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Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.

Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. The JAK/STAT signaling pathway is involved in pancreatic cancer tumorigenesis. However, the prognostic value of JAK2 expression in resectable PDAC is unclear. Method. In this study, we performed a clinicopathological analysis of 62 resectable PDAC cases with a primary focus on survival. JAK2 expression was examined by immunohistochemistry. The relationship between JAK2 expression and clinicopathological features and prognosis was analyzed. Results. Survival curve analyses revealed that high levels of JAK2 expression predict a poor prognosis in resectable PDAC patients. Multivariate analysis confirmed that JAK2 expression can predict the prognosis of PDAC. Conclusions. Assessment of JAK2 protein expression may be a promising method to predict prognosis in patients with resectable PDAC.

The brown planthopper (BPH), Nilaparvata lugens, is a serious migratory rice pest, which is distributed in the broad area of the tropical and temperate Asian-Pacific region. However, we know little about key aspects regarding its evolution such as how they diverged and dispersed worldwide. By resequencing and analyzing 358 BPH genomes from 92 populations across the world, we uncover the genetic relationships among their worldwide populations and the history of their global dispersal. We recovered five genetic groups representing the major population structures. Of these, Australian BPHs were shown large genetic divergence with Asian BPHs; two distinct groups have formed in South and Southeast/East Asia that show strong genetic admixture in the southwest border regions of China and west Thailand with Myanmar; two local populations in Bangladesh and Fujian province of China, respectively, unexpectedly separated with surrounding populations. We also find the genetic similarity and closely phylogenetic relationships between majority of East Asian BPHs and Indo-china peninsula BPHs, indicating that Southeast Asia mainland is the major insect sources and overwintering sites for East Asia. Our study provides important molecular evidence to address BPH evolution and other key aspects of its biology such as insecticides resistance and rice varieties virulence.

Aim: The present study evaluated the value of serum ferritin (SF) level for the prognosis of patients with locally advanced pancreatic cancer (LAPC). Patients & methods: A total of 79 patients with LAPC treated by chemoradiotherapy were reviewed retrospectively. Pretreatment and post-treatment levels of SF were obtained. Results: Median progression-free survival (PFS) was 11.8 months; median overall survival was 18.3 months. A total of 36 patients with elevated SF level showed significantly worse overall survival and PFS than patients with low SF level (p = 0.002 and p = 0.004, respectively). In total, 17 patients showed normal SF level after chemoradiotherapy, and their median PFS was 3.2 months longer than that of patients whose SF levels were not restored after chemoradiotherapy. Conclusion: SF may serve as a valuable tool to assess prognosis and monitor chemoradiotherapy response in patients with LAPC.

Many studies have shown that human telomerase activity could play potential role as a diagnostic biomarker of pancreatic cancer (PaC). The aim of this meta-analysis is to summarize the clinical value of human telomerase activity in the diagnosis of PaC. Eligible studies from PubMed, Embase, the Cochrane Library, Web of Science, Ovid, Sci Verse, Science Direct, Scopus, BioMed Central, Biosis previews, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang databases were searched concerning the diagnostic value of human telomerase activity in PaC without language restriction. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratio (DOR) for human telomerase activity in the diagnosis of PaC were pooled. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. Evidence of heterogeneity was evaluated using the Chi-square and I (2) test. Meta-Disc 1.4 and Stata 12.0 software were used to analyze the data. Nine studies with a total 186 PaC patients and 132 control individuals were included in this meta-analysis. All of the included studies are of high quality (QUADAS score ≥10). The summary estimate was 0.83 (95 % confidence interval (CI), 95 % CI = 0.77-0.88) for sensitivity and 0.72 (95 % CI = 0.64-0.79) for specificity. The positive likelihood (PLR), negative likelihood (NLR), and diagnostic odds (DOR) ratios were 3 (95 % CI = 1.67-5.41), 0.25 (95 % CI = 0.13-0.46), and 3 (95 % CI = 4.91-43.23), respectively. The area under the summary ROC curve (AUC) and Q* index for the diagnosis of PaC were 0.88 and 0.81, respectively. Our study demonstrates that telomerase could be a useful tumor marker for PaC diagnosis. Although more studies are needed to highlight the theoretical strengths, these results will provide theoretical basis for bringing telomerase activity detection into PaC screening plan.

Annonaceous acetogenins (ACGs) are one of the most interesting classes of natural products appearing in the past two decades. Here, we studied the antitumor activity and toxicity relationship of ACGs including annosquamin B (1), bullatacin (2) and annosquatin B (3) in vivo. A single intraperitoneal (i.p.) injection of 100 μg/kg of annosquamin B, bullatacin and annosquatin B did not cause side effects in normal mice. Bullatacin treatment with five doses of 25 and 50 μg/kg in H22 hepatoma cells bearing mice resulted in about 61% reduction in tumor growth with hematologic parameters increased significantly in normal mice. Annosquamin B and annosquatin B treatments with 10 doses of 25, 50 and 100 μg/kg in the H22 hepatoma cells transplantation tumor model mice resulted in maximum 53.7% and 58.7% reduction in tumor growth, respectively, and did not cause severe side effects in normal mice. This study provided the evidence that adjacent bis-THF ACGs showed higher antitumor activity and toxicity than mono-THF and nonadjacent bis-THF ACGs in vivo. Furthermore, it was found that bullatacin led to liver and kidney toxicity via increasing calcium concentration, ROS production, and Bax expression and Bax/Bcl-2 ratio in rats with repeated treatment with bullatacin for 3 weeks.

A Cripavirus-like long unique sequence was identified during transcriptome sequencing of the brown planthopper (BPH), Nilaparvata lugens. This unique sequence demonstrated high similarity with the whole-genome sequence of cricket paralysis virus, including 5′ and 3′ untranslated regions; thus we considered it the whole genome of a new virus. We propose that the virus be named Nilaparvata lugens C virus (NlCV). The plus-strand RNA genome spanned 9144 nt, excluding a 3′ poly(A) tail with two large ORFs encoding structural and non-structural proteins, respectively. Detection of NlCV in BPH honeydew raised the hypothesis of horizontal transmission of the virus. Honeydew from viruliferous BPHs was used to feed non-viruliferous insects, the results of which indicated that the BPH could acquire NlCV through feeding and that the virus could multiply in the insect body. A tissue-specific distribution test using real-time quantitative PCR demonstrated that NlCV was mainly present in the reproductive organs, and the virus was detected in eggs laid by viruliferous female insects using nested PCR, indicating the possibility of vertical transmission as well. As no significant symptom was detected in the viruliferous BPH, NlCV is considered a new commensal virus of BPH. Interestingly, this virus was also detected in two other hemipteran insects, the white-backed planthopper and the horned gall aphid, indicating that NlCV might be present in many other hemipteran insects and have a wide host range.

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3&ndash, 4N0&ndash, 3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70&ndash, 80 Gy), the lymph node&ndash, positive area (60&ndash, 70 Gy), and the lymph node&ndash, negative area (50&ndash, 60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan&ndash, Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis. During the median follow-up of 3.9 years (range: 1&ndash, 5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp, the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55, p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years. Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

MicroRNA (miR)-216a expression is significantly downregulated in human pancreatic cancer, however, the underlying mechanism remains unknown. In the present study, we aimed to identify and characterize the direct target gene and potential function of miR-216a in pancreatic cancer cells. Bioinformatics analysis and dual-luciferase reporter gene assay showed that Janus kinase 2 (JAK2) was a direct target gene of miR-216a. Quantitative polymerase chain reaction and western blot analysis demonstrated that miR-216a decreased the mRNA and protein levels of JAK2 in pancreatic cancer cells. Phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was also downregulated by miR-216a, whereas the anti-miR-216a treatment had an opposite effect. Treatment of pancreatic cancer cells with miR-216a significantly inhibited cell growth and promoted cell apoptosis. In addition, the downstream genes of JAK2/STAT3, survivin and X-linked inhibitor of apoptosis protein, which are anti‑apoptotic genes, were also decreased by miR-216a. Moreover, miR-216a overexpression markedly inhibited the JAK2/STAT3 signaling pathway and xenograft tumor growth in vivo. Compared with miR-216a treatment, anti-miR-216a treatment exhibited opposite effects throughout the entire experiment, confirming the inhibitory effect of miR-216a on pancreatic cancer by regulating the JAK2/STAT3 signaling pathway. The results provided evidence that miR-216a targeting JAK2 negatively regulated the development of pancreatic cancer cells and may be used to develop a miRNA-based therapeutic strategy against pancreatic cancer.