STAT1/IFIT2 signaling pathway is involved in PD-L1-mediated epithelial-to-mesenchymal transition in human esophageal cancer.

BACKGROUND: We have previously reported significant change of epithelial to mesenchymal transition (EMT) phenotype of Eca-109 cells upon PD-L1 operation, and the cytoplasmic domain of PD-L1 played an essential role in promoting EMT of esophageal cancer cells. However, the underlying mechanism of how PD-L1 regulated EMT in esophageal cancer remained unclear. METHODS: The overexpression and knockdown expression models of PD-L1 and IFIT2 were established by using lenti-virus transfection and RNAi method. Western blotting, qRT-PCR, CCK8 assay, transwell assay and wound healing assay were chosen to investigate their impact on the cells. The expression levels of IFIT2 and EMT markers in esophageal cancer tissues were examined by immunohistochemical staining. The rescue experiments were further applied to investigate the role of STAT1/IFIT2 signal pathway in the PD-L1-mediated EMT. Luciferase reporter assays were performed to examine the IFIT2 promoter activities upon knockdown expression of PD-L1 to identify the putative targeted region of IFIT2 promoter. RESULTS: The STAT1/IFIT2 signal pathway was activated when PD-L1 was knockdown in human esophageal cancer cells. Decreased IFIT2 expression significantly increased the cellular abilities of viability, invasion and migration by using RNAi method in human esophageal cancer cells. Decreased IFIT2 expression in esophageal cancer tissues significantly correlated with EMT status, and could be used as an independent prognostic predictor for the patients. Rescue experiments in PD-L1 knockdown cells further confirmed that STAT1/IFIT2 pathway was involved in the PD-L1 mediated EMT of esophageal cancer cells. Moreover, the luciferase reporter assay also confirmed that in esophageal cancer cells, the promoter region of IFIT2 (-3K~-1K) remains more active in PD-L1 knockdown expression cells compared with controls. CONCLUSION: Our present work reveals a novel mechanism of how PD-L1 regulates EMT of cancer cells, namely STAT1/IFIT2 signal pathway is required in PD-L1 mediated EMT in human esophageal cancer.

LncRNA ABHD11-AS1 promotes tumor progression in papillary thyroid carcinoma by regulating EPS15L1/EGFR signaling pathway.

OBJECTIVES: lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) acts as an oncogene involved in papillary thyroid carcinoma (PTC) occurrence and progression. ABHD11-AS1 exerts biologic functions by some miRNAs and proteins to regulate multiple targets. Identification of novel mechanism of ABHD11-AS1 could be helpful in therapeutic targeting for PTC treatment. METHODS: Differentially expressed lncRNAs were selected from TCGA database. qRT-PCR analysis was applied to examine the expression of ABHD11-AS1 in PTC cell lines and tissues. The relationship of ABHD11-AS1 expression and clinicopathological features was analyzed by Kaplan-Meier analysis. Two PTC cell lines (TPC-1 and KTC-1) were transfected with pcDNA 3.1, pcDNA3.1-ABHD11-AS1, si-NC and si-ABHD11-AS1, respectively, to verify the ABHD11-AS1 oncogene-regulating capacity to promote tumor progression. The cell metastasis and proliferation had been evaluated both in vitro and in vivo. RESULTS: High expression of ABHD11-AS1 was found in PTC tissues (P < 0.01), which was significantly correlated with lymph node metastasis (P < 0.05). ABHD11-AS1 overexpression noticeably promoted cell proliferation, migration, and invasion capabilities, which were obviously decreased upon ABHD11-AS1 knockdown. ABHD11-AS1 positively regulated EGFR/EPS15L1 pathway, as EGFR, EPS15L1, STAT3, and p-STAT3 were activated. CONCLUSION: ABHD11-AS1 promotes tumor progression in PTC by regulating EPS15L1/EGFR pathway.

The interaction of SET and protein phosphatase 2A as target for cancer therapy.

In cancer cells, tumor suppressor proteins loss-of-function are usually the result of genetic mutations. Protein Phosphatase 2A is a tumor suppressor that inactivates several signaling pathways through removal of phosphate residues important for other proteins stability and/or activation. Different from other tumor suppressors, PP2A is, in many cancer types, inactivated by endogenous inhibitors. In physiological conditions, these inhibitors are important to balance PP2A activity. However, in cancer cells, overexpression of these inhibitors can keep PP2A inactive, resulting in sustained activation of mitogenic signaling pathways and transcription factors, metabolic reprogramming, with the resulting cancer progression and the resistance to anti-cancer therapies. One of these endogenous inhibitors is the protein SET (SE Translocation). SET is a multifunctional protein, which high expression has been associated with several types of cancer, as well as other diseases such as Alzheimer's disease. Disruption of the interaction between SET and PP2A to rescue the activity of PP2A may represent a new therapeutic strategy and opportunity for cancer treatment. This review brings up-to-date advances on the interactions between SET and PP2A and their biological consequences. Moreover, we review reported inhibitors of SET-PP2A interaction under investigation as therapeutic opportunities for the treatment of cancers.

Circular RNA hsa_circ_0091579 facilitates the Warburg effect and malignancy of hepatocellular carcinoma cells via the miR-624/H3F3B axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. It has been reported that circular RNA hsa_circ_0091579 (circ_0091579) is involved in HCC progression. Nevertheless, the molecular mechanism by which circ_0091579 modulates HCC advancement is indistinct. METHODS: The expression of circ_0091579, microRNA (miR)-624, and H3 histone family member 3B (H3F3B) mRNA was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of HCC cells were analyzed using an extracellular flux analyzer. Adenosine triphosphate (ATP) level was evaluated using a commercial kit. Cell migration, invasion, and apoptosis were assessed by wound-healing, transwell, or flow cytometry assay. The relationship between miR-624 and circ_0091579 or H3F3B was verified using luciferase reporter assay and/or RNA immunoprecipitation (RIP) assay. H3F3B protein level was detected by western blotting. RESULTS: Circ_0091579 was upregulated in HCC tissues and cells. Circ_0091579 inhibition decreased xenograft tumor growth in vivo and repressed Warburg effect, migration, invasion, and induced apoptosis of HCC cells in vitro. MiR-624 was downregulated, while H3F3B was upregulated in HCC tissues and cells. Circ_0091579 acted as a miR-624 sponge and regulated H3F3B expression by adsorbing miR-624. MiR-624 inhibitor reversed circ_0091579 downregulation-mediated effects on the Warburg effect and malignant behaviors of HCC cells. H3F3B overexpression reversed the repressive impact of miR-624 mimic on the Warburg effect and malignancy of HCC cells. CONCLUSIONS: Circ_0091579 accelerated Warburg effect and tumor growth via upregulating H3F3B via adsorbing miR-624 in HCC, providing evidence to support the involvement of circ_0091579 in the progression of HCC.

Research on CRISPR/system in major cancers and its potential in cancer treatments.

Cancer is a serious public health problem in the world and the prevention and control of cancer has become one of the health strategies of governments around the world. According to the data of the International Agency for Research on Cancer (IARC), about 8 million people die of cancer every year in the world. With the continuous progress of medical technology, there are many methods to treat cancer at present. However, many treatment methods have achieved different therapeutic effects, some of them have obvious toxic and side effects. Therefore, it is necessary to study simpler and more effective new therapies for alleviating pain and prolonging lifetime of patients. In this view, we focus on the application progress of CRISPR system in some major cancers and its potential in cancer treatments.

Dietary Supplementation with Ferula Improves Productive Performance, Serum Levels of Reproductive Hormones, and Reproductive Gene Expression in Aged Laying Hens

This study investigated the effects of dietary Ferula supplementation on productive performance, egg quality, follicular development, serum levels of reproductive hormones, and reproductive gene expression in aged laying hens. A total of 300 Dawu pink laying hens (65 weeks old) were assigned to four treatments with six replicates per treatment and 10 hens per replicate. The birds were individually housed in wire cages and fed a corn-soybean meal-based diet with added Ferula at doses of 0, 50, 100, and 200 mg/kg for 12 weeks. The results showed that the laying rate in the 100 mg/kg Ferula-supplemented group was higher than in birds of the control group during weeks 1 to 12 (p<0.05). The average egg weight in the 100 mg/kg Ferula-supplemented group was significantly higher than in the other groups (p<0.01), while the feed-to-egg ratio was significantly lower than in other groups (p<0.01). The numbers of small yellow follicle, middle white follicle, and small white follicle were higher in the 100 mg/kg Ferula-supplemented birds than in the other groups (p<0.01). On weeks 69, the serum levels of estradiol, follicle-stimulating hormone, and luteinizing hormone were significantly higher in the 100 mg/kg Ferula-supplemented group than in the other groups (p<0.05). Additionally, expressions of ERα, FSHR, and LHR in the ovarian tissue were up-regulated by Ferula supplementation, especially in the 100 mg/kg group (p<0.01). These results indicate that the Ferula supplementation can significantly improve productive performance, egg quality, reproduction of hormonal profile, and reproductive gene expression of aged laying hens.

Dietary Supplementation with Ferula Improves Productive Performance, Serum Levels of Reproductive Hormones, and Reproductive Gene Expression in Aged Laying Hens

This study investigated the effects of dietary Ferula supplementation on productive performance, egg quality, follicular development, serum levels of reproductive hormones, and reproductive gene expression in aged laying hens. A total of 300 Dawu pink laying hens (65 weeks old) were assigned to four treatments with six replicates per treatment and 10 hens per replicate. The birds were individually housed in wire cages and fed a corn-soybean meal-based diet with added Ferula at doses of 0, 50, 100, and 200 mg/kg for 12 weeks. The results showed that the laying rate in the 100 mg/kg Ferula-supplemented group was higher than in birds of the control group during weeks 1 to 12 (p<0.05). The average egg weight in the 100 mg/kg Ferula-supplemented group was significantly higher than in the other groups (p<0.01), while the feed-to-egg ratio was significantly lower than in other groups (p<0.01). The numbers of small yellow follicle, middle white follicle, and small white follicle were higher in the 100 mg/kg Ferula-supplemented birds than in the other groups (p<0.01). On weeks 69, the serum levels of estradiol, follicle-stimulating hormone, and luteinizing hormone were significantly higher in the 100 mg/kg Ferula-supplemented group than in the other groups (p<0.05). Additionally, expressions of ERα, FSHR, and LHR in the ovarian tissue were up-regulated by Ferula supplementation, especially in the 100 mg/kg group (p<0.01). These results indicate that the Ferula supplementation can significantly improve productive performance, egg quality, reproduction of hormonal profile, and reproductive gene expression of aged laying hens.(AU)

Seroprevalence of toxoplasma gondii infection in goats in the five northwestern provinces of China / Seroprevalência de infecção por toxoplasma gonddi em cabras nas cinco províncias do noroeste da China

O objetivo do presente estudo foi investigar a soroprevalência de infecção com Toxoplasma gondii (T. gondii) em cabras em cinco províncias do noroeste da China. Soroprevalência foi determinado usando o kit de teste de ensaio de imunoabsorção enzimática (ELISA). A soroprevalência geral foi 21.23% (197/928). Análise estatística revlou que diferenças significativas foram observadas em fêmeas (P= 0.048, OR= 0.567, 95% CI= 0.309 a 1.041) e nos grupos ≥ 2 (P= 0.002, OR= 0.330, 95% CI= 0.224 a 0.488). Nenhuma diferença estatisticamente significativa foi observada entre diferentes províncias. Nossos resultados indicam que a infecção com T. gondii, que pode ter implicações importantes sobre a saúde pública, teve diferenças significativas em sexo e idade, mas nenhuma significância foi observada em diferentes regiões. Além disto, nossos resultados também indicam que infecção por T. gondii em cabras é generalizada nas cinco províncias do noroeste.(AU)

Seroprevalence of toxoplasma gondii infection in goats in the five northwestern provinces of China / Seroprevalência de infecção por toxoplasma gonddi em cabras nas cinco províncias do noroeste da China

O objetivo do presente estudo foi investigar a soroprevalência de infecção com Toxoplasma gondii (T. gondii) em cabras em cinco províncias do noroeste da China. Soroprevalência foi determinado usando o kit de teste de ensaio de imunoabsorção enzimática (ELISA). A soroprevalência geral foi 21.23% (197/928). Análise estatística revlou que diferenças significativas foram observadas em fêmeas (P= 0.048, OR= 0.567, 95% CI= 0.309 a 1.041) e nos grupos ≥ 2 (P= 0.002, OR= 0.330, 95% CI= 0.224 a 0.488). Nenhuma diferença estatisticamente significativa foi observada entre diferentes províncias. Nossos resultados indicam que a infecção com T. gondii, que pode ter implicações importantes sobre a saúde pública, teve diferenças significativas em sexo e idade, mas nenhuma significância foi observada em diferentes regiões. Além disto, nossos resultados também indicam que infecção por T. gondii em cabras é generalizada nas cinco províncias do noroeste.(AU)

MiR-130b/TNF-α/NF-κB/VEGFA loop inhibits prostate cancer angiogenesis.

BACKGROUND: Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined. METHODS: We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice. RESULTS: We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer. CONCLUSION: These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.

Scale-Dependent Waylaying Effect of Pollinators and Pollination of Mass-Flowering Plants.

Pollinators foraging for food resources can be waylaid by mass-flowering plants located in their foraging pathway in landscapes. The waylaying effect of pollinators is often studied at a single spatial scale; to date, little is known about the best spatial extent at which waylaying effect of pollinators can be measured. In this study, we selected a landscape with mass-flowering tufted vetches to determine the spatial scale of waylaying effect of honey bees as well as the consequence of waylaying effect on vetch pollination service. The spatial scale of waylaying effect was determined by the strongest association between honey bee density and distance, selected from a gradient of nested circular buffers centering on apiaries in three different locations. Linear models were used to predict the influence of flower visitor densities on pollination service. For our landscape, honey bee densities were best associated with distances at spatial scales of 500 m, 1150 m, and 1400 m respectively for the three locations of apiaries. Honey bee was the only pollinator whose density displayed a positive relationship with pollination service. At the scales of effect, honey bee density and pollination service declined along the distance. Our findings suggest that the waylaying effect of pollinators needs to be examined at a specific spatial scale and farmers who use honey bees to pollinate their mass-flowering crops need to consider the spatial scale of waylaying effect of pollinators in order to maximize pollination service within agricultural ecosystems.

Distinct prognostic values of Annexin family members expression in acute myeloid leukemia.

BACKGROUND: Annexin family consist of 12 members, many of them are frequently dysregulated in human cancers. However, the diagnosis and prognosis of Annexin family expression in acute myeloid leukemia (AML) remain elusive. The aim of the present study was to assess the prognostic value of Annexin expressions in adult and pediatric AML. METHODS: GenomicScape tool was used to assess the prognostic value of the expressions of Annexin family members in a cohort of 162 adult AML patients. Quantitative reverse transcript real-time PCR (QRT-PCR) was performed to detect the ANXA2 expression level in the bone marrow-derived mononuclear cells (BMMCs) obtained from 101 pediatric AML patients and 30 controls. RESULTS: The results demonstrated that high mRNA expressions of ANXA2, ANXA6, and ANXA7 were significantly associated with worse prognosis, while ANXA5 was correlated with better prognosis in adult AML. QRT-PCR analysis showed that ANXA2 expression was dramatically downregulated in BMMCs of pediatric AML patients compared to controls (p < 0.0001). ROC analysis demonstrated that ANXA2 could efficiently differentiate pediatric AML patients from controls (AUC 0.872, p < 0.0001). Likewise, ANXA2 was significantly lower in AML patients with poor-risk karyotype (p = 0.048). Also, the level of ANXA2 trended to decrease in AML patients who had not achieving complete remission. Moreover, patients with lower expression of ANXA2 had higher death rate (p = 0.042) and shorter overall survival (HR 0.55, p = 0.042). Thus, these findings suggest that ANXA2 exerts poor prognostic effect on adult AML but favorable prognostic effect on pediatric AML. CONCLUSIONS: Collectively, Annexin family members exert distinct prognostic roles in AML, and ANXA2 can be used as a biological marker for diagnosis and prognosis of pediatric AML.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

The clinicopathological and prognostic value of programmed death-ligand 1 in colorectal cancer: a meta-analysis.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) is reportedly expressed in colorectal tumors. However, the prognostic role of PD-L1 in colorectal cancer (CRC) remains controversial. Therefore, we performed a meta-analysis to investigate the clinicopathological and prognostic impact of PD-L1 in CRC. METHODS: A comprehensive search in PubMed, Embase, the Cochrane Library, Web of Science and the ClinicalTrials.gov for publications about PD-L1 expression in colorectal cancer was done. The correlation between PD-L1 expression and clinicopathological features or survival outcomes was analyzed by odds ratios (OR) or hazard ratios (HR), at 95% confidence intervals (CI). RESULTS: The results show that the pooled HR of (1.34, 95% CI 1.02-1.65, p = 0.01) indicated the association of PD-L1 expression with overall survival (OS) in CRC patients. Meanwhile, the expression of PD-L1 was positively correlated with the lymph node metastasis (OR: 0.70, 95% CI 0.51-0.95, p = 0.00), gender (OR: 0.86, 95% CI 0.76-0.98, p = 0.05) and tumor location (OR: 1.39, 95% CI 1.14-1.71, p = 0.12). CONCLUSIONS: These results suggest that high expression of PD-L1 is associated with low OS in CRC. High PD-L1 expression may act as a negative factor for patients with CRC and help to identify patients suitable for anticancer therapy.

On the forward modeling of radar Doppler spectrum width from LES: Implications for model evaluation.

Large-eddy simulations of an observed single-layer Arctic mixed-phase cloud are analyzed to study the value of forward modeling of profiling millimeter-wave cloud radar Doppler spectral width for model evaluation. Individual broadening terms and their uncertainties are quantified for the observed spectral width and compared to modeled broadening terms. Modeled turbulent broadening is narrower than the observed values when the turbulent kinetic energy dissipation rate from the subgrid-scale model is used in the forward model. The total dissipation rates, estimated with the subgrid-scale dissipation rates and the numerical dissipation rates, agree much better with both the retrieved dissipation rates and those inferred from the power spectra of the simulated vertical air velocity. The comparison of the microphysical broadening provides another evaluative measure of the ice properties in the simulation. To accurately retrieve dissipation rates as well as each broadening term from the observations, we suggest a few modifications to previously presented techniques. First, we show that the inertial subrange spectra filtered with the radar sampling volume is a better underlying model than the unfiltered -5/3 law for the retrieval of the dissipation rate from the power spectra of the mean Doppler velocity. Second, we demonstrate that it is important to filter out turbulence and remove the layer-mean reflectivity-weighted mean fall speed from the observed mean Doppler velocity to avoid overestimation of shear broadening. Finally, we provide a method to quantify the uncertainty in the retrieved dissipation rates, which eventually propagates to the uncertainty in the microphysical broadening.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge.

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/ß-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/ß-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Association between rs12252 and influenza susceptibility and severity: an updated meta-analysis.

In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03-1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39-33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08-1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08-2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36-5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.

The effect of aspirin on circulating tumor cells in metastatic colorectal and breast cancer patients: a phase II trial study.

PURPOSE: Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial-mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC). METHODS: The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression. RESULTS: Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p < 0.001) but not MBC (p = 0.0532); besides, ratio of E+ CTCs increased (p = 0.037) and M+ CTCs decreased at 2 months in MCC (p = 0.013), but neither the ratio of E+ or M+ CTCs changes significantly in MBC; vimentin expression of M+ CTCs is higher than E+ and B+ CTCs either in MBC or MCC patients at baseline (p < 0.01); and aspirin suppresses the vimentin expression in M+ (p = 0.002)and B+ (p = 0.006) CTCs of MCC and M+ CTCs of MBC (p = 0.004); besides it find vimentin expression in B+ (p = 0.004) or M+ (p < 0.001), CTCs are markedly decreased in patients with total CTC numbers declined. CONCLUSION: Aspirin could decrease CTCs numbers and block EMT transition in MCC patients and part of MBC patients.

Circular RNA hsa_circ_0000523 regulates the proliferation and apoptosis of colorectal cancer cells as miRNA sponge

Among the novel class of endogenous long non-coding RNAs, circular RNA (circRNA) is known as a key regulator in the development and progression of different cancers. Its function and mechanism in the tumorigenesis of colorectal cancer, however, has not been well studied. This study thus aimed to investigate potential regulation of colorectal cancer by circRNAs and the corresponding regulatory mechanism. We demonstrated that the expression of circRNA hsa_circ_0000523 (also known as circ_006229) was down-regulated in different colorectal cancer cell lines. It was also found that interference of hsa_circ_0000523 induced proliferation and suppressed apoptosis of colorectal cancer cells, the proliferation rate of which was reduced by the overexpression of hsa_circ_0000523. In addition, we found that miR-31 could recognize hsa_circ_0000523 sequence and that it acted as a "sponge" of miR-31, indirectly regulating Wnt/β-catenin signaling pathway, which was involved in the progression of colorectal cancer. The results suggested that the expression of hsa_circ_0000523 correlated to the tumorigenesis of colorectal cancer cells. In addition, as a sponge of miR-31, the low level of hsa_circ_0000523 led to activation of Wnt/β-catenin signaling pathway, inducing the subsequent progress of colorectal cancer.

Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes

Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3-4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.