Publications by authors named "Lu Yu"

1,537 Publications

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Spatial distribution and risk assessment of 11 organophosphate flame retardants in soils from different regions of agricultural farmlands in mainland China.

Sci Total Environ 2022 Jun 20:156806. Epub 2022 Jun 20.

Key Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

The occurrence and distribution of organophosphate flame retardants (OPFRs) in nationwide farmland soils of mainland China are rarely measured. The current study was the first to collect 325 farmland soil samples from 109 cities throughout mainland China. Ten organophosphate esters (OPEs), including alkyl-OPEs, Cl-OPEs, and aryl-OPEs, together with an organophosphate intermediates (TPPO), were determined. The results indicated that ΣOPFRs ranged from 2.41 ng/g to 35.8 ng/g dry weight (dw), and ΣOPFRs in northeastern and southern China were significantly (p < 0.01) higher than those in northwestern and central China. Alkyl-OPEs and Cl-OPEs served as the main components of OPEs, and the novel aryl-OPEs showed the highest detection frequency (> 92 %). Principal component analysis (PCA) was employed to identify the different sources of OPEs, in which atmospheric deposition, irrigation, or direct release of plastic mulch acted as the main input routes in farmland soils. The potential risks of OPFRs were assessed through soil ingestion exposure and ecotoxicological impacts. Our results showed that direct exposure to farmland soils had no high risks to the human body and ecological environments. This study provides new evidence for further understanding the spatial distributions and contamination status of OPFRs in farmland soils throughout mainland China.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156806DOI Listing
June 2022

Phosphoproteomic and Metabolomic Profiling Uncovers the Roles of CcPmk1 in the Pathogenicity of .

Microbiol Spectr 2022 Jun 23:e0017622. Epub 2022 Jun 23.

The Key Laboratory for Silviculture and Conservation of Ministry of Education, College of Forestry, Beijing Forestry Universitygrid.66741.32, Beijing, China.

Pmk1, a highly conserved pathogenicity-related mitogen-activated protein kinase (MAPK) in pathogenic fungi, is phosphorylated and activated by MAP2K and acts as a global regulator of fungal infection and invasive growth by modulating downstream targets. However, the hierarchical CcPmk1 regulatory network in , the main causal agent of canker disease in many woody plant species, is still unclear. In this study, we analyzed and compared the phosphoproteomes and metabolomes of Δ and wild-type strains and identified pathogenicity-related downstream targets of CcPmk1. We found that CcPmk1 could interact with the downstream homeobox transcription factor CcSte12 and affect its phosphorylation. In addition, the Δ displayed defective phenotypes that were similar to yet not identical to that of the Δ and included significantly reduced fungal growth, conidiation, and virulence. Remarkably, CcPmk1 could phosphorylate proteins translated from a putative secondary metabolism-related gene cluster, which is specific to , and the phosphorylation of several peptides was completely abolished in the Δ. Functional analysis of the core gene () in this gene cluster revealed its essential roles in fungal growth and virulence. Metabolomic analysis showed that amino acid metabolism and biosynthesis of secondary metabolites, lipids, and lipid-like molecules significantly differed between wild type and Δ. Importantly, most of the annotated lipids and lipid-like molecules were significantly downregulated in the Δ compared to the wild type. Collectively, these findings suggest that CcPmk1 may regulate a small number of downstream master regulators to control fungal growth, conidiation, and virulence in . Understanding the pathogenic mechanisms of plant pathogens is a prerequisite to developing effective disease-control methods. The Pmk1 MAPK is highly conserved among phytopathogenic fungi and acts as a global regulator of fungal pathogenicity by modulating downstream transcription factors or other components. However, the regulatory network of CcPmk1 from remains enigmatic. The present data provide evidence that the core pathogenicity regulator CcPmk1 modulates a few downstream master regulators to control fungal virulence in through transcription or phosphorylation and that CcPmk1 may be a potential target for disease control.
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http://dx.doi.org/10.1128/spectrum.00176-22DOI Listing
June 2022

Circ_0004951 Promotes Pyroptosis of Renal Tubular Cells the NLRP3 Inflammasome in Diabetic Kidney Disease.

Front Med (Lausanne) 2022 6;9:828240. Epub 2022 Jun 6.

Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China.

Background: Diabetic kidney disease (DKD) has become the leading cause of chronic kidney disease (CKD) in many countries. Recent studies have shown that circular RNA and pyroptosis play an important role in pathogenesis of DKD.

Methods: We analyzed expression patterns of circRNAs in human kidney biopsy tissues obtained from type 2 DKD ( = 9) and nephrectomy ( = 9) patients. Next, we cultured human renal tubular epithelial cells (HK2) in high glucose condition and detected circ_0004951, miR-93-5p, NLR Pyrin Domain Containing 3 (NLRP3) inflammasome-related indicators and pyroptosis. Furthermore, we performed Bioinformatics analysis and dual-luciferase reporter assay to analyze the relationship among circ_0004951, miR-93-5p and NLRP3.

Results: Circ_0004951 was significantly upregulated in kidney tissues from DKD patients and HK2 in high glucose condition vs. control. Knockdown of circ_0004951 mediated a significant suppression of HK2 pyroptosis, while results from bioinformatics analysis revealed that circ_0004951 has binding sites with miR-93-5p and miR-93-5p could bind to NLRP3. Results from dual-luciferase reporter assay further corroborated this finding. Finally, observations from rescue experiments showed that down-regulation of miR-93-5p and upregulation of NLRP3 markedly attenuated the anti-pyroptosis and anti-inflammatory effects of circ_0004951 knockdown on HK2.

Conclusion: Circ_0004951 promotes pyroptosis of renal tubular epithelial cells in DKD the miR-93-5p/NLRP3 inflammasome pathway, suggesting its potential for clinical diagnosis and treatment of DKD.
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http://dx.doi.org/10.3389/fmed.2022.828240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207212PMC
June 2022

Relevance of Gene Polymorphisms of NAT2 and NR1I2 to anti-tuberculosis drug-induced hepatotoxicity.

Xenobiotica 2022 Jun 20:1-23. Epub 2022 Jun 20.

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.

The recommended treatment regimen for tuberculosis is a combination of agents with antitubercular activity, during which hepatotoxicity is one of the most common side effects. In addition to the -acetyltransferase 2 () genotype, in nuclear receptor subfamily 1, group I, member 2 () has been demonstrated to be associated with anti-tuberculosis drug-induced hepatotoxicity (ATDH), but previous results have been inconsistent.A retrospective nested hospital-based case-control study was performed to investigate the association between genetic polymorphisms and the risk of ATDH. Fifteen genetic variants (13 SNPs and two null genotypes) in cytochrome P450 2E1, , UDP-glucuronosyltransferase 1A1, , superoxide dismutase 1, superoxide dismutase 2, and glutathione -transferases (, , were genotyped. Odds ratios with 95% confidence intervals were calculated with drug doses, body mass index comorbidity of diabetes mellitus, and baseline alanine transaminase value as covariates.Conditional logistic regression demonstrated that the slow acetylation genotype and the allele of in may contribute to susceptibility to ATDH.Stratified association analysis demonstrated that in non-slow acetylators, the allele of was a risk factor for ATDH, whereas the allele did not increase the susceptibility to ATDH in slow acetylators.
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http://dx.doi.org/10.1080/00498254.2022.2092783DOI Listing
June 2022

Maternal Factor Dppa3 Activates 2C-Like Genes and Depresses DNA Methylation in Mouse Embryonic Stem Cells.

Front Cell Dev Biol 2022 3;10:882671. Epub 2022 Jun 3.

School of Medicine, Nankai University, Tianjin, China.

Mouse embryonic stem cells (ESCs) contain a rare cell population of "two-cell embryonic like" cells (2CLCs) that display similar features to those found in the two-cell (2C) embryo and thus represent an model for studying the progress of zygotic genome activation (ZGA). However, the positive regulator determinants of the 2CLCs' conversion and ZGA have not been completely elucidated. Here, we identify a new regulator promoting 2CLCs and ZGA transcripts. Through a combination of overexpression (OE), knockdown (KD), together with transcriptional analysis and methylome analysis, we find that Dppa3 regulates the 2CLC-associated transcripts, DNA methylation, and 2CLC population in ESCs. The differentially methylated regions (DMRs) analysis identified 6,920 (98.2%) hypomethylated, whilst only 129 (1.8%) hypermethylated, regions in OE ESCs, suggesting that Dppa3 facilitates 2CLCs reprogramming. The conversion to 2CLCs by overexpression of is also associated with DNA damage response. knockdown manifest impairs transition into the 2C-like state. Global DNA methylome and chromatin state analysis of OE ESCs reveal that facilitates the chromatin configuration to 2CLCs reversion. Our finding for the first time elucidates a novel role of Dppa3 in mediating the 2CLC conversion, and suggests that Dppa3 is a new regulator for ZGA progress.
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http://dx.doi.org/10.3389/fcell.2022.882671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203971PMC
June 2022

miR-99a-5p inhibits glycolysis and induces cell apoptosis in cervical cancer by targeting RRAGD.

Oncol Lett 2022 Jul 27;24(1):228. Epub 2022 May 27.

Department of Gynecology, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei 430061, P.R. China.

Cervical cancer (CC) is one of the most common gynecological malignancies that endangers women's health. A negative effect of glycolysis is that it contributes to abnormal tumor growth. MicroRNA (miR)-99a expression has been found to be decreased in CC. The present study aimed to investigate the role of miR-99a-5p in glycolysis in CC. For this purpose, the association between miR-99a and the prognosis of patients with CC from The Cancer Genome Atlas database was analyzed using Kaplan-Meier analysis. miR-99a-5p expression and Ras-related GTP binding D (RRAGD) expression were assessed using reverse transcription-quantitative PCR and western blot analysis. Cell proliferation and apoptosis were examined using an MTT assay and flow cytometry, respectively. Glucose uptake, lactate concentration and extracellular acidification rate were measured using a glucose uptake colorimetric assay, a lactate colorimetric assay and a Seahorse XFe96 extracellular flux analyzer, respectively. The association between miR-99a-5p and RRAGD was predicted using TargetScan 7.1, and was confirmed using dual luciferase reporter assay. The results revealed that miR-99a-5p expression was decreased and that of RRAGD was increased in CC tissues and cell lines. RRAGD was negatively regulated by miR-99a-5p. The overexpression of miR-99a-5p induced apoptosis and inhibited glycolysis in CC cells by targeting RRAGD. On the whole, the present study revealed a novel mechanism through which miR-99a-5p regulates cell apoptosis and glycolysis in CC, thus providing a potential therapeutic target for CC.
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http://dx.doi.org/10.3892/ol.2022.13349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185141PMC
July 2022

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer.

Front Immunol 2022 3;13:905259. Epub 2022 Jun 3.

Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Prostate cancer (PCa) is one of the most prevalent cancers of the urinary system. In previous research, Kinesin family member 2C (KIF2C), as an oncogene, has been demonstrated to have a key role in the incidence and progression of different cancers. However, KIF2C has not been reported in PCa. We combined data from different databases, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and the Genomics of Drug Sensitivity in Cancer database, to explore the potential oncogenic role of KIF2C in PCa through a series of bioinformatics approaches, including analysis of the association between KIF2C and prognosis, clinicopathological features, gene mutations, DNA methylation, immune cell infiltration, and drug resistance. The results showed that KIF2C was significantly up-regulated in PCa. High KIF2C expression was associated with age, pathological stage, lymph node metastases, prostate-specific antigen (PSA), and Gleason score and significantly predicted an unfavorable prognosis in PCa patients. Results from Gene Set Enrichment Analysis (GSEA) suggested that KIF2C was involved in the cell cycle and immune response. KIF2C DNA methylation was reduced in PCa and was inversely linked with KIF2C expression. KIF2C was shown to have a strong relationship with the tumor microenvironment (TME), infiltrating cells, and immune checkpoint genes. Furthermore, high KIF2C expression was significantly resistant to a variety of MAPK signaling pathway-related inhibitors. Our study reveals that KIF2C may be a possible predictive biomarker for assessing prognosis in PCa patients with immune infiltration.
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http://dx.doi.org/10.3389/fimmu.2022.905259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203693PMC
June 2022

Sirtuin 1 Induces Choroidal Neovascularization and Triggers Age-Related Macular Degeneration by Promoting LCN2 through SOX9 Deacetylation.

Oxid Med Cell Longev 2022 9;2022:1671438. Epub 2022 Jun 9.

Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550002, China.

Increasing studies have identified the function of sirtuin-1 (SIRT1) in ocular diseases. Hence, this study is aimed at exploring the potential role of SIRT1 in choroidal neovascularization- (CNV-) induced age-related macular degeneration (AMD) development and the associated mechanism. Expression of SIRT1/SOX9/LCN2 in the hypoxic cells was determined, and their interactions were predicted by bioinformatics websites and followed by the verification by luciferase assay and chromatin immunoprecipitation (ChIP). Their effects on hypoxic cells concerning cell viability, apoptosis, migration, and angiogenesis were detected through gain- and loss-of-function assays. Besides, their effect was explored using the established CNV mouse models. Highly expressed LCN2, SOX9, and SIRT1 were observed in hypoxic cells. LCN2 was increased by SOX9 and SIRT1 deacetylated SOX9 to promote its nuclear translocation, which further inhibited the viability of human retinal pigment epithelial cells and promoted cell apoptosis and angiogenesis as well as CNV-induced AMD formation. The relieving role of LCN2 inhibition on CNV-induced AMD without toxicity for mice was also demonstrated by experiments. Overall, SIRT1 promoted the formation of CNV-induced AMD through SOX9 deacetylation-caused LCN2 upregulation, representing a promising target for CNV-induced AMD management.
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http://dx.doi.org/10.1155/2022/1671438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203240PMC
June 2022

PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase.

Biomol Ther (Seoul) 2022 Jun 20. Epub 2022 Jun 20.

College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.
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http://dx.doi.org/10.4062/biomolther.2022.066DOI Listing
June 2022

Mycorrhizal Inoculation Enhances Nutrient Absorption and Induces Insect-Resistant Defense of .

Front Plant Sci 2022 31;13:898969. Epub 2022 May 31.

Department of Grassland Resources and Ecology, College of Grassland Science and Technology, China Agricultural University, Beijing, China.

The majority of terrestrial plants can form symbiotic associations on their roots with arbuscular mycorrhizal fungi (AMF) in the soil to stimulate the growth and nutrient uptake of the host plant and to improve plant resistance to insects and disease. However, the use of AMF for insect control on gramineous forages requires further study. Here, we evaluated the effects of AMF () inoculation on the defense against attack in . Inoculation assays showed that mycorrhizal plants had a higher resistance than non-inoculated plants, as evidenced by plants having more plant biomass, a higher nitrogen and phosphorus content, and greater lipoxygenase (LOX) activity. The results of insect damage showed that in addition to a decrease in the enzyme phenylalanine-ammonia-lyase, the activities of other plant defense-related enzymes (including polyphenol oxidase and β-1,3-glucanase) were increased. A key enzyme, LOX, belonging to the jasmonic acid (JA) signaling pathway was notably increased in mycorrhizal treatment. Volatile organic compounds (VOCs) were identified using gas chromatography mass spectrometry and the results showed that several metabolites with insect-resistant properties, including D-Limonene, p-Xylene, 1,3-Diethylbenzene were detected in mycorrhizal plants. These findings suggest that mycorrhizal inoculation has potential applications in insect management on forage grasses and demonstrates that the JA signaling pathway is essential for insect resistance in .
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http://dx.doi.org/10.3389/fpls.2022.898969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194685PMC
May 2022

Plant Interaction Patterns Shape the Soil Microbial Community and Nutrient Cycling in Different Intercropping Scenarios of Aromatic Plant Species.

Front Microbiol 2022 27;13:888789. Epub 2022 May 27.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing University of Agriculture, Beijing, China.

Intercropping systems improve the soil nutrient cycle through microbial community activity and then land productivity. However, their interactions mechanism underlying that the mixed aromatic plant species intercropping regulate the soil microbiome and nutrient cycling on the perennial woody orchard is still uncovered. We designed treatments with 0, 1, and 3 aromatic plant species intercropped in two scenarios of clean tillage (T model, T1, T2, and T4) and natural grass (G model, G1, G2, and G4) in apple orchards, and investigated intercrops effects at the branch growing stage (BGS) and fruit development stage (FDS), respectively. Compared with T model, G model in FDS increased alpha diversity of bacterial community and Shannon index fungal community, the relative abundance of dominant taxa, such as Acidobacteria and Actinobacteria, and also the numbers of up and down-regulated OTUs, the most of indices of co-occurrence network in both bacterial and fungal community, and then improved invertase activity and available nitrogen content. Relative to G1, G2 and G4 reduced diversity bacterial community in FDS, the relative abundance of dominant taxa, the most of indices of co-occurrence network, and then improved soil invertase activity and total phosphorus content in soil. Moreover, Shannon index of fungal community, the altered number of OTUs and the most indices of co-occurrence network were higher in G4 than those in G2 in FDS. These changes above in FDS were more markedly than those in BGS, suggesting that chemical diversity of litter from mixed species of aromatic plants in natural grass scenario led to diversity, complexity, and stability of soil microbial community and then nutrient cycling. It provided a novel highlight and method to modulate biocenosis and then improve the soil nutrient cycling.
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http://dx.doi.org/10.3389/fmicb.2022.888789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197114PMC
May 2022

Low-grade fetal adenocarcinomas of the lung: A case report.

Authors:
Fen Zhang Lu Yu

Asian J Surg 2022 Jun 10. Epub 2022 Jun 10.

Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.092DOI Listing
June 2022

Vasculature of the Nasal Cartilage Region Related to Filler Injection.

Aesthetic Plast Surg 2022 Jun 9. Epub 2022 Jun 9.

The Second School of Clinical Medicine, Southern Medical University, 253 Industry Avenue, Guangzhou City, Guangdong Province, People's Republic of China.

Background: A filler injection in the nose can be essential but is also dangerous, especially in the nasal cartilage region. To safely and accurately perform a filler injection, surgeons must have detailed knowledge of nasal anatomy.

Objectives: Associated the vessel branches and the characteristics of different nasal regions to provide suggestions for more suitable injection sites.

Methods: Fifty specimens underwent computed tomography (CT) after contrast infusion. Qualified specimens were selected for 3D CT reconstruction. Dissection was performed to confirm the accuracy of the CT data.

Results: The branches of arteries with large diameters, the dorsal nasal artery (DNA) and the lateral nasal artery (LNA) were distributed within the superficial musculoaponeurotic system layer. The DNA was seen in only 58% of specimens. The artery crossed the midline over the upper lateral cartilage in 16% of specimens. The LNA was a constant branch that traversed the nasal tip. The LNA crossed the midline to the contralateral side in 18% of patients. We divided the nasal cartilage dorsum into two regions for easy handling: the supratip region (STR) and the nasal tip region (NTR). The branches distributed in the STR mostly originated from the DNA (81.6%, 40/49), while those in the NTR mostly originated from the LNA.

Conclusions: The vasculature of the nasal cartilage region observed in this study is similar to that observed in previous studies. However, we found that the STR was an advantageous area for filler injection. At the same time, we provided suggestions for more suitable injection methods.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-022-02942-3DOI Listing
June 2022

Response surface model comparison and combinations for remifentanil and propofol in describing response to esophageal instrumentation and adverse respiratory events.

J Formos Med Assoc 2022 Jun 6. Epub 2022 Jun 6.

Department of Biomedical Engineering, School of Intelligent Medicine, China Medical University, Shenyang, P.R. China. Electronic address:

Background: The primary aim of this essay was to explore the best fitting model in remifentanil-propofol combined administrations during esophageal instrumentation (EI) from five distinct response surface models. The secondary aim was to combine the models to give appropriate effect-site drug concentrations (Ces) range with maximal comfort and safety.

Methods: The Greco, reduced Greco, Minto, Scaled C50 Hierarchy and Fixed C50 Hierarchy models were constructed to fit four drug effects: loss of response to esophageal instrumentation (LREI), loss of response to esophageal instrumentation revised (LREIR), intolerable ventilatory depression (IVD) and respiratory compromise (RC). Models were tested by chi-square statistical test and evaluated with Akaike Information Criterion (AIC). Model prediction performance were measured by successful prediction rate (SPR) and three prediction errors.

Results: The reduced Greco model was the best fitting model for LREI and RC, and the Minto model was the best fitting model for LREIR and IVD. The SPRs of reduced Greco model for LREI and RC were 81.76% and 79.81%. The SPRs of Minto model for LREIR and IVD were 80.32% and 80.12%. Overlay of the reduced Greco model for LREI and Minto model for IVD offered visual aid for guidance in drug administration.

Conclusions: Using proper response surface model to fit different drug effects will describe the interactions between anesthetic drugs better. Combining response surface models to select the more reliable effect-site drug concentrations range can be used to guide clinical drug administration with greater safety and provide an improvement of anesthesia precision.
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http://dx.doi.org/10.1016/j.jfma.2022.05.011DOI Listing
June 2022

Biodegradable Imiquimod-Loaded Mesoporous Organosilica as a Nanocarrier and Adjuvant for Enhanced and Prolonged Immunity against Foot-and-Mouth Disease Virus in Mice.

ACS Appl Bio Mater 2022 Jun 9;5(6):3095-3106. Epub 2022 Jun 9.

Institute of Veterinary Immunology & Engineering, National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base, Ministry of Science and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, P. R. China.

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 μg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, [email protected] can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that [email protected] triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes . Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.
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http://dx.doi.org/10.1021/acsabm.2c00382DOI Listing
June 2022

Upregulation of MDH1 acetylation by HDAC6 inhibition protects against oxidative stress-derived neuronal apoptosis following intracerebral hemorrhage.

Cell Mol Life Sci 2022 Jun 9;79(7):356. Epub 2022 Jun 9.

Institute of Nervous System Diseases and Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, No. 99 West Huaihai Road, Xuzhou, 221006, Jiangsu Province, People's Republic of China.

Oxidative stress impairs functional recovery after intracerebral hemorrhage (ICH). Histone deacetylase 6 (HDAC6) plays an important role in the initiation of oxidative stress. However, the function of HDAC6 in ICH and the underlying mechanism of action remain elusive. We demonstrated here that HDAC6 knockout mice were resistant to oxidative stress following ICH, as assessed by the MDA and NADPH/NADP assays and ROS detection. HDAC6 deficiency also resulted in reduced neuronal apoptosis and lower expression levels of apoptosis-related proteins. Further mechanistic studies showed that HDAC6 bound to malate dehydrogenase 1 (MDH1) and mediated-MDH1 deacetylation on the lysine residues at position 121 and 298. MDH1 acetylation was inhibited in HT22 cells that were challenged with ICH-related damaging agents (Hemin, Hemoglobin, and Thrombin), but increased when HDAC6 was inhibited, suggesting an interplay between HDAC6 and MDH1. The acetylation-mimetic mutant, but not the acetylation-resistant mutant, of MDH1 protected neurons from oxidative injury. Furthermore, HDAC6 inhibition failed to alleviate brain damage after ICH when MDH1 was knockdown. Taken together, our study showed that HDAC6 inhibition protects against brain damage during ICH through MDH1 acetylation.
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http://dx.doi.org/10.1007/s00018-022-04341-yDOI Listing
June 2022

Methodological Study on the Establishment of HLA/HPA Gene Bank of Platelet Donors and Its Clinical Application.

Indian J Hematol Blood Transfus 2022 May 26:1-9. Epub 2022 May 26.

The Ningbo Central Blood Station, Ningbo, China.

The current study aimed at establishing a large-scale platelet donor database with known HPA and HLA genotypes in Ningbo, to provide matched platelets for the clinic and prevent the occurrence of ineffective immune platelet transfusion refractoriness (PTR). The platelet banks of clinical donor wtih HLA-A, HLA-B, HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA10, HPA15 and HPA21 genotyps were established. Meanwile, the platelet gene matching was performed on the donor. It was found that there were phenotype polymorphisms in 1000 donnors with HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA10, HPA15 and HPA21 genotyps, and allel polymorphism distribution in donnors with HPA1, HPA2, HPA3, HPA4, HPA5, HPA6, HPA15, HPA21 genotyps. The frequency of HPA10 was a gene, and not b gene, showing a single linear distribution. The HPA 2, HPA3, HPA15 system were the most polymorphic with three phenotypes: aa, ab, bb. In the HLA-A allele, the highest frequency is A*11:01 (24.25%). There were 13 alleles that were greater than 1%, such as A*24:02, A*02:01, A*33:03, and the accumulated frequency reached 96.20%. In the HLA-B allele, the highest gene frequency was B*40:01 (13.40%). There were 24 alleles that were greater than 1%, such as B*46: 01, B*58: 01, B*15: 01, and the accumulated frequency reached 91.60%. Platelet antibody cross matching was performed on 100 blood samples from patients with thrombocytopenia after multiple platelet transfusions. The number of consistent samples was 46 (46%). Twenty patients were transfused with platelet cross matching. Among them, 18 patients had obvious improvement in clinical symptoms and good hemostatic effect after transfusion, which was judged to be effective. Platelet donor HPA and HLA-A, B antigen genotyping database provided patients with individual appropriate platelets, and provided the effectiveness of immune platelet infusion ensuring effective platelet transfusion.
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http://dx.doi.org/10.1007/s12288-022-01547-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135102PMC
May 2022

Electric Control of Exchange Bias at Room Temperature by Resistive Switching via Electrochemical Metallization.

ACS Appl Mater Interfaces 2022 Jun 6. Epub 2022 Jun 6.

National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093, P. R. China.

Electric field control of exchange bias (EB) plays an important role in spintronics due to its attractive merit of lower energy consumption. Here, we propose a novel method for electrically tunable EB at room temperature in a device with the stack of Si/SiO/Ta/Pt/Ag/Mn-doped ZnO (MZO)/Pt/FeMn/Co/ITO by resistive switching (RS) via electrochemical metallization (ECM). The device shows enhanced and weakened EB when set at high-resistance state (HRS) and low-resistance state (LRS), respectively. For the device at LRS, the aberration-corrected scanning transmission electron microscopy (STEM) characterizations unambiguously reveal that the Ag filaments grow initially from the Ag anode and then elongate toward the ITO cathode. It is inferred that at LRS, a small portion of Ag filaments have passed through the MZO and the intervening thin Pt layer and extended into the FeMn layer. After applying reverse voltage, these Ag filaments are electrochemically dissolved and ruptured near the MZO/Pt interface. This is considered to be the main mechanism responsible for RS and switchable EB as well. This work presents a new strategy for designing low-power, nonvolatile magnetoelectric random access memory devices.
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http://dx.doi.org/10.1021/acsami.2c05764DOI Listing
June 2022

Prognostic Significance of Lineage Diversity in Bladder Cancer Revealed by Single-Cell Sequencing.

Front Genet 2022 19;13:862634. Epub 2022 May 19.

Shantou University Medical College, Shantou University, Shantou, China.

Bladder cancer is the most common malignant tumor of the urinary system. We investigated the clinical implications of cell lineages in bladder cancer by integrating single-cell and bulk transcriptome data. By investigating the single-cell transcriptional profiles of 12,424 cells from normal bladder, eleven cell types and five types of epithelial sub-population were identified. Based on the signature of cell types identified in single-cell profiles, deconvolution analysis was employed to estimate cell types and epithelial lineages in the bulk RNA sequencing bladder cancer cohort. Cancer subtypes with clinical implications were further identified based on the heterogeneity of the epithelial lineage across patients. This study suggests that the EMT-like subtype is robustly correlated with poor prognosis and the umbrella subtype is a positive factor for the patient survival. Our research has a high potential for accurate prognostic and therapeutic stratification of bladder cancer.
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http://dx.doi.org/10.3389/fgene.2022.862634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162490PMC
May 2022

Increase Crop Resilience to Heat Stress Using Omic Strategies.

Front Plant Sci 2022 17;13:891861. Epub 2022 May 17.

College of Horticulture, Nanjing Agricultural University, Nanjing, China.

Varieties of various crops with high resilience are urgently needed to feed the increased population in climate change conditions. Human activities and climate change have led to frequent and strong weather fluctuation, which cause various abiotic stresses to crops. The understanding of crops' responses to abiotic stresses in different aspects including genes, RNAs, proteins, metabolites, and phenotypes can facilitate crop breeding. Using multi-omics methods, mainly genomics, transcriptomics, proteomics, metabolomics, and phenomics, to study crops' responses to abiotic stresses will generate a better, deeper, and more comprehensive understanding. More importantly, multi-omics can provide multiple layers of information on biological data to understand plant biology, which will open windows for new opportunities to improve crop resilience and tolerance. However, the opportunities and challenges coexist. Interpretation of the multidimensional data from multi-omics and translation of the data into biological meaningful context remained a challenge. More reasonable experimental designs starting from sowing seed, cultivating the plant, and collecting and extracting samples were necessary for a multi-omics study as the first step. The normalization, transformation, and scaling of single-omics data should consider the integration of multi-omics. This review reports the current study of crops at abiotic stresses in particular heat stress using omics, which will help to accelerate crop improvement to better tolerate and adapt to climate change.
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http://dx.doi.org/10.3389/fpls.2022.891861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152541PMC
May 2022

Chiral Lewis Base Catalyzed Enantioselective Selenocyclization of 1,1-Disubstituted Alkenes: Asymmetric Synthesis of Selenium-Containing 4-3,1-Benzoxazines.

Org Lett 2022 Jun 1;24(22):4093-4098. Epub 2022 Jun 1.

School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.

An enantioselective selenocyclization of 1,1-disubstituted alkenes was achieved for the first time, which is enabled by a novel combination of a chiral BINAM-derived sulfide and an achiral Lewis acid. Various selenium-containing 4-3,1-benzoxazines, which are widely present in a range of medicinally relevant molecules, were readily obtained in moderate to good yields and good to excellent enantioselectivities. A series of tetrasubstituted carbon stereocenters were facilely constructed.
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http://dx.doi.org/10.1021/acs.orglett.2c01731DOI Listing
June 2022

Self-assembling, pH-responsive nanoflowers for inhibiting PAD4 and neutrophil extracellular trap formation and improving the tumor immune microenvironment.

Acta Pharm Sin B 2022 May 12;12(5):2592-2608. Epub 2021 Nov 12.

Department of Medicinal Chemistry, College of Pharmaceutical Sciences of Capital Medical University, Beijing 100069, China.

Self-assembling carrier-free nanodrugs are attractive agents because they accumulate at tumor by an enhanced permeability and retention (EPR) effect without introduction of inactive substances, and some nanodrugs can alter the immune environment. We synthesized a peptidyl arginine deiminase 4 (PAD4) molecular inhibitor, ZD-E-1M. It could self-assembled into nanodrug ZD-E-1. Using confocal laser scanning microscopy, we observed its cellular colocalization, PAD4 activity and neutrophil extracellular traps (NETs) formation. The populations of immune cells and expression of immune-related proteins were determined by single-cell mass cytometry. ZD-E-1 formed nanoflowers in an acidic environment, whereas it formed nanospheres at pH 7.4. Accumulation of ZD-E-1 at tumor was pH-responsive because of its pH-dependent differences in the size and shape. It could enter the nucleus and bind to PAD4 to prolong the intracellular retention time. In mice, ZD-E-1 inhibited tumor growth and metastasis by inhibiting PAD4 activity and NETs formation. Besides, ZD-E-1 could regulate the ratio of immune cells in LLC tumor-bearing mice. Immunosuppressive proteins like LAG3 were suppressed, while IFN- and TNF- as stimulators of tumor immune response were upregulated. Overall, ZD-E-1 is a self-assembling carrier-free nanodrug that responds to pH, inhibits PAD4 activity, blocks neutrophil extracellular traps formation, and improves the tumor immune microenvironment.
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http://dx.doi.org/10.1016/j.apsb.2021.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136569PMC
May 2022

Mir-22-incorporated polyelectrolyte coating prevents intima hyperplasia after balloon-induced vascular injury.

Biomater Sci 2022 Jun 1. Epub 2022 Jun 1.

Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China.

Drug-coated balloons (DCBs) offer potential to deliver drugs to treat coronary lesions but without leaving permanent implants behind. Paclitaxel and sirolimus are anti-proliferation drugs that are commonly used in commercially available DCBs. However, these drugs present significant cytotoxicity concern and low efficacy . Here, we use microRNA-22 (miR-22) as balloon loaded drugs and polyelectrolyte complexes (PECs) polyethyleneimine/polyacrylic acid (PEI/PAA) as balloon coatings to establish a new DCB system through the ultrasonic spray method. The PEI/PAA forms a stable and thin coating on the balloon, which resulted in a good transfer capacity to the vessel wall both and . miR-22 that could modulate smooth muscle cell (SMC) phenotype switching is incorporated into the PEI/PAA coating and shows a sustained release profile. The PEI/PAA/miR-22 coated balloon successfully inhibits intima hyperplasia after balloon-induced vascular injury in a rat model through decreasing proliferative SMCs the miR-22-methyl-CpG binding protein 2 (MECP2) axis. Our findings indicate that balloons coated with PEI/PAA/miR-22 have great potential to be promising DCBs in the treatment of cardiovascular disease.
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http://dx.doi.org/10.1039/d2bm00536kDOI Listing
June 2022

Identification of a novel DFNA5 mutation, IVS7-2 a > G, in a Chinese family with non-syndromic sensorineural hearing loss.

Acta Otolaryngol 2022 May 31;142(5):448-453. Epub 2022 May 31.

Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.

Background: To date, seven mutations have been reported in families with autosomal dominant non-syndromic hearing loss worldwide. All the mutations cause exon 8 skipping at the mRNA level, that led to the protein truncated and the protein could exert a gain of ototoxic function.

Objective: In this study, we found an autosomal-dominant non-syndromic hearing loss Chinese pedigree which spanned four generations and comprised 43 members. We want to identify the causative gene and mutation.

Methods: Application of microsatellite markers on DFNA 23 loci preliminary screening of 25 genes, data were analyzed by linkage analysis.

Results: We mapped the locus to the region between D7S629 and D7S516 (two-point lod-score of 5.39) with the application of 8 microsatellite markers. By direct sequencing of candidate genes in mapping region, we identified a novel missense mutation ivs7-2 A > G in DFNA5 gene, which was faithfully cosegregated with hearing loss in the family.

Conclusion And Significance: The missense mutation in intron 7 of causes skipping of exon 8, resulting in premature termination of the open reading frame. This type of mutation has repeatedly confirmed that it provides more evidence for the previous view and provides a more solid foundation for future research.
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http://dx.doi.org/10.1080/00016489.2019.1597984DOI Listing
May 2022

Identification of Mutations Associated With Macozinone-Resistant in Mycobacterium Tuberculosis.

Curr Microbiol 2022 May 26;79(7):205. Epub 2022 May 26.

Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China.

Novel anti-tuberculosis drug macozinone (MCZ) is identified as a drug candidate and is currently under clinical development for the treatment of tuberculosis. However, the mutations conferring resistance to MCZ remain inadequately characterized. In this study we investigated resistant mutations to the MCZ through de novo resistance selection in vitro. This was accomplished by passing the Mycobacterium tuberculosis H37Rv on solid agar plates, which were infused with the antibiotic. Through whole genome sequencing and targeted PCR genomic resistance conferring SNPs were catalogued, and the resistant phenotype was analyzed by MABA test. Of MCZ-resistant clones obtained in vitro the mutation of C387S in dprE1 is only observed in high-level resistant clones (MIC > 500 ng/mL) indicating that C387S mutation is directly related to high-level MCZ-resistance. In addition, high-level resistance to MCZ can occur in clone grew on agar plates infused with low concentration MCZ, which means low concentration MCZ induction can produce high-level drug-resistance and it is easy to produce high-level MCZ-resistance. We also found two new mutations (G61A and G248A) in dprE1 for the first time. The MIC of other clones except the clones carrying the C387S mutation was at the same level (20 ng/mL > MIC > 2 ng/mL). Of low-level resistant clones other gene mutations involved in drug efflux or membrane permeability were found (pepQ, Rv0678, arsC, etc.), with highest mutation frequency in Rv0678 (50/64, 78.12%). It suggests that there may be new mechanisms independent of dprE1 mutations.
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http://dx.doi.org/10.1007/s00284-022-02881-xDOI Listing
May 2022

Mass Production of Hierarchically Designed Engine-Intake Air Filters by Multinozzle Electroblow Spinning.

Nano Lett 2022 Jun 25;22(11):4354-4361. Epub 2022 May 25.

Institute of Materials Research, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, P.R. China.

Particulate matter damages engines of vehicles when blown into the ventilation system. Conventional engine-intake filter is cellulose microfiber board with an average diameter larger than ten microns, which has low removal efficiency of ultrafine particular matter. In this work, we apply ultrafine polyurethane nanofibers (∼122.8 nm) onto pleated cellulose board using scalable multinozzle electroblow spinning technology, which improves filtration efficiency of particulate matter with a diameter of less than 0.3 μm PM greatly. The thermoplastic polyurethane 85A nanofiber membranes are transparent, and display superior filtration performance which meets up with the 95% filtration efficiency standard in GB 19083-2010 technical requirements for protective face mask for medical use. The lightweight pleated thermoplastic polyurethane/cellulose composites intercept ∼90% ultrafine PM under airflow velocity of 32 L min and possess great resistance to shock. These hierarchically designed filters follow a mechanical mechanism and can be used in on-road and off-road cars in the long run.
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http://dx.doi.org/10.1021/acs.nanolett.2c00704DOI Listing
June 2022

Spatial variations of root-associated bacterial communities of alpine plants in the Qinghai-Tibet Plateau.

Sci Total Environ 2022 Sep 21;839:156086. Epub 2022 May 21.

College of Grassland Science and Technology, China Agricultural University, Beijing 100193, China. Electronic address:

Exploring the geospatial variation of root-associated microbiomes is critical for understanding plant-microbe-environment interactions and plant environmental adaptability. Root-associated bacterial communities from the three compartments [rhizosphere surrounding soil (RSS), rhizosphere soil (rhizosphere), and root endosphere (endophytic)] are influenced by multiple factors, including plant species and geographical locations. Nonetheless, these communities remain poorly understood under harsh conditions. In this study, we selected four dominant alpine plants on the Qinghai-Tibet Plateau (i.e., Elymus nutans, Festuca sinensis, Kobresia pygmaea, and Kobresia humilis) to investigate their root-associated bacterial communities across 11 geographical locations and determine the factors driving spatial variation. The results showed that the microbiota of the three compartments had significantly different community compositions, with more Pseudomonadaceae and Enterobacteriaceae present in the endosphere. Spatial variations in root endophytic microbiota were mainly governed by stochastic processes, which were different from the deterministic processes in the other two compartments. Meanwhile, the geographical location had greater effects on bacterial communities than plant species, and the spatial variation of α-diversity in the endosphere was much higher than that in the RSS and rhizosphere. We further found that the differentiation of bacterial diversity in the endosphere among sympatric plant species was enhanced by higher annual precipitation, lower soil nutrients (carbon and nitrogen), and pH. For example, the coefficient of variation of endosphere Pseudomonadaceae abundance was positively correlated with annual mean precipitation, whereas that of Enterobacteriaceae abundance was negatively correlated with soil pH. The co-occurrence network analysis identified a higher proportion of bacterial coexistence in the endosphere (70.9%) than in the RSS (49.5%) and rhizosphere soil (50.9%). Finally, we revealed the relative convergence of endophytic communities among sympatric plant species in the alpine grasslands.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156086DOI Listing
September 2022

Evaluation of Electronic Service-Learning (e-Service-Learning) Projects in Mainland China under COVID-19.

Appl Res Qual Life 2022 May 13:1-24. Epub 2022 May 13.

Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

The use of electronic service-learning (e-Service-Learning or e-SL) is valuable under COVID-19 because we can provide the service without physical contact. Unfortunately, evaluation of e-SL is not widespread and there is no known study in different Chinese societies. Besides, there are many methodological limitations of the existing studies in the field. In this paper, we evaluated e-SL projects implemented in summer 2020 and 2021 in three sites in China. First, we examined service providers' changes based on pretest and posttest scores (i.e., objective outcome evaluation) and their perceptions of the e-SL projects (i.e., subjective outcome evaluation based on the service providers). Second, graduate student assessors in Chinese mainland universities and teachers of primary school students (i.e., service recipients) rated the SL program quality, service providers' performance and benefits to the service recipients after program completion (i.e., subjective outcome evaluation of SL projects based on other stakeholders). Third, trained graduate student assessors evaluated service quality during the implementation process (i.e., process evaluation). We found that university students (i.e., service providers) showed higher posttest scores in positive youth development attributes, leadership attributes and life satisfaction relative to pretest scores. Besides, service providers showed positive perceptions of their learning experience, own performance, benefits to the service recipients and themselves in the SL projects. Similarly, other stakeholders also had positive evaluation of the SL projects and related benefits. Finally, trained graduate student assessors had positive assessment of the quality of program implementation. The findings underscore the utility of e-SL involving both online teaching and learning as well as online service, particularly in a Chinese context.
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http://dx.doi.org/10.1007/s11482-022-10058-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103608PMC
May 2022

TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway.

Br J Cancer 2022 May 21. Epub 2022 May 21.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC.

Methods: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance.

Results: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2.

Conclusions: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.
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http://dx.doi.org/10.1038/s41416-022-01835-1DOI Listing
May 2022
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