses indicated that high STC2 expression predicted a worse prognosis, and multivariate Cox regression analysis revealed that STC2 was an independent prognostic factor for overall survival (HR =1.976, 95% CI: 1.092-3.576, =0.024) in patients with CRC.

Conclusion: Our results suggested that STC2 played an important role in CRC progression and prognosis, and could be a useful biomarker for survival prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S191609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389002PMC
February 2019

Synergistic utilization of red mud for flue-gas desulfurization and fly ash-based geopolymer preparation.

J Hazard Mater 2019 05 16;369:503-511. Epub 2019 Feb 16.

Department of Civil and Environmental Engineering, The University of Tennessee, Knoxville, TN, 37996, USA.

As an industrial waste characterized by huge volume and high alkalinity, red mud has become a serious environmental problem. The reuse of red mud has been explored in previous studies, including as building materials and for soil and waste water treatment. In this study, an innovation was made for the reuse of red mud to create a synergistic effect. Red mud was first used in flue gas desulfurization (FGD), and then the desulfurized red mud was again reused to make a geopolymer material. By using one type of original red mud and three types of fly ash, this study revealed that with high alkalinity and desulfurization capacity, the red mud could serve as an excellent FGD sorbent. After FGD, the sodium sulfate in the desulfurized red mud acted as a chemical activator for geopolymer made with class C fly ash. A 25% increase in strength was observed between the geopolymers with the red mud after FGD and with the original one. There are no significant benefits of FGD on the class F fly ash-based geopolymers and further study is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2019.02.059DOI Listing
May 2019

Opiate Exposure and Predictors of Increased Opiate Use After Ureteroscopy.

J Endourol 2019 06 8;33(6):480-485. Epub 2019 Feb 8.

1 Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee.

Kidney stone formers are at risk for opioid dependence. The aim of this study is to describe opiate exposure and determine predictors of prolonged opiate use among kidney stone formers after surgery. A retrospective review was performed among patients who underwent ureteroscopy for upper tract stone disease. Prescription data were ascertained from a statewide prescribing database. Demographic data and surgical factors were collected from the electronic medical record. Predictors of additional postsurgery prescriptions filled within 30 days and persistent opiate use 60 days after ureteroscopy were determined. Among 208 patients, 127 (61%) had received preoperative opiate prescriptions within 30 days before surgery. Overall, 12% ( = 25) of patients required an additional opiate prescription within 30 days after ureteroscopy, and 7% ( = 14) of patients continued to use opiate medications more than 60 days postoperatively. Patients continuing to use opiates long-term were not chronic opiate users. For both outcomes, preoperative opiate exposure, including number of prescriptions, days prescribed, and unique providers had significant associations (all  < 0.05). Additionally, younger age ( = 0.049) was associated with obtaining an additional opiate prescription within 30 days. Lower BMI ( = 0.02) and higher ASA score ( = 0.03) were predictors of continued opiate use more than 60 days after ureteroscopy. The majority of stone formers have had opiate exposure before surgery, often from multiple providers. Approximately 1 in 8 stone formers who undergo ureteroscopy require additional opiate prescriptions within 30 days. A small but significant population receive opiates beyond the immediate postoperative period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/end.2018.0796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366266PMC
June 2019

Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk.

Cancer Res 2019 02 17;79(3):505-517. Epub 2018 Dec 17.

The Center for Bioinformatics and Functional Genomics at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study ( = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of < 7.94 × 10. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely , and . We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-18-2726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359948PMC
February 2019
-->