Autophagy-mediating microRNAs in cancer chemoresistance.

Chemoresistance is a complex phenomenon responsible for failure in response to chemotherapy agents and more than 90% of deaths in cancer patients. MicroRNAs (miRNAs), as a subgroup of non-coding RNAs with lengths between 21 and 25 nucleotides, are involved in various cancer processes like chemoresistance via interacting with their target mRNAs and suppressing their expression. Autophagy is a greatly conserved procedure involving the lysosomal degradation of cytoplasmic contents and organelles to deal with environmental stresses like hypoxia and starvation. Autophagy contributes to response to chemotherapy agents: autophagy can act as a protective mechanism for mediating the resistance in response to chemotherapy or can induce autophagic cell death and mediate the sensitivity to chemotherapy. On the other hand, one of the processes targeted by microRNAs in the regulation of chemoresistance is autophagy. Hence, we studied the literatures on chemoresistance mechanisms, the miRNAs' role in cancer, and the miRNAs' role in chemoresistance by modulating autophagy. Graphical Abstract.

Bioelectrochemical Ammoniation Coupled with Microbial Electrolysis for Nitrogen Recovery from Nitrate in Wastewater.

Nitrate-N in wastewaters is hard to be recovered because it is difficult to volatilize with an opposite charge to ammonium. Here, we have proved the feasibility of dissimilatory nitrate reduction to ammonia (DNRA) by the easy-acclimated mixed electroactive bacteria, achieving the highest DNRA efficiency of 44%. It was then coupled with microbial electrolysis to concentrate ammonium by a factor of 4 in the catholyte for recovery. The abundance of electroactive bacteria in the biofilm before nitrate addition, especially Geobacter spp., was found to determine the DNRA efficiency. As the main competitors of DNRA bacteria, the growth of denitrifiers was more sensitive to C/N ratios. The DNRA microbial community contrarily showed a stable and recoverable ammoniation performance over C/N ratios ranging from 0.5 to 8.0. A strong competition of the electrode and nitrate on electron donors was observed at the early stage (15 d) of electroactive biofilm formation, which can be weakened when the biofilm was mature on 40 d. Quantitative PCR showed a significant increase in nirS and nrfA transcripts in the ammoniation process. nirS was inhibited significantly after nitrate depletion while nrfA was still upregulated. These findings provided a novel way to recover nitrate-N using organic wastes as both electron donor and power, which has broader implications on the sustainable wastewater treatment and the ecology of nitrogen cycling.

[From random mutagenesis to precise genome editing: the development and evolution of genome editing techniques in Drosophila].

Drosophila melanogaster, an important model organism for studying life science, has contributed more to the research of genetics, developmental biology and biomedicine with the development of genome editing techniques. Drosophila genome-editing techniques have evolved from random mutagenesis to precise genome editing and from simple mutant construction to diverse genome editing methods since the 20th century. Chemical mutagenesis, using Ethyl methanesulfonate (EMS), is an important technique to study gene function in forward genetics, however, the precise knockout of Drosophila genes could not be achieved. The gene targeting technology, based on homologous recombination, has accomplished the precise editing of Drosophila genome for the first time, but with low efficiency. The CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)-mediated precise genome editing is simple, fast and highly efficient compared with the gene targeting technology in Drosophila. In this review, we focus on Drosophila gene knockout, and summarize the evolution of genome editing techniques in Drosophila, emphasizing the development and applications of gene targeting, zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR/Cas9 techniques.

Drosophila Ectoderm-expressed 4 modulates JAK/STAT pathway and protects flies against Drosophila C virus infection.

Sterile alpha and HEAT/Armadillo motif-containing protein (SARM) is conserved in evolution and negatively regulates TRIF-dependent Toll signaling in mammals. The SARM protein from Litopenaeus vannamei and its Drosophila orthologue Ectoderm-expressed (Ect4) are also involved in immune defense against pathogen infection. However, the functional mechanism of the protective effect remains unclear. In this study, we show that Ect4 is essential for the viral load in flies after a Drosophila C virus (DCV) infection. Viral load is increased in Ect4 mutants resulting in higher mortality rates than wild-type. Overexpression of Ect4 leads to a suppression of virus replication and thus improves the survival rate of the animals. Ect4 is required for the viral induction of STAT-responsive genes, TotA and TotM. Furthermore, Ect4 interacts with Stat92E, affecting the tyrosine phosphorylation and nuclear translocation of Stat92E in S2 cells. Altogether, our study identifies the adaptor protein Ect4 of the Toll pathway contributes to resistance to viral infection and regulates JAK/STAT signaling pathway.

The Role of Mesenchymal Stem Cells in the Induction of Cancer-Stem Cell Phenotype.

Cancer stem cells (CSCs) modify and form their microenvironment by recruiting and activating specific cell types such as mesenchymal stem cells (MSCs). Tumor-infiltrating MSCs help to establish a suitable tumor microenvironment for the restoration of CSCs and tumor progression. In addition, crosstalk between cancer cells and MSCs in the microenvironment induces a CSC phenotype in cancer cells. Many mechanisms are involved in crosstalk between CSCs/cancer cells and MSCs including cell-cell interaction, secretion of exosomes, and paracrine secretion of several molecules including inflammatory mediators, cytokines, and growth factors. Since this crosstalk may contribute to drug resistance, metastasis, and tumor growth, it is suggested that blockade of the crosstalk between MSCs and CSCs/cancer cells can provide a new avenue to improving the cancer therapeutic tools. In this review, we will discuss the role of MSCs in the induction of cancer stem cell phenotype and the restoration of CSCs. We also discuss targeting the crosstalk between MSCs and CSCs/cancer cells as a therapeutic strategy.

Drug-eluting bead transarterial chemoembolization (TACE) exhibits superior efficacy and equal tolerance to conventional TACE in hepatocellular carcinoma patients with conventional TACE history.

OBJECTIVE: Multiple conventional transarterial chemoembolization (cTACE) procedures would cause treatment resistance in hepatocellular carcinoma (HCC) patients, whether drug-eluting bead transarterial chemoembolization (DEB-TACE) would resolve this issue is a necessary topic. Thus, this study aimed to compare the efficacy and safety between DEB-TACE and cTACE in HCC patients with cTACE treatment history. METHODS: Totally, 134 HCC patients with cTACE treatment history were retrospectively reviewed. They were categorized into DEB-TACE group (N = 70) and cTACE group (N = 64) based on the current treatment they received. RESULTS: After 1-month treatment, DEB-TACE group exhibited an elevated objective response rate (ORR) (71.9% vs. 47.3%, P = 0.008) while similar disease control rate (DCR) (93.0% vs. 81.8%, P = 0.074) compared to cTACE group. Besides, after 3-month treatment, DEB-TACE group also displayed higher ORR (68.4% vs. 44.1%, P = 0.038) and DCR (81.6% vs. 58.8%, P = 0.034) compared to cTACE group. Furthermore, the median progression-free survival (PFS) (11.5 months vs. 6.5 months P = 0.014) and overall survival (OS) (18.5 months vs. 13.0 months, P = 0.025) were longer in DEB-TACE group compared to cTACE group. Moreover, DEB-TACE (vs. cTACE) independently correlated with prolonged PFS (P = 0.021) and OS (P = 0.017) after adjustment by multivariate Cox's regression. Besides, most of liver function indexes were similar before and after treatment between these two groups. Also, the commonly observed adverse events were pain, fever, nausea/vomiting and blood pressure elevation with similar incidence between these two groups (all P > 0.050). CONCLUSION: DEB-TACE exhibits superiority over cTACE in HCC patients with cTACE treatment history.

WSV181 inhibits JAK/STAT signaling and promotes viral replication in Drosophila.

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway plays a critical role in host defense against viral infections. Here, we report the use of the Drosophila model system to investigate the modulation of the JAK/STAT pathway by the white spot syndrome virus (WSSV) protein WSV181. WSV181 overexpression in transgenic flies resulted in the downregulation of STAT92E and STAT92E-targeted genes. This result indicates that WSV181 can suppress JAK/STAT signaling by controlling STAT92E expression. An infection experiment was carried out on transgenic Drosophila infected with Drosophila C virus and on Litopenaeus vannamei injected with recombinant WSV181 and WSSV. The increased viral load and suppressed transcript levels of JAK/STAT pathway components indicate that WSV181 can promote viral proliferation by inhibiting the JAK/STAT pathway. This study provided evidence for the role of WSV181 in viral replication and revealed a new mechanism through which WSSV evades host immunity to maintain persistent infection.

Prognostic significance of coronary artery calcium scoring and single-photon emission computed tomographic myocardial perfusion imaging on major adverse cardiac events in patients at low risk for suspected coronary artery disease.

Background: To explore the prognostic value of combination of coronary artery calcium scoring (CACS) and single-photon emission computed tomography (SPECT) on the long-term risk of major adverse cardiac events (MACEs) in Chinese patients at low risk of suspected coronary artery disease (CAD).Methods: The medical records of 1876 adult patients who were referred for clinically indicated non-invasive CAD detection with SPECT/CT from January 2011 to December 2013 were retrospectively reviewed. The primary outcome was the occurrence of MACEs, including cardiac death, non-fatal myocardial infarction (MI), unstable angina (UA), and late revascularisation.Results: During a median follow-up of 28.4 ± 9.1 months, 210 patients were identified to have at least one MACEs. Multivariate Cox regression analysis showed that patients with abnormal SPECT had more MACEs compared to those with normal SPECT (HR = 3.41, 95% CI: 2.08-4.71, p < .01). Both moderate (HR = 3.35, 95% CI: 1.76-4.32, p < .01) and severe CACS (HR = 6.56, 95% CI: 4.71-8.23, p < .01) were associated with occurrence of HACEs compared with normal CACS. Moreover, interaction terms for CACS and SPECT findings were reported to be significantly associated with MACE outcomes (p < .01).Conclusions: CACS and SPECT provided both independent and compensatory prognostic information for risk of MACE in patients at low risk of suspected CAD. Our findings strongly support adding a CACS testing in addition to SPECT in asymptomatic patients to better define the risk of cardiac events during follow-up.

Stress-induced phosphoprotein 1 promotes pancreatic cancer progression through activation of the FAK/AKT/MMP signaling axis.

BACKGROUND: Dependent on the extent of adenosine triphosphate (ATP) hydrolysis and/or ATP/ADP exchange, the stress-induced phosphoprotein 1 (STIP1) mediates molecular interaction and complex formation between the molecular chaperones heat shock protein (Hsp)70 and Hsp90. The overexpression of STIP1 is increasingly being documented in various human malignancies, including ovarian, cholangiocellular, renal and gastric cancers. However, the role of STIP1 in pancreatic cancer (PANC) and probable molecular mechanism remains largely unexplored. METHODS & RESULTS: In the present study, using clinical samples (n = 88) and human PANC cell lines PANC-1, Capan-2, SW1990, and BxPC-3, we demonstrated that STIP1 is aberrantly expressed in human PANC tissues or cell lines compared to adjacent non-tumor pancreas samples or human pancreatic duct epithelial cells (HPDEC), respectively. Clinicopathological correlation studies revealed significant positive correlation between high STIP1 expression and lymph node involvement (p = 0.001), cancer metastasis (p = 0.002), microvascular invasion (p = 0.002), advance TNM stage (p = 0.024), perineural invasion (PNI; p = 0.013), and cancer-related death (p = 0.002) among patients with PANC. Univariate and multivariate analyses indicate that STIP1overexpression is an independent prognostic factor of PANC. Furthermore, STIP1 knockdown significantly inhibit the migration and invasive ability of PANC-1 and SW1990 cells, while downregulating N-cadherin and Vimentin, but upregulating E-cadherin mRNA expression levels, concurrently. We also demonstrated that STIP1 knockdown suppressed p-FAK, p-AKT, MMP2, MMP9, and Slug protein and mRNA expression levels, thus, indicating, at least in part, a role for STIP1 in the activation of FAK/AKT/MMP signaling. CONCLUSION: Taken together, our results demonstrate a critical role for STIP1 in cancer metastasis, disease progression and poor prognosis, as well as, provide evidence suggestive of the therapeutic efficacy of STIP1-mediated targeting of the FAK/AKT/MMP signaling axis in patients with PANC.

[CT and pathological manifestations of intraductal papillary mucinous neoplasm of pancreas: a comparative study].

OBJECTIVE: To evaluate the diagnostic value of CT in pancreas intraductal papillary mucinous neoplasm (IPMN) by analyzing its CT feature and pathological findings. METHODS: The clinical and CT data was analyzed among 39 patients with IPMN whose diagnosis was confirmed by pathology. The CT manifestations were classified into 3 types: simple main pancreatic duct enlargement; main pancreatic duct enlargement combined with pancreatic cystic lesion; and simple pancreatic cystic lesion. The correlation between the CT types and Takada pathological types (main duct type, branch type, and mixed type) was analyzed. All the cases were pathologically classified into benign and malignant/boundary groups. Statistical tests of the difference of CT features (mural nodule, septa, size, caliber of main pancreatic duct and common bile duct) between the 2 groups were performed. RESULTS: The CT type I matched the main duct type, the CT type II mainly matched the branch type and mixed type, and the CT type III matched the branch type (P < 0.001). The probability of benign lesion was 92% with no mural nodule in the lesion, while the probability of benign lesion was only 42% with mural nodule presented (P = 0.003). In terms of the septa, there was no significant difference between benign and malignant lesions (P = 0.793). The size of malignant/boundary lesions exceeded that of benign lesions (P = 0.016). There were no significant difference in calibers of main pancreatic duct and common bile duct between the benign and malignant/ boundary groups. Without considering pathological grouping the caliber of main pancreatic duct exceeded that of the common bile duct in all the cases (P = 0.02). CONCLUSION: CT typing of IPMN well matches the pathological typing which benefits the CT diagnosis of IPMN. The caliber of main pancreatic duct usually exceeds that of common bile duct in IPMN. This feature contributes to its diagnosis.

Repeated transfer enriches highly active electrotrophic microbial consortia on biocathodes in microbial fuel cells.

Cathodic oxygen reduction catalyzed by autotrophic bacteria instead of a precious metal is a promising method to make use of microbial fuel cells (MFCs) in wastewater treatment with electricity production. However, the ecology of electrotrophic microbial consortia in wastewater systems that function as the catalyst for cathodic oxygen reduction is complicated and the electron transfer mechanisms are still unknown, which prevents further improvements of the biocathode performance. Enriched by the repeated transfer of a mature electrotrophic microbial consortia to new cathodes over 10 generations in 230 days, the start-up time was shortened from 21.4 to 7.6 days and the maximum current densities over the potential range of 0.5 to - 0.3 V increased by up to 112%, from 75 ±â€¯5 A m-3 to 159 ±â€¯3 A m-3, which was further confirmed in half-cell biocathode systems. The electrotrophic microbial consortia approached a relatively stable state after 8 generations. Acinetobacter, which is a member of Proteobacteria, was selectively enriched after 10 generations, which was closely related to the current production. Nitrospiraceae and Nitrosomonas may jointly perform a nitrogen cycling metabolic process and promote cathodic bioelectron transfer. Our findings confirmed that the electrotrophic microbial consortia on the cathode was able to be specifically evolved, leading to higher electroactivity, and also revealed which bacteria in fresh water are closely related to cathodic electron transfer.