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Background: It is still a challenging problem for clinicians to explore the nature of the indeterminate biliary strictures (IBSs). Approximately 20% of biliary strictures remain undetermined after a thorough preoperative assessment. Case presentation: Here, we present two cases of indeterminate biliary strictures patients, whose cross- sectional imaging and endoscopic examination were nondiagnostic. The patients underwent exploratory laparotomy finally and were confirmed as malignancy. We also reviewed the recent reports in literatures regarding the evaluation of IBSs. Conclusions: Given the majority of the biliary strictures are malignancy, preoperative differentiation between benign and malignant is critical for choosing the best therapeutic regimen. Thus, close follow-up, multiple multidisciplinary discussion, and prompt surgical exploration are necessary for some difficult diagnostic cases.
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Anti-tuberculosis drug-induced liver injury (ADLI) is a common adverse reaction during anti-tuberculosis treatment and often leads to treatment interruptions. Circular RNAs (circRNAs) have been identified as key modulators in liver diseases. CircRNAs is a special class of noncoding RNAs that have been found to have significant impacts on the progression of inflammation via various mechanisms. In the serum of ADLI patients, upregulation of the circular RNA hsa_circ_0082152 (derived from the host gene snd1) was observed, along with increased ALT and AST levels, as well as alterations in the levels of inflammation-related factors such as NF-κB, IL-1ß and TNF-α. To elucidate the underlying mechanisms, we established an HL-7702-ADLI cell model and confirmed similar upregulation of hsa_circ_0082152. Downregulation of hsa_circ_0082152 significantly inhibited inflammatory injury in ADLI cells, while upregulation had the opposite effect. RNA immunoprecipitation showed that hsa_circ_0082152 functions by interacting with metadherin (MTDH). Our study further verified that the interaction of hsa_circ_0082152 with the MTDH protein binding to NF-κB mRNA to maintain NF-κB mRNA stability, which increases the expression of NF-κB and its targets IL-1ß and TNF-α. Conversely, depletion of MTDH rescued the promotive effect of hsa_circ_0082152 overexpression on ADLI inflammation. Therefore, hsa_circ_0082152 overexpression promotes ADLI progression via the MTDH/NF-κB axis.
Subject(s)
Antitubercular Agents , Cell Adhesion Molecules , Chemical and Drug Induced Liver Injury , Membrane Proteins , NF-kappa B , RNA, Circular , RNA-Binding Proteins , Female , Humans , Male , Middle Aged , Antitubercular Agents/adverse effects , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Cell Line , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/genetics , Gene Expression Regulation/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Protein Binding , RNA Stability , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Base excision repair (BER) is a critical genome defense pathway that copes with a broad range of DNA lesions induced by endogenous or exogenous genotoxic agents. AP endonucleases in the BER pathway are responsible for removing the damaged bases and nicking the abasic sites. In plants, the BER pathway plays a critical role in the active demethylation of 5-methylcytosine (5mC) DNA modification. Here, we have determined the crystal structures of Arabidopsis AP endonuclease AtARP in complex with the double-stranded DNA containing tetrahydrofuran (THF) that mimics the abasic site. We identified the critical residues in AtARP for binding and removing the abasic site and the unique residues for interacting with the orphan base. Additionally, we investigated the differences among the three plant AP endonucleases and evaluated the general DNA repair capacity of AtARP in a mammalian cell line. Our studies provide further mechanistic insights into the BER pathway in plants.
Subject(s)
Arabidopsis Proteins , Arabidopsis , DNA Repair , DNA-(Apurinic or Apyrimidinic Site) Lyase , Models, Molecular , Humans , Arabidopsis/metabolism , Arabidopsis/enzymology , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Binding Sites , Catalytic Domain , Crystallography, X-Ray , DNA/metabolism , DNA/chemistry , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/chemistry , Furans/metabolism , Furans/chemistry , Protein BindingABSTRACT
OBJECTIVES: In this study, by comparing the difference in protein expression in bronchoalveolar lavage fluid between silicosis patients in different stages and healthy controls, the pathogenesis of pneumoconiosis was discussed, and a new idea for the prevention and treatment of pneumoconiosis was provided. METHODS: The lung lavage fluid was pretreated by 10 K ultrafiltration tube, Agilent 1100 conventional liquid phase separation, strong cation exchange column (SCX) HPLC pre-separation, and C18 reverse phase chromatography desalting purification, and protein was labeled with isotope. GO, KEGG pathway, and PPI analysis of differential proteins were conducted by bioinformatics, and protein types and corresponding signal pathways were obtained. RESULTS: Thermo Q-Exactive mass spectrometry identified 943 proteins. T-test analysis was used to evaluate the different significance of the results, and the different protein of each group was obtained by screening with the Ratio≥1.2 or Ratio≤0.83 and P<0.05. We found that there are 16 kinds of protein throughout the process of silicosis. There are different expressions of protein in stages â ¢/control, stages â ¡/control, stage â /control, stages â ¢/ stages â ¡, stages â ¢/ stage â and stages â ¡/ stage â groups. The results of ontology enrichment analysis of total differential protein genes show that KEGG pathway enrichment analysis of differential protein suggested that there were nine pathways related to silicosis. CONCLUSION: The main biological changes in the early stage of silicosis are glycolysis or gluconeogenesis, autoimmunity, carbon metabolism, phagocytosis, etc., and microfibril-associated glycoprotein 4 may be involved in the early stage of silicosis. The main biological changes in the late stage of silicosis are autoimmunity, intercellular adhesion, etc. Calcium hippocampus binding protein may participate in the biological changes in the late stage of silicosis. It provides a new idea to understand the pathogenesis of silicosis and also raises new questions for follow-up research.
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BACKGROUND: Rab1A not only regulates eukaryotic secretion, autophagy and intracellular traffic, but also extensively participates in the development of cancer. Thus, we collected data to investigate the clinical value of Rab1A in cancers. METHODS: English web database was searched for appropriate studies. The role of Rab1A in cancer patients was evaluated by combining hazard ratios and odds ratios. RESULTS: There were 15 studies in 14 articles, including 1,791 cancer patients. The results showed that upregulated Rab1A led to poor prognosis in cancer patients (pooled HR = 2.545, 95% CI = 1.924 - 3.367, p < 0.001). Notably, a high level of Rab1A was associated with a poorer prognosis than patients with a low level of Rab1A in digestive system cancer (pooled HR = 2.484, 95% CI = 1.796 - 3.437, p < 0.001). In order to explore the possible carcinogenic mechanism, we further analyzed and confirmed that high expression of Rab1A was associated with worse histologic grade, deeper tumor invasion, higher TNM stage, positive LN metastasis, positive neural invasion, positive vascular invasion, and larger tumor size (p < 0.05). CONCLUSIONS: Rab1A overexpression was associated with poor prognosis and adverse clinicopathological parameters in cancer patients and had the potential to be a target for future cancer therapy.
Subject(s)
Digestive System Neoplasms , Humans , Prognosis , Proportional Hazards Models , Biomarkers, Tumor/metabolismABSTRACT
PURPOSE: The purpose this study is to investigate the impact of SIRT1 on the anti-HBV activity of IFN-α and further elucidate its underlying mechanism. METHODS: HepG2.2.15 cells stably transfected with HBV virus were chosen as the primary study subject. IFN-α was used to stimulate the cells and regulate the expression of SIRT1, and the JAK-STAT pathway and HBV-related indices were measured by qRT-PCR, Western blotting and ELISA. Immunofluorescence (IF) was used to detect the nuclear translocation of STAT1 and STAT2. Coimmunoprecipitation (Co-IP) was used to detect the binding of SIRT1 to HBV Polymerase (Pol). RESULTS: In HepG2.2.15 cells, we found changes in SIRT1 expression. We show that silencing SIRT1 promotes the IFN-α-triggered Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and consequently enhances the antiviral effects of IFN-α against HBV replication. Importantly, SIRT1 can interact with Pol and increase JAK-STAT activity by regulating Pol expression. Additionally, the inhibition of SIRT1 activity by treatment with the SIRT1 inhibitor selisistat enhanced the anti-HBV effect of IFN-α and JAK-STAT pathway activity. CONCLUSION: In conclusion, our results demonstrate that silencing SIRT1 activates the JAK-STAT pathway and enhances the anti-HBV activity of IFN-α by inhibiting Pol expression. This would be a promising therapeutic target to improve the efficacy of IFN-α in the treatment of CHB.
Subject(s)
Janus Kinases , Signal Transduction , Janus Kinases/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Hepatitis B virus/physiology , STAT Transcription Factors/metabolism , Interferon-alpha/pharmacology , Interferon-alpha/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolismABSTRACT
Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials.
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Introduction: Similar attention patterns have been found in individuals with autism spectrum disorder (ASD) and autistic traits (ATs). The Intense World Theory and previous studies suggest that individuals with ASD may demonstrate a vigilance-avoidance attention pattern toward emotional faces. However, the attention patterns in individuals with ATs remain unclear. Therefore, this study employs eye-tracking technology to examine the characteristics and temporal course of attention bias toward emotional faces in individuals with ATs. Methods: The Autism-spectrum Quotient (AQ) was used to evaluate the level of ATs among 2,502 college students. A total of 50 participants were selected from the 2,502 college students: 25 high-AQ group participants were randomly selected from the 10% of individuals with the highest AQ scores. Similarly, 25 low-AQ group participants were randomly selected from the 10% of participants with the lowest AQ scores. All selected participants completed an eye-tracking study while performing a dot-probe task with emotional faces (positive-neutral, negative-neutral, and negative-positive). By analyzing data from different time periods, the attention bias and time course of individuals with ATs toward emotional faces were investigated. Results: The results show that compared to the low-AQ group, the high-AQ group detected negative faces faster in the early stages of emotional face processing. As the presentation time of emotional faces increased (at the 2-3 s mark), the fixation scores for negative-neutral faces of the high-AQ group were less than 0.5, which was significantly lower than those of the low-AQ group. Meanwhile, the high-AQ group showed brief attentional avoidance toward positive emotion at 3-4 s in the positive-neutral trials, indicating that the high-AQ group exhibited attention avoidance to both negative and positive faces during the middle and later stages of emotional processing. Conclusion: This study suggests that individuals with ATs display a vigilance-avoidance pattern toward emotional faces. It contributes to a deeper understanding of the mechanisms of attention in persons with ATs and further supports the Intense World Theory.
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OBJECTIVE: To construct a prognostic model using artificial neural network (ANN) approach, providing an idea for the prediction and diagnosis of cholangiocarcinoma (CCA). STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of General Surgery, Zhenjiang Hospital, Zhenjiang Province, China, between January and March 2022. METHODOLOGY: Available datasets were obtained from the Gene Expression Omnibus (GEO) database to construct the train cohort and the test cohort of CCA, and screened out the differentially expressed genes (DEGs) of CCA. Next, an ANN model for CCA diagnosis was constructed based on the scores of the DEGs and evaluated its accuracy and efficiency using ROC curves. Finally, the immune infiltration and the function of extracellular matrix (ECM) protein SPACRL1 were analysed to reveal the characteristic alterations in CCA. RESULTS: This analysis revealed 166 DEGs, mainly concentrated in the ECM organisation, neutrophil activation and other pathways. Then a set of 17 CCA disease signature genes scores were obtained to build an ANN prediction model and the ROC curve was plotted. The AUC in the train group (0.980) indicated that the accuracy of the diagnosis model is extremely high. Finally, there was a significant increase of B cells naïve (p=0.025), tregs (p=0.004), and macrophages M1 (p<0.001) in the tumour-microenvironment of CCA, while SPARCL1 was a protective factor on disease-specific survival (DSS) in CCA (p=0.009). CONCLUSION: This study has developed an accurate prediction model for CCA diagnosis, and identified SPARCL1 as pivotal factor in CCA by modulating the tumour immune-microenvironment. KEY WORDS: Cholangiocarcinoma, Artificial neural network, Immune microenvironment, Bioinformatics, Prognosis model, SPARCL1.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Random Forest , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/genetics , Neural Networks, Computer , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/genetics , Tumor MicroenvironmentABSTRACT
Benzotriazole UV stabilizers (BUVSs) are a class of emerging contaminants of concern; the development of rapid and convenient monitoring method for these trace-level pollutants in waters is of crucial significance in environmental science. Here, a novel magnetic flower-like molybdenum disulfide/cobalt ferrite nanocomposite (MoS2/CoFe2O4) was synthesized by hydrothermal reaction. Compared with the conventional Fe3O4-based magnetic composites, the proposed material just required a minimum consumption of Co/Fe towards the equivalent of MoS2 while providing superior magnetization performance. Taking advantages of high adsorption capacity, extraordinary stability, and repeatability in construction, MoS2/CoFe2O4 was applied to the extraction to BUVSs. The enrichment factors of three BUVSs were in the range 164-193 when 20 mL of environmental water sample was loaded on 40 mg of the adsorbent. MoS2/CoFe2O4 could be regenerated and recycled at least 10 cycles of adsorption/desorption with recoveries of 80.1-111%. The method of MoS2/CoFe2O4-based extraction coupled with high-performance liquid chromatography-variable wavelength detector was applied to the monitoring of BUVSs in seawater, lake water, and wastewater, which gave detection limits (S/N = 3) of 0.023-0.030 ng·mL-1 and recoveries of 80.1-110%. The intra-day and inter-day precisions (relative standard deviation, RSDs, n = 3) were in the range 1.6-7.5% and 3.2-11.5%, respectively. The approach is an alternative for efficient and sensitive extraction and determination of trace-level environmental pollutants in waters.
ABSTRACT
The antimicrobial peptide was considered an important target for developing novel antibacterial drugs. However, the unstable biological activity and the low antibacterial activity are challenges for the application of recombinant proteins. In this study, the fusion peptide of Melittin-Thanatin (MT) was designed and produced, and its derivative sequence (MT-W) was obtained by replacing three glycines (Gly, G) with tryptophan (Trp, W). The MT-W peptide were synthesized in Bacillus subtilis WB700 by EDDIE self-cleavage protein fusion. Compared with MT, MT-W exhibited 2-4 times higher antibacterial rate against Escherichia coli K88. In addition, MT-W showed lower cytotoxicity (IC50 > 300 mg·L-1) to the red blood cell, and more stable biological activities under the conditions of different temperatures (20, 30, 40, 50, 60, 70, 80, and 90 °C), pH values (2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0) and different proteases. Especially, MT-W showed a broader antibacterial effect on three drug-resistant strains than florfenicol and oxytetracycline calcium. In conclusion, compared with MT, the MT-W showed increased antibacterial activity, stability, lower cytotoxicity, and broader antimicrobial effect. Therefore, it would become a promising alternative to conventional antibiotics.
Subject(s)
Melitten , Tryptophan , Melitten/pharmacology , Melitten/genetics , Tryptophan/genetics , Glycine/pharmacology , Recombinant Proteins/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Mutation , Microbial Sensitivity TestsABSTRACT
BACKGROUND: It has been previously reported that CD155 is often over-expressed in a variety of cancer types. In fact, it is known to be involved in cancer development, and its role in cancer has been widely established. However, clinical and mechanistic studies involving CD155 yielded conflicting results. Thus, the present study aimed to evaluate overall prognostic value of CD155 in cancer patients, using a comprehensive analysis. METHODS: Online databases were searched, data was collected, and clinical value of CD155 was evaluated by combining hazard ratios (HRs) or odds ratios (ORs). RESULTS: The present study involved meta-analysis of 26 previous studies that involved 4325 cancer patients. These studies were obtained from 25 research articles. The results of the study revealed that increased CD155 expression was significantly associated with reduced OS in patients with cancer as compared to low CD155 expression (pooled HR = 1.772, 95% CI = 1.441-2.178, P < 0.001). Furthermore, subgroup analysis demonstrated that the level of CD155 expression was significantly associated with OS in patients with digestive system cancer (pooled HR = 1.570, 95% CI = 1.120-2.201, P = 0.009), hepatobiliary pancreatic cancer (pooled HR = 1.677, 95% CI = 1.037-2.712, P = 0.035), digestive tract cancer (pooled HR = 1.512, 95% CI = 1.016-2.250, P = 0.042), breast cancer (pooled HR = 2.137, 95% CI = 1.448-3.154, P < 0.001), lung cancer (pooled HR = 1.706, 95% CI = 1.193-2.440, P = 0.003), head and neck cancer (pooled HR = 1.470, 95% CI = 1.160-1.862, P = 0.001). Additionally, a significant correlation was observed between enhanced CD155 expression and advanced tumor stage (pooled OR = 1.697, 95% CI = 1.217-2.366, P = 0.002), LN metastasis (pooled OR = 1.953, 95% CI = 1.253-3.046, P = 0.003), and distant metastasis (pooled OR = 2.253, 95% CI = 1.235-4.110, P = 0.008). CONCLUSION: Altogether, the results of the present study revealed that CD155 acted as an independent marker of prognosis in cancer patients, and it could provide a new and strong direction for cancer treatment.
Subject(s)
Breast Neoplasms , Digestive System Neoplasms , Humans , Female , Prognosis , Biomarkers, Tumor/metabolism , Proportional Hazards ModelsABSTRACT
BACKGROUND: The sex-determining region Y-box 2 (SOX2) has been identified to be involved in tumor progression and prognosis in patients with gastric cancer (GC). However, its action is paradoxical. Thus, we conducted the first meta-analysis based on eligible studies to evaluate the clinical utility of SOX2 in GC only. METHODS: A thorough electronic search was performed to collect eligible studies. The hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were generated from included studies to assess the strength of the association between SOX2 and prognosis and clinicopathological characteristics in GC. RESULTS: A total of 10 studies comprising 1321 patients with GC were identified for the meta-analysis. The pooled results revealed that high SOX2 expression was significantly associated with poor overall survival compared to low SOX2 expression (pooled HR = 1.485; 95% CI: 1.022-2.160; ð = .04). The statistical significance between SOX2 expression and overall survival was also established in univariate analysis (pooled HR = 1.606; 95% CI: 1.134-2.274; ð < .01), as well as recruitment time exceeding 2010 (pooled HR = 1.873; 95% CI: 1.041-3.371; ð = .04), follow-up time more than 5 years (pooled HR = 1.642; 95% CI: 1.066-2.527; ð = .02), and cutoff value of more than 5% of cells stained (pooled HR = 1.730; 95% CI: 1.162-2.577; ð < .01). Moreover, we verified that positive SOX2 expression was correlated with advanced tumor invasion depth (pooled OR = 0.494; 95% CI: 0.362-0.675; ð < .01) and positive vascular invasion (pooled OR = 1.515; 95% CI: 1.078-2.130; ð = .02). CONCLUSION: SOX2 could not only be an independent prognostic marker in GC but might also be a novel target for cancer therapy.
Subject(s)
Stomach Neoplasms , Biomarkers, Tumor/metabolism , Humans , Odds Ratio , Prognosis , Proportional Hazards Models , SOXB1 Transcription Factors , Stomach Neoplasms/pathologyABSTRACT
Anti-tuberculosis drug-induced liver injury (ADLI) is one of the main factors hindering the efficacy of routine chemotherapy against tuberculosis. Understanding the mechanism of ADLI will aid in the effective treatment of patients with tuberculosis. Recently, we found that the expression of hsa_circ_0093884, a circular RNA derived from the NAD-dependent deacetylase, sirtuin-1 (SIRT1), was down-regulated in ADLI. Hsa_circ_0093884 was negatively correlated with the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its overexpression increased the expression levels of NLRP3, interleukin-1ß, and caspase-1. Mechanistically, RNA immunoprecipitation and immunofluorescence assays revealed that the ribosomal protein S3 (RPS3) could bind to hsa_circ_0093884 and SIRT1. Additionally, the expression of hsa_circ_0093884 was positively correlated with that of SIRT1, and the upregulation of hsa_circ_0093884 expression was crucial for the upregulation of SIRT1 expression. We confirmed that the mRNA and protein expression levels of SIRT1 were influenced by hsa_circ_0093884 and RPS3. Furthermore, hsa_circ_0093884 recruited RPS3 to increase SIRT1 mRNA and protein levels. Importantly, we found a marked decrease in the upregulating effect of hsa_circ_0093884 on SIRT1 owing to RPS3 depletion. To the best of our knowledge, this study is the first to reveal that hsa_circ_0093884 regulates SIRT1 expression and inhibits the inflammatory response by binding to RPS3 in ADLI, which may be used to develop novel strategies for ADLI treatment.
Subject(s)
Chemical and Drug Induced Liver Injury , MicroRNAs , Cell Proliferation/genetics , Hepatocytes/metabolism , Humans , Inflammation , MicroRNAs/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RNA, Messenger , RNA-Binding Proteins , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolismABSTRACT
Pseudouridine (Ψ) is one of the most abundant RNA modifications in cellular RNAs that post-transcriptionally impact many aspects of RNA. However, the metabolic fate of modified RNA nucleotides has long been a question. A pseudouridine kinase (PsuK) and a pseudouridine monophosphate glycosylase (PsuG) in Escherichia coli were first characterized as involved in pseudouridine degradation by catalyzing the phosphorylation of pseudouridine to pseudouridine 5'-phosphate (ΨMP) and further hydrolyzing 5'-ΨMP to produce uracil and ribose 5'-phosphate. Recently, their homolog proteins in eukaryotes were also identified, which were named PUKI and PUMY in Arabidopsis. Here, we solved the crystal structures of apo-EcPsuK and its binary complex with Ψ or N 1-methyl-pseudouridine (m1Ψ). The structure of EcPsuK showed a homodimer conformation assembled by its ß-thumb region. EcPsuK has an appropriate binding site with a series of hydrophilic and hydrophobic interactions for Ψ. Moreover, our complex structure of EcPsuK-m1Ψ suggested the binding pocket has an appropriate capacity for m1Ψ. We also identified the monovalent ion-binding site and potential ATP-binding site. Our studies improved the understanding of the mechanism of Ψ turnover.
ABSTRACT
Decreased lung function is an early hazard of respiratory damage from fine particulate matter (PM2.5) exposure. Limited studies have explored the association between PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and lung function, but studies at the personal level in healthy young adults are scarce. Here, we assessed personal PM2.5 and PM2.5-bound PAH levels in a panel of 45 healthy young adults by a time-weighted model. The aims were to investigate the relationship between personal exposure and lung function by a linear mixed effect model, and to explore the mediating effects of oxidative stress in this association. The results showed that personal exposure to PM2.5 and PAHs had the greatest negative effect on forced expiratory volume in 1 s (FEV1), peak expiratory flow rate (PEF) and forced expiratory flow between 25% and 75% vital capacity (FEF25-75) at lag 3 days. An IQR increase in personal PM2.5 exposure was associated with a change of 0.35% (95% CI: 0.27%, 0.42%) in FEV1, 0.39% (95% CI: 0.29%, 0.47%) in PEF and 0.36% (95% CI: 0.27%, 0.45%) in FEF25-75. An IQR increase in personal PAH exposure was associated with a decrease of 0.63% (95% CI: 0.55%, 0.69%) in FEV1, 0.69% (95% CI: 0.61%, 0.75%) in PEF and 0.66% (95% CI: 0.57%, 0.72%) in FEF25-75. Additionally, exposure to PM2.5 and PAHs resulted in the strongest positive effects on urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Of these, 8-OHdG mediated 10.33%, 8.87% and 9.45% of the associations of personal PM2.5 exposure with FEV1, PEF and FEF25-75, respectively. Our results revealed that personal exposure to PM2.5 and PAHs was associated with lung function decline in healthy young adults, and urinary 8-OHdG mediated the association between personal PM2.5 and lung function.
Subject(s)
Air Pollutants , Lung/physiopathology , Oxidative Stress , Polycyclic Aromatic Hydrocarbons , Air Pollutants/analysis , Air Pollutants/toxicity , Environmental Exposure/analysis , Humans , Lung/drug effects , Particulate Matter/analysis , Particulate Matter/toxicity , Polycyclic Aromatic Hydrocarbons/analysis , Polycyclic Aromatic Hydrocarbons/toxicity , Young AdultABSTRACT
As medicinal plants can accumulate harmful metals from the native soil, people's consumption of these materials may cause the human body to accumulate toxic metal elements. This has given rise to people's concerns about the quality and safety of Chinese medicinal materials. This research aims to determine the levels of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in four medicinal plant species (Aster tataricus L.f., Salvia miltiorrhiza Bge, Radix Aucklandiae, Scutellaria baicalensis Georgi) and their native soil. All samples were collected from Qian'an city, beside Yanshan Mountain Range in Tangshan city, east Hebei Province, north China. The contents of heavy metals we detected in the soil conformed to the current limits. However, the Cd and Hg in the soil had a very high potential ecological risk because of their contents higher than the base level of local soil. The contents of Cu, Cd, Hg and Pb in some medicinal herbs exceeded the standards. The content of Cu in Radix Aucklandiae exceeded the standard by 3 times, and others exceeded the standard by less than one time. The comprehensive health risk assessment of heavy metals with chronic non-carcinogenic effects for human body showed that none of the four medicinal herbs can create a health risk. Thus, there is no strong positive correlation between heavy metal pollution in medicinal herbs and that in the native soil. Further research should be investigated to the connection between the heavy metal levels in the soil and plants, and the comprehensive effects of soil, air and irrigation water on heavy metal pollution of Chinese herbal medicines. We also recommend that Chinese herbal medicines should be cultivated and gathered only from controlled or uncontaminated areas.
Subject(s)
Metals, Heavy , Soil Pollutants , China , Environmental Monitoring , Environmental Pollution , Humans , Metals, Heavy/analysis , Metals, Heavy/toxicity , Risk Assessment , Soil , Soil Pollutants/analysis , Soil Pollutants/toxicityABSTRACT
BACKGROUND: MicroRNA-140 (miR-140) is one of the most widely investigated miRNAs in cell carcinogenesis and cancer development. Despite present proposals of employing miR-140 as a candidate biomarker for cancer prognosis, its effectiveness in predicting patient survival and clinicopathological outcome is still under debate. METHODS: A systematic search for English literature using online databases was performed with pre-established criteria. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to delineate the correlation between miR-140 levels and cancer patient prognosis. RESULTS: For this meta-analysis, we selected 12 papers for analysis, involving 1386 participants. Based on our analysis, high levels of miR-140 were strongly correlated with enhanced patient overall survival (OS) (HR = 0.728, 95% CI = 0.601-0.882, P = 0.001). In addition, we also observed that elevated miR-140 levels significantly led to better OS in patients with cancers in different parts of the body like digestive system (HR = 0.675, 95% CI = 0.538-0.848, P = 0.001), digestive tract (HR = 0.709, 95% CI = 0.565-0.889, P = 0.003), and head and neck (HR = 0.603, 95% CI = 0.456-0.797, P < 0.001). Additionally, we verified that the low miR-140 levels was related to advanced TNM stage (OR = 0.420, 95% CI = 0.299-0.590, P < 0.001), worse histologic grade (OR = 0.410, 95% CI = 0.261-0.643, P < 0.001), and positive lymph node metastasis status (OR = 0.341, 95% CI = 0.144-0.807, P = 0.014). CONCLUSIONS: Taken together, our results suggest that elevated miR-140 levels can be employed as a favorable biomarker for cancer patient prognosis. This information can greatly benefit in the formation of an individualized therapeutic plan for the treatment of cancer patients.
Subject(s)
MicroRNAs , Neoplasms , Biomarkers, Tumor/genetics , Humans , Lymphatic Metastasis , MicroRNAs/genetics , Neoplasms/genetics , Prognosis , Proportional Hazards ModelsABSTRACT
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data featured in Fig. 5B and C, and also in Fig. 6B, were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 35: 18511858, 2016; DOI: 10.3892/or.2015.4495].