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Glioblastoma is the most common malignant central nervous system tumor. Patient outcome remains poor despite the development of therapy and increased understanding of the disease in the past decades. Glioma cells invade the peritumoral brain, which results in inevitable tumor recurrence. Previous studies have demonstrated that the extracellular matrix (ECM) is altered in gliomas and serves a major role in glioma invasion. The present study focuses on differences in the ECM composition of tumors in patients with poor and improved prognosis. The mRNA and protein expression of 16 invasion-associated ECM molecules was determined using reverse trascription-quantitiative polymerase chain reaction and immunohistochemistry, respectively. Clinical factors of patients with different prognoses was also analyzed. It was determined that age and postoperative Karnofsky performance score were associated with patient survival. Furthermore, Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR3), murine double minute 2 (MDM2) and matrix metallopeptidase 2 (MMP2) mRNA levels were significantly different between the two prognostic groups. Additionally, brevican, cluster of differentiation 44, hyaluronan mediated motility receptor, integrin-αV and -β1, and MDM2 protein expression were indicated to be significantly different in immunohistochemistry slides. Using the expression profile, including the invasion spectrum of the samples, it was possible to identify the prognostic group of the sample with high efficacy, particularly in cases with poor prognosis. In conclusion, it was determined that ECM components exhibit different expression levels in tumors with different prognoses and thus the invasion spectrum can be used as a prognostic factor in glioblastoma.
Colorectal cancer (CRC) is a common malignancy with high morbidity. MicroRNAs (miRNAs or miRs) have been demonstrated to be critical post-transcriptional regulators in tumorigenesis. The current study aimed to investigate the effect of miR-410 on the proliferation and metastasis of CRC. The expression of miR-410 was examined in CRC cell lines. SW-480 and HCT-116 CRC cell lines were employed and transfected with miR-410 inhibitor or miR-410 mimics. The association between miR-410 and dickkopf-related protein 1 (DKK-1) was verified by luciferase reporter assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Cell migration and invasion capacity were determined by Transwell assay. The protein level of DKK1, β-catenin and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were analyzed by western blotting. miR-410 was revealed to be upregulated in CRC cell lines. Further studies identified DKK-1 as a direct target of miR-410. In addition, knockdown of miR-410 promoted the expression of DKK, inhibited CRC cell proliferation, migration and invasion capacity, and induced cell apoptosis, while overexpression of miR-410 reversed these results. miR-410 silencing also decreased β-catenin and pGSK-3β levels. The current study indicated that miR-410 negatively regulates the expression of DKK-1 in vitro. miR-410 promotes malignancy phenotypes in CRC cell lines. This regulatory effect of miR-410 may be associated with the Wnt/β-catenin signaling pathway. Therefore, miR-410 could be used as a biomarker for predicting the progression of CRC.
Previous studies have demonstrated that microRNAs (miRs) serve important roles in the progression of human cancer types, including pancreatic cancer (PC), a highly lethal malignancy. In the past few decades, several miRs have been identified to be associated with the overall survival of patients with PC and have been demonstrated to be potential therapeutic targets. However, to the best of our knowledge, the association between miR-205 expression and the progression of PC has rarely been investigated. In the current study, low miR-205 expression was revealed in PC tumor tissues and indicated poor prognosis in patients with PC. In addition, miR-205 overexpression reduced and miR-205 depletion enhanced PC cell proliferation and migration in vitro. Using bioinformatics, a luciferase reporter assay and western blot analyses, the current study identified that runt-related transcription factor 2 (RUNX2) was a target of miR-205 in PC and overexpression of miR-205 suppressed the expression of RUNX2. Notably, overexpression of RUNX2 partially reversed the inhibitory effect of miR-205 on PC cell proliferation and migration in vitro. Therefore, the results of the present study revealed that miR-205 functions as a tumor suppressor in PC by targeting RUNX2.
Effects of mir-128a on the proliferation and migration of human glioma U251 cells were explored. The constructed mir-128a-shRNA lentivirus vector (infection group) and scramble shRNA (interference group) were transfected into glioma U251 cells, and uninfected U251 cells as control group. The expression level of mir-128a, the ability of proliferation, invasion, apoptosis and migration of cells in each group were detected by RT-qPCR, MTT assay, Transwell migration in vitro, cell wound scratch assay and TUNEL cell apoptosis assay. The expression level of mir-128a in U251 cells of infection group was significantly higher than that in U251 cells of interference group (P<0.05). Τhe expression level of mir-128a in U251 cells of control group was significantly lower than that in U251 cells of infection group (P<0.05). The OD values of infection and control group were lower than that of interference group at 6, 12, 24, 48 and 72 h, and the OD values of infection were lower than that of control group at 6, 12, 24, 48 and 72 h (P<0.05). Compared with infection and control group, the number of membrane-penetrating cells in U251 cells of interference group increased significantly (P<0.05). The apoptosis rate of U251 cells of infection and control group was significantly higher than that of interference group, and the apoptosis rate of infection was significantly higher than that of control group (P<0.05). The migration distance of U251 cells of infection and interference group was significantly larger than that of control group (P<0.05). Τhe migration distance of U251 cells of interference group was significantly larger than that of infection group (P<0.05). mir-128a may play a role similar to anti-oncogene in glioma, inhibiting the ability of proliferation, invasion and migration of glioma cells, and promoting the apoptosis of glioma cells.
The expression levels of seven types of cytokeratin (CK) in different kinds of skin adnexal tumors were evaluated. One hundred and thirty-two patients with different kinds of skin adnexal tumors admitted and treated in the Department of Dermatology of Dongying People's Hospital from May 2013 to May 2015 were selected and underwent tissue section staining. Another 20 cases of normal skin were enrolled as the control group. The expression levels of the seven types of CK in different kinds of skin appendages were observed and recorded. The expression levels of the seven types of CK in the 132 cases of skin adnexal tumor tissues were different. CK10 was mainly expressed in squamous cell carcinoma, but it was not expressed in basal cell carcinoma. CK19 was expressed in basal cell carcinoma, but its expression was not detected in squamous cell carcinoma. As the degree of differentiation was increased in the epidermis, hair follicle and sebaceous gland, the expressed molecular weight of CK was augmented gradually. The expression levels of five types of CK (namely, CK8, CK10, CK14, CK18 and CK19) could be measured in the squamous cell carcinoma and basal cell carcinoma. Statistical analysis revealed that there were statistically significant differences in the expression levels of these five types of CK in the two cell carcinomas (P<0.05). Five types of CK, i.e., CK7, CK8, CK17, CK18 and CK19, had markedly different expression levels in hair follicle tumor and sweat gland tumor, which were statistically significant (P<0.05). The expression levels of a group of CKs detected by virtue of semi-quantitative analysis via immunohistochemistry can be regarded as one of the important indexes for clinical diagnosis of skin adnexal tumors.
Sirtuin-7 is an evolutionarily conserved NAD-dependent deacetylase, which serves an important role in carcinogenesis. However, the potential mechanism of sirtuin-7 in endometrial cancer has not yet been investigated. The purpose of the present study was to investigate whether sirtuin-7 exhibits inhibitory effects on endometrial cancer cells. The potential mechanisms mediated by sirtuin-7 in endometrial cancer cells were also investigated. The expression levels of sirtuin-7 in endometrial cancer cells were compared with normal endometrial cells using western blotting. The results demonstrated that sirtuin-7 is overexpressed in endometrial cancer cells compared with normal endometrial cells. The downregulation of sirtuin-7 inhibited the growth and invasiveness of endometrial cancer cells. The knockdown of sirtuin-7 was observed to increase the sensitivity of the endometrial cancer cells to cisplatin treatment in vitro. An investigation into the potential molecular mechanism demonstrated that sirtuin-7 knockdown promoted the apoptosis of endometrial cancer cells by regulating the nuclear factor (NF)-κB signaling pathway. The knockdown of sirtuin-7 inhibited NF-κB expression and resulted in a decrease in the expression of NF-κB target proteins that are anti-apoptotic: Bcl-xl, Bcl-2 and Mcl-1. Sirtuin-7 knockdown also resulted in an increase of the NF-κB target proteins that are pro-apoptotic: Caspase-3, Bad and Bax. In conclusion, the present study demonstrated that sirtuin-7 knockdown was able to markedly inhibit the growth of endometrial cancer cells, suggesting that sirtuin-7 may be a potential therapeutic target for endometrial cancer therapy.
Glioblastoma is a malignant primary brain tumor with poor prognosis with a median survival of only 12-15 months. The high mortality rate of this disease is mainly due to the chemoresistance resulting from various reasons. Ubiquitin-specific protease 4 (USP4) has recently been found to be elevated in various types of cancer through regulating P53 activity. However, whether USP4 is responsible for chemoresistance in glioblastoma is not clear. In the present study, the expression of USP4 in glioblastoma tissues and cell lines, as well as its association with temozolomide (TMZ) chemoresistance was analyzed. The results demonstrated that USP4 was significantly upregulated in glioblastoma tissues and cell lines at the mRNA and protein levels. Notably, USP4 knockdown alone did not affect glioblastoma cell viability; however, when USP4 knockdown cells were treated with TMZ, the cell viability was decreased significantly. In addition, the results revealed that cleaved poly(ADP-ribose) polymerase level increased when USP4 was knocked down in glioblastoma cells treated with TMZ. It was also observed that P53 was increased in U251 and U87 cells with USP4 knockdown. Following treatment with a P53 specific inhibitor, the results suggested that USP4 mediated chemoresistance through inhibiting apoptosis in a P53-dependent manner. In conclusion, the data revealed the critical role of USP4 in TMZ resistance in glioblastoma and provided new insight for future drug development for the treatment of this disease.
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. Despite improvements in treatment, CLL is still considered an incurable disease. The aim of the present study was to evaluate galectin-1, -3 and -9 (Gal-1, -3 and -9) and Gal-3 binding protein (Gal-3BP) as prognostic and predictive factors in patients with CLL. Serum concentrations of Gal-1, -3 and -9 and Gal-3BP were measured in 48 patients with CLL and 30 control patients, using multiplex bead arrays. In patients with CLL, galectin concentrations were assessed prior to, during and following treatment. In patients with CLL who were untreated, galectin concentrations were measured twice with a 6-month interval. The serum level of Gal-9 was significantly increased (P<0.0001) in patients with CLL compared with the control group, and was associated with the clinical stage according to Binet classification, as well as poor cytogenetic and serum CLL prognostic factors. In addition, patients with CLL, who exhibited treatment failure, exhibited higher concentrations of Gal-9 (P=0.06) and Gal-3BP (P=0.009) at the end of the treatment when compared with patients under complete remission or stabilization of the disease. The serum level of Gal-3 was significantly decreased (P=0.012) in patients with CLL compared with the control group. These results suggest that Gal-9 is a potential prognostic factor in patients with CLL. The predictive value of Gal-9 requires further study in larger cohorts of patients.
Intestinal bacteria are symbiotic microbiota within the human gut and are implicated in the occurrence and development of colorectal cancer (CRC). The current study investigated the changes in bacterial composition prior to and following surgery, as well as the differences in the bacterial community structure between cancer tissue and adjacent normal tissue. The diversity of the bacterial community and the composition of the bacteria were assessed. In addition, phylogenetic analysis and principle component analysis (PCA) were performed. The results revealed that cancer tissue and adjacent normal tissue exhibited similar bacterial compositions. However, a significant difference was identified in the composition of intestinal bacteria in stool samples collected from patients following surgery compared with stool samples collected prior to surgery. Each patient had their own unique intestinal bacterial community, likely due to a number of factors, including diet, genetic factors and health status. In addition, phylogenetic trees revealed that the most abundant operational taxonomic unit, 0001, was associated with Escherichia coli in all samples. Finally, PCA suggested that the bacterial community structure in all patient stools was similar following surgery. The current study provides information regarding the diversity of the intestinal bacterial community of patients with CRC and provides a basis for postoperative intestinal assessments.
This study investigated whether microRNA-183 and microRNA-141 in nasopharyngeal carcinoma (NPC) lesions are potential risk factors for poor prognosis. A total of 317 NPC patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2010 to March 2015 were included. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression of microRNA-183 and microRNA-141 in lesions and adjacent tissues, and the relationship between the microRNA-183 and microRNA-141 expression levels and prognosis was analyzed. The expression levels of microRNA-183 and microRNA-141 in lesions were significantly higher than those in adjacent tissues (p<0.05). Patients with distant metastasis had significantly higher expression levels of microRNA-183 and microRNA-141 than patients without distant metastasis (p<0.01). Patients with disease-free survival (DFS) <3 years showed significantly higher expression levels of microRNA-183 and microRNA-141 than those with DFS ≥3 years (p<0.01). NPC patients with high expression levels of microRNA-183 and microRNA-141 showed poor prognosis. MicroRNA-183 and microRNA-141 may play an important role in the distant metastasis of NPC, and have a great impact on prognosis.
Glioma is the most common and rapidly progressive type of malignant primary brain tumor in adults. miR-153 plays a major role in many malignancies; nevertheless, few studies have been conducted on glioma. The aim of the present study was to explore the role of miR-153 and SNAI1 on invasion in glioma. Reverse transcription-quantitative PCR was employed to measure the expression levels of miR-153 and SNAI1 mRNA. Transwell assay was utilized to calculate the capacity of invasion. Luciferase report assay was applied to detect whether SNAI1 was a target of miR-153. miR-153 was downregulated in glioma tissues and cells versus paracancerous tissues and normal immortalized gliocyte HEB cells. Transwell assay was used to measure whether a low expression of miR-153 in glioma indicated inhibition of cell invasion. We verified that SNAI1 was a target of miR-153 and had a negative association with miR-153 detected by luciferase reporter assay. Additionally, miR-153 suppressed cell invasive ability by regulating SNAI1 expression, whose partial function was reversed by SNAI1. miR-153 suppressed cell invasion of glioma by directly targeting SNAI1. Thus, miR-153/SNAI1 axis may be a novel target for cervical cancer treatment.
Obesity is a well-known of risk factor for atherosclerosis. However, recently an "obesity paradox" has been discussed, which is considered as a protective effect of obesity on the development coronary artery disease (CAD). An aim of the study was to investigate the risk of CAD in morbidly obese patients using coronary artery calcium measurement.
The emergence of multidrug- or extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. It is urgently necessary to search for alternatives to conventional antibiotics for control of severe A. baumannii infections. In recent years, bacteriophages and their derivatives, such as depolymerases, showed great potential as antibacterial or antivirulence agents against bacterial infections. Nonetheless, unlike broad-spectrum bactericidal antibiotics, phage-encoded depolymerase targets only a limited number of bacterial strains. Therefore, identification of novel depolymerases and evaluation of their ability to control A. baumannii infections is important.
Seed germination is one of the earliest key events in the plant life cycle. The timing of transition from seed to seedling is an important developmental stage determining the survival of individuals that influences the status of populations and species. Because of wide geographical distribution and occurrence in diverse habitats, wild pea (Pisum sativum subsp. elatius) offers an excellent model to study physical type of seed dormancy in an ecological context. This study addresses the gap in knowledge of association between the seed dormancy, seed properties and environmental factors, experimentally testing oscillating temperature as dormancy release clue.
Purpose This study evaluates regional poverty level-dependent differences in lung cancer (LC) survival, focusing on patients receiving radiation therapy (RT). Methods and materials The Surveillance, Epidemiology, and End Results (SEER) database was used to retrospectively identify patients diagnosed with LC between 2000 and 2009. Patients were divided into socioeconomic status (SES) quintiles, with quintiles 1 and 5 representing the highest and lowest SES cohorts, respectively. The Kaplan-Meier method with the log-rank test was used to compare overall survival (OS) from diagnosis between demographic and clinical factor levels. Multivariate (MVA) Cox proportional hazards regression was used to examine the association of quintile and mortality, adjusting for demographic and clinical factors. Results Compared to those not receiving RT, the univariate (UVA) results showed a higher mortality associated with receiving RT (HR:1.091; CI:1.081-1.102) while the MVA demonstrated a protective effect (HR:0.882; CI:0.873-0.891). The MVA revealed that men had higher mortality rates than women (HR:1.192; CI:1.180-1.203). Caucasians had a lower mortality rate as compared to African Americans (adjusted HR:0.932; CI:0.918-0.947) while Asians, Pacific Islanders, and Native Americans had the highest overall survival rates (adjusted HR:0.752, CI:0.734-0.771). Among the entire study population, quintile 2 (HR:1.059, CI:1.043-1.076), quintile 3 (HR:1.091, CI:1.075-1.108), quintile 4 (HR:1.094, CI:1079-1.110), and quintile 5 (HR:1.201, CI:1.181-1.221) reported increased mortality rates compared with quintile 1. This trend was also observed among those undergoing RT, with quintile 2 (HR:1.034, CI:1.010-1.059), quintile 3 (HR:1.045; CI:1.021-1.069), quintile 4 (HR:1.056; CI:1.033-1.080), and quintile 5 (HR:1.153; CI:1.124-1.183) demonstrating incrementally worse OS. Conclusions Upon accounting for age, gender, race, SES, and tumor stage, RT may provide a positive survival benefit among those who received treatment. Minimal differences existed among SES quintiles regarding diagnoses made by tumor stage or patients receiving RT. An incrementally worse OS rate was associated with increasing regional poverty level. This trend persevered among those receiving RT.
The Active School program was designed to positively impact health and academic-related outcomes in school. The core intervention component was physically active academic lessons, a teaching activity that combines physical activity and educational content. The purpose of this study was to investigate the effect of a 10-month, cluster-randomized controlled trial on physical activity level and aerobic fitness conducted in the city of Stavanger, Norway, in 2014-15. The physical activity level during physically active academic lessons was also studied. A total of 447 children (9-10 years) participated. The weekly intervention consisted of physically active academic lessons, physically active homework and physically active recess. Physical activity level and aerobic fitness were measured objectively by accelerometry and a 10-minute interval running test. Intervention effects were found for time in moderate to vigorous physical activity (MVPA) (adjusted mean difference of 8 min/day, 95% CI: 3.4-13, p < 0.001) and total physical activity (60 counts/min, 95% CI: 15-105, p = 0.009). Children with low aerobic fitness increased their running distance compared to controls (d = 0.46; p = 0.001). During physically active academic lessons children spent 26% of the time in MVPA, which was comparable to physical education lessons. The Active School program successfully increased physical activity for the intervention group and aerobic fitness for the least fit children. The activity level during physically active academic lessons was as high as in physical education lessons. Clinicaltrail.gov ID identifier: NCT03436355.
The Guillain-Barré syndrome (GBS) is an acute, immune-mediated disease of peripheral nerves. Plasmablasts and plasma cells play a central role in GBS by producing neurotoxic antibodies. The standard treatment for GBS is high-dose intravenous immunoglobulins (IVIg), however the working mechanism is unknown and the response to treatment is highly variable. We aimed to determine whether IVIg changes the frequency of B-cell subsets in patients with GBS.
Over the last two decades there has been an exponential rise in the number of patients receiving deep brain stimulation (DBS) to manage debilitating neurological symptoms in conditions such as Parkinson's disease, essential tremor, and dystonia. Novel applications of DBS continue to emerge including treatment of various psychiatric conditions (e.g. obsessive-compulsive disorder, major depression) and cognitive disorders such as Alzheimer's disease. Despite widening therapeutic applications, our understanding of the mechanisms underlying DBS remains limited. In addition to modulation of local and network-wide neuronal activity, growing evidence suggests that DBS may also have important neuroprotective effects in the brain by limiting synaptic dysfunction and neuronal loss in neurodegenerative disorders. In this review, we consider evidence from preclinical and clinical studies of DBS in Parkinson's disease, Alzheimer's disease, and epilepsy that suggest chronic stimulation has the potential to mitigate neuronal loss and disease progression.
Peronospora destructor (Berk.) is an important biotrophic oomycete that causes downy mildew on onion (Allium Cepa L.) worldwide, especially in humid and temperate regions. The disease attacks bulb and seed production of onion, resulting in losses in yield and quality of bulbs. Epidemiological studies have increased our understanding and control of downy mildew on onion; however, little is known about the molecular aspects of P. destructor behavior during infection. Here, we isolated RNA from four samples of sporangia and sporangiophores of P. destructor, which were maintained by spore inoculation onto onions in a growth chamber. We then used an Ion PGM next generation sequencer to acquire and assemble the RNA sequences of P. destructor. By transcriptome shotgun assembly, we obtained 2335 contigs (N50, 884 nucleotides (nt); mean length, 881.6 nt). The data are accessible at NCBI (BioProject PRJNA391849). Our data resource will facilitate further studies of the molecular events during P. destructor infection.
Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL.
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