Visual analysis of abdominal aortitis treatment using the CiteSpace bibliometric method.

BACKGROUND: Abdominal aortitis can induce aneurysms, and tumor rupture can lead to organ ischemia or even sudden death. At present, there is a lack of extensive understanding and identification of key problems in the treatment of abdominal aortitis, which needs to be further analyzed using bibliometric analysis. AIM: To discuss the research hotspot and development trend of abdominal aortitis treatment. METHODS: We searched the English literature (published from January 1, 2000 to March 12, 2024) on the treatment of abdominal aortitis in the Web of Science database. Then, we identified and screened duplicate literature using CiteSpace 6.1R2 software. We conducted an analysis of the number of papers, a co-occurrence analysis of the authors and institutions, and co-occurrence and cluster analyses of the keywords. Then, we drew the author, institution, and keywords of the studies into graphs for visualization. Finally, we expounded on the author, institutional network interactions, and hot keywords of the studies on the treatment of abdominal aortitis. RESULTS: We included 210 English literature articles involving 190 authors; the author cooperation team was mainly represented by Caradu Caroline, Berard Xavier, Lu Guanyi, Harada Kenichi, and Sharma Ashish K. In the keyword analysis, high-frequency keywords include abdominal aortic aneurysm (38), abdominal aorta (24), Takayasu arteritis (22), etc. The three most central keywords were disease (0.69), classification (0.68), and abdominal aortic aneurysm (0.55). The first nine clusters of keywords are case report, abdominal aortic aneurysm, Takayasu arteritis, dyspnea hematuria, aortic elastic, IgG4-related disease, report, mid aortic dysplastic syndrome, and statin. In the keyword emergent analysis, 14 emergent words were obtained. Among them, seven keywords with strong abruptness were Takayasu arteritis, abdominal aortic aneurysm, disease, retroperitoneal fibrosis, expression, management, and large vessel vasculitis. In the past 3 years, the incidences of abdominal aortic aneurysm (intensity: 4.62) and inflammation (intensity: 1.99) were higher. CONCLUSION: The number of published papers is on the increase, but the cooperation among authors is scattered. The research focus is mainly on the pathogenesis and treatment of abdominal aortitis-related diseases.

Mealybug salivary microbes inhibit induced plant defenses.

BACKGROUND: Phenacoccus solenopsis is a polyphagous invasive mealybug that caused serious damage to crops worldwide. Phloem-sucking hemipterans are known to carry symbiotic microbes in their saliva. However, the role of salivary bacteria of P. solenopsis in modulating plant defenses remains limited. Exploring the impact of salivary bacteria on plant defense responses will contribute to the development of new targets for efficient control of invasive mealybugs. RESULTS: Salivary bacteria of the invasive mealybug P. solenopsis can suppress herbivore-induced plant defenses and thus enhance mealybug fitness. Mealybugs treated with an antibiotic showed decreased weight gain, fecundity and survival. Untreated mealybugs suppressed jasmonic acid (JA)-regulated defenses but activated salicylic acid (SA)-regulated defenses in cotton plants. In contrast, antibiotic-treated mealybugs triggered JA-responsive gene expression and JA accumulation, and showed shortened phloem ingestion. Reinoculating antibiotic-treated mealybugs with Enterobacteriaceae or Stenotrophomonas cultivated from mealybug saliva promoted phloem ingestion and fecundity, and restored the ability of mealybugs to suppress plant defenses. Fluorescence in situ hybridization visualization revealed that Enterobacteriaceae and Stenotrophomonas colonize salivary glands and are secreted into the mesophyll cells and phloem vessels. Exogenous application of the bacterial isolates to plant leaves inhibited JA-responsive gene expression and activated SA-responsive gene expression. CONCLUSION: Our findings imply that symbiotic bacteria in the saliva of the mealybug play an important role in manipulating herbivore-induced plant defenses, enabling this important pest to evade induced plant defenses and promoting its performance and destructive effects on crops. © 2023 Society of Chemical Industry.

PbrWRKY70 increases pear (Pyrus bretschneideri Rehd) black spot disease tolerance by negatively regulating ethylene synthesis via PbrERF1B-2.

Various pear plant cultivars exhibit diverse abilities to resist pear black spot disease (BSD), while the precise molecular mechanisms of resistance against pear BSD remain unclear. This study proposed a profound expression of a WRKY gene, namely PbrWRKY70, derived from Pyrus bretschneideri Rehd, within a BSD-resistant pear cultivar. Comparative analysis against the wild-type revealed that the overexpression of PbrWRKY70 engendered augmented BSD resistance of transgenic Arabidopsis thaliana and pear calli. Notably, the transgenic plants exhibited higher activities of superoxide dismutase and peroxidase, along with an elevated capacity to counteract superoxide anions via increased anti-O2-. Additionally, these plants displayed diminished lesion diameter, as well as reduced levels of hydrogen peroxide, malondialdehyde and 1-aminocyclopropane-1-carboxylic acid (ACC) contents. We subsequently demonstrated that PbrWRKY70 selectively bound to the promoter region of ethylene-responsive transcription factor 1B-2 (PbrERF1B-2), a potential negative regulator of ACC, thereby downregulating the expression of ACC synthase gene (PbrACS3). Consequently, we confirmed that PbrWRKY70 could enhance pear resistance against BSD by reducing ethylene production via modulation of the PbrERF1B-2-PbrACS3 pathway. This study established the pivotal relationship among PbrWRKY70, ethylene synthesis and pear BSD resistance, fostering the development of novel BSD-resistant cultivars. Furthermore, this breakthrough holds the potential to enhance pear fruit yield and optimize storage and processing during the later stages of fruit maturation.

A new NASH model in aged mice with rapid progression of steatohepatitis and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, with a significant proportion of patients progressing into non-alcoholic steatohepatitis (NASH) and further into cirrhosis and hepatocellular carcinoma (HCC). Most of the current animal models of NASH have limitations, such as incompatibility with human pathogenesis characteristics or long induction periods, which severely limit the development of new drugs and preclinical studies for NASH. We investigated the progression of NASH and fibrosis, as well as metabolic indicators, at different time points in aged mice induced by the Gubra Amylin NASH (GAN) diet, a high-fat, high-sugar, high-cholesterol diet, and attempted to establish a rapid and useful mouse model of NASH. Young and aged C57BL/6 mice were induced on a normal chow or GAN diet for 12 and 21 weeks, respectively. After 12 weeks of induction, aged mice developed NASH, including hepatic steatosis, lobular inflammation and hepatic ballooning, and the phenotype was more severe compared with young mice. After 21 weeks of induction, aged mice developed hepatic fibrosis, which greatly shortened the induction time compared with young mice. Furthermore, analysis of immune cell infiltration in the liver by flow cytometry elucidated the changes of multiple immune cells during the pathogenesis of NASH. These findings suggest that aged mice may develop NASH and fibrosis more rapidly under GAN diet induction, which may significantly shorten the period for preclinical studies of NASH.

Preparation and performance characteristics of spider venom peptide nanocapsules.

BACKGROUND: ω-hexatoxin-Hvn1b is an insecticidal toxin produced by the Tasmanian funnel-web spider (Hadronyche venenata), that can be exploited for development of novel bioinsecticides. Due to its larger size and low membrane permeability, this toxin usually has a slower mode of action compared to conventional small molecule insecticides. Nanoscale materials have unique optical, electrical, mechanical and biological properties, and show great application prospects for pesticide delivery. RESULTS: The physical and chemical properties of nanocapsules were characterized using transmission electron microscopy, laser particle size analysis, Fourier transform infrared spectroscopy, contact angle testing and with a fluorescence spectrophotometer. The results indicated that the nanocapsules were spherical, with an average particle size of 197.70 nm, the encapsulation efficiency rate was 75.82% and the Zeta potential was -32.90 mV. Penetration experiments showed that the nanocapsules could promote protein passage through the intestinal tract of Spodoptera litura and reach the body fluid. Then we expressed ω-hexatoxin-Hvn1b by prokaryotic expression. Bioassay results showed that the oral toxicity of ω-hexatoxin-Hvn1b nanocapsules to S. litura was higher than that of the ω-hexatoxin-Hvn1b. CONCLUSION: In this paper, we reported a construction method of spider venom peptide nanocapsules based on polylactic-co-glycolic acid by multiple emulsion for delivery of protein to improve the insecticidal effect and oral activity of ω-hexatoxin-Hv1a. © 2022 Society of Chemical Industry.

Lingguizhugan decoction protects PC12 cells against Aß25-35-induced oxidative stress and neuroinflammation by modulating NF-κB/MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases. Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. AIM OF THE STUDY: The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aß25-35-induced PC12 cells. MATERIALS AND METHODS: PC12 cells were used MTT assays, ELISA, fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. RESULTS: In Aß25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1ß, IL-6, MDA and ROS, increased the activity of GSH-Px, inhibited cell apoptosis, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3ß and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. CONCLUSIONS: Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aß25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.

In Situ Regeneration of Silicon Microring Biosensors Coated with Parylene C.

Optical biosensors support disease diagnostic applications, offering high accuracy and sensitivity due to label-free detection and their optical resonance enhancement. However, optical biosensors based on noble metal nanoparticles and precise micro-electromechanical system technology are costly, which is an obstacle for their applications. Here, we proposed a biosensor reuse method with nanoscale parylene C film, taking the silicon-on-insulator microring resonator biosensor as an example. Parylene C can efficiently adsorb antibody by one-step modification without any surface treatment, which simplifies the antibody modification process of sensors. Parylene C (20 nm thick) was successfully coated on the surface of the microring to modify anti-carcinoembryonic antigen (anti-CEA) and specifically detect CEA. After sensing, parylene C was successfully removed without damaging the sensing surface for the sensor reusing. The experimental results demonstrate that the sensing response did not change significantly after the sensor was reused more than five times, which verifies the repeatability and reliability of the reusable method by using parylene C. This framework can potentially reduce the cost of biosensors and promote their further applications.

Comprehensive analysis of immune related lncRNAs in the tumor microenvironment of stage II-III colorectal cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) associated with immunological function have increasingly been found to act as effective prognostic biomarkers of the overall survival (OS) of colorectal cancer (CRC) patients. We sought to identify a signature of immune-related lncRNAs that offered value as a tool for the prospective prognostic evaluation of patients with stage II-III CRC. METHODS: The clinical and gene expression data of CRC patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases was obtained and separated into a training cohort composed of 202 samples, a test cohort of 124 samples from the GSE72970 dataset, and a validation cohort of 91 samples from the GSE143985 dataset. RESULTS: We firstly evaluated intratumoral immune cell infiltration by conducting a Single-sample gene set enrichment analyses (ssGSEA) analysis to separate patient tumors into those with low immune cell infiltration and those with high immune cell infiltration. We then compared lncRNA and mRNA expression profiles between these two tumor types, leading us to focus on eight lncRNAs identified within the resultant mRNA-lncRNA co-expression network. Multivariate Cox regression models were then utilized to detect an immune-associated lncRNA signature that offered value for prognostic model construction. Functional analyses revealed this lncRNA signature to be associated with key immunological pathways including the JAK-STAT signaling, T cell receptor signaling, and Rap1 signaling pathways. CONCLUSIONS: Together, our results suggest that our immune-related 4 lncRNA signature can reliably predict stage II-III CRC patient prognosis, thereby guiding efforts to better understand this disease and to effectively treat it.

The Value of Magnetic Resonance Imaging Histograms in the Preoperative Differential Diagnosis of Endometrial Stromal Sarcoma and Degenerative Hysteromyoma.

Objective: The present study aimed to explore the application value of magnetic resonance imaging (MRI) histograms with multiple sequences in the preoperative differential diagnosis of endometrial stromal sarcoma (ESS) and degenerative hysteromyoma (DH). Methods: The clinical and preoperative MRI data of 20 patients with pathologically confirmed ESS and 24 patients with pathologically confirmed DH were retrospectively analyzed, forming the two study groups. Mazda software was used to select the MRI layer with the largest tumor diameter in T2WI, the apparent diffusion coefficient (ADC), and enhanced T1WI (T1CE) images. The region of interest (ROI) was outlined for gray-scale histogram analysis. Nine parameters-the mean, variance, kurtosis, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile-were obtained for intergroup analysis, and the receiver operating curves (ROCs) were plotted to analyze the differential diagnostic efficacy for each parameter. Results: In the T2WI histogram, the differences between the two groups in seven of the parameters (mean, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile) were statistically significant (P < 0.05). In the ADC histogram, the differences between the two groups in three of the parameters (skewness, 10th percentile, and 50th percentile) were statistically significant (P < 0.05). In the T1CE histogram, no significant differences were found between the two groups in any of the parameters (all P > 0.05). Of the nine parameters, the 50th percentile was found to have the best diagnostic efficacy. In the T2WI histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.742), sensitivity of 70%, and specificity of 83.3%. In the ADC histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.783), sensitivity of 81%, and specificity of 76.9%. Conclusion: The parameters of the mean, 10th percentile and 50th percentile in the T2WI histogram have good diagnostic efficacy, providing new methods and ideas for clinical diagnosis.

Bioinformatics analysis reveals biomarkers with cancer stem cell characteristics in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a renal cortical tumor. KIRC is the most common subtype of kidney cancer, accounting for 70%-80% of kidney cancer. Early identification of the risk of KIRC patients can facilitate more accurate clinical treatment, but there is a lack of effective prognostic markers. We aimed to identify new prognostic biomarkers for KIRC on the basis of the cancer stem cell (CSC) theory. METHODS: RNA-sequencing (RNA-seq) data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was used to identify significant modules and hub genes, and predictive hub genes were used to construct prognostic characteristics. RESULTS: The messenger RNA expression-based stemness index (mRNAsi) in tumor tissues of patients in the TCGA database is higher than that of the corresponding normal tissues. In addition, some clinical features and results are highly correlated with mRNAsi. WGCNA found that the green module is the most prominent module associated with mRNAsi; the genes in the green module are mainly concentration in Notch binding, endothelial cell development, Notch signaling pathway, and Rap 1 signaling pathway. A protein-protein interaction (PPI) network showed that the top 10 central genes were significantly associated with the transcriptional level. Moreover, the 10 hub genes were up-regulated in KIRC. Regarding survival analysis, the nomogram of the prognostic markers of the seven pivotal genes showed a higher predictive value. The classical receiver operating characteristic (ROC) curve analysis showed that risk score biomarkers had the highest accuracy and specificity with an area under the curve (AUC) value of 0.701. CONCLUSIONS: mRNAsi-related genes may be good prognostic biomarkers for KIRC.

Establishment and Validation of Nomogram Based on Combination of Pretreatment C-Reactive Protein/Albumin Ratio-EBV DNA Grade in Nasopharyngeal Carcinoma Patients Who Received Concurrent Chemoradiotherapy.

BACKGROUND: A higher ratio of pretreatment C-reactive protein/albumin ratio (CAR) is associated with poor prognosis in nasopharyngeal carcinoma (NPC), and Epstein-Barr virus (EBV) DNA level is known to not only participate in the occurrence of nasopharyngeal carcinoma but also affect the development and prognosis of the disease. Herein, we proposed that a combination of both these markers could improve the predictive prognostic ability. METHODS: In all, 842 NPC patients who received concurrent chemoradiotherapy (CCRT) were entered in this study. We collected all patients' blood samples and EBV DNA copy numbers within one week before any treatment. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off. We employed the Kaplan-Meier method for survival analyses and the univariate and multivariate analyses (Cox proportional hazards regression model) for statistical analysis. A nomogram was constructed based on multivariate analyses results of the validation set. The model was internally validated using 1000 bootstrap samples to avoid overfitting. Another validation of 10-fold cross-validation was also applied. Calibration curves and concordance index (C-index) were calculated to determine predictive and discriminatory capacity. RESULTS: In the whole cohort, we observed that higher CAR, EBV DNA level, and CAR-EBV DNA (C-E) grade were associated with shorter overall survival (OS) and distant metastasis-free survival (DMFS) (all P<0.05). In univariate and multivariate analyses, C-E grade was an independent prognostic factor (all P<0.05). In the training set, we gained the similar results with the whole set. According to multivariate analyses of the training set, we constructed a nomogram. The results of bootstrap samples and 10-fold cross-validation showed favorable predictive efficacy. And calibration curves of the model provided credibility to its predictive capability. CONCLUSION: C-E grade was confirmed as an independent prognostic predictor in patients with NPC who received CCRT. Higher level of pretreatment C-E grade could signify a higher risk of metastasis and shorter OS. The prognostic nomogram based on C-E grade was dependable in nasopharyngeal carcinoma patients.

Curcumin-loaded liposomes with the hepatic and lysosomal dual-targeted effects for therapy of hepatocellular carcinoma.

Curcumin can induce cancer cell apoptosis through lysosomal permeabilization pathway. However, the poor selectivity of curcumin restricts its use in the therapy of hepatocellular carcinoma. Because galactose group can recognize ASGPR overexpressed on hepatoma cells and morpholine group can target to the lysosome, they are integrated into a dual-targeted lipid material with low toxicity. The corresponding galactose-morpholine modified liposomes loaded with curcumin (Gal-Mor-LPs) were prepared and evaluated in comparison with conventional liposomes (LPs) and galactose modified liposomes (Gal-LPs). The in vitro and in vivo hepatic targeting capacity of liposomes followed a trend of LPs < Gal-LPs < Gal-Mor-LPs. The endocytosis of Gal-Mor-LPs was competitively inhibited by galactose, which confirmed the galactose modified liposomes entered hepatoma cells via ASGPR-mediated pathway. Gal-Mor-LPs displayed more excellent lysosomal targeting efficacy than LPs and Gal-LPs due to the attraction of acidic lysosome on basic morpholine group of Gal-Mor-LPs. The in vivo tumor inhibition effects of formulations also followed a trend of free curcumin < LPs < Gal-LPs < Gal-Mor-LPs, confirming that hepatic and lysosomal dual-targeting vehicle can improve the antitumor efficacy of curcumin. Moreover, the curcumin-loaded liposomes modified with galactose and morpholine moieties show good biocompatibility in vivo.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Comparison of tooth movement and biological response resulting from different force magnitudes combined with osteoperforation in rabbits

Abstract Objective To compare tooth movement rate and histological responses with three different force magnitude designs under osteoperforation in rabbit models. Methodology 48 rabbits were divided into three groups: Group A, Group B, and Group C, with traction force of 50 g, 100 g, 150 g, respectively. Osteoperforation was performed at the mesial of the right mandibular first premolar, the left side was not affected. One mini-screw was inserted into bones between two central incisors. Coil springs were fixed to the first premolars and the mini-screw. Tooth movement distance was calculated, and immunohistochemical staining of PCNA, OCN, VEGF, and TGF-β1 was analyzed. Results The tooth movement distance on the surgical side was larger than the control side in all groups (P<0.01). No significant intergroup difference was observed for the surgical side in tooth movement distance among the three groups (P>0.05). For the control side, tooth movement distance in Group A was significantly smaller than Groups B and C (P<0.001); no significant difference in tooth movement distance between Group B and Group C was observed (P>0.05). On the tension area of the moving premolar, labeling of PCNA, OCN, VEGF and TGF-β1 were confirmed in alveolar bone and periodontal ligament in all groups. PCNA, OCN, VEGF and TGF-β1 on the surgical side was larger than the control side in all groups (P<0.001). Conclusion Osteoperforation could accelerate orthodontic tooth movement rate in rabbits. Fast osteoperforation-assisted tooth movement in rabbits was achieve with light 50 g traction.

Prognostic significance of the Controlling Nutritional Status (CONUT) score in surgically treated breast cancer patients.

BACKGROUND: Breast cancer is one of the most common malignancy in women with high mortality rate. Given the growing evidence shows that immune-inflammatory system influences the survival of patients with cancer, we assessed the prognostic significance of the preoperative Controlling Nutritional Status (CONUT) score in patients with breast cancer who underwent surgery. METHODS: We conducted a retrospective analysis of 1,367 breast cancer patients who underwent surgery between December 2010 and October 2012. All individual preoperative serum albumin concentration, total cholesterol concentration, and total peripheral lymphocyte count were counted to calculate CONUT. Higher CONUT score is in line with worse nutritional status. The optimal cut-off of CONUT score was set at 3 to categorize the investigated patients into two groups, namely a high- or low-CONUT score group. We adopted univariate and multivariate analyses (Cox proportional hazards regression model) statistical method. RESULTS: Patients in the high-CONUT score group had shorter overall survival (OS) and recurrence-free survival (RFS) in comparison with those in the low-CONUT score group, 66.43 vs. 69.30 months and 54.70 vs. 59.98 months respectively (all P value <0.05). Univariate and multivariate analyses revealed that the CONUT score was an independent predictor of OS (P=0.029 and 0.046, respectively) and RFS (P=0.001, P=0.013, respectively). CONCLUSIONS: The CONUT score was identified as an independent prognostic indicator in surgically treated breast cancer patients, indicating that, compared with the low CONUT score, a high CONUT score may lead to poorer prognosis.

The Prognostic Prediction Value of Systemic Inflammation Score and the Development of a Nomogram for Patients With Surgically Treated Breast Cancer.

Background: Systemic inflammation score (SIS) has been verified as a novel prognostic indicator in several cancer types. However, its prognostic value in breast cancer remains unknown. Furthermore, a nomogram based on SIS is yet to be constructed for breast cancer. We conducted this study to explore the association between SIS and prognosis of breast cancer, and to construct a good prognostic nomogram model. Methods: A total of 1,180 breast cancer patients who underwent curative surgery between December 2010 and January 2013 were recruited. They were randomly assigned to the training set (n = 944) or the validation set (n = 236). All patient blood samples were collected within 1 week prior to operation. According to previous reports, SIS was calculated for all patients, who were then classified into two groups: high-SIS and low-SIS. The Kaplan-Meier method was employed for survival analyses, and univariate and multivariate analyses (Cox proportional hazards regression model) were used for prognostic assessment. A nomogram was constructed based on the results of multivariate analysis. Calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. Results: In the training set, the median follow-up time was 6.07 years. Patients in the high-SIS group had an average OS time of 68.05 months, which is shorter than that of the low-SIS group (72.87 months; P = 0.033). Patients in the high-SIS group had average RFS and DMFS times of 56.04 and 54.46 months, respectively, which are shorter than those of the low-SIS group (60.85 and 59.47 months, respectively; P = 0.247 and P = 0.032). Univariate and multivariate analyses revealed SIS to be an independent prognostic factor for OS and DMFS time. The nomogram for the training set indicated OS and DMFS C-indexes of 0.794 (95% CI, 0.772-0.816) and 0.712 (95% CI, 0.684-0.740), respectively. In the validation set, the OS and DMFS C-indexes were 0.889 (95% CI, 0.845-0.933) and 0.696 (95%. CI, 0.611-0.781), respectively. Conclusions: SIS was confirmed as an independent prognostic predictor among patients with breast cancer who had undergone surgery with curative intent. Higher preoperative SIS may indicate higher risk of metastasis and shorter overall survival time. The prognostic nomogram based on SIS was dependable for breast cancer patients who underwent curative surgery.

MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC. METHODS: Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells. RESULTS: The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects. CONCLUSION: miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.

EZH2 Regulates Protein Stability via Recruiting USP7 to Mediate Neuronal Gene Expression in Cancer Cells.

Misexpression of chromatin modification factors and changed epigenetic modifications play crucial roles for tumorigenesis. Our previous studies demonstrated that inhibition of epigenetic modification enzymes EZH2, LSD1, DNMTs, and HDACs caused post-mitotic neuron-like differentiation in different cancer cells. However, how they regulate neuronal differentiation in cancer cells was unknown. Here, we show that EZH2, LSD1, DNMT1, and HDAC1 form interactions themselves, meanwhile, they also interact with SMAD proteins and ß-CATENIN in cancer cells. Chemical inhibition of these enzymes leads to reduced level of proteins except HDAC1. The change in protein level and/or enzymatic activities further result in changed chromatin modifications on neuronal gene promoters, and activation of neuronal genes. Inhibition of these enzymes in neural progenitor cells (NPCs) also caused neuronal differentiation, similar to cancer cells. Particularly, EZH2 interacts with and required for the stability of LSD1, HDAC1, DNMT1, ß-CATENIN, or SMAD2/4, via recruitment of deubiquitinase USP7. Reduced EZH2 leads to enhanced ubiquitination and degradation of these proteins, and decreased binding of LSD1, HDAC1, and DNMT1 to neuronal gene promoters, and lessened Wnt and TGFß target gene activation. Hence, EZH2 sustains a series of proteins that promote tumorigenesis, in addition to its original function of histone methylation. Considering together with other studies, we conclude that these chromatin modification factors function in the same way in cancer cells as in neural progenitor/stem cells. The similarity between cancer cells and neural progenitor/stem cells provides an insight into the essence and unified framework for cancer initiation and progression, and are suggestive for novel strategies of cancer therapy.

Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells.

Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines. The regulatory effect of these enzymes in neuronal differentiation resided in their intrinsic activity in embryonic neural precursor/progenitor cells. We further found that a major part of pan-cancer-promoting genes and the signal transducers of the pan-cancer-promoting signaling pathways, including the epithelial-to-mesenchymal transition (EMT) mesenchymal marker genes, display neural specific expression during embryonic neurulation. In contrast, many tumor suppressor genes, including the EMT epithelial marker gene that encodes cadherin 1 (CDH1), exhibited non-neural or no expression. This correlation indicated that cancer cells and embryonic neural cells share a regulatory network, mediating both tumorigenesis and neural development. This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells.