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Background: Burkitt lymphoma/leukemia (BL/BAL) is the most common lymphoma in children, and the sporadic subtype is dominant in Chinese populations. MYC gene translocations are essential for sporadic BL/BAL (sBL/BAL), but other gene mutations also play important roles in the development of sBL/BAL. Methods: The clinical data of ten Chinese children with sBL/BAL were collected, and next generation sequencing of their tumor tissues was conducted. Cases of BL and diffuse large B cell lymphoma (DLBCL) were also collected from a database, and bioinformatics analysis was conducted.Results: Nine boys and one girl were enrolled in the study, including six BL patients (stage III) and four BAL patients (stage IV). The average age at diagnosis was 100.10±13.39m; overexpression of CD20 was detectable, and MYC rearrangements were confirmed. The patients received combination treatment of chemotherapy and rituximab. All patients achieved complete remission and survived. Germline causal gene mutations were detected in four (40%) patients by whole-exome sequencing (WES); ID3, BRCA2, ARID1A and SMARCA4 mutations, in addition to MYC mutations, were the most common somatic mutations. The gene functions in etiology were different between the BL and DLBCL datasets. The identified mutated genes were enriched and connected by GO or KEGG pathways, and it seemed that the PI3K-Akt signaling pathway or the EGFR-TKI resistance pathway played important roles in the etiology of sBL/BAL. Conclusion: sBL/BAL is a highly aggressive but curable lymphoma; its etiology and pathology require additional research. The molecular hallmark of sBL/BAL is MYC translocation, whereas additional chromosomal abnormalities and gene mutations also occur and play roles in the progression of the disease. The PI3K-Akt signaling pathway seems to play important roles in the development of sBL/BAL, and sBL/BAL may be inhibited by this signaling pathway. The EGFR-TKI resistance pathway was also analyzed in sBL/BAL patients, revealing that EGFR-TKI treatment is invalid in this disease. Further research is needed for hypothesis development and possible mechanism discovery.

The androgen receptor (AR) has a crucial role in prostate cancer. RNA‑binding protein‑mediated post‑transcriptional regulation is important in the initiation and development of cancer. The present study attempted to elucidate the mutual association of AR and RNA‑binding protein quaking (QKI) in the development of prostate cancer. Dual‑luciferase reporter demonstrated that AR can positively regulate the expression of QKI in prostate cancer cell lines due to its effective transcription regulating function. In addition, QKI may increase expression of AR by heat shock protein 90, which is a coactivator of AR, and silencing QKI can increase the sensitive of Casodex, which is an antagonist of AR in castration‑resistant prostate cancer. This may be a new strategy for advanced prostate cancer.

Hepatitis B virus (HBV) infection is a critical incentive for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Different genotypes and genome mutations of HBV have been found to be related to the progression of these liver diseases. However, their clinical significance is still under debate. The objective of this study was to determine the association of HBV genotypes and hot spot mutations in the reverse transcriptase (RT) and basal core promoter-precore (BCP-PreC) region with HBV-infected diseases in a northwest Chinese population. HBV genotyping and DNA sequencing were performed in samples of 980 patients. Appropriate statistical methods were adopted to assess HBV genetic features and its clinical association. It was found that the prevalent HBV genotype in northwestern Chinese patients was HBV/C (61.33%), followed by HBV/B (36.63%). In RT region, in addition to the reported nucleoside analogue- (NA-) resistance missense mutations, new silent mutations at rt169 and rt180 were found to raise the risk of HCC in patients with HBV/C. And the heterozygous mutation status of rt169/rt180 was associated with the increased risk of both HCC and NA resistance (OR > 1, P<0.01) regardless of HBV genotypes. In BCP-PreC region, multiple mutations and combinations, especially at nt 1762/1764 and nt 1896/1899, were characterized to be the causes of spurious HBeAg negativity and liver function injury, as well as the risk factors for HCC progression (P<0.01). Additionally, a novel mutation at nt1799G>C was likely found to increase the risk of HCC in patients with HBV/B. These findings revealed an association between HBV genotypes and HBV genetic mutations in RT and BCP-PreC region and progression of hepatitis B. It would be helpful for risk evaluation and diagnostic improvement based on these genetic features.

The reported risk susceptibility between phospholipase C epsilon 1 (PLCE1) polymorphisms and esophageal cancer (EC) and gastric cancer (GC) remained inconsistent and controversial, especially on variants other than rs2274223. The relationship between PLCE1 polymorphisms and gene expression is also unclear. Here we conducted a case-control study from northwest China, genotyped seven tag single nucleotide polymorphisms (SNPs) in PLCE1 with multiplexed SNP MassARRAY assay. Stratified analysis was carried out and PLCE1 expression was evaluated in specified groups with the method of qRT-PCR and immunohistochemistry. Results showed that the minor alleles of rs3765524, rs2274223, and rs10509670 were associated with increased risk of EC and GC. Linkage disequilibrium analysis revealed protective haplotypes of CCAAGTC and CCAA. By stratification, a more significant association was found in subgroups of male, age ≥ 54, tumor stages of I-II and tumor size ≤ 5 cm, EC and cardia cancer (CC) of stomach, and moderate to well differentiated squamous carcinoma. In addition, a significant association for rs3765524 with noncardia cancer (NCC) and adenocarcinoma which is predominant in China was also observed. Further expression analysis identified that PLCE1 was downregulated in NCC tissues comparing to their adjacent noncancerous tissues, and its protein expression was higher in genotype rs3765524 CT/TT than in rs3765524 CC. In summary, our study suggests that PLCE1 polymorphisms may affect its gene expression and are associated with not only EC and CC, but also, to some extent, NCC risk in this study population.

Sepsis is a life-threatening disease characterized by uncontrolled inflammatory responses upon pathogen infections, especially for the antibiotic-resistant strains, such as Methicillin-resistant S. aureus (MRSA). Here we demonstrated that a Mitochondria-derived peptide (MOTS-c) could significantly improve the survival rate and decrease bacteria loads in MRSA-challenged mice, accompanied with declined levels of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, but with increased level of anti-inflammatory cytokine IL-10. Moreover this peptide enhanced bactericidal capacity of macrophages. Meanwhile, MOTS-c inhibited the phosphorylation mitogen-activated protein kinases (MAPK), and enhanced the expression of aryl hydrocarbon receptor (AhR) and signal transducer and activator of transcriptional 3 (STAT3) in macrophages. Overall, MOTS-c plays a beneficial role in curbing the overwhelming inflammatory bursts in the fight against MRSA infection. It may serve as a potential therapeutic agent in sepsis treatment. Highlight.

// Feixue Feng 1, 2, * ,Yinghao Jiang 1, * , Huanyu Lu 3, * , Xiaozhao Lu 1 , Shan Wang 1 , Lifeng Wang 4 , Mengying Wei 4 , Wei Lu 1 , Zhichao Du 1 , Zichen Ye 1 , Guodong Yang 4 , Fang Yuan 2 , Yanxia Ma 2 , Xiaoying Lei 1 , Zifan Lu 1 1 The State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an, China 2 Department of Clinical Laboratory, the Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, China 3 Department of Occupational and Environmental Health, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China 4 The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China * These authors contributed equally to this work Correspondence to: Zifan Lu, email: luzfliuq@fmmu.edu.cn Xiaoying Lei, email: leixiaoy@fmmu.edu.cn Keywords: Rab27A, colon cancer stem cells, NF-κB, secretion of cytokines, microenvironment Received: May 13, 2016 Accepted: August 11, 2016 Published: August 20, 2016 ABSTRACT Recent evidences have unveiled critical roles of cancer stem cells (CSCs) in tumorigenicity, but how interactions between CSC and tumor environments help maintain CSC initiation remains obscure. The small GTPases Rab27A regulates autocrine and paracrine cytokines by monitoring exocytosis of extracellular vesicles, and is reported to promote certain tumor progression. We observe that overexpression of Rab27A increased sphere formation efficiency (SFE) by increasing the proportion of CD44 + and PKH26 high cells in HT29 cell lines, and accelerating the growth of colosphere with higher percentage of cells at S phase. Mechanism study revealed that the supernatant derived from HT29 sphere after Rab27A overexpression was able to expand sphere numbers with elevated secretion of VEGF and TGF-β. In tumor implanting nude mice model, tumor initiation rates and tumor sizes were enhanced by Rab27A with obvious angiogenesis. As a contrast, knocking down Rab27A impaired the above effects. More importantly, the correlation between higher p65 level and Rab27A in colon sphere was detected, p65 was sufficient to induce up-regulation of Rab27A and a functional NF-κB binding site in the Rab27A promoter was demonstrated. Altogether, our findings reveal a unique mechanism that tumor environment related NF-κB signaling promotes various colon cancer stem cells (cCSCs) properties via an amplified paracrine mechanism regulated by higher Rab27A level.

A few warfarin pharmacogenetic dosing algorithms have been proposed,based on multiethnic or homogeneous populations, to estimate warfarin therapeutic doses. However, it remains to be proven that which algorithm is accurate in predicting warfarin dose in Chinese people. We selected eight warfarin dose predictive pharmacogenetic algorithms and retrospectively assessed the predictive accuracy of each algorithm in a total of 368 eligible outpatients by comparing the actual stable therapeutic dose to the dose predicted by the algorithm. Our results showed that a high level of performance was demonstrated by three algorithms,Gage et al., Anderson et al., and Wu et al., having a similar performance in coefficient of determination (R2) and percentage of patients predicted dose within 20% of actual dose. The Gage et al. algorithm had the lowest mean absolute error (MAE). These results indicated that the algorithm by Gage et al. provided a more accurate prediction than did the others,which suggests that this pharmacogenetic algorithm might be used in clinical practice to guide rational administration of warfarin.

Brown adipose tissue converts energy from food into heat via the mitochondrial uncoupling protein UCP1, defending against cold. In some conditions, inducible 'brown-like' adipocytes, also known as beige adipocytes, can develop within white adipose tissue (WAT). These beige adipocytes have characteristics similar to classical brown adipocytes and thus can burn lipids to produce heat. In the current study, we demonstrated that curcumin (50 or 100 mg/kg/day) decreased bodyweight and fat mass without affecting food intake in mice. We further demonstrated that curcumin improves cold tolerance in mice. This effect was possibly mediated by the emergence of beige adipocytes and the increase of thermogenic gene expression and mitochondrial biogenesis in inguinal WAT. In addition, curcumin promotes β3AR gene expression in inguinal WAT and elevates the levels of plasma norepinephrine, a hormone that can induce WAT browning. Taken together, our data suggest that curcumin can potentially prevent obesity by inducing browning of inguinal WAT via the norepinephrine-β3AR pathway.

The rapid detection of microcystin-leucine-arginine (MC-LR), the most highly toxic among MCs, is significantly important to environmental and human health protection and prevention of MC-LR from being used as a bioweapon. Although aptamers offer higher affinity, specificity, and stability with MC-LR than antibodies in the immunodetection of MC-LR due to steric hindrance between two antibodies and limited epitopes of MC-LR for use in a sandwich immunoassay, no sandwich immunoassay using an aptmer has been developed for MC-LR detection. This study is aimed at developing an aptamer-antibody immunoassay (AAIA) to detect MC-LR using a portable analyzer. The aptamers were immobilized onto the glass surface of a microchamber to capture MC-LR. MC-LR and horseradish peroxidase (HRP)-labeled antibody were pulled into the microchamber to react with the immobilized aptamer. The chemiluminescence (CL) catalyzed by HRP was tested by a photodiode-based portable analyzer. MC-LR at 0.5-4.0 μg/L was detected quantitatively by the AAIA, with a CL signal sensitivity of 0.3 μg/L. The assay took less than 35 min for a single sample and demonstrated a high specificity, detecting only MC-LR, but not MC-LA, MC-YR, or nodularin-R. The recovery of two spiked real environmental samples calculated as 94.5-112.7%. Therefore, this AAIA was proved to be a rapid and simple method to detect MC-LR in the field by a single analyst.

China has the highest incidence of hepatitis B virus (HBV) infection worldwide. HBV genotypes have variable impacts on disease pathogenesis and drug tolerance. We have developed a technically simple and accurate method for HBV genotyping that will be applicable to pre-treatment diagnosis and individualized treatment. Multiple sequence alignments of HBV genomes from GenBank were used to design primers and probes for genotyping of HBV A through H. The hybridization was carried out on nitrocellulose (NC) membranes with probes fixed in an array format, which was followed by hybrid amplification by an extension step with DNA polymerase to reinforce the double-stranded DNA hybrids on the NC membrane and subsequent visualization using an avidin–biotin system. Genotyping results were confirmed by DNA sequencing and bioinformatics analysis using the National Center for Biotechnology Information genotyping database, and compared with results from the line probe assay. The data show that multiple sequence alignment defined a 630 bp region in the HBV PreS and S regions that was suitable for genotyping. All genotyping significant single nucleotides in the region were defined. Two-hundred-and-ninety-one HBV-positive serum samples from Northwest Chinese patients were genotyped, and the genotyping rate from the new modified hybridization-extension method was 100% compared with direct sequencing. Compared with line probe assay, the newly developed method is superior, featuring reduced reaction time, lower risk of contamination, and increased accuracy for detecting single nucleotide mutation. In conclusion, a novel hybridization-extension method for HBV genotyping was established, which represents a new tool for accurate and rapid SNP detection that will benefit clinical testing.

Influenza A/H1N1 virus spreads worldwide and has been a threat to human health and the poultry industry. Although H1N1 lateral-flow immunoassay strips are available for the detection of 2009/A/H1N1 antigens, the specificity and sensitivity of these strips are limited. Because of the monodispersity, the strong magnetic signal and the stable brown color of superparamagnetic nanoparticles, which were employed in this study as label instead of commonly used colloidal gold particles. Two different monoclonal anti-HA (hemagglutinin) and anti-HA-tag mAbs were paired for conjugating with paramagnetic beads and immobilizing on the surface of nitrocellulose (NC) membrane as capture antibody respectively. After optimizing the experimental condition, we generated a superparamagnetic bead-based immunochromatographic strip. The strip could detect HA antigen from H1N1 influenza A virus sample sensitively, its detection limit was 100 pg/mL. It had low cross reactivity with H3N2 influenza A virus and did not detect influenza B virus. It had no false positive detection in all of the tested control samples. With the help of magnetic assay reader (MAR), the magnetic intensity on test lines could be recorded and quantified proportionally with the amount of antigens captured. Those properties were indeed superior to the colloidal gold-based strips. More importantly, the strip was affordable and easy to use. Conceivably, superparamagnetic bead-based immunochromatographic strip should be a valuable point-of-care test for the rapid and specific detection of influenza A virus.

To develop a simple micro-platform for gene mutation detection, we used a DNA hybridization approach in a combined microchannel. A glass groove immobilized with oligonucleotide probes by UV-crosslinking, and encased in a transparent heat-shrinkable polythene tube. After heat treatment, the polythene tube stretched tightly over the glass groove and was designated as a combined capillary chip (CCC). The CCC assay was optimized with 10 μL reaction solutions shuttling back and forth at 50 μL min−1 for 10 min, give a detection minimum of 0.1 nM target DNA sequences. In hepatitis B virus (HBV) YMDD mutations detection, 61.3% (92/150) was of a single genotype and it was authenticated with sequence analysis. The other 38.7% (58/150) was mixed genotype detected, but 18.9% (11/58) has a missed diagnosis in sequence analysis. It proved a higher sensitivity than sequence analysis. The CCC assay has a simple fabricating process, simple structure and higher specificity in gene mutation detection. These features are promising for clinical gene mutation analysis.