miR-140-3P Induces Chemotherapy Resistance in Esophageal Carcinoma by Targeting the NFYA-MDR1 Axis.

Esophageal carcinoma (EC) is recognized as the 6th most frequent carcinoma in China, with esophageal squamous cell carcinoma (ESCC) being the predominant histologic type. Currently, chemotherapy is one among the most important therapy modalities for patients with ESCC. However, resistance to chemotherapeutic drugs leads to limited treatment options and poor prognosis. In our study, the analysis of small RNA sequencing and digital gene expression (DGE) profiling was done to recognize the microRNAs (miRNAs) and key genes related with drug resistance in ESCC. It was noticed that the hsa-miRNA-140-3p (miR-140-3p) expression was considerably higher in drug-resistant cells than in sensitive cells. In addition, DGE identified target genes of miR-140-3p might perform key roles in ESCC. Furthermore, this work exhibited that miR-140-3p represents the nuclear transcription factor Y subunit alpha (NFYA) gene by targeting its 3'-untranslated regions. Such an interaction might influence the formation of the transcription factor NFY trimer, which in turn may inhibit the transcription of the multidrug resistance 1 gene and, ultimately, to multidrug resistance in ESCC. The inhibition of miR-140-3p decreased resistance to oxaliplatin in EC. Therefore, miR-140-3p may serve as a molecular marker for treatment response, efficacy, and prognosis of chemotherapy in ESCC patients.

S. boulardii Early Intervention Maintains Gut Microbiome Structure and Promotes Gut Mucosal Barrier Function in Early-Weaned Rats.

Early weaning leads to the disorder of the gut microbiome and gut mucosal barrier injury. Early intervention of gut microbiome colonization contributes to the development of the gut microbiome and gut function. The aim of this study was to explore the effects of Saccharomyces boulardii (S. boulardii) early intervention on the gut microbiome structure and gut mucosal barrier function of early-weaned rats. The results showed that S. boulardii early intervention improved growth performance along with a decrease in pathogenic bacteria, an increase in beneficial bacteria, a stable and complex microbiome, and a high level of microbial metabolism. Moreover, S. boulardii upregulated the mucosal barrier function including goblet cells and relative gene expression, tight junction, and sIgA level. Furthermore, S. boulardii suppressed the inflammatory response and promoted the anti-inflammatory response. Our study may provide a possible early intervention strategy for preventing an early weaning-induced disorder of the gut microbiome and loss of gut mucosal barrier function.

The Quantitative Profiling of Oxylipins from Arachidonic Acid by LC-MS/MS in Feces at Birth 3 Days and 21 Days of Piglets.

Oxylipins (also called eicosanoids) are enzymatically or nonenzymatically generated by oxidation of arachidonic acid (ARA) and are major mediators of ARA effects in the body. Previous studies demonstrated the importance of ARA in infant growth, brain development, immune response, and health. With the developments in lipidomic methodologies, it is important for exploring more ARA-deprived oxylipins to better understand the physiological functions of ARA. The concentrations of oxylipins in feces were determined from days 3 to 21 postnatally of suckling piglets in vivo. Feces were collected at two critical time points of the suckling piglets (3d and 21d after birth) and about 48 oxylipins were analyzed by using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Here, 21 oxylipins were derived from ARA, and 11 differential oxylipins (Log2|fold change| ≥ 1.0) at birth 3d and 21d were identified. Particularly, 12-HETE was more abundant in feces at birth 3 days rather than 21 days. Considering that 12-HETE was a racemic mixture of stereoisomers containing the S and R enantiomers, we further detected the concentrations of 12(S)-HETE and 12(R)-HETE between the two time points by chiral LC-MS/MS analysis. There was no significant difference in the concentrations of 12(S)-HETE and 12(R)-HETE. It was showed that ARA - derived oxylipins might be related to the physiological changes of piglets during growing. Our results provided new information for describing the physiological changes of the piglets over the suckling period.

Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention.

Early life is a vital period for mammals to be colonized with the microbiome, which profoundly influences the development of the intestinal immune function. For neonates to resist pathogen infection and avoid gastrointestinal illness, the intestinal innate immune system is critical. Thus, this review summarizes the development of the intestinal microbiome and the intestinal innate immune barrier, including the intestinal epithelium and immune cells from the fetal to the weaning period. Moreover, the impact of the intestinal microbiome on innate immune development and the two main way of early-life intervention including probiotics and fecal microbiota transplantation (FMT) also are discussed in this review. We hope to highlight the crosstalk between early microbial colonization and intestinal innate immunity development and offer some information for early intervention.

Bioactive triple peptide inhibits inflammasome activation to alleviate Salmonella-induced intestinal inflammation in mice via modulation of host defense and bacterial virulence.

Over the past years, Salmonella typhimurium has been considered an important pathogen that causes intestinal diseases and spells enormous economic shock to animal husbandry all over the world. Pyroptosis and inflammasome are involved in intestinal S. typhimurium infections. This study aims to explore the protective effects and potential mechanisms of a bioactive triple peptide (BTP) on S. typhimurium-induced intestinal infection. In this report, BTP exhibited anti-inflammatory and antibacterial activities in vivo (S. typhimurium-infected C57BL/6 mice) and in vitro (S. typhimurium-challenged THP-1 cells). We found that BTP significantly alleviated intestinal injuries and inflammation in S. typhimurium-infected mice. Besides, organ hypertrophy and bacteria translocation were improved effectively after BTP treatment. In macrophages, inflammasome activation caused by S. typhimurium infection was inhibited by BTP treatment. Of note, BTP significantly inhibited the adhesion and invasion of S. typhimurium to THP-1 cells. Moreover, the gene expressions of fljB and fliC were suppressed by BTP. All in all, our results suggest that BTP has the potential for alleviating S. typhimurium-induced inflammation.

Palbociclib Enhances Migration and Invasion of Cancer Cells via Senescence-Associated Secretory Phenotype-Related CCL5 in Non-Small-Cell Lung Cancer.

Palbociclib is the first CDK4/6 inhibitor approved by FDA and has been studied in many types of cancer. However, some studies showed that it could induce epithelial-mesenchymal transition (EMT) of cancer cells. To test the effect of palbociclib on non-small-cell lung cancer (NSCLC) cells, we treated NSCLC cells with different concentrations of palbociclib and detected its effects via MTT, migration and invasion assays, and apoptosis test. Further RNA sequencing was performed in the cells treated with 2 µM palbociclib or control. And Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction network (PPI) were analyzed to explore the mechanism of palbociclib. The results showed that palbociclib significantly inhibited the growth of NSCLC cells and promoted apoptosis of cells, however, enhanced the migration and invasion abilities of cancer cells. RNA sequencing showed that cell cycle, inflammation-/immunity-related signaling, cytokine-cytokine receptor interaction, and cell senescence pathways were involved in the process, and CCL5 was one of the significantly differential genes affected by palbociclib. Further experiments showed that blocking CCL5-related pathways could reverse the malignant phenotype induced by palbociclib. Our results revealed that palbociclib-induced invasion and migration might be due to senescence-associated secretory phenotype (SASP) rather than EMT and suggested that SASP could act as a potential target to potentiate the antitumor effects of palbociclib in cancer treatment.

Effects of Plant Crown Shape on Microwave Backscattering Coefficients of Vegetation Canopy.

A microwave scattering model is a powerful tool for determining relationships between vegetation parameters and backscattering characteristics. The crown shape of the vegetation canopy is an important parameter in forestry and affects the microwave scattering modeling results. However, there are few numerical models or methods to describe the relationships between crown shapes and backscattering features. Using the Modified Tor Vergata Model (MTVM), a microwave scattering model based on the Matrix Doubling Algorithm (MDA), we quantitatively characterized the effects of crown shape on the microwave backscattering coefficients of the vegetation canopy. FEKO was also used as a computational electromagnetic method to make a complement and comparison with MTVM. In a preliminary experiment, the backscattering coefficients of two ideal vegetation canopies with four representative crown shapes (cylinder, cone, inverted cone and ellipsoid) were simulated: MTVM simulations were performed for the L (1.2 GHz), C (5.3 GHz) and X (9.6 GHz) bands in fully polarimetric mode, and FEKO simulations were carried out for the C (5.3 GHz) band at VV and VH polarization. The simulation results show that, for specific input parameters, the mean relative differences in backscattering coefficients due to variations in crown shape are as high as 127%, which demonstrates that the crown shape has a non-negligible influence on microwave backscattering coefficients of the vegetation canopy. In turn, this also suggests that investigation on effects of plant crown shape on microwave backscattering coefficients may have the potential to improve the accuracy of vegetation microwave scattering models, especially in canopies where volume scattering is the predominant mechanism.

[Optimization of a cucurbit[6]uril-based real-time label-free method for analyzing the activity of ornithine decarboxylase].

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthetic pathway of polyamines and catalyzes the decarboxylation of ornithine to produce putrescine. Inhibition of ODC activity is a potential approach for the prevention and treatment of many diseases including cancer, as the expression levels and the activities of ODC in many abnormal cells and tumor cells are generally higher than those of normal cells. The discovery and evaluation of ODC inhibitors rely on the monitoring of the reaction processes catalyzed by ODC. There are several commonly used methods for analyzing the activity of ODC, such as measuring the yield of putrescine by high performance liquid chromatography, or quantifying the yield of isotope labelled carbon dioxide. However, the cumbersome operation and cost of these assays, as well as the difficulty to achieve high-throughput and real-time detection, hampered their applications. In this work, we optimized a real-time label-free method for analyzing the activity of ODC based on the macromolecule cucurbit[6]uril (CB6) and a fluorescent dye, DSMI (trans-4-[4-(dimethylamino) styryl]-1-methylpyridinium iodide). Finally, the optimized method was used to determine the activities of different ODC inhibitors with different inhibition mechanisms.

Combining Preoperative and Postoperative Inflammatory Indicators Can Better Predict the Recurrence of Hepatocellular Carcinoma After Partial Hepatectomy.

PURPOSE: Previous studies have shown that various preoperative inflammatory indicators can predict the prognosis of hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of postoperative inflammatory indicators and whether combining preoperative and postoperative inflammatory indicators can improve the predictive performance of the prognostic model. PATIENTS AND METHODS: Eighty-eight patients with primary HCC were included in this study. A preoperative model, postoperative model, and combined model that integrated preoperative and postoperative inflammatory indicators were established. The prognostic value of the models was evaluated by the area under the curve of time-dependent receiver operating characteristic curves (td-AUC). RESULTS: Multivariate analysis of preoperative and postoperative inflammatory indicators and clinicopathological indicators found that tumor number, alpha-fetoprotein (AFP) level, and the preoperative platelet-lymphocyte ratio (prePLR), preoperative prognostic nutritional index (prePNI), and postoperative neutrophil-lymphocyte ratio (postNLR) were independent prognostic factors for the disease-free survival. The prognostic efficacy of the postNLR at 2 years and 3 years was better than that of tumor number, AFP level, and the prePLR, and prePNI. The combined model had higher td-AUC values than the preoperative model, postoperative model, American Joint Committee on Cancer 8th edition stage, and Barcelona Clinic Liver Cancer stage at 2 years (0.814 vs 0.754, 0.765, 0.513 and 0.527, respectively), and 3 years (0.786 vs 0.749, 0.753, 0.509 and 0.529, respectively). The predictive performance of the combined model was better than that of the preoperative model, postoperative model, and traditional clinical stage. CONCLUSION: Postoperative inflammatory indicators were valuable prognostic indicators. The combination of preoperative and postoperative inflammatory indicators improved the predictive performance of the prognostic model. We should pay more attention to postoperative inflammatory indicators.

Analysis of Combining SAR and Optical Optimal Parameters to Classify Typhoon-Invasion Lodged Rice: A Case Study Using the Random Forest Method.

Lodging, a commonly occurring rice crop disaster, seriously reduces rice quality and production. Monitoring rice lodging after a typhoon event is essential for evaluating yield loss and formulating suitable remedial policies. The availability of Sentinel-1 and Sentinel-2 open-access remote sensing data provides large-scale information with a short revisit time to be freely accessed. Data from these sources have been previously shown to identify lodged crops. In this study, therefore, Sentinel-1 and Sentinel-2 data after a typhoon event were combined to enable monitoring of lodging rice to be quickly undertaken. In this context, the sensitivity of synthetic aperture radar (SAR) features (SF) and spectral indices (SI) extracted from Sentinel-1 and Sentinel-2 to lodged rice were analyzed, and a model was constructed for selecting optimal sensitive parameters for lodging rice (OSPL). OSPL has high sensitivity to lodged rice and strong ability to distinguish lodged rice from healthy rice. After screening, Band 11(SWIR-1) and Band 12(SWIR-2) were identified as optimal spectral indices (OSI), and VV, VV + VH and Shannon Entropy were optimal SAR features (OSF). Three classification results of lodging rice were acquired using the Random Forest classification (RFC) method based on OSI, OSF and integrated OSI-OSF stack images, respectively. Results indicate that an overall level of accuracy of 91.29% was achieved with the combination of SAR and optical optimal parameters. The result was 2.91% and 6.05% better than solely using optical or SAR processes, respectively.

Extrahepatic bile duct reconstruction in pigs with heterogenous animal-derived artificial bile ducts: A preliminary experience.

BACKGROUND: Extrahepatic biliary duct injury (BDI) remains a complicated issue for surgeons. Although several approaches have been explored to address this problem, the high incidence of complications affects postoperative recovery. As a nonimmunogenic scaffold, an animal-derived artificial bile duct (ada-BD) could replace the defect, providing good physiological conditions for the regeneration of autologous bile duct structures without changing the original anatomical and physiologic conditions. AIM: To evaluate the long-term feasibility of a novel heterogenous ada-BD for treating extrahepatic BDI in pigs. METHODS: Eight pigs were randomly divided into two groups in the study. The animal injury model was developed with an approximately 2 cm segmental defect of various parts of the common bile duct (CBD) for all pigs. A 2 cm long novel heterogenous animal-derived bile duct was used to repair this segmental defect (group A, ada-BD-to-duodenum anastomosis to repair the distal CBD defect; group B, ada-BD-to-CBD anastomosis to repair the intermedial CBD defect). The endpoint for observation was 6 mo (group A) and 12 mo (group B) after the operation. Liver function was regularly tested. Animals were euthanized at the above endpoints. Histological analysis was carried out to assess the efficacy of the repair. RESULTS: The median operative time was 2.45 h (2-3 h), with a median anastomosis time of 60.5 min (55-73 min). All experimental animals survived until the endpoints for observation. The liver function was almost regular. Histologic analysis indicated a marked biliary epithelial layer covering the neo-bile duct and regeneration of the submucosal connective tissue and smooth muscle without significant signs of immune rejection. In comparison, the submucosal connective tissue was more regular and thicker in group B than in group A, and there was superior integrity of the regeneration of the biliary epithelial layer. Despite the advantages of the regeneration of the bile duct smooth muscle observed in group A, the effect on the patency of the ada-BD grafts in group B was not confirmed by macroscopic assessment and cholangiography. CONCLUSION: This approach appears to be feasible for repairing a CBD defect with an ada-BD. A large sample study is needed to confirm the durability and safety of these preliminary results.

Preoperative plus postoperative neutrophil-lymphocyte ratio for predicting overall survival following partial hepatectomy for hepatocellular carcinoma.

The preoperative neutrophil-lymphocyte ratio (NLR) and the postoperative NLR have been reported to be prognostic factors for malignant tumors. However, the prognostic value of combining the preoperative NLR and postoperative NLR for hepatocellular carcinoma (HCC) remains unclear. In the present study, a cohort of 70 patients with primary HCC were retrospectively reviewed. The optimal cut-offs for continuous variables were determined by the maximally selected rank statistics. The prognostic factors included preoperative NLR, postoperative NLR, preoperative NLR plus postoperative NLR, change in postoperative NLR, and postoperative NLR minus preoperative NLR. The predictive powers of the aforementioned prognostic factors were analyzed by the area under the time-dependent receiver operating characteristic (td-AUC) curve. Prognostic values were assessed by univariate and multivariate analyses. An increased preoperative NLR was found to be associated with higher preoperative neutrophil levels, lower preoperative lymphocyte levels and larger tumor sizes (all P<0.05). An increased postoperative NLR was associated with higher postoperative neutrophil levels and lower postoperative lymphocyte levels (all P<0.05). Multivariate analysis identified the preoperative NLR plus postoperative NLR as an independent prognostic risk factor (HR, 2.985; 95% CI, 1.648-5.407; P<0.001). The preoperative NLR plus postoperative NLR had higher td-AUC values than the preoperative NLR, postoperative NLR, postoperative NLR change, and postoperative NLR minus the preoperative NLR in the first to fourth years after surgery. The preoperative NLR plus postoperative NLR, considering both the preoperative and postoperative treatment phases, is a novel and promising prognostic factor for patients with HCC and requires further investigation in the future.

Decreased ZNF750 promotes angiogenesis in a paracrine manner via activating DANCR/miR-4707-3p/FOXC2 axis in esophageal squamous cell carcinoma.

ZNF750 is one novel significantly mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinically relevant and potential mechanisms have remained elusive. Using genomic sequencing of 612 ESCC patients, we analyzed the associations of ZNF750 mutations with clinicopathologic features and its prognostic value. We further investigated the function and underlying mechanism of ZNF750 in angiogenesis. The results showed ZNF750 mutations/deletions are significantly associated with malignant progression and poor prognosis of ESCC patients. Decreased ZNF750 in ESCC cells induces enhanced angiogenesis of human umbilical vein endothelial cells (HUVECs) and human arterial endothelial cells (HAECs), and the effect may be indirectly mediated by FOXC2. RNA-seq and ChIP shows lncRNA DANCR is a direct downstream target of ZNF750. Furtherly, knockdown ZNF750 evokes DANCR expression, which prevents miR-4707-3p to interact with FOXC2 as a microRNA sponge in a ceRNA manner, leading to enhanced FOXC2 signaling and angiogenesis. In contrast, ZNF750 expression reverses the effect. Our study reveals a novel mechanism of ZNF750, highlights a significance of ZNF750 as a metastatic and prognostic biomarker, and offers potential therapeutic targets for ESCC patients harboring ZNF750 mutations.

Novel ESCC-related gene ZNF750 as potential Prognostic biomarker and inhibits Epithelial-Mesenchymal Transition through directly depressing SNAI1 promoter in ESCC.

Background: Cancer genomic studies have identified Zinc Finger Protein 750 (ZNF750) was a novel significantly mutated gene in esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of ZNF750 in the development of ESCC. Methods: Genomic data from 4 reported ESCC cohorts were used to analyze the mutation profile of ZNF750. Tissue microarrays were used to detect its expression in 308 ESCC samples. Furtherly, the effects of ZNF750 on proliferation, colony formation, migration and invasion were tested in ESCC cells. PCR-array, chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay were used to explore the mechanism of ZNF750. Correlation of ZNF750 with its target genes was analyzed in TCGA data from various SCC types. Results: ZNF750 was frequently mutated in ESCC and the most common type was nonsense mutation. Its nucleus/cytoplasm ratio in ESCC was significantly lower than that in paired non-tumor tissues; it was an independent and potential predictor for survival in ESCC patients. Furtherly, ZNF750 knockdown significantly promoted proliferation, colony formation, migration and invasion in ESCC cells. PCR-array showed epithelial-to-mesenchymal transition (EMT) was the main biologic process affected by ZNF750. Moreover, ZNF750 directly bound to the promoter region of SNAI1 and depressed its activity. Decreased ZNF750 up-regulated SNAI1 expression and promoted EMT phenotype. SNAI1 knockdown partially reversed the malignant phenotype induced by ZNF750 knockdown. Further TCGA data analyses showed ZNF750 expression was positively correlated with E-cadherin and negatively correlated with SNAI1, N-cadherin and Vimentin in ESCC and other SCC samples. Conclusion: Our results suggest that ZNF750 may act as a tumor suppressor by directly repressing SNAI1 and inhibiting EMT process in ESCC and other types of SCC.

EP300 as an oncogene correlates with poor prognosis in esophageal squamous carcinoma.

E1A Binding Protein P300 (EP300) is one of the mutations of genes involved in histone modifications in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance, potential function and mechanisms have remained elusive. Methods: Genomic sequencing datas from 325 esophageal squamous cell carcinoma (ESCC) cases were integrated and screened a series of frequently mutated histone modifier genes. EP300 was selected to further analyze its clinical significance, function and RNA-sequencing was performed to explore its potential mechanism. Results: Of 35 histone modifier genes, EP300 was not only a significantly mutated gene but also a frequently mutated gene with a mutation frequency of more than 10% in ESCC. EP300 mutation was associated with tumor grade, pathological T stage and lymph node metastasis, predicting a shorter cumulative survival status. Immunohistochemical analysis showed that EP300 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with poor survival of ESCC patients. Moreover, we found that EP300 knockdown led to inhibition of cell proliferation, colony formation, migration and invasion. RNA-sequencing showed EP300 knockdown led to a significant change of genes expression associated with angiogenesis, hypoxia and epithelial-to-mesenchymal transition (EMT). Conclusions: Taken together, our study identified a novel role and mechanism of EP300 in ESCC and provided epigenetic therapeutic strategies for the treatment of ESCC.

Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer.

The predictive value of serum miRNAs (ser-miRNA) for the response to neoadjuvant chemotherapy (NCT) and the prognosis of breast cancer patients were investigated in the current study. The study included 118 stage II/III breast cancer patients and 30 healthy adult women. Peripheral blood was drawn from participants before the start (baseline [BL]), at the end of the second cycle (first evaluation during NCT [FEN]), and at the end of NCT (second evaluation during NCT [SEN]). The expression of ser-miRNAs was examined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and their association with chemotherapy response and prognosis was analyzed. MiR-19a, miR-21, miR-125b, miR-155, miR-205, and miR-373 were significantly up-regulated in the serum of breast cancer patients at BL, miR-451 was significantly down-regulated, and miR-122 was unchanged compared with the levels in healthy women. The expression of ser-miR-125b and the changes of ser-miR-21 expression during NCT were associated with chemotherapy response and disease-free survival (DFS). In chemotherapy responders, ser-miR-125b expression was lower than that of non-responders at BL, FEN, and SEN, and ser-miR-21 levels decreased from BL to FEN and from BL to SEN. Survival analysis showed that patients with lower ser-miR-125b expression at BL, FEN, and SEN had favorable DFS, and those with decreased ser-miR-21 expression from BL to FEN and from BL to SEN had better DFS. In conclusion, ser-miR-21 and ser-miR-125b were identified as novel, noninvasive predictive markers for NCT response and prognosis in breast cancer.

Changes of serum miR34a expression during neoadjuvant chemotherapy predict the treatment response and prognosis in stage II/III breast cancer.

OBJECTIVE: To investigate the predictive value of serum miR34a (ser-miR34a) expression for the neoadjuvant chemotherapy (NACT) response and prognosis in breast cancer patients. METHODS: This study included 86 diagnosed stage II/III breast cancer patients and 20 healthy volunteers. Peripheral blood from every participant was collected before the start, at the end of the second cycle, and at the end of NACT. The expression of ser-miR34a was examined by qRT-PCR and its association with the chemotherapy response and prognosis was analyzed. RESULTS: The expression of ser-miR34a in breast cancer patients before NACT was significant higher than that of healthy volunteers. During the NACT, the changes in ser-miR34a expression were significantly associated with treatment response and disease-free survival (DFS). In responding patients, ser-miR34a levels at the end of the second cycle and at the end of NACT were significantly lower than before NACT (P=0.016 and P=0.002, respectively), and in non-responding patients, the changes were insignificant. Survival analyses showed that the patients with decreased ser-miR34a expression from the end of the second cycle and the end of NACT to before NACT had improved DFS compared with that of the patients with increasing ser-miR34a expression (P<0.001 for both). Cox regression analyses showed that the changes of ser-miR34a expression were independent prognostic indicators. CONCLUSIONS: Ser-miR34a is a novel, noninvasive predictive marker for NACT response and prognosis in breast cancer patients.

Influence of two common polymorphisms in the EPHX1 gene on warfarin maintenance dosage: a meta-analysis.

We conducted a meta-analysis to investigate the influence of two common single nucleotide polymorphisms (SNPs) (rs2292566 G>A and rs4653436 A>G) in the EPHX1 gene on warfarin maintenance dosages. Relevant literatures were searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, TX, USA) was used for this meta-analysis. Standard mean difference and its corresponding 95% confidence interval (95% CI) were calculated. Seven studies met the inclusion criteria, including 2,063 warfarin-treated patients. Meta-analysis results illustrated that EPHX1 rs2292566 G>A polymorphism might be strongly correlated with a higher maintenance dose of warfarin. However, no interaction of EPHX1 rs4653436 A>G polymorphism with warfarin maintenance dosage was detected. A further subgroup analysis based on stratification by ethnicity indicated that EPHX1 rs2292566 G>A polymorphism was positively correlated with warfarin maintenance dosage among Caucasians, but not Asians. No associations were observed between EPHX1 rs4653436 A>G polymorphism warfarin maintenance dosage among both Caucasians and Asians. Our meta-analysis provides robust and unambiguous evidence that EPHX1 rs2292566 polymorphism may affect the maintenance dose of warfarin in Caucasians.

Effects of cigarette smoke extracts on the growth and senescence of skin fibroblasts in vitro.

Epidemiological studies have shown that cigarette smoke (CS), a very common environmental factor, plays an important role in skin aging. Although some in vivo studies have suggested that CS affects skin aging, the detailed effects of CS on skin cells in vitro remain largely unknown. In this study, we investigated the effects of cigarette smoke extract (CSE) on the growth, proliferation, and senescene of skin fibroblasts and the possible mechanism underlying these effects. Primary cultured human fibroblasts were exposed to a range of concentrations of CSE. Cell viability and cell proliferation after CSE exposure were analyzed with the methyl thiazolyl tetrazolium (MTT) assay and bromodeoxyuridine incorporation assay, respectively. Growth curves of fibroblasts exposed to different concentrations of CSE were developed and prolonged CSE-exposed cells were observed. Morphological and ultrastructural changes in fibroblasts were assessed by inverted light microscopy and transmission electron microscopy (TEM). Dying cells were stained with senescence-associated ß-galactosidase (SA ß-gal). Intracellular reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were determined by a colorimetric method. We found that proliferative capacity and growth were inhibited by CSE exposure in a dose- and time-dependent manner. Fibroblasts exposed to even low concentrations of CSE for a long period of time (5 passages) showed significantly increased SA ß-gal activity and typical features of aging cells. Meanwhile, CSE inhibited superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and augmented ROS levels. Our observations suggest that CSE exposure impairs fibroblast growth and proliferation and leads to features similar to those seen in senescent cells. Oxidative stress injury and inhibition of antioxidant defense activity may be involved in CSE-induced fibroblast senescence.