This study aimed at exploring the role of microRNA-21 (miR-21) in predicting brain metastases (BM) from non-small cell lung cancer (NSCLC).
A total of 132 NSCLC patients, including 68 patients with BM and 64 patients without BM, were included in the study. NSCLC cells were collected and assigned to the inhibitor (IN) group, the mock group, and the negative control (NC) group. The quantitative real-time polymerase chain reaction assay was used to detect the miR-21 expression. Cell proliferation, migration, invasion, and apoptosis were detected by colony-forming assay, MTT assay, transwell assay, and flow cytometry, respectively. Angiogenesis was measured by endothelial cell tube formation assay.
The miR-21 expression was higher in NSCLC patients with BM than in those without BM. The miR-21 expression in the IN group was lower than that in the NC and mock groups. Compared with the NC and mock groups, the values of optical density (OD) and the colony-forming number decreased in the IN group. Compared with the NC and mock groups, cell invasion and migration abilities significantly reduced in the IN group. The IN group had higher apoptosis rate than the NC and mock groups. The tube length was shorter and the number of junction points was less in the IN group in comparison to the NC and mock groups.
miR-21 might be a potential biomarker for the development of BM in NSCLC patients and could promote the proliferation, migration, invasion, and angiogenesis of NSCLC cells.
non-small cell lung cancer; microRNA-21; brain metastases; angiogenesis
Nasopharyngeal carcinoma (NPC) is a multi-factorial malignancy closely associated with environmental factors, genetic factors and Epstein-Barr virus infection. Human leukocyte antigen (HLA) complex, specially the region near HLA-A locus, was regarded as a major candidate region bearing NPC genetic susceptibility loci in many previous studies including two recent genome-wide association (GWA) studies. To provide further evidence for the NPC susceptibility in the region near HLA-A locus based on other previous studies, we carried out a two-stage hospital-based case control association study including 535 sporadic NPC patients and 525 cancer-free control subjects from Guangdong, a high prevalence area of NPC in China.
38 tag SNPs were initially selected by Heploview from the segment around HLA-A locus (from D6S211 to D6S510) and genotyped on GenomeLab SNPstream platform in 206 cases and 180 controls in the stage 1. Subsequently, the stage 1 significant SNPs and 17 additional SNPs were examined on another platform (Sequenom iPlex Assay) in another independent set of study population including 329 cases and 345 controls.
Totally eight SNPs from the segment from D6S211 to D6S510 within HLA complex were found to be significantly associated with NPC. Two of the most significant SNPs (rs9260734 and rs2517716) located near to HLA-A and HCG9 respectively were in strong LD with some other SNPs of this region reported by two previous GWA studies. Meanwhile, Meanwhile, novel independent susceptibility loci (rs9404952, Pcombined = 6.6 × 10-5, OR combined = 1.45) was found to be close to HLA-G.
Therefore, our present study supports that the segment from D6S211 to D6S510 in HLA complex region might contain NPC susceptibility loci which indeed needs to be fully investigated in the future.
Nasopharyngeal carcinoma; Single nucleotide polymorphism; Human leukocyte antigen (HLA)
The methylotrophic yeast, Pichia pastoris, offers the possibility to generate a high amount of recombinant proteins in a fast and easy way to use expression system. Being a single-celled microorganism, P. pastoris is easy to manipulate and grows rapidly on inexpensive media at high cell densities. A simple and direct method for the selection of high-producing clones can dramatically enhance the whole production process along with significant decrease in production costs.
A visual method for rapid selection of high-producing clones based on mannanase reporter system was developed. The study explained that it was possible to use mannanase activity as a measure of the expression level of the protein of interest. High-producing target protein clones were directly selected based on the size of hydrolysis holes in the selected plate. As an example, the target gene (9elp-hal18) was expressed and purified in Pichia pastoris using this technology.
A novel methodology is proposed for obtaining the high-producing clones of proteins of interest, based on the mannanase reporter system. This system may be adapted to other microorganisms, such as Saccharomyces cerevisiae for the selection of clones.
Early anastomotic leakage (AL), usually defined as leakage within 30 post-operative days, represents a severe entity. However, mounting evidence has indicated that majorities of leakage occur within one week after surgery, making late AL rarity. Here we analyzed 101 consecutive colorectal AL, all of which occurred within 30 post-operative days, during Jan 2013 and Dec 2015 in cancer hospital of Fudan University. AL occurring within 5 post-operative days was defined as very early AL (vE-AL). We evaluated risk factors of vE-AL compared with non-vEAL and correlated with post-leakage peritonitis and need of relaparatomy. We found that AL occurred at median time of 7 days after surgery. 23 cases were vE-AL. Reconstruction of post-peritoneum for mid-low rectal carcinoma significantly reduced incidence of vE-AL compared with non-vE-AL (p = 0.042). Patients with vE-AL was associated with presence of peritonitis (p = 0.031), the latter significantly correlated with increased re-operation rate (p = 6.8E-13). Besides, patients with vE-AL trended to correlate with increased re-operation rate after leakage (p = 0.088). In concludsion, vE-AL occurring within 5 post-operative days represents a severe subtype associated with general peritonitis and need of relaparatomy.
In the last decade, scrub typhus (ST) has been emerging or re-emerging in some areas of Asia, including Guangzhou, one of the most affected endemic areas of ST in China.
Based on the data on all cases reported in Guangzhou from 2006 to 2014, we characterized the epidemiological features, and identified environmental determinants for the spatial distribution of ST using a panel negative binomial model.
A total of 4821 scrub typhus cases were reported in Guangzhou during 2006―2014. The annual incidence increased noticeably and the increase was relatively high and rapid in rural townships and among elderly females. The majority of cases (86.8%) occurred during May―October, and farmers constituted the majority of the cases, accounting for 33.9% in urban and 61.6% in rural areas. The number of housekeeper patients had a rapid increment in both rural and urban areas during the study period. Atmospheric pressure and relative humidity with lags of 1 or 2 months, distributions of broadleaved forest and rural township were identified as determinants for the spatiotemporal distribution of scrub typhus.
Our results indicate that surveillance and public education need to be focused on the elderly farmers in rural areas covered with broadleaf forest in southern China.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-016-2153-3) contains supplementary material, which is available to authorized users.
The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.
Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa.
CTCF is an essential chromatin regulator implicated in important nuclear processes including in nuclear organization and transcription. Herpes Simplex Virus-1 (HSV-1) is a ubiquitous human pathogen, which enters productive infection in human epithelial and many other cell types. CTCF is known to bind several sites in the HSV-1 genome during latency and reactivation, but its function has not been defined. Here, we report that CTCF interacts extensively with the HSV-1 DNA during lytic infection by ChIP-seq, and its knockdown results in the reduction of viral transcription, viral genome copy number and virus yield. CTCF knockdown led to increased H3K9me3 and H3K27me3, and a reduction of RNA pol II occupancy on viral genes. Importantly, ChIP-seq analysis revealed that there is a higher level of CTD Ser2P modified RNA Pol II near CTCF peaks relative to the Ser5P form in the viral genome. Consistent with this, CTCF knockdown reduced the Ser2P but increased Ser5P modified forms of RNA Pol II on viral genes. These results suggest that CTCF promotes HSV-1 lytic transcription by facilitating the elongation of RNA Pol II and preventing silenced chromatin on the viral genome.
The development of monoclonal antibodies (mAb) with affinity to small molecules can be a time-consuming process. To evaluate shortening the time for mAb production, we examined mouse antisera at different time points post-immunization to measure titer and to evaluate the affinity to the immunogen PBA (pyrene butyric acid). Fusions were also conducted temporally to evaluate antibody production success at various time periods. We produced anti-PBA antibodies 7 weeks post-immunization and selected for anti-PAH reactivity during the hybridoma screening process. Moreover, there were no obvious sensitivity differences relative to antibodies screened from a more traditional 18 week schedule. Our results demonstrate a more time efficient immunization strategy for anti-PAH antibody development that may be applied to other small molecules.
PAH; mAbs; Immunization strategy; anti-sera titer; affinity; fusion
Oral preexposure prophylaxis (PrEP) trials report disparate efficacy attributed to variable adherence. HPTN 066 was conducted to establish objective, quantitative benchmarks for discrete, regular levels of adherence using directly observed dosing of tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC). Healthy, HIV-uninfected men and women were randomized to one of four oral regimens of fixed-dose TDF 300 mg/FTC 200 mg tablet for 5 weeks with all doses observed: one tablet weekly (one/week), one tablet twice weekly (two/week), two tablets twice weekly (four/week), or one tablet daily (seven/week). Trough serum TFV and FTC, peripheral blood mononuclear cell (PBMC), and CD4+ TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) concentrations were determined throughout dosing and 2 weeks after the last dose. Rectosigmoidal, semen, and cervicovaginal samples were collected for drug assessment at end of dosing and 2 weeks later in a subset of participants. The 49 enrolled participants tolerated the regimens well. All regimens achieved steady-state concentrations by the second dose for serum TFV/FTC and by 7 days for PBMC TFV-DP/FTC-TP. Steady-state median TFV-DP predose concentrations demonstrated dose proportionality: one/week 1.6 fmol/106 PBMCs, two/week 9.1, four/week 18.8, seven/week, 36.3. Further, TFV-DP was consistently quantifiable 2 weeks after the last dose for the ≥4/week regimens. Adherence benchmarks were identified using receiver operating characteristic curves, which had areas under the curve ≥0.93 for all analytes in serum and PBMCs. Intersubject and intrasubject coefficients of variation (%CV) ranged from 33% to 63% and 14% to 34%, respectively, for all analytes in serum and PBMCs. Steady-state PBMC TFV-DP was established earlier and at lower concentrations than predicted and was the only analyte demonstrating predose concentration dose proportionality. Steady-state daily dosing serum TFV and PBMC TFV-DP was consistent with highly effective PrEP clinical trials. HPTN 066 provides adherence benchmarks for oral TFV/FTC regimens to assist interpreting study outcomes.
To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV).
This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.
The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal.
CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.
Cirrhosis; Co-infections; Liver failure; Liver decompensation; Stages of hepatitis B virus infection
This paper presents data related to an article entitled “Green tea flavor determinants and their changes over manufacturing processes” (Han et al., 2016) . Green tea samples were prepared with steaming and pan firing treatments from the tender leaves of tea cultivars ‘Bai-Sang Cha’ (‘BAS’) and ‘Fuding-Dabai Cha’ (‘FUD’). Aroma compounds from the tea infusions were detected and quantified using HS-SPME coupled with GC/MS. Sensory evaluation was also made for characteristic tea flavor. The data shows the abundances of the detected aroma compounds, their threshold values and odor characteristics in the two differently processed tea samples as well as two different cultivars.
The ability to control the level of gene expression is a major quest in biology. A widely used approach employs deletion of a nonessential gene of interest (knockout), or multi-step recombineering to move a gene of interest under a repressible promoter (knockdown). However, these genetic methods are laborious, and limited for quantitative study. Here, we report a tunable CRISPR-cas system, “tCRISPRi”, for precise and continuous titration of gene expression by more than 30-fold. Our tCRISPRi system employs various previous advancements into a single strain: (1) We constructed a new strain containing a tunable arabinose operon promoter PBAD to quantitatively control the expression of CRISPR-(d)Cas protein over two orders of magnitude in a plasmid-free system. (2) tCRISPRi is reversible, and gene expression is repressed under knockdown conditions. (3) tCRISPRi shows significantly less than 10% leaky expression. (4) Most important from a practical perspective, construction of tCRISPRi to target a new gene requires only one-step of oligo recombineering. Our results show that tCRISPRi, in combination with recombineering, provides a simple and easy-to-implement tool for gene expression control, and is ideally suited for construction of both individual strains and high-throughput tunable knockdown libraries.
Maize foundation parents (FPs) play no-alternative roles in hybrid breeding because they were widely used in the development of new lines and hybrids. The combination of different identity-by-descent (IBD) segments and genes could account for the formation patterns of different FPs, and knowledge of these IBD regions would provide an extensive foundation for the development of new candidate FP lines in future maize breeding. In this paper, a panel of 304 elite lines derived from FPs, i.e., B73, 207, Mo17, and Huangzaosi (HZS), was collected and analyzed using 43,252 single nucleotide polymorphism (SNP) markers. Most IBD segments specific to particular FP groups were identified, including 116 IBD segments in B73, 105 in Mo17, 111 in 207, and 190 in HZS. In these regions, 423 quantitative trait nucleotides (QTNs) associated with 15 agronomic traits and 804 candidate genes were identified. Some known adaptation-related genes, e.g., dwarf8 and vgt1 in HZS, zcn8 and epc in Mo17, and ZmCCT in 207, were validated as being tightly linked to particular IBD segments. In addition, numerous new candidate genes were also identified. For example, GRMZM2G154278 in HZS, which belongs to the cell cycle control family, was closely linked to a QTN of the ear height/plant height (EH/PH) trait; GRMZM2G051943 in 207, which encodes an endochitinase precursor (EP) chitinase, was closely linked to a QTN for kernel density; and GRMZM2G170586 in Mo17 was closely linked to a QTN for ear diameter. Complex correlations among these genes were also found. Many IBD segments and genes were included in the formation of FP lines, and complex regulatory networks exist among them. These results provide new insights on the genetic basis of complex traits and provide new candidate IBD regions or genes for the improvement of special traits in maize production.
Increasing ammonia emissions could exacerbate air pollution caused by fine particulate matter (PM2.5). Therefore, it is of great importance to investigate ammonia oxidation in PM2.5. This study investigated the diversity, abundance and activity of ammonia oxidizing archaea (AOA), ammonia oxidizing bacteria (AOB) and complete ammonia oxidizers (Comammox) in PM2.5 collected in Beijing-Tianjin-Hebei megalopolis, China. Nitrosopumilus subcluster 5.2 was the most dominant AOA. Nitrosospira multiformis and Nitrosomonas aestuarii were the most dominant AOB. Comammox were present in the atmosphere, as revealed by the occurrence of Candidatus Nitrospira inopinata in PM2.5. The average cell numbers of AOA, AOB and Ca. N. inopinata were 2.82 × 104, 4.65 × 103 and 1.15 × 103 cell m−3 air, respectively. The average maximum nitrification rate of PM2.5 was 0.14 μg (NH4+-N) [m3 air·h]−1. AOA might account for most of the ammonia oxidation, followed by Comammox, while AOB were responsible for a small part of ammonia oxidation. Statistical analyses showed that Nitrososphaera subcluster 4.1 was positively correlated with organic carbon concentration, and Nitrosomonas eutropha showed positive correlation with ammonia concentration. Overall, this study expanded our knowledge concerning AOA, AOB and Comammox in PM2.5 and pointed towards an important role of AOA and Comammox in ammonia oxidation in PM2.5.
Ferrites–bismuth ferrite is an intriguing option for medical diagnostic imaging device due to its magnetoelectric and enhanced near-infrared fluorescent properties. However, the embedded XFO nanoparticles are randomly located on the BFO membranes, making implementation in devices difficult. To overcome this, we present a facile bio-approach to produce XFe2O4–BiFeO3 (XFO–BFO) (X = Cr, Mn, Co, or Ni) membranes using Shewanella oneidensis MR-1. The perovskite BFO enhances the fluorescence intensity (at 660 and 832 nm) and surface potential difference (−469 ~ 385 meV and −80 ~ 525 meV) of the embedded spinel XFO. This mechanism is attributed to the interfacial coupling of the X–Fe (e− or h+) and O–O (h+) interfaces. Such a system could open up new ideas in the design of environmentally friendly fluorescent membranes.
Ferrite; Heterostructures; Hematite; Shewanella oneidensis MR-1; Fluorescence
A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterised by cartilage degeneration and debilitating pain, is that the severity of joint pain does not strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase Cδ (PKCδ), a key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease.
OA was induced in 10-week-old PKCδ null (PKCδ−/−) and wild-type mice by destabilisation of the medial meniscus (DMM) followed by comprehensive examination of the histology, molecular pathways and knee-pain-related-behaviours in mice, and comparisons with human biopsies.
In the DMM model, the loss of PKCδ expression prevented cartilage degeneration but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading enzymes in the joints of PKCδ-deficient DMM mice. Hyperalgesia was associated with stimulation of nerve growth factor (NGF) by fibroblast-like synovial cells and with increased synovial angiogenesis. Results from tissue specimens of patients with symptomatic OA strikingly resembled our findings from the OA animal model. In PKCδ null mice, increases in sensory neuron distribution in knee OA synovium and activation of the NGF-tropomyosin receptor kinase (TrkA) axis in innervating dorsal root ganglia were highly correlated with knee OA hyperalgesia.
Increased distribution of synovial sensory neurons in the joints, and augmentation of NGF/TrkA signalling, causes OA hyperalgesia independently of cartilage preservation.
Knee Osteoarthritis; Chondrocytes; Fibroblasts; Synovitis
High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5′dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes.
morphology-based tissue aptamer selection; thioaptamer; laser microdissection; targeted protein; ovarian cancer
Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue, defined as the fibrous connective tissue lined with synovium that surrounds the joint. The role of these alterations in FJC tissues in pain stimulation was also assessed.
Lumbar facet joints (FJs) were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no medical history of back pain. Histological analyses of the FJ were performed to assess general structure, cellular morphology, and proteoglycan content; immunohistochemistry was used to reveal inflammatory factors and neovascularization. Cytokine antibody array and quantitative real- time polymerase chain reaction (qPCR) were used to determine the production of multiple pro- and anti- inflammatory cytokines, and western blotting (WB) was used to assay for cartilage-degrading enzymes and pain mediators. Studies using ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues were also performed.
Increased neovascularization, infiltration of inflammatory cells, and pain-related axonal-promoting factors were observed in degenerative FJC tissues surgically obtained from symptomatic subjects; this was not seen in normal donor tissues. Increased angiogenic factor, VEGF, axonal promoting factor (NGF/TrkA) and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs compared to normal. The DRG and FJC tissue ex vivo co-culture results demonstrated that degenerative FJCs from subjects reporting severe LBP altered the functional properties of DRG sensory neurons, as reflected by the increased expression of inflammatory pain molecules.
Degenerative FJC tissues possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.
human facet joint capsular tissue; low back pain; inflammatory cytokines; angiogenesis; nerve ingrowth; inflammatory pain mediators
Background and Purpose
The epithelial sodium channel (ENaC) is expressed in vascular endothelial cells and is a negative modulator of vasodilation. However, the role of endothelial ENaCs in salt‐sensitive hypertension remains unclear. Here, we have investigated how endothelial ENaCs in Sprague‐Dawley (SD) rats respond to high‐salt (HS) challenge.
BP and plasma aldosterone levels were measured. We used patch‐clamp technique to record ENaC activity in split‐open mesenteric arteries (MAs). Western blot and Griess assay were used to detect expression of α‐ENaCs, eNOS and NO. Vasorelaxation in second‐order MAs was measured with wire myograph assays.
Functional ENaCs were observed in endothelial cells and their activity was significantly decreased after 1 week of HS diet. After 3 weeks of HS diet, ENaC expression was also reduced. When either ENaC activity or expression was reduced, endothelium‐dependent relaxation (EDR) of MAs, in response to ACh, was enhanced. This enhancement of EDR was mimicked by amiloride, a blocker of ENaCs. By contrast, HS diet significantly increased contractility of MAs, accompanied by decreased eNOS activity and NO levels. However, ACh‐induced release of NO was much higher in MAs isolated from HS rats than those from NS rats.
Conclusions and Implications
HS intake increased the BP of SD rats, but simultaneously enhanced EDR by reducing ENaC activity and expression due to feedback inhibition. Therefore, ENaCs may play an important role in endothelial cells allowing the vasculature to adapt to HS conditions.
This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer’s disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with non-carriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD.
APOE promoter; brain connectome; cognition; diffusion MRI; graph theory
Current food safety issues are deleteriously reshaping the lifestyle of the population in the developing world. The globalization of food supply impacts patterns of foodborne disease outbreaks worldwide, and consumers are having increased concern about microbiological food safety.
A total of 2305 samples including sauced meat, sausage, smoked meat, shrimp, sashimi and shellfish were collected from different farmer’s markets and supermarkets. The prevalence of selected foodborne pathogens was evaluated in cooked meat and seafood from 2010 to 2013 in Shandong Province, China.
The average contamination rate was 6.39% (93.1456) for the selected pathogens in cooked meat and 16.84% (143.849) for V. parahaemolyticus in seafood. For the selected pathogens, 0.55%, 1.03%, 1.17%, 3.64% and 16.84% samples were contaminated with E.coli O157: H7, Salmonella spp., L. monocytogenes, S. aureus and VP, respectively. There was a significant (P<0.05) difference in the contamination rate between the farmer’s markets and supermarkets.
The contamination was decreasing in cooked meat and maintaining a relatively high level in seafood from 2010 to 2013. E. coli O157: H7, S. aureus, L. monocytogenes and Salmonella spp. existed at a relatively low rate in retail foods. For VP, the contamination rate has been maintained at a relatively high level in Shandong Province in China. Moreover, cooked meat and seafood obtained from farmer’s markets are more susceptible to be contaminated compared to those from supermarkets.
Food safety; Foodborne pathogens; Cooked meat; Seafood
Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects.
Pancreatic cancer; translational medical research; review
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. Since PAs exposure is obscure and clinical presentation of HSOS is unspecific, it is challenge to establish the diagnosis of PAs-induced HSOS. Gynura segetum is one of the most wide-use herbals containing PAs. The aim of our study is to describe the features of contrast-enhanced computed tomography (CT) in gynura segetum-induced HSOS, and then determine diagnostic performance of radiological signs. We retrospectively analyzed medical records and CT images of HSOS patients (71 cases) and the controls (222 cases) enrolled from January 1, 2008, to Oct 31, 2015. The common findings of contrast CT in PAs-induced HSOS included: ascites (100%), hepatomegaly (78.87%), gallbladder wall thickening (86.96%), pleural effusion (70.42%), hepatic vein narrowing (87.32%), patchy liver enhancement (92.96%), and heterogeneous hypoattenuation (100%); of these signs, patchy enhancement and heterogeneous hypoattenuation were valuable features. Then, the result of diagnostic performance demonstrated that contrast CT possessed better performance in diagnosing PAs-induced HSOS compared with various parameters of Seattle criteria. In conclusion, the patients with PAs-induced HSOS display distinct radiologic features at CT-scan, which reveals that contrast-enhanced CT provides an effective noninvasive method for diagnosing PAs-induced HSOS.
Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.
Intensive care; Hematological malignancies; Prognostic factors; Asian countries