cGAS Mediates Inflammation by Polarizing Macrophages to M1 Phenotype via the mTORC1 Pathway.

Cyclic GMP-AMP synthase (cGAS), as a cytosolic DNA sensor, plays a crucial role in antiviral immunity, and its overactivation induces excess inflammation and tissue damage. Macrophage polarization is critically involved in inflammation; however, the role of cGAS in macrophage polarization during inflammation remains unclear. In this study, we demonstrated that cGAS was upregulated in the LPS-induced inflammatory response via the TLR4 pathway, and cGAS signaling was activated by mitochondria DNA in macrophages isolated from C57BL/6J mice. We further demonstrated that cGAS mediated inflammation by acting as a macrophage polarization switch, which promoted peritoneal macrophages and the bone marrow-derived macrophages to the inflammatory phenotype (M1) via the mitochondrial DNA-mTORC1 pathway. In vivo studies verified that deletion of Cgas alleviated sepsis-induced acute lung injury by promoting macrophages to shift from the M1 phenotype to the M2 phenotype. In conclusion, our study demonstrated that cGAS mediated inflammation by regulating macrophage polarization through the mTORC1 pathway, and it further provided a potential therapeutic strategy for inflammatory diseases, especially sepsis-induced acute lung injury.

TRIM50 promotes NLRP3 inflammasome activation by directly inducing NLRP3 oligomerization.

Tripartite motif protein (TRIM) 50 is a new member of the tripartite motif family, and its biological function and the molecular mechanism it is involved in remain largely unknown. The NOD-like receptor family protein (NLRP)3 inflammasome is actively involved in a wide array of biological processes while mechanisms of its regulation remain to be fully clarified. Here, we demonstrate the role of TRIM50 in NLRP3 inflammasome activation. In contrast to the conventional E3 ligase functions of TRIM proteins, TRIM50 mediates direct oligomerization of NLRP3, thereby suppressing its ubiquitination and promoting inflammasome activation. Mechanistically, TRIM50 directly interacts with NLRP3 through its RING domain and induces NLRP3 oligomerization via its coiled-coil domain. Finally, we show that TRIM50 promotes NLRP3 inflammasome-mediated diseases in mice. We thus reveal a novel regulatory mechanism of NLRP3 via TRIM50 and suggest that modulating TRIM50 might represent a therapeutic strategy for NLRP3-dependent pathologies.

Incidence and risk factors of postoperative delirium after pancreatic cancer surgery: a retrospective study.

PURPOSE: Postoperative delirium (POD) commonly occurs after major abdominal surgery and is associated with increased morbidity and mortality. There have been many studies on the relationship between POD and various surgeries, but research on POD after pancreatic cancer surgery is limited. The aim of this study was to identify the incidence and risk factors of POD after pancreatic cancer surgery. METHODS: The subjects of this retrospective analysis were 196 patients who were transferred for postoperative care after pancreatic cancer surgery, to a 12-bed critical care medicine ward at Shandong Provincial Hospital, affiliated with Shandong First Medical University, between January 2015 and December 2019. The patients were divided according to whether they suffered POD into a delirium group and a non-delirium group. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit and two independent medical practitioners analyzed all the data. Univariate and multiple logistic regression analyses were performed. RESULTS: The overall delirium incidence was 20.41%, which increased to 29.03% for patients aged ≥ 70 years. POD was associated with age, smoking, the American Society of Anesthesiologists classification, the Acute Physiology and Chronic Health Evaluation II score, and the TNM stage of the cancer. The variables concerning sex, drinking, hypertension, a history of cerebral disease, surgery type, operation time, amount of bleeding, and the intraoperative use of dexmedetomidine did not differ significantly between the two groups. There was no significant difference in the length of ICU stay, with the exclusion of long-term stay for complications, between the groups, but POD tended to prolong the postoperative hospital stay and increase the risk of mortality. There was also a gradual decline in the incidence of POD between 2015 and 2019, especially from 2015 to 2018, after preventive measures were implemented. CONCLUSION: POD is related to many risk factors and worthy of attention. Appropriate management can reduce its incidence or at least shorten its duration.

Temporal-spatial distributions of road silt loadings and fugitive road dust emissions in Beijing from 2019 to 2020.

Road silt loading (sL) is an important parameter in the fugitive road dust (FRD) emissions. In this study, the improved Testing Re-entrained Aerosol Kinetic Emissions from Roads (TRAKER) combined with the AP-42 method was firstly developed to quickly measure and estimate the sLs of paved roads in Beijing, China. The annual average sLs in Beijing was 0.59±0.31 g/m2 in 2020, and decreased by 22.4% compared with that in 2019. The seasonal variations of sLs followed the order of spring > winter > summer > autumn in the two years. The seasonal mean road sLs on the same type road in the four seasons presented a decline trend from 2019 to 2020, especially on the Express way, decreasing 47.4%-72.7%. The road sLs on the different type roads in the same season followed the order of Major arterial ∼ Minor arterial ∼ Branch road > Express road, and Township road ∼ Country highway > Provincial highway ∼ National highway. The emission intensities of PM10 and PM2.5 from FRD in Beijing in 2020 were lower than those in 2019. The PM10 and PM2.5 emission intensities at the four planning areas in the two years all presented the order of the capital functional core area > the urban functional expansion area > the urban development new area > the ecological conservation and development area. The annual emissions of PM10 and PM2.5 from FRD in Beijing in 2020 were 74,886 ton and 18,118 ton, respectively, decreasing by ∼33.3% compared with those in 2019.

Tripartite motif 31 promotes resistance to anoikis of hepatocarcinoma cells through regulation of p53-AMPK axis.

Anoikis-resistance is an essential feature of cancer cells to obtain successful metastasis, whereas the molecular mechanism involved in this process of hepatocellular carcinoma (HCC) cells is not fully understood. Here we demonstrated that tripartite motif-containing (TRIM) 31, a new member of the TRIM family, was significantly upregulated in the anchorage-deprived HCC cells compared with their attached counterpart. When we blocked TRIM31 expression by its specific interference RNAs, the anoikis-resistance of HCC cells was significantly reversed. We further verified that overactivation of AMPK pathway was responsible for TRIM31-mediated resistance to anoikis of HCC cells; and TRIM31 could directly target p53, the upstream suppressor of AMPK pathway, and mediate K48-linked ubiquitous degradation of p53 in a RING-domain-dependent way. Therefore we demonstrated that TRIM31 promoted anoikis-resistance by targeting p53 for degradation and subsequently overactivating AMPK pathway. Thus our study defined for the first time the role of TRIM31 in the anoikis-resistant process of HCC cells， and it may pave a new avenue for manipulation of metastatic cancer by targeting TRIM31.

Mint3 potentiates TLR3/4- and RIG-I-induced IFN-ß expression and antiviral immune responses.

Type I IFNs (IFN-α/ß) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated. In the present study, we show that munc18-1-interacting protein 3 (Mint3) expression can be markedly induced during viral infection in macrophages. Mint3 enhances TLR3/4- and RIG-I-induced IRF3 activation and IFN-ß production by promoting K63-linked polyubiquitination of TNF receptor-associated factor 3 (TRAF3). Consistently, Mint3 deficiency greatly attenuated antiviral immune responses and increased viral replication. Therefore, we have identified Mint3 as a physiological positive regulator of TLR3/4 and RIG-I-induced IFN-ß production and have outlined a feedback mechanism for the control of antiviral immune responses.

Characteristics and source apportionment of atmospheric volatile organic compounds in Beijing, China.

This paper focused on VOCs and their source apportionment in urban Beijing. Our monitoring measured 52 VOCs in July 2014 and January 2015. The concentration of VOCs was in the range of 14.5~95.2 ppb in July and 2.1~93.1 ppb in January, with the top five compounds of toluene (10.7%), ethane (6.9%), ethylene (6.3%), n-butane (5.7%), and propane (5.6%) in July and ethylene (14.7%), n-butane (14.2%), ethane (9.6%), propylene (8.0%), toluene (7.9%), and benzene (6.9%) in January. The ratio of VOCs to CO reached 0.059 in July and 0.022 in January on average. These differences implied a potential seasonal difference in the VOC source contribution. Then, we conducted a source apportionment study based on 21 major VOCs and CO by using probabilistic matrix factorization (PMF) receptor model. According to the similarity between the PMF analysis profiles and the known source profiles, combustion sources, petrochemical industry sources, solvent utilization sources, and gasoline evaporation sources were identified. The correlation coefficient (R) between the PMF analysis profile and the source profile reached 0.68~0.87 in July and 0.53~0.92 in January. The better apportionment performance in July was mainly due to the use of intensive VOC observations at a 3-h resolution. When we conducted another PMF source apportionment for July based on 12-h resolved concentration input, the R values decreased to 0.47~0.73. Thus, the PMF model depends heavily on the sample number of concentration inputs, and intensive observation is more propitious. Our PMF apportionment results showed that combustion sources, petrochemical industry, solvent utilization, gasoline evaporation, and other sources contributed ambient VOCs in Beijing urban areas of 13.7 ppb, 5.1 ppb, 7.7 ppb, 12.8 ppb, and 3.3 ppb in July and 13.2 ppb, 2.0 ppb, 5.7 ppb, 6.6 ppb, and 1.0 ppb in January, respectively, on a monthly average. These apportionment results match well with the 2013 VOC emission inventory calculated by this study, but also presented significant seasonal differences in the petrochemical industry and gasoline evaporation, in which VOC emissions strongly respond to environmental temperature.

Phosphatase PTPN4 preferentially inhibits TRIF-dependent TLR4 pathway by dephosphorylating TRAM.

TLR4 recruits TRIF-related adaptor molecule (TRAM, also known as TICAM2) as a sorting adaptor to facilitate the interaction between TLR4 and TRIF and then initiate TRIF-dependent IRF3 activation. However, the mechanisms by which TRAM links downstream molecules are not fully elucidated. In this study, we show that TRAM undergoes tyrosine phosphorylation upon TLR4 activation and that is required for TLR4-induced IRF3 activation. Protein tyrosine phosphatase nonreceptor type 4 (PTPN4), a protein tyrosine phosphatase, inhibits tyrosine phosphorylation and subsequent cytoplasm translocation of TRAM, resulting in the disturbance of TRAM-TRIF interaction. Consequently, PTPN4 specifically inhibits TRIF-dependent IRF3 activation and IFN-ß production in TLR4 pathway. Therefore, our results provide new insight into the TLR4 pathway and identify PTPN4 as a specific inhibitor of TRIF-dependent TLR4 pathway. Targeting PTPN4 would be beneficial for the development of new strategy to control TLR4-associated diseases without unwanted side effects.

Prognostic and diagnostic potential of miR-146a in oesophageal squamous cell carcinoma.

BACKGROUND: Accumulating evidence indicates that dysregulated microRNA-146a (miR-146a) is involved in tumour genesis and cancer progression. We aimed to evaluate its expression level and the potential for the diagnosis and prognosis in oesophageal squamous cell cancer (ESCC). METHODS: We examined miR-146a expression in 62 pairs of ESCC cancerous and matched paracancerous tissue, 115 formalin-fixed paraffin-embedded (FFPE) tissue samples and serum samples from 154 ESCC patients and 154 healthy volunteers using quantitative reverse transcription-PCR (qRT-PCR). Kaplan-Meier method, Cox regression and receiver-operating characteristic (ROC) curve analysis were applied to analyse its prognostic and diagnostic value. RESULTS: MicroRNA-146a expression level was significantly decreased in ESCC tissue compared with paracancerous tissue (P<0.001). Its regulation level was negatively associated with T factor and TNM stage. Kaplan-Meier curve revealed that its downregulation level predicted worse overall survival (OS) and progression-free survival (PFS). Both univariate and multivariate analyses identified miR-146a expression as independent prognostic factor for OS and PFS. Serum miR-146a was significantly reduced in ESCC patients than in healthy controls (P<0.001). Area under the curve ROC value, sensitivity and specificity for this marker were 0.863 ± 0.033, 85.7% and 68.6% in the Discovery Group, and 0.891 ± 0.027, 82.1% and 83.3% in the Validation Group. CONCLUSIONS: MicroRNA-146a is significantly reduced in cancerous tissue and serum samples of ESCC patients. It is an ideal biomarker for the prognosis and diagnosis of ESCC.

The clinical significance of systemic inflammation score in esophageal squamous cell carcinoma.

The objective of this study was to investigate the clinical significance of systemic inflammation score (SIS) and prognostic nutritional index (PNI) in esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy. Records from 206 patients with histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of Shandong University from January 2007 to December 2008 were retrospectively reviewed. The median disease-free survival (DFS) of this cohort was 32.3 months and 5-year DFS was 34.5 %. The median overall survival (OS) was 39.5 months and 5-year OS was 40.8 %. We found that high SIS was significantly associated with increased tumor length (p = 0.021), increased depth of invasion (p = 0.001), lymph node metastasis (p = 0.038), and advanced pathological stage (p = 0.004). Kaplan-Meier survival analysis revealed that both high SIS and low PNI were significantly associated with inferior DFS (for the SIS, p = 0.005; for the PNI, p = 0.003) and OS (for the SIS, p = 0.007; for the PNI, p = 0.002). In multivariate analysis, SIS was an independent prognostic indicator for both DFS and OS. However, PNI was not an independent prognosticator in multivariate analysis. SIS was a novel and promising inflammation-based prognostic score than PNI in ESCC patients who underwent esophagectomy.

MiR-613: a novel diagnostic and prognostic biomarker for patients with esophageal squamous cell carcinoma.

MicroRNA-613 (miR-613) plays important roles in tumorigenesis and cancer progression. We aimed to evaluate its expression level and potential for diagnosis and prognosis in esophageal squamous cell cancer (ESCC). We examined miR-613 expression in 60 pairs of ESCC cancerous and matched paracancerous tissues, serum samples from 75 ESCC patients and 75 healthy volunteers, and 105 formalin-fixed paraffin-embedded (FFPE) tissue samples using quantitative reverse transcription polymerase chain reaction. Receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier method, and Cox regression were applied to analyze its diagnostic and prognostic value. MiR-613 was significantly decreased in ESCC tissue compared with paracancerous tissue (P < 0.001). Moreover, the expression level of miR-613 was significantly reduced with increased T stage of ESCC. Statistically significant difference between ESCC patients and healthy controls in expression level of miR-613 (0.89 ± 0.73 vs. 1.71 ± 1.03, P < 0.001) was found. The area under the ROC curve (AUC) based on serum miR-613 was 0.767 ± 0.040. We also performed analysis on early-stage patients and revealed that the AUC value was 0.728 ± 0.052 (P < 0.001). The Kaplan-Meier curve revealed that the downregulation of miR-613 was related to worse overall survival (OS) and progression-free survival (PFS) of ESCC patients (P = 0.018 and P = 0.035, respectively). Furthermore, the multivariate analysis identified miR-613 to be an independent prognostic factor for OS and PFS (P = 0.031 and P = 0.006, respectively) In conclusion, miR-613 is significantly reduced in cancerous tissue and serum samples of ESCC patients. It can serve as an ideal indicator for the diagnosis and prognosis of ESCC.

Serum miR-1297: a promising diagnostic biomarker in esophageal squamous cell carcinoma.

We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC.

Estrogen suppresses hepatocellular carcinoma cells through ERß-mediated upregulation of the NLRP3 inflammasome.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The incidence of HCC is strikingly higher in males than in females. The remarkable gender disparity suggests an important role for sex hormones in HCC pathogenesis. Recently, estrogen has emerged as a protective factor in the development and progression of HCC, but whether it prevents and attenuates HCC, and the mechanism of protection, have not been elucidated. The present study shows that expression of estrogen receptor (ER) ß was significantly downregulated in HCC tissue compared with normal liver tissue; moreover, its expression level showed a significant negative correlation with disease progression and a positive correlation with the expression level of NLRP3 inflammasome components. In a previous study, we showed that loss of NLRP3 inflammasome in HCC tissue contributed to tumor progression, whereas the mechanism of its deregulation was not elucidated. In this study, we investigated the potential link between NLRP3 inflammasome and estrogen. Our data reveal that treatment with 17ß-estradiol (E2) significantly inhibited the malignant behavior of HCC cells through E2/ERß/MAPK pathway-mediated upregulation of the NLRP3 inflammasome. This study shows a novel link between ERß and the NLRP3 inflammasome in HCC progression, which provides a potentially valuable therapeutic strategy for treatment of HCC patients.

Clinical potential of miR-3651 as a novel prognostic biomarker for esophageal squamous cell cancer.

Accumulating evidence indicates that dysregulated microRNA-3651(miR-3651) is involved in tumorigenesis and cancer progression. In this study, we investigated the expression of miR-3651 in esophageal squamous cell cancer(ESCC) and its relationship with tumor progression and clinical prognosis. The expression level of miR-3651 was examined by quantitative Real-time PCR (qRT-PCR) in fresh ESCC tissues and FFPE tissues. The correlation between miR-3651 expression and clinical features and prognosis were statistically analyzed. The results showed that the miR-3651 expression was significantly down-regulated in tumor tissues compared with the paracancerous tissues. Moreover, miR-3651 expression was negatively correlated with T stage of ESCC (P = 0.022) and tumor length (P = 0.015). Kaplan-Meier analysis demonstrated that low miR-3651 expression level was associated with poorer overall survival (OS) (P = 0.004) and disease-free survival (DFS) (P = 0.001). Multivariate analysis identified miR-3651 expression as independent prognostic factor for OS and DFS (P = 0.001 and P = 0.001, resp.). Further stratified analysis revealed the significant association between low miR-3651 expression and worse survival in early patients, but not in the advanced patients. Taken together, miR-3651 was down-regulated in cancerous tissues of ESCC. It may play an important role in cancer progression and could be used as an independent prognostic biomarker for ESCC patients.

VEGFR-1 activation-induced MMP-9-dependent invasion in hepatocellular carcinoma.

AIM: VEGFR-1 can promote invasion through epithelial-mesenchymal transition induction in hepatocellular carcinoma (HCC). This study aims to elucidate VEGFR-1 impact on proteolytic enzymes profile involved with invasion. MATERIALS & METHODS: The effect on cell invasion was evaluated by invasive and migration assays with and without VEGFR-1 activation. The mechanism was investigated by real-time PCR, western blot and gelatin zymography using inhibitors for MMP-9. In total, 95 HCC patients were enrolled for its clinical value evaluation. RESULTS: VEGFR-1 activation induced invasion in HCC cells with an increase in the expression and activity of MMP-9 and Snail. MMP-9 blockage effectively inhibited VEGFR-1-induced invasion. High coexpression of both in HCC predicted a worse clinical outcome. CONCLUSION: Data show a novel VEGFR-1 activation-to-MMP-9 mechanism promoting HCC invasion.

Characterizing ozone pollution in a petrochemical industrial area in Beijing, China: a case study using a chemical reaction model.

This study selected a petrochemical industrial complex in Beijing, China, to understand the characteristics of surface ozone (O3) in this industrial area through the on-site measurement campaign during the July-August of 2010 and 2011, and to reveal the response of local O3 to its precursors' emissions through the NCAR-Master Mechanism model (NCAR-MM) simulation. Measurement results showed that the O3 concentration in this industrial area was significantly higher, with the mean daily average of 124.6 µg/m(3) and mean daily maximum of 236.8 µg/m(3), which are, respectively, 90.9 and 50.6 % higher than those in Beijing urban area. Moreover, the diurnal O3 peak generally started up early in 11:00-12:00 and usually remained for 5-6 h, greatly different with the normal diurnal pattern of urban O3. Then, we used NCAR-MM to simulate the average diurnal variation of photochemical O3 in sunny days of August 2010 in both industrial and urban areas. A good agreement in O3 diurnal variation pattern and in O3 relative level was obtained for both areas. For example of O3 daily maximum, the calculated value in the industrial area was about 51 % higher than in the urban area, while measured value in the industrial area was approximately 60 % higher than in the urban area. Finally, the sensitivity analysis of photochemical O3 to its precursors was conducted based on a set of VOCs/NOx emissions cases. Simulation results implied that in the industrial area, the response of O3 to VOCs was negative and to NOx was positive under the current conditions, with the sensitivity coefficients of -0.16~-0.43 and +0.04~+0.06, respectively. By contrast, the urban area was within the VOCs-limitation regime, where ozone enhancement in response to increasing VOCs emissions and to decreasing NOx emission. So, we think that the VOCs emissions control for this petrochemical industrial complex will increase the potential risk of local ozone pollution aggravation, but will be helpful to inhibit the ozone formation in Beijing urban area through reducing the VOCs transport from the industrial area to the urban area.

Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide, and it is always the consequence of chronic hepatitis and liver cirrhosis. The nucleotide-binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3) inflammasome has been shown to orchestrate multiple innate and adaptive immune responses. However, little is known about its role in cancer. This study was performed to investigate the role of the NLRP3 inflammasome in the development and progression of HCC. The expression of NLRP3 inflammasome components was analyzed in HCC tissues and corresponding non-cancerous liver tissues at both the mRNA and protein levels. Our data demonstrate that the expression of all of the NLRP3 inflammasome components was either completely lost or significantly downregulated in human HCC, and that the deficiency correlated significantly with advanced stages and poor pathological differentiation. In addition, our data provide an overview of the expression of NLRP3 inflammasome components in the multi-stage development of HCC and indicate a surprising link between deregulation of the NLRP3 inflammasome molecular platform and HCC progression. In conclusion, this study presents a dynamic expression pattern of NLRP3 inflammasome components in multi-stage hepatocarcinogenesis and demonstrates that deregulated expression of the inflammasome is involved in HCC progression.

Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/ENTPD1 null mice.

UNLABELLED: Liver cancer is associated with chronic inflammation, which is linked to immune dysregulation, disordered metabolism, and aberrant cell proliferation. Nucleoside triphosphate diphosphohydrolase-1; (CD39/ENTPD1) is an ectonucleotidase that regulates extracellular nucleotide/nucleoside concentrations by scavenging nucleotides to ultimately generate adenosine. These properties inhibit antitumor immune responses and promote angiogenesis, being permissive for the growth of transplanted tumors. Here we show that Cd39 deletion promotes development of both induced and spontaneous autochthonous liver cancer in mice. Loss of Cd39 results in higher concentrations of extracellular nucleotides, which stimulate proliferation of hepatocytes, abrogate autophagy, and disrupt glycolytic metabolism. Constitutive activation of Ras-mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR)-S6K1 pathways occurs in both quiescent Cd39 null hepatocytes in vitro and liver tissues in vivo. Exogenous adenosine 5'-triphosphate (ATP) boosts these signaling pathways, whereas rapamycin inhibits such aberrant responses in hepatocytes. CONCLUSION: Deletion of Cd39 and resulting changes in disordered purinergic signaling perturb hepatocellular metabolic/proliferative responses, paradoxically resulting in malignant transformation. These findings might impact adjunctive therapies for cancer. Our studies indicate that the biology of autochthonous and transplanted tumors is quite distinct.

Upregulation of BNIP3 mediated by ERK/HIF-1α pathway induces autophagy and contributes to anoikis resistance of hepatocellular carcinoma cells.

AIM: Acquisition of anoikis resistance is the hallmark of cancer and has been shown to be involved in metastasis of melignant cells. Our previous work showed that anoikis resistance is associated with the metastasis of hepatocellular carcinoma (HCC) cells. The aim of this study is to elucidate the mechanisms of this course. MATERIALS & METHODS: Expression of BNIP3 and HIF-1α at the mRNA and protein level in HCC cells were detected by realtime PCR and western blot, respectively. Autophagy activation and signaling transduction pathway were detected by western blot. Cell viabilities were detected by CCK8 assay and trypan blue exclusion assay. RESULTS: Upregulation of BNIP3 promoted the activation of autophagy, one type of cell survival strategy in response to external stress, by suppressing mTOR/S6K1 signaling system. The upregulation of BNIP3 was mediated by ERK/HIF-1α pathway, which further contributed to anoikis resistance of HCC cells through the mTORC1 signaling pathway. CONCLUSION: Upregulation of BNIP3 contributs to anoikis resistance of HCC cells, and BNIP3 may serve as a novel therapeutic target for manipulation of cancer metastasis.

[Determination of arsenic speciation in Scomberomorus niphonius by capillary electrophoresis-inductively coupled plasma mass spectrometry].

A method for the detection of arsenocholine (AsC), arsenobetaine (AsB), As(III), dimethylarsinic (DMA), monomethylarsonic (MMA) and As (V) by capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) was established. The results showed that the six species of arsenic were separated within 20 min under the optimized conditions. Good linearities of 6 arsenic species were observed in the range from 2 to 50 µg x L(-1) with the linear correlation greater than 0.996, the detection limits were 0.10-1.08 µg x L(-1) and the RSDs (n = 5) of the peak areas were smaller than 7%. The method was successfully adopted to the determination of the species in Scomberomorus niphonius. The recoveries were between 93% and 98%, and we found the arsenobetaine (AsB) was the main species in the sample. The method was suitable for the analysis of other biological samples with the advantages of good stability, less sample consumption, short analysis time and convenience.