Showing papers by "Binzhou Medical College published in 2017"
TL;DR: CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs, and warrants further investigation in the treatment of hepatocellular carcinoma.
Abstract: Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo Gene expression profiling of tumor-associated macrophages (TAM) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors In addition, PLX3397 treatment increased CD8+ T-cell infiltration, whereas CD4+ T-cell infiltration was decreased Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397 In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs CSF-1R blockade warrants further investigation in the treatment of hepatocellular carcinoma Mol Cancer Ther; 16(8); 1544-54 ©2017 AACR
110 citations
TL;DR: Treatment with RB-222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion, and indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.
Abstract: Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.
73 citations
TL;DR: The internalization study and MTT assay confirm that these core-shell DNA microgels are excellent candidates which can enhance the cytotoxicity of cancer cells controlled by near-IR laser and shield the high toxicity of chemotherapeutic agents to improve the killing efficacy of chemotherapy agents efficiently in due course.
Abstract: Functional DNA molecules have been introduced into polymer-based nanocarrier systems to incorporate chemotherapy drugs for cancer therapy. Here is the first report of dual-responsive microgels composed of a core of Au nanorods and a shell of magnetic ionic liquid and DNA moieties in the cross-linking network simultaneously, as effective drug delivery vectors. TEM images indicated a magnetic polymer shell has an analogous “doughnut” shape which loosely surround the AuNRs core. When irradiated with a near-infrared-light (near-IR) laser, Au nanorods are the motors which convert the light to heat, leading to the release of the encapsulated payloads with high controllability. DNA acts not only as a cross-linker agent, but also as a gatekeeper to regulate the release of drugs. The internalization study and MTT assay confirm that these core–shell DNA microgels are excellent candidates which can enhance the cytotoxicity of cancer cells controlled by near-IR laser and shield the high toxicity of chemotherapeutic a...
39 citations
TL;DR: It is demonstrated that 23.98% of 196 H NSCC cases in Southwest China could be classified as HPV16 infection, and the number of MDSCs in HPV-positive HNSCC was significantly higher than normal control, indicating that HPV infection may promote MDSCS aggregation.
Abstract: // Xiangrui Ma 1, 2, * , Surui Sheng 1, * , Jingbiao Wu 1, * , Yaping Jiang 1, 3 , Xiaolei Gao 1 , Xiao Cen 1 , Jiashun Wu 1 , Shasha Wang 1 , Yajie Tang 4 , Yaling Tang 1, 5 and Xinhua Liang 1, 6 1 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China 2 Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256600, China 3 Department of Implant, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China 4 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, Hubei 430068, China 5 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China 6 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, Sichuan 610041, China * These authors have contributed equally to this work Correspondence to: Yaling Tang, email: tangyaling@scu.edu.cn Xinhua Liang, email: lxh88866@scu.edu.cn Keywords: head and neck squamous cell carcinomas (HNSCC), human papillomavirus (HPV), the non-coding RNA (lncRNA), myeloid-derived suppressor cells (MDSCs) Received: November 08, 2016 Accepted: December 27, 2016 Published: February 01, 2017 ABSTRACT The emerging evidence showed that long noncoding RNAs (lncRNAs) are involved in cell growth and apoptosis as well as cancer progression and metastasis of malignant tumor, however, limited data are available on the role of lncRNAs in human papillomavirus (HPV)-associated Head and neck squamous cell carcinomas (HNSCC). Here, we demonstrated that 23.98% of 196 HNSCC cases in Southwest China could be classified as HPV16 infection. The number of MDSCs in HPV-positive HNSCC was significantly higher than normal control, indicating that HPV infection may promote MDSCs aggregation. Then, we applied an array-based approach to monitor the lncRNA expression between HPV-positive HNSCC, HPV-negative HNSCC and normal oral mucous, and obtained 132 different lncRNAs in different HPV infected states of HNSCC. HOTAIR, PROM1, CCAT1, and MUC19 mRNA levels, determined by qRT-PCR were inversely correlated with MDSCs collection of HPV-associated HNSCC in 2 independent patient cohorts. The results may provide a rationale for the further evaluation of lncRNAs as a molecular target to elucidate the molecular mechanism of HPV promoting MDSCs collection of HNSCC.
36 citations
TL;DR: This review focuses on studies that provide insights into the role of desmosomes in carcinogenesis and address their molecular functions.
Abstract: Desmosomes, which are intercellular adhesive complexes, are essential for the maintenance of epithelial homeostasis. They are located at the cell membrane, where they act as anchors for intermediate filaments. Downregulation of desmosome proteins in various cancers promotes tumor progression. However, the role of desmosomes in carcinogenesis is still being elucidated. Recent studies revealed that desmosome family members play a crucial role in tumor suppression or tumor promotion. This review focuses on studies that provide insights into the role of desmosomes in carcinogenesis and address their molecular functions.
34 citations
TL;DR: The correlation between IL‐35 expression in tumor‐infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics was analyzed and it was shown that patients with elevated IL‐ 35 expression in TILs had significantly worse progression‐free survival (PFS) and overall survival (OS) than patients with weak or no IL-35 expression.
32 citations
TL;DR: Maternal folate supplementation ameliorates behavior disorders induced by prenatal high-fat diet and the beneficial effects were associated with methylation and expression alteration of BDNF and Grin2b genes.
Abstract: cope
: Maternal consumption of a high-fat diet (HFD) during pregnancy increases the risk of behavioral problems. Folate plays an important role in neuroplasticity and the preservation of neuronal integrity. This study aimed at determining the influence of diets supplemented with folate on offspring behavior, and the mechanisms involved.
Methods and results
: Female mice were fed a control diet, a high-fat diet, control diet supplemented with folate, or a high-fat diet supplemented with folate for 5 wks before mating. Open field task and elevated plus maze were used to evaluate the offspring behaviors. Results showed that offspring cognitive performance and anxiety-related behaviors, including those related to open field exploration and elevated plus maze, were significantly improved when dams were treated with folate in pregnancy. Moreover, the maternal folate supplement decreased BDNF and Grin2b methylation and upregulated their expressions in the brain of offspring, which associated with decreasing the expression of DNA methyltransferases compared with those dams were treated only HFD in pregnancy.
Conclusion
: Maternal folate supplementation ameliorates behavior disorders induced by prenatal high-fat diet. The beneficial effects were associated with methylation and expression alteration of BDNF and Grin2b genes.
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29 citations
TL;DR: The results indicated that SKA1 might be a promising target for cancer gene therapy in human ACC by demonstrating that the lentivirus-mediated shRNA-targeting SKA 1 lead to a significant down-regulation of SKA2 expression.
22 citations
TL;DR: Results showed that deglycosylation of epithelial cell adhesion molecule promoted apoptosis and inhibited cell proliferation, and suggest epithelialcell adhesion molecules as a potential target for the treatment of breast cancer.
Abstract: Glycosylation of cell surface proteins plays an important role in the regulation of apoptosis. It has been demonstrated that knockdown of epithelial cell adhesion molecule promoted apoptosis, inhib...
22 citations
TL;DR: Fucoidan inhibited cell growth, induced apoptosis and suppressed angiogenesis in the thyroid cancer cells, and revealed the presence of apoptotic bodies and DNA fragmentation.
Abstract: The present study demonstrated the effect of fucoidan, isolated from Fucus vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The cell viability was analyzed using a Cell Counting Kit‑8 cell proliferation kit. Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP nick‑end labeling assays were used to examine the apoptotic effect of fucoidan, which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan inhibited the growth of FTC133 and TPC1 ATC cells in a dose‑dependent manner. It also induced the apoptosis of FTC133 cells by promoting the expression levels of cleaved poly ADP‑ribose polymerase and caspase‑3. Significant decreases in the levels expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were observed in the FTC133 cells following treatment of the cells with fucoidan. In addition, inhibition in tube formation and the migration of FTC133 cells were observed in the cells treated with fucoidan, compared with the cells in the control group. Therefore, fucoidan inhibited cell growth, induced apoptosis and suppressed angiogenesis in the thyroid cancer cells.
22 citations
TL;DR: A lot of lncRNAs are aberrantly expressed in RCC that may offer useful resource for identification novel prognostic markers in this disease, and some novel metastasis associated lnc RNAs in R CC are identified.
Abstract: Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC. We identified that hundreds of lncRNAs were differentially expressed in RCC tissues compared with normal tissues, and genomic variation analyses revealed that copy number amplification or deletion happened in some of these lncRNAs genome loci. Moreover, lots of lncRNAs expression levels are significantly associated RCC patients overall survival time, such as PVT1 and DUXAP8. Finally, we identified some novel metastasis associated lncRNAs in RCC (such as DUXAP8) by analyzing lncRNAs profiling in the RCC tissues from patients with metastasis compared with the primary RCC tissues without metastasis; knockdown of DUXAP8 could impair RCC cells invasive ability in vitro. Overall, our findings illuminate a lot of lncRNAs are aberrantly expressed in RCC that may offer useful resource for identification novel prognostic markers in this disease.
TL;DR: A new colorimetric strategy based on polymer nanoparticles (PNPs) and Au nanoparticle (AuNPs) is developed to detect heparin (Hep), which shows good selectivity and sensitivity.
Abstract: Herein, a new colorimetric strategy based on polymer nanoparticles (PNPs) and Au nanoparticles (AuNPs) is developed to detect heparin (Hep). The cationic PNPs can directly induce the aggregation of AuNPs, which are stabilized by negatively charged coating of citrate ions, and hence the absorption peak of AuNPs moves to 675 nm corresponding with a color change from wine red to blue. However, the negatively charged Hep competes with AuNPs and binds to PNPs, hindering the interaction between PNPs and AuNPs. As a result, the absorption band of AuNPs blue shifts and the color turns to red again. The reaction can be completed within 10 min, and the color variation produced by 150 nM of Hep can be distinguished by the naked eye. In addition, this strategy also shows good selectivity and sensitivity, and the linear range of Hep is from 10 to 400 nM with detection limit of 2.5 nM. Finally, this colorimetric assay has been applied to measure Hep in Hep sodium injection and human serum samples with satisfactory recoveries.
TL;DR: MPFL is most easily injured at the PAT in children, and complete MPFL tear predisposes to a higher grade of patellar chondral lesion.
Abstract: To assess the relationship between injury patterns of medial patellofemoral ligament (MPFL) and anatomical variants and patellar cartilage lesions after acute lateral patellar dislocation (LPD) in children. MR images were obtained in 140 children with acute LPD. Images were acquired and evaluated using standardised protocols. Fifty-eight cases of partial MPFL tear and 75 cases of complete MPFL tear were identified. Injuries occurred at an isolated patellar insertion (PAT) in 52 cases, an isolated femoral attachment (FEM) in 42 cases and an isolated mid-substance (MID) in five cases. More than one site of injury was identified in 34 cases. Compared with Wiberg patellar type C, Wiberg patellar type B predisposed to complete MPFL tear (P = 0.042). No correlations were identified between injury patterns of MPFL and trochlear dysplasia, patellar height and tibial tuberosity-trochlear groove distance (P > 0.05). Compared with partial MPFL tear, complete MPFL tear predisposed to Grade-IV and Grade-V patellar chondral lesion (P = 0.02). There were no correlations between incidence of patellar cartilage lesion and injury locational-subgroups of MPFL (P = 0.543). MPFL is most easily injured at the PAT in children. Wiberg patellar type B predisposes to complete MPFL tear. Complete MPFL tear predisposes to a higher grade of patellar chondral lesion. • MPFL is most easily injured at its patellar insertion in children.
• Wiberg patellar type B predisposes to complete MPFL tear.
• No correlations between injury patterns of MPFL and other three anatomical variants.
• Complete MPFL tear predisposes to higher grade patellar chondral lesion.
• No correlations between injury locations of MPFL and patellar cartilage lesion.
TL;DR: As a new method, BI-RADS classification in conjunction with SWE that combines the average Young's modulus yields a high value in terms of the differential diagnosis of breast nodules and peri-nodule tissue.
Abstract: Ultrasound (US) has become one of the important imaging methods for differentiating benign from malignant breast lesions. In 2013, the American College of Radiology published the fifth edition of the Breast Imaging-Reporting and Data System (BI-RADS). BI-RADS is a guide with recommendations for the standardization of breast imaging (US, mammography and magnetic resonance imaging) reports and for the auditing of centers employing such methods. Its objective is to standardize the nomenclature used in the reports. However, current US examinations are neither adequately sensitive nor sufficiently specific enough. The average Young's modulus was measured through shear wave elastography (SWE) to evaluate the diagnostic value of the BI-RADS classification in conjunction with SWE in differentiating BI-RADS 3 and 4 nodules. A total of 100 consecutive women with 126 breast lesions, including 65 benign and 61 malignant lesions, were included. The average Young's modulus of breast nodules and peri-nodule tissue (Emean1 and Emean2) was also determined through SWE. A receiver operating characteristic curve was drawn on the basis of pathologic results. The highest cut-off values were C1 and C2. At Emean1 > C1 or Emean2 > C2, BI-RADS 3 was increased to 4a and BI-RADS 4a was increased to 4b. At Emean1 ≤ C1 and Emean2 ≤ C2, BI-RADS 4b was decreased to 4a. Other BI-RADS classifications remained unchanged. BI-RADS 3 and 4a were considered benign. BI-RADS 4b and 4c were malignant. The area under the curve, sensitivity and specificity of the BI-RADS classification in conjunction with SWE were 0.952, 93.4% and 95.4%, respectively. The area under the curve, sensitivity and specificity of the original BI-RADS classification were 0.883, 82.0% and 87.7%, respectively. Differences were statistically significant (p = 0.028, Z-test). The diagnostic sensitivity and specificity were increased effectively. As a new method, BI-RADS classification in conjunction with SWE that combines the average Young's modulus yields a high value in terms of the differential diagnosis of breast nodules.
TL;DR: The data suggest that miR-138-5p regulates NSCs proliferation and differentiation, and may be useful in developing novel treatments for neurological disorders via manipulation of miR (miR)-138- 5p in N SCs.
Abstract: Research on neural stem cells (NSCs) has recently focused on microRNAs (miRNAs), a class of small non‑coding RNAs that have crucial roles in regulating NSC proliferation and differentiation. In the present study, a quantitative‑polymerase chain reaction assay revealed that the expression of miRNA (miR)‑138‑5p was significantly decreased during neural differentiation of NSCs in vitro. Overexpression of miR‑138‑5p reduced NSC proliferation and increased NSC differentiation. Furthermore, suppression of miR‑138‑5p via transfection with a miRNA inhibitor enhanced NSC proliferation and attenuated NSC differentiation. Additionally, expression of thyroid hormone receptor interacting protein 6 (TRIP6), a critical regulator of NSCs, was negatively correlated with the miR‑138‑5p level. A luciferase assay demonstrated that miR‑138‑5p regulate TRIP6 by directly binding the 3'‑untranslated region of the mRNA. Additionally, upregulation of TRIP6 rescued the NSC proliferation deficiency induced by miR‑138‑5p and abolished miR‑138‑5p‑promoted NSCs differentiation. By contrast, downregulation of TRIP6 produced the opposite effect on proliferation and differentiation of NSCs transfected with anti‑miR‑138‑5p. Taken together, the data suggest that miR‑138‑5p regulates NSCs proliferation and differentiation, and may be useful in developing novel treatments for neurological disorders via manipulation of miR‑138‑5p in NSCs.
TL;DR: TNFR2 expression was detected in BC tissue using immunohistochemistry and it was confirmed for the first time that TNFR2 was positively associated with increased tumor size, advanced clinical stage and higher pathological grade, which indicated that TNfr2 may perform important roles in the progression and prognosis of BC.
Abstract: Tumor necrosis factor receptor 2 (TNFR2) is a member of the tumor necrosis factor receptor family. Its high expression and oncogenic roles have been reported in several types of tumors in previous years. However, the clinical implication of TNFR2 in breast cancer (BC) tissue (i.e., not soluble TNFR2 in blood or genetic variation of TNFR2) has not been reported. In the present study, TNFR2 expression was detected in BC tissue using immunohistochemistry and, to the best of our knowledge, it was confirmed for the first time that TNFR2 was positively associated with increased tumor size, advanced clinical stage and higher pathological grade. Survival analysis revealed that TNFR2 was positively associated with shorter overall survival (OS) time and disease-free survival (DFS) time. In addition, univariate regression analysis demonstrated that TNFR2 expression (P=0.045), tumor size (P<0.0001), clinical stage (P<0.0001), pathological grade (P=0.002), estrogen and progesterone receptor and human epidermal growth factor receptor 2 (HER2) triple-status (P=0.001) all had a significant impact on the OS rate of patients with BC. TNFR2 expression (P=0.017), age (P=0.011), menopausal status (P<0.0001), tumor size (P=0.016), clinical stage (P=0.005), pathological grade (P=0.002) and estrogen/progesterone receptor and HER2 triple-status (P=0.008) were all shown to significantly impact the DFS rate of patients with BC. Multivariate regression analysis showed that only clinical stage (P=0.024), estrogen and progesterone receptor status and HER2 status (P=0.009) had a significant impact on the OS rate of patients with BC, while TNFR2 expression (P=0.043) and menopausal status (P=0.033) were shown to significantly impact the DFS rate of patients with BC. These data indicated that TNFR2 may perform important roles in the progression and prognosis of BC. This enriches previous understanding about TNFR2 in BC.
TL;DR: A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantitatively or qualitatively determine multiple-components in rat plasma following the oral administration of Denshen-Chuanxiong-Honghua (DCH) extract.
TL;DR: It was demonstrated that miR-612 is downregulated by PDGF-BB treatment and has inhibitory effects on VSMC proliferation and migration via targeting AKT2, and may be used as a potential therapeutic candidate for neointimal formation in patients with atherosclerosis.
Abstract: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in neointimal formation, and therefore is suggested to contribute to arteriosclerosis and restenosis. Previous studies have suggested that some microRNAs (miRs) serve crucial roles in VSMC proliferation and invasion; however, the underlying mechanism remains largely unknown. In the present study, it was demonstrated that treatment with platelet-derived growth factor (PDGF)-BB significantly promoted the proliferation and migration of VSMCs, and decreased miR-612 levels in VSMCs. Overexpression of miR-612 significantly inhibited PDGF-BB-induced migration and invasion of VSMCs, through inducing cell cycle arrest at G1 stage. AKT2 was further identified as a direct target gene of miR-612, and its expression was negatively regulated by miR-612 in VSMCs. Further investigation confirmed that overexpression of miR-612 suppressed the PDGF-BB-induced upregulation of AKT2 protein expression. In conclusion, the present study demonstrated that miR-612 is downregulated by PDGF-BB treatment and has inhibitory effects on VSMC proliferation and migration via targeting AKT2. These findings suggest that miR-612 may be used as a potential therapeutic candidate for neointimal formation in patients with atherosclerosis.
TL;DR: It is demonstrated that EpCAM was involved in the regulation of COX‑2 expression, and a positive correlation between the proteins was associated with poor prognosis in patients with breast cancer.
Abstract: Upregulation of the epithelial cell adhesion molecule (EpCAM) is involved in tumor progression. Cyclooxygenase (COX)‑2 is the key enzyme catalyzing prostaglandin synthesis and is involved in breast cancer progression and metastasis. However, the prognostic value of EpCAM and its putative correlation with COX‑2 in breast cancer have yet to be elucidated. The aim of the present study was to assess the clinical relevance of the relationship between EpCAM and COX‑2, via examining the putative correlation between EpCAM and COX‑2 expression in various types of human breast cancer. A total of 134 breast cancer tissue samples was examined in the present study. Immunohistochemistry approach was used to detect EpCAM and COX‑2 expression in the tissue microarrays. Spearman's correlation analysis was performed to evaluate the correlation between the protein expression and clinicopathological parameters present in patients with various tumor subtypes, with the aim to potentially establish a relationship between EpCAM/COX‑2 and clinical prognosis. Expression of EpCAM and COX‑2 was revealed to be associated with tumor progression, and poor prognosis in breast cancer. The present findings demonstrated that EpCAM was involved in the regulation of COX‑2 expression, and a positive correlation between the proteins was associated with poor prognosis in patients with breast cancer. The present results suggest that EpCAM and COX‑2 may have potential as prognostic biomarkers in the diagnosis and treatment of patients with breast cancer.
TL;DR: In conclusion, serum PCT and hs-CRP levels can be used as auxiliary diagnosis index for acute exacerbation of COPD and may be helpful in guiding antibacterial drug therapy.
Abstract: The level of of procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the acute exacerbation of COPD (AECOPD) was investigated Total of 20 patients with acute exacerbation of COPD who were admitted to the Department of Respiratory Medicine, Binzhou Center Hospital in the period of October 2012 to April 2015 were enrolled in the AECOPD group According to the color of the sputum, the patients with AECOPD were divided into purulent sputum group (n=8) and non-purulent sputum group (n=12) In addition, 15 healthy people from the outpatient medical center were also selected as healthy control group The levels of serum PCT and hs-CRP in both groups were determined by chemiluminescence and immunoturbidimetry, respectively for the comparison analysis The serum PCT concentration in AECOPD group was 207±557 ng/ml, while that in healthy control group was 021±017 ng/ml Significant difference was found between serum PCT levels in the two groups (p 005) PCT level of the patients in purulent sputum group was 372±880 ng/ml, while that of the patients in non-purulent sputum group was 097±106 ng/ml The serum hs-CRP level of patients in purulent sputum group was 494±460 mg/l, while that of the patients in non-purulent sputum group was (280±338 mg/l) Both the above parameters showed no significant difference between the purulent sputum group and the non-purulent sputum group (p>005) In conclusion, serum PCT and hs-CRP levels can be used as auxiliary diagnosis index for acute exacerbation of COPD Measurement of serum PCT and hs-CRP levels in patients with AECOPD may be helpful in guiding antibacterial drug therapy
TL;DR: Gelsolin upregulation promotes radioresistance in non–small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.
Abstract: Gelsolin is an actin-binding protein and acts as an important regulator of cell survival. This study aimed to determine the function of gelsolin in the radioresistance of non-small cell lung cancer cells. We examined the expression of gelsolin in radioresistant A549 and H460 cells and their parental cells. The effects of gelsolin overexpression and knockdown on the clonogenic survival and apoptosis of non-small cell lung cancer cells after irradiation were studied. The involvement of phosphoinositide 3-kinase/Akt signaling in the action of gelsolin was checked. We found that gelsolin was significantly upregulated in radioresistant A549 and H460 cells. Overexpression of gelsolin significantly ( P < .05) increased the number of colonies from irradiated A549 and H460 cells compared to transfection of empty vector. In contrast, knockdown of gelsolin significantly ( P < .05) suppressed colony formation after irradiation. Gelsolin-overexpressing cells displayed reduced apoptosis in response to irradiation, which was coupled with decreased levels of cleaved caspase-3 and poly adenosine diphosphate-ribose polymerase. Ectopic expression of gelsolin significantly ( P < .05) enhanced the phosphorylation of Akt compared to nontransfected cells. Pretreatment with the phosphoinositide 3-kinase inhibitor LY294002 (20 μmol/L) significantly decreased clonogenic survival and enhanced apoptosis in gelsolin-overexpressing A549 and H460 cells after irradiation. Taken together, gelsolin upregulation promotes radioresistance in non-small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.
TL;DR: In this paper, the switch effect of Bi3+, a sensitive turn off on ratiometric fluorescent sensor based on dual-emission carbon-dots has been developed for captopril in aqueous solutions.
Abstract: Utilizing the switch effect of Bi3+, a sensitive turn off–on ratiometric fluorescent sensor based on dual-emission carbon-dots has been developed for captopril in aqueous solutions.
TL;DR: Results point to polymorphisms in XRCC1 and XPD genes as being related to the clinical characteristics of HCC, making them suitable prognostic markers of H CC.
Abstract: In this study genotyping of hepatocellular carcinoma (HCC) patients was conducted to detect polymorphisms on the X-ray repair cross-complementing 1 (XRCC1) and xeroderma pigmentosum complementary group D (XPD) genes and analyze the relationship of their presence with the clinical features of the cancer. A total of 172 patients with HCC were selected in Qilu Hospital, Shandong University, from January 2010 to September 2011. All patients underwent resection of HCC and no tumor metastases were found. Peripheral venous blood samples (3-5 ml) were collected from the patients to extract genomic DNA. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing. During the five-year follow-up, the survival of patients with various genotypes of XRCC1 and XPD genes were observed and compared. Logistic regression analysis was used to analyze the association between single nucleotide polymorphisms of XRCC1 and XPD genes and the prognosis of patients with HCC. χ2 tests showed that XRCC1-194, XRCC1-280 and XPD-312 gene polymorphisms were significantly correlated with the number, location and diameter of the tumors (p 0.05). Nevertheless, a significant difference was found in the survival curve of patients with AA and GG genotypes of the XRCC1-280 locus and in the patients with AA, GA and GG genotypes of the XPD-312 locus (p 0.05), but XRCC1-280 (OR=1.815, p<0.01) and XPD-312 (OR=1.815, p<0.01) genotypes were independent risk factors for a poor prognosis. Taken together our results point to polymorphisms in XRCC1 and XPD genes as being related to the clinical characteristics of HCC, making them suitable prognostic markers of HCC.
TL;DR: It is demonstrated that miR-206 has a suppressive role in medulloblastoma cell viability and invasion, partly at least, via the targeting of LASP1.
Abstract: MicroRNA (miR)-206 has been found to be deregulated in various types of human cancer, including medulloblastoma. However, the regulatory mechanism of miR-206 in medulloblastoma growth and metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction data indicated that miR-206 was significantly downregulated in medulloblastoma tissues compared with adjacent non-tumor tissues (P<0.01). Furthermore, low expression of miR-206 was significantly associated with seeding at presentation and anaplastic histology (P<0.01), but not with sex, age, or residual tumors. Overexpression of miR-206 significantly reduced the viability and migration of medulloblastoma D341 cells (P<0.01). LIM and SH3 protein 1 (LASP1) was further identified as a novel target of miR-206 in D341 cells. mRNA levels of LASP1 were significantly higher in medulloblastoma tissues compared to adjacent non-tumor tissues (P<0.01), with an inverse correlation to the miR-206 levels in medulloblastoma tissues. In addition, protein expression levels of LASP1 ere negatively regulated by miR-206 in D341 cells. Further investigation showed that overexpression of LASP1 significantly eliminated the inhibitory effects of miR-206 on the migration and invasion of D341 cells (P<0.01). In conclusion, our study demonstrates that miR-206 has a suppressive role in medulloblastoma cell viability and invasion, partly at least, via the targeting of LASP1. Our study highlights the importance of the miR-206/LASP1 in medulloblastoma.
TL;DR: The data demonstrated that LPS exposure resulted in hypermethylation in KLF2 promoter in HUVECs, which subsequently led to downregulation of the KLf2 expression, and suggested that epigenetic alteration is involved in LPS-induced inflammatory response and provided a new insight into atherogenesis.
Abstract: KLF2 plays a protective role in antiinflammation and endothelial function, and can be regulated by promoter methylation alteration Lipopolysaccharide (LPS) is a mediator of inflammatory responses, which causes epigenetic change of certain genes in host cells We thus aimed to determine whether LPS could control the KLF2 expression by inducing methylation in promoter region DNA methylation of 16 CpG sites within KLF2 promoter region was detected by bisulfite sequencing PCR Results showed that methylation at 12 CpG sites were significantly increased in HUVECs after exposure to LPS among the total 16 sites, and the average level was increased by 57% The KLF2 expressions assessed by reverse transcription quantitative real-time PCR and Western blot were significantly downregulated compared that without LPS simulation Moreover, both messenger RNA and protein levels of KLF2 in HUVEC co-treated with LPS and DNA methyltransferase (DNMT) 1 small interfering RNA were dramatically higher than that treated with LPS only Similar result was obtained when the cells were incubated in combination with LPS and 5-aza-2'-deoxycytidine (AZA), suggesting that the reduction of KLF2 expression induced by LPS can be reversed by DNMT1 inhibition Finally, the presence of AZA changed the expression of genes that depends on KLF2 in LPS-stimulated HUVECs, which downregulated the E-selectin and VCAM and increased the eNOS and thrombomodulin expression Our data demonstrated that LPS exposure resulted in hypermethylation in KLF2 promoter in HUVECs, which subsequently led to downregulation of the KLF2 expression The study suggested that epigenetic alteration is involved in LPS-induced inflammatory response and provided a new insight into atherogenesis
TL;DR: BIIB021 is an orally available, fully synthetic novel small-molecule heat shock protein 90 inhibitor that has shown strong antitumor activities in a large number of preclinical models and is now under clinical investigation.
Abstract: Heat shock protein 90 is induced in response to the cell stress. Its overexpression has been reported in many cancers with poor prognosis. It acts as a chaperone to the client proteins, especially the activated oncoproteins in malignancies to protect them from degradation. Heat shock protein 90 inhibition represented anti-cancer effects in many studies. Previous natural product–based compounds are limited by their association with target toxicities. BIIB021 is an orally available, fully synthetic novel small-molecule heat shock protein 90 inhibitor that has shown strong antitumor activities in a large number of preclinical models and is now under clinical investigation. This review will summarize its therapeutic effects and highlight the prospect of targeting heat shock protein 90 in the cancer therapy.
TL;DR: The combined results of univariate and multivariate Cox regression analysis showed that the SNP in ERCC1-118 was closely associated with survival time and XRCCl-399 SNP was associated with the short-term therapeutic efficacy and tumor metastasis/relapse in ESCC patients who received the docetaxel plus cisplatin regimen-based concurrent radiochemotherapy.
Abstract: The aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in X-ray repair cross-complementing 1-399 (XRCC1-399) or excision repair cross-complementation group 1-118 (ERCC1-118) and the short-term efficacy of radiochemotherapy, tumor metastasis and relapse, as well as the survival time in patients with esophageal squamous cell carcinoma (ESCC). TaqMan probe-based quantitative polymerase chain reaction (qPCR) was conducted to examine the levels of XRCC1-399 and ERCC1-118 SNPs in the peripheral blood of 50 patients with pathologically confirmed ESCC. In addition, the associations between different genotypes and short-term therapeutic efficacy [the complete remission (CR) rate], tumor metastasis and relapse, as well as the survival time following concurrent radiochemotherapy, were determined. A total of 50 ESCC patients who received concurrent radiochemotherapy were enrolled. It was found that the short-term therapeutic efficacy (CR rate) was higher in the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) than in the group of patients without the XRCC1-399 mutation (G/G genotype). In addition, the CR rate was significantly increased in patients carrying one or two ERCC1-118 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype). The differences were statistically significant (A/A vs. G/G, P=0.014; TT vs. C/T+C/C, P=0.040). During the follow-up period, the group of patients carrying the homozygous mutation of XRCC1-399 (A/A genotype) exhibited a markedly reduced risk of metastasis and relapse compared with the group of patients carrying non-mutated XRCC1-399 (G/G genotype; P=0.031). By contrast, ERCC1-118 SNP was not associated with the risk of metastasis and recurrence (P>0.05). The combined results of univariate and multivariate Cox regression analysis showed that the SNP in ERCC1-118 was closely associated with survival time. The mean survival time was significantly prolonged in patients carrying 1 or 2 C alleles (C/C or C/T genotype) compared with patients lacking the C allele (T/T genotype) [T/T vs. C/C, HR=12.96, 95% confidence interval (CI)=3.08-54.61, P 0.05). XRCCl-399 SNP was associated with the short-term therapeutic efficacy (the CR rate) and tumor metastasis/relapse in ESCC patients who received the docetaxel plus cisplatin (TP) regimen-based concurrent radiochemotherapy. By contrast, ERCC1-118 SNP was significantly associated with the short-term therapeutic efficacy (the CR rate) and survival time in ESCC patients who received TP regimen-based concurrent radiochemotherapy.
TL;DR: The results indicate that the MTHFR C677T polymorphism may be a promising ALL biomarker and studies to explore the protein levels of the variants and their functional role are required for the definitive conclusions.
TL;DR: The level of plasma PSS-LPA may be an important biomarker for diagnosis of MCI, according to logistic regression analysis, which indicates that elevated plasma PSSLPA was associated with increased risk ofMCI in type 2 diabetic patients.
Abstract: Background: Phospholipids and their metabolisms are closely allied to nosogenesis and aggravation of Type 2 diabetes mellitus and cognitive impairment. The aim of this study is to characterize the plasma levels of phospholipids in type 2 diabetes patients and type 2 diabetes patients with mild cognitive impairment (MCI), and to identify potential biomarkers of type 2 diabetes patients with MCI. Methods: In this cross-sectional study, a total of 374 type 2 diabetes patients were prospectively enrolled. There were 103 patients with MCI and 271 patients without MCI. Plasma levels of lysophosphatidic acid (LPA) and phospholipids with solubility similar to that of LPA (PSS-LPA) were assayed. Results: Plasma LPA and PSS-LPA levels were significantly higher in patients with MCI than those without MCI (P = 0.007, P ＜ 0.001). A logistic regression analysis indicates that elevated plasma PSSLPA was associated with increased risk of MCI in type 2 diabetic patients, with an OR of 1.87 (1.04- 3.47) after additional adjustment for hyperlipidemia, hypertension, High-sensitivity C-reactive protein, hemoglobin A1c, Intima-media thickness, ankle brachial index, and brachial-ankle pulse wave velocity. In type 2 diabetic patients with MCI, there were negative correlations between plasma LPA, PSS-LPA and the MoCA scores (r =﹣0.322, P < 0.01; r =﹣0.349, P < 0.001). Furthermore, plasma PSS-LPA exhibited a fair diagnostic value for MCI, with an area under the curve of 0.86. Conclusion: The level of plasma PSS-LPA may be an important biomarker for diagnosis of MCI.
TL;DR: The CGG expanded allele of the FMR1 gene might be associated with unexplained multiple miscarriages; whether such an association is coincidental or causal can be confirmed by future studies using a larger patient cohort.
Abstract: Up to 50% of recurrent miscarriage cases in women occur without an underlying etiology. In the current prospective case-control study, we determined the impact of CGG trinucleotide expansions of the fragile-X mental retardation 1 (FMR1) gene in 49 women with unexplained recurrent miscarriages. Case group consisted of women with two or more unexplained consecutive miscarriages. Blood samples were obtained and checked for the presence of expanded alleles of the FMR1 gene using PCR. Patients harboring the expanded allele, with a threshold set to 40 repeats, were further evaluated by sequencing. The number of abortions each woman had, was not associated with her respective CGG repeat number (P=0.255). The repeat sizes of CGG expansion in the FMR1 gene were significantly different in the two population groups (P=0.027). All the positive cases involved intermediate zone carriers. Hence, the CGG expanded allele of the FMR1 gene might be associated with unexplained multiple miscarriages; whether such an association is coincidental or causal can be confirmed by future studies using a larger patient cohort.