MicroRNAs as potential biomarkers for gastric cancer

Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need for novel biomarkers detectable at earlier stages.Recently,aberrantly expressed microRNAs(miRNAs)have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis.This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013.Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis,tumor proliferation,distant metastasis and invasion.Furthermore,tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing.As miRNAs in plasma/serum are well protected from RNases,they remain stable under harsh conditions.Thus,potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection.Circulating miRNAs,as well as tissue miRNAs,may allow for the detection of gastric cancer at an early stage,prediction of prognosis,and monitoring of recurrence and/or lymph node metastasis.Taken together,the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.

Association between polymorphism rs6983267 and gastric cancer risk in Chinese population

AIM: To explore the association between single nucleotide polymorphisms (SNPs) at 8q24 and gastric cancer risk. METHODS: A case-control investigation including 212 gastric cancer patients and 377 healthy controls was conducted. The genotypes of SNPs (rs6983267, rs7008482 and rs10808555) were examined and established through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to evaluate the association between SNPs and gastric cancer. RESULTS: The genotype frequencies of rs6983267 in gastric cancer patients were obviously different from those in the control (P = 0.005). GT genotype of rs6983267 was associated with an increased risk of gastric cancer compared with GG genotype (adjusted odds ratio = 2.01, 95% confidence interval: 1.28-3.14). Further stratified analysis indicated that rs6983267 GT genotype facilitated the risk of gastric cancer of non-cardiac and intestinal type (OR: 2.638, 95% CI: 1.464-4.753; OR: 1.916, 95% CI: 1.166-3.150, respectively). CONCLUSION: This study demonstrates for the first time that rs6983267 is involved in susceptibility to gastric cancer, although further large-sample investigations are still needed.

Adipogenesis licensing and execution are disparately linked to cell proliferation

房间区别和增长的协作是在多细胞的有机体和干细胞的发展过程的一个关键问题。这里，我们提供 3T3-L1 房间的 adipocyte 区别的建立要求二个过程的证据：在一个特别生长拘捕阶段以内准许一个 adipogenesis 基因表示程序，即，以一种 cell-cycle-independent 方式，准许的祖先被面对导致因素区分进 adipocytes 的这个程序的接触抑制阶段，然后执行。我们的结果证明在接触抑制阶段期间 3T3-L1 房间准许的区别包含了象 DNA methylation 那样的 epigenetic 修正和 histone 修正，而显著地在接触抑制阶段期间由 DNA methylation 禁止者或 RNAi 扰乱这些 epigenetic 修正减少的 adipogenesis 效率。更重要地，当这些准许的 3T3-L1 房间在非区分的条件下面是 re 有教养的或仅仅与胰岛素对待时，这 adipogenesis 承诺能从一房间代被维持到下一个，一旦这些房间受到导致 adipogenesis，准许的节目由此能以一种 cell-cycle-independent 方式被激活，调节。这结果建议准许的区别和区别执行能被解开并且迥异地连接了到房间增长。我们的调查结果陈述房间命运决定能被细分进至少二个阶段的一个新概念，准许并且执行，它可能与房间增长有不同规章的关系。另外，这个新概念可以为对肥胖开发新策略提供线索。

Microsatellite variation between Japanese eel (Anguilla japonica) and European eel (Anguilla anguilla)

Allelic variation in a total of 7 microsatellites was examined between elvers of freshwater eels (Anguilla japonica and Anguilla anguilla). The number of alleles at these loci ranged from 8 to 26. A single test of each locus revealed significant deficits of heterozygotes (P<0.01). Significant departure from expectations of Hardy-Weinberg equilibrium (HWE) was found for all loci within four subpopulations of A. japonica, which opposes the panmixia hypothesis of Schmidt. Also exact tests of population differentiation based on allelic fre- quency distribution disagree the hypothesis of random distribution of individuals among populations. Population structure among four populations of A. japonica was revealed with FST value of 0.009 8 (P=0.000 48; 10 000 iteration). Pairwise matrixes of FST and RST showed a significant difference between two distantly related spe- cies—A. japonica and A. anguilla. Divergent time of the two species calculated by Goldstein method is over 2 million years. The results may challenge the Schmidt’s theory about the distribution of freshwater eels.

Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray

AIM: To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS: We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffin-embedded blocks, including carcinomas (n = 85), adenomatous polyps (n = 18), as well as normal para-cancerous colon tissues (n = 9). Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Akt1, β-catenin, c-myc, nm23-h1 and Cox-2.RESULTS: The protein expressions of p53, bcl-2, bax, cyclin D1, β-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa (P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively). Chi-square analysis showed that the statistically significant variables were p53, p21, bax, β-catenin, c-myc, PTEN, p-Akt1, Cox-2 and nm23-h1 for histological grade (P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively), β-catenin, c-myc and p-Akt1 for lymph node metastasis (P = 0.011, P =0.005, and P = 0.032, respectively), β-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis (P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively), and cyclin D1, β-catenin, c-myc, Cox-2 and nm23h1 for clinical stages (P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively). CONCLUSION: Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, β-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in progression of human colon cancer.

A new b/aLEN-17 gene in a clinical isolate of Staphylococcus epidermidis in Shanghai, China

The introduction of the antibiotics into clinical practice has significantly reduced the mortality of infectious diseases. Although chromosomally mediated β-1actamase is natural in many genera of bacteria, the intensive use of antibiotics is the main cause for the increasing emergence of new β-1actamases. So far, more than 340 β-lactamases have been identified,1 among which, more than 200 are extended-spectrum β-lactamases （ESBLs）.2 The most prevalent β-lactamases are class A enzymes, including SHV and TEM. Genes encoding these enzymes generally located in large transferable plasmids. The dissemination of these plasmids attributes to the increasing incidence and spread of v-lactam resistance. It is important to investigate the prevalence and allelic distribution of genes encoding β-lactamase in the bacterial population in order to prevent the emergence of ESBLs in those bacteria and the spread of ESBLs in the clinical setting.

Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential

Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant(DR)cells from three types of drug-surviving cancer cells,which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells,and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells.By using this strategy which relies on fluorescent glycan nanoparticle(FGNP)-based fluorescence-activated cell sorting(FACS)assays,two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated,and we found that the lower fluorescence(LF)subpopulation consisted of DR cells,while the higher fluorescence(HF)subpopulation was comprised of non-DR cells.Besides,the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes.More intriguingly,by using the FGNP-based FACS assay to detect DR/non-DR phenotypes,we found that the DR phenotype had a potential to differentiate into the non-DR progeny,which demonstrates the differentiation feature of stem-like cancer cells.Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells,as well as the reversal of drug resistance that are tackled by various therapeutic methods.The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.

Erratum to: Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential

Erratum to Nano Research 2020,13(11):3110-3122 https://d0i.0rg/l 0.1007/s 12274-020-2981-8 The article Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential,written by Chenglong Wang et al.,was erroneously originally published electronically on the publishers internet portal(currently SpringerLink)on 10 August 2020 with the Acknowledgements.

Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood pressure response to antihypertensive treatment

Background The renin-angiotensin-aldosterone system （RAAS） is important for the development of essential hypertension, and many antihypertensive drugs target it. This study was undertaken to determine whether polymorphisms in the renin-angiotensin-aldosterone system are related to the blood pressure （BP） response to diuretic treatment in a Chinese Han ethnic population. Methods Fifty-four patients with essential hypertension received hydrochlorothiazide （12.5 mg, once daily） as monotherapy for four weeks. Seven polymorphisms in RAAS genes were genotyped by gene chip technology. The relationship between these polymorphisms and the change in blood pressure was observed after the 4-week treatment. Results The patients with angiotensinogen （AGT） -6G allele showed a greater reduction in diastolic BP （P=- 0.025） and mean BP （P=-0.039） than those carrying AA genotype. Patients carrying aldosterone synthase （CYP11B2） CC genotype exhibited a greater BP reduction than those carrying CT and TT genotypes （systolic BP： P=- 0.030; diastolic BP： P=- 0.026; mean BP： P=-0.003）. In addition, patients with a combination of CYP11B2 CC genotype and angiotensin converting enzyme （ACE） D allele might have a more pronounced reduction of systolic BP than those with any other genotypic combinations of the two genes （P=0.007）. Conclusions AGT-6G allele, CYP11B2 -344CC genotype and its combination with ACE D allele are associated with BP response to hydrochlorothiazide treatment. Larger studies are warranted to validate this finding.

Impact of the next-generation sequencing data depth on various biological result inferences

Next-generation sequencing(NGS) technologies have revolutionized the field of genomics and provided unprecedented opportunities for high-throughput analysis at the levels of genomics,transcriptomics and epigenetics.However,the cost of NGS is still prohibitive for many laboratories.It is imperative to address the trade-off between the sequencing depth and cost.In this review,we will discuss the effects of sequencing depth on the detection of genes,quantification of gene expression and discovering of gene structural variants.This will provide readers information on choosing appropriate sequencing depth that best meet the needs of their particular project.

Arabidopsis Acetyl-Amido Synthetase GH3.5 Involvement in Camalexin Biosynthesis through Conjugation of Indole-3-Carboxylic Acid and Cysteine and Upregulation of Camalexin Biosynthesis Genes

Camalexin （3-thiazol-2＇-yl-indole） is the major phytoalexin found in Arabidopsis thaliana. Several key intermediates and corresponding enzymes have been identified in camalexin biosynthesis through mutant screening and biochemical experiments. Camalexin is formed when indole-3-acetonitrile （IAN） is catalyzed by the cytochrome P450 monooxygenase CYP71A13. Here, we demonstrate that the Ara- bidopsis GH3.5 protein, a multifunctional acetyl-amido synthetase, is involved in camalexin biosynthesis via conjugating indole-3-carboxylic acid （ICA） and cysteine （Cys） and regulating camalexin biosynthesis genes. Camalexin levels were increased in the activation-tagged mutant gh3.5-1D in both Col-0 and cyp71A13-2 mutant backgrounds after pathogen infection. The recombinant GH3.5 protein catalyzed the conjugation of ICA and Cys to form a possible intermediate indole-3-acyl-cysteinate （ICA（Cys）） in vitro. In support of the in vitro reaction, feeding with ICA and Cys increased camalexin levels in Col-0 and gh3.5-1D. Dihydrocamalexic acid （DHCA）, the precursor of camalexin and the substrate for PAD3, was accumulated in gh3.5-1DIpad3-1, suggesting that ICA（Cys） could be an additional precursor of DHCA for camalexin biosynthesis. Furthermore, expression of the major camalexin biosynthesis genes CYP79B2, CYP71A12, CYP71A13 and PAD3 was strongly induced in gh3.5-1D. Our study suggests that GH3.5 is involved in camalexin biosynthesis through direct catalyzation of the formation of ICA（Cys）, and upregulation of the major biosynthetic pathway genes.

Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-omics Integrated Analysis

Objective:To compare the circular pathological changes of chronic hepatitis B(CHB)patients according to the tongue diagnosis.Methods:Totally 41 CHB patients with typical white tongue coating(WTC)or yellow tongue coating(YTC)were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls.The mRNA expression of peripheral leukocytes was detected by GeneChips,and 9 genes were randomly selected for expression validation.Circular metabolites were detected by gas chromatographymass spectrometry.Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.Results:A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively.The biological information analysis indicated that CHB patients had obviously increased functions in cell death,apoptosis and necrosis(Z-score 2,P<0.05)and decreased activation in T lymphocytes(Z-score–2,P<0.05),regardless of the tongue manifestation.Compared to patients with WTC,the YTC patients were predicted to be more active in functions related to virus replication(Z-score 2,P<0.05),and the content of circular fatty acids,such as oleic acid(P=0.098)and lauric acid(P=0.035),and citric acid cycle-related metabolites were higher in the YTC patients(P<0.1).The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.Conclusions:CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC.The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

A novel splicing mutation in CLCNKB in a Chinese patient with Bartter syndrome type Ⅲ

Bartter syndrome type Ⅲ is a Bartter syndrome subtype, which has a group of autosomal-recessive inherited disorders with clinical characteristics such as renal salt wasting, hypokalemic metabolic alkalosis,elevated renin and aldosterone levels, with normal or low blood pressure.1 Unlike other subtypes that often begin in the neonatal period, type Ⅲ, due to mutations in the CLCNKB gene,2-4 is highly variable and usually presents as a ＂classic＂ Barrter variant characterized by an onset in early childhood and less severe or absent hypercalciuria and nephrocalcinosis.

Different developmental potential of pluripotent stem cells generated by different reprogramming strategies

Dear Editor,Recent studies show that induced pluripotent stem cells(iPSCs)generated through ectopic expression of transcription factors retain an epigenetic memory of their original somatic cells(Kim et al.,2010;Polo et al.,2010)or aberrant silencing of a single imprinted gene cluster(Liu et al.,2010;Stadtfeld et al.,2010),which affects their developmental and differentiation potentials.

Genome-wide Analysis of Smad Targets Reveals the Role of BMP Signaling in Embryonic Stem Cell Fate Determination

Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades.