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1.
Epigenetics ; 19(1): 2337085, 2024 Dec.
Article En | MEDLINE | ID: mdl-38595049

The PhiC31 integration system allows for targeted and efficient transgene integration and expression by recognizing pseudo attP sites in mammalian cells and integrating the exogenous genes into the open chromatin regions of active chromatin. In order to investigate the regulatory patterns of efficient gene expression in the open chromatin region of PhiC31 integration, this study utilized Ubiquitous Chromatin Opening Element (UCOE) and activating RNA (saRNA) to modulate the chromatin structure in the promoter region of the PhiC31 integration vector. The study analysed the effects of DNA methylation and nucleosome occupancy changes in the integrated promoter on gene expression levels. The results showed that for the OCT4 promoter with moderate CG density, DNA methylation had a smaller impact on expression compared to changes in nucleosome positioning near the transcription start site, which was crucial for enhancing downstream gene expression. On the other hand, for the SOX2 promoter with high CG density, increased methylation in the CpG island upstream of the transcription start site played a key role in affecting high expression, but the positioning and clustering of nucleosomes also had an important influence. In conclusion, analysing the DNA methylation patterns, nucleosome positioning, and quantity distribution of different promoters can determine whether the PhiC31 integration site possesses the potential to further enhance expression or overcome transgene silencing effects by utilizing chromatin regulatory elements.


Chromatin , Nucleosomes , Animals , Chromatin/genetics , Nucleosomes/genetics , DNA Methylation , CpG Islands , Promoter Regions, Genetic , Mammals/genetics
2.
Mol Nutr Food Res ; 68(8): e2300745, 2024 Apr.
Article En | MEDLINE | ID: mdl-38581304

SCOPE: Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. CONCLUSION: NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.


Apoptosis , Flavanones , Mice, Inbred C57BL , Reactive Oxygen Species , TRPV Cation Channels , Animals , Flavanones/pharmacology , Humans , TRPV Cation Channels/metabolism , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Male , Mice , Radiation-Protective Agents/pharmacology , Intestinal Mucosa/drug effects , Intestinal Mucosa/radiation effects , Intestinal Mucosa/metabolism , HCT116 Cells , Calcium Channels/metabolism , Intestines/drug effects , Intestines/radiation effects , Calcium/metabolism , Radiation Injuries/drug therapy
3.
J Cancer Res Clin Oncol ; 149(20): 18215-18240, 2023 Dec.
Article En | MEDLINE | ID: mdl-38078963

INTRODUCTION: Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance. METHODS: A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS). RESULTS: The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult. CONCLUSION: In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.


Head and Neck Neoplasms , Papillomavirus Infections , Humans , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , B7-H1 Antigen/analysis , Squamous Cell Carcinoma of Head and Neck/drug therapy , Head and Neck Neoplasms/drug therapy , Biomarkers , Tumor Microenvironment
5.
Sensors (Basel) ; 23(10)2023 May 18.
Article En | MEDLINE | ID: mdl-37430788

The total harmonic distortion (THD) index and its calculation methods are presented to calibrate the sinusoidal motion of the low-frequency angular acceleration rotary table (LFAART) and make up the incomprehensive evaluation based on the angular acceleration amplitude and frequency error indexes. The THD is calculated from two measurement schemes: a unique scheme combining the optical shaft encoder and the laser triangulation sensor and a regular scheme using the fiber optical gyroscope (FOG). An improved reversing moments recognition method is presented to upgrade the accuracy of solving the angular motion amplitude based on optical shaft encoder output. The field experiment shows that the difference in the THD values achieved using the combining scheme and FOG is within 0.11% when the signal-to-noise ratio of the FOG signal is higher than 7.7 dB, indicating the accuracy of the proposed methods and the feasibility of taking THD as the index.

6.
Technol Cancer Res Treat ; 22: 15330338231164875, 2023.
Article En | MEDLINE | ID: mdl-36972517

Purpose: The present retrospective study aimed to explore the relationship between pancreatitis and pancreatic cancer in the population cohort of the UK Biobank (UKB) (https://www.ukbiobank.ac.uk). Methods: From the 500 thousand population cohort of UKB, according to the age and gender of patients with pancreatic cancer 1:10, matching the control without pancreatic cancer, the binary Logistic regression model was used to analyze the relationship between pancreatitis and pancreatic cancer, and subgroup analyses were used to identify potential effect modifiers. Results: A total of 1538 patients with pancreatic cancer were compared with 15 380 controls. In the fully adjusted model, patients with pancreatitis had a significantly increased risk of pancreatic cancer compared with no pancreatitis. The risk of pancreatitis and pancreatic cancer increased with the age of pancreatitis, and the risk of pancreatic cancer was highest in the 61 to 70 age group. In addition, in the first 3 years of acute pancreatitis, the risk of pancreatic cancer increased significantly with the increase in the duration of the disease (odds ratio [OR] 29.13, 95% confidence interval [CI]: 16.34-51.93), after 3 years, the trend of increase decreased. After more than 10 years, there was no significant correlation between the risk of acute pancreatitis and pancreatic cancer. However, patients with chronic pancreatitis were significantly associated with an increased risk of pancreatic cancer only in the first 3 years (OR 28.14, 95% CI: 14.86-53.31). Conclusion: Pancreatitis may associate with an increased risk of pancreatic cancer. The older the age of pancreatitis, the higher the risk of pancreatic cancer. The risk of pancreatic cancer increases significantly in the first 3 years of the course of pancreatitis. This may provide an alternative strategy for the early identification of individuals at high risk of pancreatic cancer.


Pancreatic Neoplasms , Pancreatitis , Humans , Pancreatitis/complications , Pancreatitis/epidemiology , Risk Factors , Retrospective Studies , Acute Disease , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/etiology , Pancreatic Neoplasms
7.
Article En | MEDLINE | ID: mdl-36833759

Abamectin (ABM) has been recently widely used in aquaculture. However, few studies have examined its metabolic mechanism and ecotoxicity in microorganisms. This study investigated the molecular metabolic mechanism and ecotoxicity of Bacillus sp. LM24 (B. sp LM24) under ABM stress using intracellular metabolomics. The differential metabolites most affected by the bacteria were lipids and lipid metabolites. The main significant metabolic pathways of B. sp LM24 in response to ABM stress were glycerolipid; glycine, serine, and threonine; and glycerophospholipid, and sphingolipid. The bacteria improved cell membrane fluidity and maintained cellular activity by enhancing the interconversion pathway of certain phospholipids and sn-3-phosphoglycerol. It obtained more extracellular oxygen and nutrients to adjust the lipid metabolism pathway, mitigate the impact of sugar metabolism, produce acetyl coenzyme A to enter the tricarboxylic acid (TCA) cycle, maintain sufficient anabolic energy, and use some amino acid precursors produced during the TCA cycle to express ABM efflux protein and degradative enzymes. It produced antioxidants, including hydroxyanigorufone, D-erythroascorbic acid 1'-a-D-xylopyranoside, and 3-methylcyclopentadecanone, to alleviate ABM-induced cellular and oxidative damage. However, prolonged stress can cause metabolic disturbances in the metabolic pathways of glycine, serine, threonine, and sphingolipid; reduce acetylcholine production; and increase quinolinic acid synthesis.


Bacillus , Metabolomics , Serine , Glycine , Threonine
8.
Article En | MEDLINE | ID: mdl-36429655

Bi2WO6-based heterojunction photocatalyst for antibiotic degradation has been a research hotspot, but its photocatalytic performance needs to be further improved. Therefore, 2D/2D P-doped g-C3N4/Bi2WO6 direct Z-scheme heterojunction photocatalysts with different composition ratios were prepared through three strategies of phosphorus (P) element doping, morphology regulation, and heterojunction, and the efficiency of its degradation of tetracycline hydrochloride (TC-HCl) under visible light was studied. Their structural, optical, and electronic properties were evaluated, and their photocatalytic efficiency for TC-HCl degradation was explored with a detailed assessment of the active species, degradation pathways, and effects of humic acid, different anions and cations, and water sources. The 30% P-doped g-C3N4/Bi2WO6 had the best photocatalytic performance for TC-HCl degradation. Its photocatalytic rate was 4.5-, 2.2-, and 1.9-times greater than that of g-C3N4, P-doped g-C3N4, and Bi2WO6, respectively. The improved photocatalytic efficiency was attributed to the synergistic effect of P doping and 2D/2D direct Z-scheme heterojunction construction. The stability and reusability of the 30% P-doped C3N4/Bi2WO6 were confirmed by cyclic degradation experiments. Radical scavenging experiments and electron spin resonance spectroscopy showed that the main active species were •O2- and h+. This work provides a new strategy for the preparation of direct Z-scheme heterojunction catalysts with high catalytic performance.


Phosphorus , Tetracycline , Tetracycline/chemistry , Bismuth/chemistry , Anti-Bacterial Agents/chemistry , Catalysis
9.
Front Oncol ; 12: 1015302, 2022.
Article En | MEDLINE | ID: mdl-36605427

Background: Chemotherapy combined with immune checkpoints inhibitors (ICIs) has been established as a standard treatment for locally advanced, metastatic, or recurrent esophageal squamous cell cancer (ESCC). However, the optimal chemotherapy regimen in combination therapy is still unclear. Purpose: To investigate the efficacy and adverse events of the fluorouracil plus platinum (FP) and taxane plus platinum (TP) regimens in ESCC patients receiving chemo-immunotherapy, we conducted this systematic review and meta-analysis. Methods: Potentially eligible studies were searched from Medline, Embase, Web of Science, and the Cochrane Library. Pooled rates of overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were compared between ICIs+TP and ICIs+FP groups in ESCC patients receiving first-line chemo-immunotherapy. Results: A total of 10 clinical trials were included, of which 5 were randomized controlled trials. Compared with chemotherapy alone, chemo-immunotherapy significantly improved the OS of ESCC patients (pooled HR=0.69; 95% CI, 0.63-0.76; p<0.01). Pooled analysis revealed that ESCC patients receiving ICIs+TP had significantly higher ORR, DCR, PFS, and OS rates than those receiving ICIs+FP. No statistically significant difference in the pooled incidence rate of treatment-related death was found (2.3% vs 0.9%, P=0.08). ICIs+TP had significantly higher rates of hematologic toxicity but lower rates of gastrointestinal toxicity than ICIs+FP. Conclusions: Based on the current data, the first-line treatment using ICIs+TP may be a better option than ICIs+FP in advanced, metastatic, or recurrent ESCC.

11.
Int J Radiat Oncol Biol Phys ; 111(2): 582, 2021 10 01.
Article En | MEDLINE | ID: mdl-34473982
12.
Int Immunopharmacol ; 99: 108031, 2021 Oct.
Article En | MEDLINE | ID: mdl-34358857

OBJECTIVE: Immunotherapies targeting immune checkpoints have achieved encouraging survival benefits in patients with various solid cancers. Corticosteroids are frequently administrated for cancer/non-cancer related indications and immune-related adverse events (irAEs). This study aimed to clarify the prognostic significance of corticosteroid administration in solid cancer patients receiving immune checkpoint inhibitor (ICI) treatment. METHOD: First, a meta-analysis was performed using the literatures searched from PubMed, Cochrane Library, Web of Science, Embase, and Clinicaltrials.gov before January 2021. The Hazard ratios (HRs) coupled with 95% confidence intervals (CIs) were used to evaluate the correlation of corticosteroid administration with overall survival (OS) and progression-free survival (PFS). Then, a retrospective analysis enrolling 118 ICI-treated cancer patients was performed for validation, among which 26 patients received corticosteroids for cancer-related indications. RESULT: In the meta-analysis, corticosteroid administration for cancer-related indications was significantly correlated with worse PFS (HR = 1.735(1.381-2.180)) and OS (HR = 1.936(1.587-2.361)) of the ICI-treated patients. However, corticosteroid administration for non-cancer-related indications and irAEs was unrelated with PFS (non-cancer-related indications: HR = 0.830(0.645-1.067); irAEs: HR = 1.302(0.628-2.696)) and OS (non-cancer-related indications: HR = 0.786(0.512-1.206); irAEs: HR = 1.107(0.832-1.474)) of the ICI-treated patients. The following retrospective analysis identified corticosteroid administration for cancer-related indications was an independent unfavorable predictor for PFS (P = 0.006) and OS (P = 0.044) of the ICI-treated patients. The subgroup analysis based on non-small cell lung cancer (NSCLC) demonstrated the similar results (P = 0.002 for PFS and P = 0.047 for OS). CONCLUSION: Our study demonstrated corticosteroid administration for cancer-related indications is an unfavorable prognostic factor in solid cancer patients receiving ICI treatment. Therefore, careful selection of corticosteroid-treated patients for ICI therapy is quite necessary in individualized clinical management.


Glucocorticoids/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/mortality , Aged , Fatigue/drug therapy , Fatigue/immunology , Female , Humans , Male , Middle Aged , Nausea/drug therapy , Nausea/immunology , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/immunology , Patient Selection , Prognosis , Progression-Free Survival , Retrospective Studies , Vomiting/drug therapy , Vomiting/immunology
13.
Cell Transplant ; 30: 9636897211025230, 2021.
Article En | MEDLINE | ID: mdl-34318709

Radiation enteritis is the most common and serious complication of abdominal or pelvic radiation therapy. Mesenchymal stem cells (MSCs), as well as cell protection agents, inhibit apoptosis and promote the proliferation of injured tissues. 3 human umbilical cords MSCs (UCMSCs) were injected into the tail vein or peritoneal cavity of a rat model of radiation enteritis. The temporary protective effect was assessed by identification of donor cells, detection of cellular immune parameters and inflammatory cytokine levels, quantitation of jejunum mucosal preservation and examination of the rat remaining life. Only the rats in the intraperitoneal injection group exhibited a few positive donor cells 7 days after transplantation. CD4+/CD8+ T cells, a cellular immune parameter, decreased in the abdominal exudate of intraperitoneal injection group, compared with the model-only control and tail vein groups (both P < .05). Both serum and abdominal exudate TNF-α and IL-6 levels in the intraperitoneally injected rats rapidly decreased and were significantly different from those in the model-only control and tail vein injection groups (all P < .05). Mucosal surface area and survival time increased in the intraperitoneal injection group compared with the vehicle and tail vein injection groups (all P = .000). Therefore, the administration of UCMSCs with intraperitoneal injection approach postponed death in a rat model of radiation enteritis, which was associated with reduced serum levels of proinflammatory cytokines (TNF-α, IL-6). However, UCMSCs injected via the tail vein triggered an intense cellular immune response in the serum that adversely affects their survival. This treatment failed to suppress circulating serum and abdominal exudate levels of TNF-α and IL-6 and could not provide a therapeutic benefit for prolonging life against acute radiation enteritis.


Enteritis/radiotherapy , Enteritis/therapy , Mesenchymal Stem Cell Transplantation/methods , Umbilical Cord/metabolism , Acute Disease , Animals , Disease Models, Animal , Female , Humans , Rats , Umbilical Cord/cytology
14.
Int J Radiat Oncol Biol Phys ; 111(2): 405-416, 2021 10 01.
Article En | MEDLINE | ID: mdl-33964352

PURPOSE: Neoadjuvant concurrent chemoradiation therapy (nCRT) plus surgery has been a standard treatment for locoregionally advanced esophageal cancer and carcinoma of the gastroesophageal junction (EC/GEJ), but the optimal preoperative radiation dose is still unclear. We performed this systematic review to explore the treatment efficacy and toxicity of different radiation dose levels and find an optimal dose-fractionation strategy in EC/GEJ patients receiving nCRT. METHODS AND MATERIALS: Embase and Ovid Medline were searched for articles involving cases of operable squamous and adenocarcinoma of the esophagus and GEJ in which patients received nCRT up to a dose of 50.4 Gy in 28 fractions that were published until July 2019, when the search was performed. Physical dose distributions were converted to biologically equivalent doses (BEDs), which were described in units of gray (alpha/beta). Pooled rates of overall survival (OS), progression-free survival (PFS), failure patterns, and toxicities were compared between lower-dose radiation therapy (LDRT; BED ≤48.85 Gy10) and higher-dose radiation therapy (HDRT; BED >48.85 Gy10) for patients treated with nCRT. RESULTS: A total of 110 studies with 7577 EC/GEJ patients receiving nCRT were included in this pooled analysis. Both the PFS and OS rates of patients receiving LDRT were significantly higher than those of patients receiving HDRT. Patients receiving LDRT had improved safety regarding treatment-related adverse events and lower distant failure rates than patients receiving HDRT. Utilization of modern radiation therapy (RT) techniques, including 3-dimensional conformal RT and intensity modulated RT, was associated with improved oncologic outcomes compared with 2-dimensional methods. Subgroup analysis showed that EC/GEJ patients receiving conventionally fractionated radiation to a dose of 40.0 to 41.4 Gy in 20-23 fractions showed improved OS compared with those receiving radiation above this dose. CONCLUSIONS: Based on the limited data, nCRT using BED ≤48.85 Gy10 was suitable for locoregionally advanced, resectable EC/GEJ. A total dose of 40.0 to 41.4 Gy in 20 to 23 fractions using modern RT techniques might provide the optimal therapeutic ratio.


Chemoradiotherapy/methods , Esophageal Neoplasms/radiotherapy , Esophagogastric Junction , Chemoradiotherapy/adverse effects , Esophageal Neoplasms/mortality , Esophageal Squamous Cell Carcinoma/radiotherapy , Humans , Neoadjuvant Therapy , Radiotherapy Dosage , Treatment Failure , Treatment Outcome
15.
Cell Death Dis ; 12(2): 185, 2021 02 15.
Article En | MEDLINE | ID: mdl-33589592

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.


Lung Neoplasms/metabolism , MicroRNAs/metabolism , Protein Serine-Threonine Kinases/metabolism , RNA, Circular/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Tumor Suppressor Proteins/metabolism , A549 Cells , Carcinogenesis , Cell Movement/physiology , Cell Proliferation/physiology , Female , HEK293 Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , RNA, Circular/biosynthesis , RNA, Circular/genetics
16.
Cancer Manag Res ; 12: 2697-2709, 2020.
Article En | MEDLINE | ID: mdl-32425592

PURPOSE: Biliverdin reductase A (BLVRA) is a pleiotropic enzyme that converts biliverdin-IX-alpha into the antioxidant and anti-nitrosative compound, bilirubin-IX-alpha. It is related to various diseases, including cancer. It is overexpressed in many types of cancers and promotes cancer development and metastasis, but the effects of BLVRA in colorectal cancer have not been researched at present. This study was aimed to investigate the effects of biliverdin reductase A (BLVRA) in vivo and vitro experiments and its possible mechanism. METHODS: The clinical samples of CRC patients and CRC cell lines HT-29 and SW620 were chosen to perform the experiments. ELISA and Immunohistochemistry (IHC) were applied to test the level of BLVRA in patients. HT-29 knockdown of BLVRA and SW620 overexpression of BLVRA was established by the lentiviral vector transfection. Reverse transcription-quantitative real-time polymerase chain reaction and Western blotting were performed to examine the expression of BLVRA. MTT was used to detect the proliferation of CRC cells. Flow cytometry was applied to assess the rate of apoptosis. Transwell assay was performed to examine the capacity of migration and invasion. Immunofluorescence staining was adopted to assess the expression of E-cadherin and vimentin. Western blotting was utilized to detect the expression of apoptosis-related proteins, EMT-related proteins and target proteins of Wnt/ß-catenin signaling pathway. RESULTS: Analysis of the clinical samples revealed that BLVRA was overexpressed in CRC patients and implied poor prognosis. BLVRA overexpression in the in vitro studies revealed that it increased the potential of CRC cells for proliferation, migration and invasion; augmented EMT; and hindered apoptosis. In addition, BLVRA overexpression was found to upregulate positive target genes and downregulate negative target genes of the Wnt/ß-catenin signaling pathway, which implied that the biological effects of BLVRA in CRC were mediated by this pathway. In contrast, knockdown of BLVRA manifested the opposite effects. CONCLUSION: Our results suggested that BLVRA might be a promising prognostic marker and a potential therapeutic target in CRC.

17.
Exp Cell Res ; 389(1): 111894, 2020 04 01.
Article En | MEDLINE | ID: mdl-32035950

FTO, a demethylase for N6-methyladenosine (m6A) modification, has been implicated in multiple tumors. However, its roles in esophageal squamous cell carcinoma (ESCC) remain uncovered. This study aims to evaluate the clinical relevance and functional roles in this disease. Through immunohistochemistry, qRT-PCR and Western blot analyses, we found FTO expression in ESCC tissues was stronger than that in adjacent normal tissues, and the survival curves displayed high FTO expression had a trend toward poor prognosis. Functionally, silencing of FTO inhibited ESCC cell growth and migration in CCK8, EdU, colony formation and transwell assays and FTO overexpression showed the opposite results. Furthermore, FTO was also required for the tumorigenicity of ESCC cells in nude mice. The data from RNA-seq analysis revealed that MMP13 expression was significantly affected by FTO knockdown. qRT-PCR and Western blot assays confirmed that MMP13 was positively regulated by FTO in both mRNA and protein levels. Additionally, the functional link between FTO and MMP13 was explored by CCK8 and transwell chamber approaches. These findings suggest that FTO is up-regulated and plays oncogenic roles in ESCC. MMP13 may function as a downstream target of FTO.


Alpha-Ketoglutarate-Dependent Dioxygenase FTO/physiology , Cell Movement/genetics , Cell Proliferation/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Matrix Metalloproteinase 13/genetics , Animals , Cell Line, Tumor , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Mice, Nude , Neoplasm Invasiveness , Up-Regulation/genetics
18.
RSC Adv ; 8(47): 26928-26933, 2018 Jul 24.
Article En | MEDLINE | ID: mdl-35541049

An integrated OCO reactor was used to investigate the performance and microbial community successional changes under long-term exposure to relatively low levels of ZnO nanoparticles (NPs). Relatively higher concentrations of ZnO NPs (1.5 mg L-1) could adversely affect the nitrogen and phosphorus removal in the reactor. The diversity and richness of the microbial communities chronically declined with an increasing concentration of ZnO NPs higher than 1.5 mg L-1. With the elevated ZnO NPs, the phyla abundances of Proteobacteria, Firmicutes and Actinobacteria decreased slightly, whereas those of Bacteroidetes and Acidobacteria increased. Bacteroidetes and Proteobacteria were the predominant phyla in each phase (with a variation in abundance), together with some common taxa responses to ZnO NP stress as revealed by Venn diagram analysis. Some genera associated with the removal of nitrogen and phosphorus, such as Acinetobacter, Stenotrophomonas and Pseudomonas, decreased significantly. The present results are significant for expanding our understanding of the functional performance and microbial community successions of activated sludge which has experienced long-term exposure to environmentally relevant concentrations of ZnO NPs.

19.
Cytotechnology ; 68(6): 2677-2686, 2016 Dec.
Article En | MEDLINE | ID: mdl-27318496

Nuclear Warfare and nuclear leakage can result in a large number of patients with radiation-induced bone marrow damage. Based on the fact that hematopoietic stem cells and hematopoietic growth factors are characterized as a novel strategy for therapy, the aim of this study was to explore a safe and routine stem cell/cytokine therapeutic strategy. Allogeneic multiplacenta derived hematopoietic and mesenchymal stem cells/cytokines were intraperitoneally injected into a moderate dose of total body irradiation-induced mouse bone marrow damage model a single time. Then, the mouse posttransplantation survival time, peripheral blood hemoglobin count, bone marrow architecture, and donor cell engraftment were assessed. Each mouse that received placenta-derived stem cells exhibited positive donor hematopoietic and mesenchymal stem cell engraftment both in the bone marrow and peripheral blood after transplantation. The peripheral blood hemoglobin count and survival time were greater in the group with the combined treatment of multiplacenta-derived stem cells and cytokines, compared with model-only controls (both P < 0.001). The blood smear mesenchymal/hematopoietic stem cell count was significantly higher in the combined treatment group than in the mice treated only with placenta-derived cells (28.08 ± 5.824 vs. 20.40 ± 5.989, P < 0.001; 7.74 ± 2.153 vs. 4.23 ± 1.608, P < 0.001, respectively). However, there was no marked change on the bone marrow pathology of any of the experimental mice after the transplantation. These results indicate that for radiation-induced bone marrow damage treatment, multiplacenta-derived stem cells and cytokines can increase the life span of model mice and delay but not abrogate the disease progression. Intraperitoneally transplanted stem cells can survive and engraft into the host body through the blood circulation. Improvement of peripheral blood hemoglobin levels, but not the bone marrow architecture response, probably explains the increase in survival time observed in this study.

20.
Environ Technol ; 35(17-20): 2628-33, 2014.
Article En | MEDLINE | ID: mdl-25145220

An integrated OCO reactor with two side-ditch separators based on the anaerobic/anoxic/oxic (A2/O) process was developed for municipal wastewater treatment in this study. The effects of dissolved oxygen (DO) concentration, hydraulic retention time (HRT) and the ratio of chemical oxygen demand (COD) to total nitrogen (C/N) in the influent were investigated for optimization, in order to achieve the removal of total nitrogen (TN), total phosphorus (TP) and COD in the reactor simultaneously. When the DO concentration of 2.0 mg/L in the aerobic zone, HRT of 12 h and C/N ratio of 8:1 were applied in the reactor, the superior removal efficiencies of COD, TN and TP reached 96%, 81% and 92%, respectively. The modification in integrated OCO system was characterized by the mixing of the liquid refluxed from anoxic and aerobic zones with the influent in the anaerobic zone. And the risk of activated sludge bulking was decreased successfully by enhancing phosphorus removal without any chemical auxiliary methods. Quite precise prediction results with the correlation coefficients (R) of 0.9584-0.9948 were forecasted by the back-propagation neural network model. All the results indicated that the integrated OCO process is able to remove TN, TP and COD in a reactor simultaneously.


Bioreactors , Nitrogen/isolation & purification , Phosphorus/isolation & purification , Waste Disposal, Fluid/methods , Water Purification/methods , Biological Oxygen Demand Analysis , Equipment Design , Models, Biological , Nitrogen/analysis , Nitrogen/chemistry , Oxygen/chemistry , Phosphorus/analysis , Phosphorus/chemistry , Wastewater/chemistry
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