Publications by authors named "Ping Deng"

135 Publications

Rapamycin antagonizes cadmium-induced breast cancer cell proliferation and metastasis through directly modulating ACSS2.

Ecotoxicol Environ Saf 2021 Aug 16;224:112626. Epub 2021 Aug 16.

School of Medicine, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Cadmium (Cd) is a carcinogen that stimulates breast cancer (BC) progression. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus that possesses a wide array of pharmacological activities, including anti-BC activity. However, the effects of rapamycin on Cd-increased BC progression and the underlying mechanism have not been fully elucidated. Here, we hypothesize that rapamycin antagonizes Cd-induced BC cell proliferation and metastasis by directly modulating ACSS2. In this study, we found that rapamycin efficiently inhibited Cd-induced proliferation, invasion and migration in MCF-7 and T47-D cells. Moreover, a surface plasmon resonance (SPR) assay confirmed that rapamycin directly binds to the ACSS2 protein with a calculated equilibrium dissociation constant (KD) of 18.3 μM. Molecular docking showed that there are three binding sites in the ACSS2 protein and that rapamycin binds at the coenzyme A (COA) binding site with a docking score of - 12.26 and a binding free energy of - 26.34 kcal/mol. More importantly, rapamycin suppresses Cd-induced BC progression by activating ACSS2. After cells were cotreated with an ACSS2 inhibitor, the effects of rapamycin were abolished. In conclusion, our findings suggest that rapamycin suppresses Cd-augmented BC progression by upregulating ACSS2, and ACSS2 may serve as a direct target of rapamycin for inhibiting xenobiotic (e.g., Cd)-mediated BC progression.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112626DOI Listing
August 2021

Concentrations and health risks of heavy metals in five major marketed marine bivalves from three coastal cities in Guangxi, China.

Ecotoxicol Environ Saf 2021 Oct 28;223:112562. Epub 2021 Jul 28.

Department of Cell Biology, School of Life Sciences, and School of Medicine, Guangxi University, Nanning 530004, China. Electronic address:

Seafood consumption provides essential elements to humans while also posing risks to human health. A total of 2610 individuals of five edible marine bivalve species (Ruditapes philippinarum, Paphia undulata, Meretrix meretrix, Sinonovacula constricta and Meretrix lyrata) were randomly sampled from six farmer markets in three cities (Beihai, Qinzhou and Fangchenggang) in the southernmost coastal region of China. The concentrations of heavy metals (Cu, Pb, Zn, Cd, Cr, Hg and As) were determined by inductively coupled plasma mass spectrometry (ICP-MS). The estimated daily intake (EDI), target hazard quotient (THQ), total hazard index (HI), and target cancer risk (TR) were calculated to evaluate potential human health risks from bivalve consumption. The mean concentrations of metals in the tissues of bivalves descended in the order Zn > Cu > As > Cd > Cr >Pb > Hg in descending order, and the concentrations varied substantially among the five bivalves. Heavy metal concentrations in edible tissues of most bivalve samples were below the safety limits set by national and international regulations, and there were significant correlations between certain metal concentrations. The EDI values for each metal in each bivalve were significantly lower than the corresponding PTDI (provisional tolerable daily intake) values. Health risk assessment showed that although there is no noncarcinogenic health risk for local residents exposed to individual or combined metals from these bivalves, there is a carcinogenic risk from Cd and Cr exposure. Thus, in the long term, monitoring and controlling bivalve consumption will be important. Although current accumulation levels of bivalves are safe, continued and excessive lifetime consumption over 70 years may pose a target cancer risk.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112562DOI Listing
October 2021

NAC antagonizes arsenic-induced neurotoxicity through TMEM179 by inhibiting oxidative stress in Oli-neu cells.

Ecotoxicol Environ Saf 2021 Oct 28;223:112554. Epub 2021 Jul 28.

Department of Occupational Health, Army Medical University, 400038, Chongqing, People's Republic of China. Electronic address:

Arsenic is one of the most common environmental pollutants. Neurotoxicity induced by arsenic has become a major public health concern. However, the effects of arsenic-induced neurotoxicity in the brain and the underlying molecular mechanisms are not well understood. N-acetyl-cysteine (NAC) is a thiol-based antioxidant that can antagonize heavy metal-induced neurotoxicity by scavenging reactive oxygen species (ROS). Here, we used the mouse oligodendrocyte precursor cell (OPC) line Oli-neu to explore the neurotoxic effects of arsenic and the protective effects of NAC. We found that arsenic exposure decreased cell viability, increased oxidative stress, caused mitochondrial dysfunction, and led to apoptosis of Oli-neu cells. Furthermore, we revealed that NAC treatment reversed these neurotoxic effects of arsenic. TMEM179, a key membrane protein, was found highly expressed in OPCs and to be an important factor in maintaining mitochondrial functions. We found that TMEM179 played a critical role in mediating the neurotoxic effects of arsenic and the protective role of NAC. PKCβ is a downstream factor through which TMEM179 regulates the expression of apoptosis-related proteins. This study improves our understanding of the neurotoxic effects and mechanisms of arsenic exposure and the protective effects of NAC. It also identifies a potential molecular target, TMEM179, for the treatment of arsenic-induced neurotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112554DOI Listing
October 2021

Fe(III)-mediated reversible catalytic activity of MoS nanozymes for bisphosphonate drug sensing.

Colloids Surf B Biointerfaces 2021 Oct 29;206:111953. Epub 2021 Jun 29.

Chongqing Key Laboratory of Green Synthesis and Applications, College of Chemistry, Chongqing Normal University, Chongqing 401331, PR China. Electronic address:

Peroxidase-like activity of MoS quantum dots (QDs) can be reversibly regulated by means of Fe/alendronate sodium (ALDS)-induced aggregation/disaggregation of the QDs in solution. Specifically, Fe can selectively aggregate the MoS QDs and thus greatly enhance their peroxidase-like activity, while such enhancement can be inhibited in the presence of ALDS owing to the competitive coordination of ALDS with Fe. By regulating the enzyme-like activity of MoS QDs, different colorimetric signal of a typical substrate of horseradish peroxidase, 3,3΄,5,5΄-tetramethylbenzidine, can be measured in the presence of HO. Based on this mechanism, we develop a colorimetric approach for the determination of ALDS and further applied in quality control of pharmaceutical products, utilizing either smartphone or UV-vis spectrometer as a readout. This detection method is rapid and selective, where derivatization of ALDS before detection is not needed. Such a smartphone-based colorimetric detection platform is promising to be applied in point-of-care testing at home, small clinics, or underdeveloped regions.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111953DOI Listing
October 2021

Histone hypoacetylation contributes to neurotoxicity induced by chronic nickel exposure in vivo and in vitro.

Sci Total Environ 2021 Aug 10;783:147014. Epub 2021 Apr 10.

Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China. Electronic address:

Nickel (Ni) is a heavy metal that is both an environmental pollutant and a threat to human health. However, the effects of Ni on the central nervous system in susceptible populations have not been well established. In the present study, the neurotoxicity of Ni and its underlying mechanism were investigated in vivo and in vitro. Ni exposure through drinking water (10 mg Ni/L, 12 weeks) caused learning and memory impairment in mice. Reduced dendrite complexity was observed in both Ni-exposed mouse hippocampi and Ni-treated (200 μM, 72 h) primary cultured hippocampal neurons. The levels of histone acetylation, especially at histone H3 lysine 9 (H3K9ac), were reduced in Ni-exposed mouse hippocampi and cultured neurons. RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing analyses revealed that H3K9ac-modulated gene expression were downregulated. Treatment with sodium butyrate, a histone deacetylase inhibitor, attenuated Ni-induced H3K9 hypoacetylation, neural gene downregulation and dendrite complexity reduction in cultured neurons. Sodium butyrate also restored Ni-induced memory impairment in mice. These results indicate that Ni-induced H3K9 hypoacetylation may be a contributor to the neurotoxicity of Ni. The finding that Ni disturbs histone acetylation in the nervous system may provide new insight into the health risk of chronic Ni exposure.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147014DOI Listing
August 2021

8-Formylophiopogonanone B antagonizes doxorubicin-induced cardiotoxicity by suppressing heme oxygenase-1-dependent myocardial inflammation and fibrosis.

Biomed Pharmacother 2021 Aug 29;140:111779. Epub 2021 May 29.

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, No. 63, Wenhua Road, Shunqing District, Nanchong, Sichuan 637000, China; Academician Workstation, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China. Electronic address:

Doxorubicin (DOX) is a widely used antitumor drug that causes severe cardiotoxicity in patients; no effective strategy yet exists to address this problem. We previously reported that 8-formylophiopogonanone B (8-FOB), a natural isoflavone in Ophiopogon japonicas, antagonizes paraquat-induced hepatotoxicity. Here, we explored the mechanisms underlying DOX-induced cardiotoxicity as well as whether 8-FOB can alleviate DOX-induced cardiotoxicity. Acute cardiotoxicity was established by injecting C57BL/6J mice with a single dose of DOX (20 mg/kg, intraperitoneal). To elucidate the mechanisms underlying DOX-induced cardiotoxicity, differentially expressed genes between hearts from DOX-treated and control mice were identified from the Gene Expression Omnibus (GEO) database via GEO2R. Using the Cytoscape software plugin cytoHubba, five hub genes associated with DOX-induced cardiotoxicity were identified: CD68, PTEN, SERPINE1, AIF1, and HMOX1. However, of these, only HMOX1 protein expression levels were significantly increased after DOX treatment. We also confirmed that HMOX1-dependent myocardial inflammation and fibrosis were closely associated with DOX-induced cardiotoxicity. More importantly, 8-FOB protected against DOX-cardiotoxicity by ameliorating cardiac injury and dysfunction, reducing cardiac fibrosis and inflammatory cytokine release, and inhibiting HMOX1 expression. In conclusion, our results suggest that inhibition of HMOX1-dependent myocardial inflammatory insults and fibrosis is essential for 8-FOB to ameliorate DOX-caused cardiotoxicity.
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http://dx.doi.org/10.1016/j.biopha.2021.111779DOI Listing
August 2021

Cooperative Heterobimetallic Zinc/Alkaline Earth Metal Catalysis: A Zn/Sr Aminophenol Sulfonamide Complex for Catalytic Asymmetric Michael Addition of 3-Acetoxy-2-oxindoles to β-Ester Enones.

J Org Chem 2021 05 7;86(10):7119-7130. Epub 2021 May 7.

Chongqing Research Center for Pharmaceutical Engineering, Research Center for Innovative Pharmaceutical and Excipient Analysis Technology, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

A heterobimetallic zinc/strontium catalyst has been developed for the asymmetric Michael addition of 3-acetoxy-2-oxindoles to β-ester enones in high yields with excellent enantioselectivities and high diastereoselectivities. This process represents that 3-acetoxy-2-oxindoles can be used as a stable air- and base-tolerant precursor for chiral 3-substituted 3-hydroxy-2-oxindoles.
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http://dx.doi.org/10.1021/acs.joc.1c00379DOI Listing
May 2021

1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling.

Front Cell Dev Biol 2021 12;9:657623. Epub 2021 Apr 12.

Department of Occupational Health, Third Military Medical University, Chongqing, China.

The increasing intensity of environmental radiofrequency electromagnetic fields (RF-EMF) has increased public concern about its health effects. Of particular concern are the influences of RF-EMF exposure on the development of the brain. The mechanisms of how RF-EMF acts on the developing brain are not fully understood. Here, based on high-throughput RNA sequencing techniques, we revealed that transcripts related to neurite development were significantly influenced by 1800 MHz RF-EMF exposure during neuronal differentiation. Exposure to RF-EMF remarkably decreased the total length of neurite and the number of branch points in neural stem cells-derived neurons and retinoic acid-induced Neuro-2A cells. The expression of Eph receptors 5 (EPHA5), which is required for neurite outgrowth, was inhibited remarkably after RF-EMF exposure. Enhancing EPHA5 signaling rescued the inhibitory effects of RF-EMF on neurite outgrowth. Besides, we identified that cAMP-response element-binding protein (CREB) and RhoA were critical downstream factors of EPHA5 signaling in mediating the inhibitory effects of RF-EMF on neurite outgrowth. Together, our finding revealed that RF-EMF exposure impaired neurite outgrowth through EPHA5 signaling. This finding explored the effects and key mechanisms of how RF-EMF exposure impaired neurite outgrowth and also provided a new clue to understanding the influences of RF-EMF on brain development.
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http://dx.doi.org/10.3389/fcell.2021.657623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075058PMC
April 2021

Author Correction: Grain boundary oxidation of proton-irradiated nuclear grade stainless steel in simulated primary water of pressurized water reactor.

Sci Rep 2021 Apr 22;11(1):9162. Epub 2021 Apr 22.

Key Laboratory of Nuclear Materials and Safety Assessment, Institute of Metal Research, Chinese Academy of Sciences, Shenyang City, 110016, China.

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http://dx.doi.org/10.1038/s41598-021-88868-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062565PMC
April 2021

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound.

BMC Complement Med Ther 2021 Apr 22;21(1):129. Epub 2021 Apr 22.

Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.

Backgrounds: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated.

Methods: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-β-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-β-CD inclusion compound in rats were assessed in comparison to VOC.

Results: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC.

Conclusion: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-β-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC.
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http://dx.doi.org/10.1186/s12906-021-03289-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063472PMC
April 2021

Accumulation Pattern of Amygdalin and Prunasin and Its Correlation with Fruit and Kernel Agronomic Characteristics during Apricot ( L.) Kernel Development.

Foods 2021 Feb 11;10(2). Epub 2021 Feb 11.

Key Comprehensive Laboratory of Forestry, College of Forestry, Northwest A&F University, Shaanxi Province, Yangling 712100, China.

To reveal the accumulation pattern of cyanogenic glycosides (amygdalin and prunasin) in bitter apricot kernels to further understand the metabolic mechanisms underlying differential accumulation during kernel development and ripening and explore the association between cyanogenic glycoside accumulation and the physical, chemical and biochemical indexes of fruits and kernels during fruit and kernel development, dynamic changes in physical characteristics (weight, moisture content, linear dimensions, derived parameters) and chemical and biochemical parameters (oil, amygdalin and prunasin contents, β-glucosidase activity) of fruits and kernels from ten apricot ( L.) cultivars were systematically studied at 10 day intervals, from 20 days after flowering (DAF) until maturity. High variability in most of physical, chemical and biochemical parameters was found among the evaluated apricot cultivars and at different ripening stages. Kernel oil accumulation showed similar sigmoid patterns. Amygdalin and prunasin levels were undetectable in the sweet kernel cultivars throughout kernel development. During the early stages of apricot fruit development (before 50 DAF), the prunasin level in bitter kernels first increased, then decreased markedly; while the amygdalin level was present in quite small amounts and significantly lower than the prunasin level. From 50 to 70 DAF, prunasin further declined to zero; while amygdalin increased linearly and was significantly higher than the prunasin level, then decreased or increased slowly until full maturity. The cyanogenic glycoside accumulation pattern indicated a shift from a prunasin-dominated to an amygdalin-dominated state during bitter apricot kernel development and ripening. β-glucosidase catabolic enzyme activity was high during kernel development and ripening in all tested apricot cultivars, indicating that β-glucosidase was not important for amygdalin accumulation. Correlation analysis showed a positive correlation of kernel amygdalin content with fruit dimension parameters, kernel oil content and β-glucosidase activity, but no or a weak positive correlation with kernel dimension parameters. Principal component analysis (PCA) showed that the variance accumulation contribution rate of the first three principal components totaled 84.56%, and not only revealed differences in amygdalin and prunasin contents and β-glucosidase activity among cultivars, but also distinguished different developmental stages. The results can help us understand the metabolic mechanisms underlying differential cyanogenic glycoside accumulation in apricot kernels and provide a useful reference for breeding high- or low-amygdalin-content apricot cultivars and the agronomic management, intensive processing and exploitation of bitter apricot kernels.
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http://dx.doi.org/10.3390/foods10020397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918717PMC
February 2021

The rice aldehyde oxidase OsAO3 gene regulates plant growth, grain yield, and drought tolerance by participating in ABA biosynthesis.

Biochem Biophys Res Commun 2021 04 26;548:189-195. Epub 2021 Feb 26.

College of Life Sciences, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Abscisic acid (ABA) regulates many aspects of plant growth and development and the responses to abiotic stresses. Arabidopsis aldehyde oxidase 3 (AAO3) catalyzes the final step of ABA biosynthesis. We cloned and functionally characterized a novel aldehyde oxidase gene, OsAO3, the rice homolog of AAO3. OsAO3 was expressed in germinated seeds, roots, leaves, and floral organs, particularly in vascular tissues and guard cells, and its expression was significantly induced by exogenous ABA and mannitol. Mutation and overexpression of OsAO3 decreased and increased ABA levels, respectively, in seedling shoots and roots under both normal and drought stress conditions. The osao3 mutant exhibited earlier seed germination, increased seedling growth, and decreased drought tolerance compared to the wild-type, OsAO3-overexpressing lines exhibited the opposite phenotype. Mutation and overexpression of OsAO3 increased and decreased grain yield, respectively, by affecting panicle number per plant, spikelet number per panicle, and spikelet fertility. Thus, OsAO3 may participate in ABA biosynthesis, and is essential for regulation of seed germination, seedling growth, grain yield, and drought tolerance in rice.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.047DOI Listing
April 2021

Cadmium disrupts mitochondrial distribution and activates excessive mitochondrial fission by elevating cytosolic calcium independent of MCU-mediated mitochondrial calcium uptake in its neurotoxicity.

Toxicology 2021 04 19;453:152726. Epub 2021 Feb 19.

Center of Laboratory Medicine, Chongqing Prevention and Treatment Center for Occupational Diseases, Chongqing 400060, People's Republic of China; Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China; Institute of Occupational Diseases and Poisoning, School of Public Health, Nanjing Medical University, Chongqing 400060, People's Republic of China. Electronic address:

Cadmium (Cd) is a ubiquitous environmental and occupational pollutant that is considered as a high-risk factor for neurodegenerative diseases. However, the mechanism underlying Cd-induced neurotoxicity has not been fully elucidated. Abnormal mitochondrial distribution and excessive mitochondrial fission are increasingly implicated in various neurological pathologies. Herein, by exposing primary cortical neurons to Cd (10 and 100 μM) for various times (0, 6, 12, and 24 h), we observed that the rapid motility of the mitochondria in neurons progressively slowed. Many more mitochondria were transported and distributed to the somas of Cd-treated neurons. Coupled with abnormal mitochondrial distribution, Cd exposure triggered excessive mitochondrial fragmentation, followed by mitochondrial membrane potential loss and neuronal damage. However, BAPTA-AM, a chelator of cytosolic calcium ([Ca]), significantly attenuated Cd-induced abnormal mitochondrial distribution and excessive mitochondrial fission, which protected against Cd-induced mitochondrial damage and neuronal toxicity. In contrast to the increase in [Ca], Cd exposure had no effect on the level of mitochondrial calcium ([Ca]). Inhibiting [Ca] uptake, either by ruthenium 360 (Ru360) or by knock-out of mitochondrial calcium uniporter (MCU), failed to alleviate Cd-induced mitochondrial damage and neuronal toxicity. Additionally, in MCU knock-out neurons, BAPTA-AM effectively prevented Cd-induced abnormal mitochondrial distribution and excessive mitochondrial fission. Taken together, Cd exposure disrupts mitochondrial distribution and activates excessive mitochondrial fission by elevating [Ca] independent of MCU-mediated mitochondrial calcium uptake, thereby leading to neurotoxicity. Chelating overloaded [Ca] is a promising strategy to prevent the neurotoxicity of Cd.
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http://dx.doi.org/10.1016/j.tox.2021.152726DOI Listing
April 2021

Circ_0082182 promotes oncogenesis and metastasis of colorectal cancer in vitro and in vivo by sponging miR-411 and miR-1205 to activate the Wnt/β-catenin pathway.

World J Surg Oncol 2021 Feb 17;19(1):51. Epub 2021 Feb 17.

Department of Anorectal Surgery, Jingmen No.1 People's Hospital, No.167, Xiangshan Avenue, Dadao District, Jingmen, 448000, Hubei, China.

Background: Circular RNAs (circRNAs) are a class of endogenous single-strand RNA transcripts with crucial regulation in human cancers. The objective of this study is to investigate the role of circ_0082182 in CRC and its specific functional mechanism.

Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the levels of circ_0082182, microRNA-411 (miR-411) and microRNA-1205 (miR-1205). Cell proliferation was detected by Cell counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used for determining cell cycle and cell apoptosis. Cell apoptosis was also assessed by caspase3 and caspase9 activities. Cell migration and invasion were examined using scratch assay and transwell assay. The interaction between circ_0082182 and miRNA was validated by the dual-luciferase reporter and biotinylated RNA pull-down assays. Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by Western blot. Xenograft model was established for the research of circ_0082182 in vivo.

Results: Circ_0082182 was upregulated in CRC and could predict the poor prognosis of CRC patients. Functionally, circ_0082182 promoted CRC cell proliferation, cell cycle progression, and metastasis while inhibited apoptosis. Subsequently, circ_0082182 was shown to act as the sponges of miR-411 and miR-1205. MiR-411 and miR-1205 were identified as tumor inhibitors in CRC. Furthermore, circ_0082182 promoted the CRC progression via sponging miR-411 and miR-1205. Moreover, circ_0082182 facilitated the Wnt/β-catenin pathway and EMT process by targeting miR-411 and miR-1205. In vivo, circ_0082182 accelerated the CRC tumorigenesis and EMT process by activating the Wnt/β-catenin pathway by downregulating the expression of miR-411 or miR-1205.

Conclusion: This study showed that circ_0082182 functioned as an oncogene in the developing process of CRC by sponging miR-411 or miR-1205 to activate the Wnt/β-catenin pathway. Circ_0082182 might be a molecular target in the diagnosis and treatment of CRC.
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http://dx.doi.org/10.1186/s12957-021-02164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891146PMC
February 2021

Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study.

Infect Dis Ther 2021 Mar 30;10(1):457-470. Epub 2021 Jan 30.

Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.

Introduction: Diabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM.

Methods: The study of patients with MDR/XDR-TB with or without DM (enrolled February 2018-September 2019, 21 Chinese hospitals) was supervised by the New Drug Introduction and Protection Program (NDIP). Of 640 patients with MDR/XDR-TB receiving BDQ-containing anti-TB treatments, two propensity score-matched groups (107 DM/107 non-DM) were compared for cumulative culture conversion rate, time to culture conversion, adverse events, and corrected QT interval.

Results: Body mass index was higher in patients with DM than patients without DM (23.29 ± 3.9 vs. 20.5 ± 3.6, P < 0.001); lung cavity prevalence (86.9% vs. 72.9%, P = 0.037) was also higher in patients with DM; the non-DM group had higher hepatitis prevalence (29.0% vs. 15.9%, P = 0.022). No significant intergroup differences were found for sputum culture conversion rate at week 8 (80.0% vs. 81.4%, P = 0.884), at week 24 (95.6% vs. 98.2%, P = 0.629), or for median time to sputum culture conversion [56 days (IQR 28-63) vs. 56 days (IQR 28-84) (P = 0.687)]. Favorable post-24-week treatment outcomes were presented by 90.7% and 93.5% in the DM group and non-DM group, respectively, without significant intergroup differences (P = 0.448). The DM adverse event rate exceeded non-DM rate (77.6% vs. 64.5%, P = 0.035).

Conclusion: Despite some differences in baseline characteristics, Chinese patients with MDR/XDR-TB with or without DM had similar sputum culture conversion rates and favorable treatment outcomes post-24-week BDQ-containing anti-TB treatment. Low BMI but not DM is risk factor associated with unfavorable outcome of patients with MDR/XDR-TB.
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http://dx.doi.org/10.1007/s40121-021-00396-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954881PMC
March 2021

Discovery of the EL-0052 as a potential anesthetic drug.

Comput Struct Biotechnol J 2021 8;19:710-718. Epub 2021 Jan 8.

College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

As a γ-aminobutyric acid A receptor (GABAR) inhibitor, etomidate fulfills several characteristics of an ideal anesthetic agent, such as rapid onset with rapid clearance and high potency, along with cardiovascular stability. Unfortunately, etomidate has been reported to inhibit CYP11B1 at hypnotic doses, which is associated with a marked increase in patient deaths due to this unexpected off-target effect. In this study, molecular docking was used to simulate the binding mode of etomidate with GABAR and CYP11B1. Based on the in-depth analysis of the binding mode, strong electron-withdrawing group on the C4 position of the imidazole ring was introduced to reduce the charge density of the nitrogen, which is beneficial in reducing the coordination bond between the imidazole nitrogen and heme iron in CYP11B1, as well as in reducing the adrenocortical suppression. Based on the results of ADMET property prediction, MEP analysis, and molecular docking simulation, 4-fluoroetomidate (EL-0052) was designed and synthesized. studies in rats and mice confirmed that EL-0052 had the efficacy similar to etomidate, but without adrenocortical suppression. These findings suggested that EL-0052 was superior to etomidate and support the continued development of EL-0052 as a preclinical candidate as an anesthetic.
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http://dx.doi.org/10.1016/j.csbj.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817531PMC
January 2021

Cadmium promotes breast cancer cell proliferation, migration and invasion by inhibiting ACSS2/ATG5-mediated autophagy.

Environ Pollut 2021 Jan 15;273:116504. Epub 2021 Jan 15.

School of Medicine, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, China; Department of Environmental Medicine, School of Public Health, And Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Cadmium (Cd), which is considered a carcinogenic metal, promotes breast cancer (BC) progression, but the precise mechanism remains unclear. Herein, MCF-7 and T47-D cells were treated with 0.1, 1, and 10 μM cadmium chloride (CdCl) for 24, 48 and 72 h. In our study, Cd exposure significantly accelerated the proliferation, migration and invasion of MCF-7 and T47-D cells. Notably, Cd inhibited autophagic flux by suppressing ATG5-dependent autophagosome formation but had no significant effect on autophagosome-lysosome fusion and lysosomal function. The genetic enhancement of autophagy through ATG5 overexpression suppressed the Cd-mediated increases in proliferation, migration and invasion, which indicated a carcinogenic role of autophagy impairment in Cd-exposed BC cells. GSEA and GeneMANIA were utilized to demonstrate that the Cd-induced decrease in ACSS2 expression mechanistically inhibited ATG5-dependent autophagy in BC cells. Importantly, ACSS2 overexpression increased the level of H3K27 acetylation in the promoter region of ATG5, and this result maintained autophagic flux and abolished the Cd-induced increases in proliferation, migration and invasion. We also verified that the expression of ACSS2 in BC tissues was low and positively related to ATG5 expression. These findings indicated that the promoting effect of Cd on BC cell proliferation, migration and invasion through the impairment of ACSS2/ATG5-dependent autophagic flux suggests a new mechanism for BC cell proliferation and metastasis stimulated by Cd.
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http://dx.doi.org/10.1016/j.envpol.2021.116504DOI Listing
January 2021

Grain boundary oxidation of proton-irradiated nuclear grade stainless steel in simulated primary water of pressurized water reactor.

Sci Rep 2021 Jan 14;11(1):1371. Epub 2021 Jan 14.

Key Laboratory of Nuclear Materials and Safety Assessment, Institute of Metal Research, Chinese Academy of Sciences, Shenyang City, 110016, China.

Grain boundary (GB) oxidation of proton-irradiated 304 nuclear grade stainless steel in primary water of pressurized water reactor was investigated. The investigation was conducted by studying microstructure of the oxide and oxide precursor formed at GB on an "atom-by-atom" basis by a combination of atom-probe tomography and transmission electron microscope. The results revealed that increasing irradiation dose promoted the GB oxidation, in correspondence with a different oxide and oxide precursor formed at the GB. Correlation of the oxide and oxide precursor with the GB oxidation behavior has been discussed in detail.
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http://dx.doi.org/10.1038/s41598-020-80600-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809272PMC
January 2021

BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells.

Invest New Drugs 2021 Jun 2;39(3):686-696. Epub 2021 Jan 2.

Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

G9a, a histone methyltransferase, has been found to be upregulated in a range of tumor tissues, and contributes to tumor growth and metastasis. However, the impact of G9a inhibition as a potential therapeutic target in nasopharyngeal carcinoma (NPC) is unclear. In the present study we aimed to investigate the anti-proliferative effect of G9a inhibition in the NPC cell lines CNE1 and CNE2, and to further elucidate the molecular mechanisms underlying these effects. The expression of G9a in NPC tumor tissues was significantly higher than that in normal nasopharyngeal tissues. The pharmacological inhibition of G9a by BIX-01294 (BIX) inhibited proliferation and induced caspase-independent apoptosis in NPC cells in vitro. Treatment with BIX induced autophagosome accumulation, which exacerbated the cytotoxic activity of BIX in NPC cells. Mechanistic studies have found that BIX impairs autophagosomes by initiating autophagy in a Beclin-1-independent way, and impairs autophagic degradation by inhibiting lysosomal cathepsin D activation, leading to lysosomal dysfunction. BIX was able to suppress tumor growth, possibly by inhibiting autophagic flux; it might therefore constitute a promising candidate for NPC therapy.
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http://dx.doi.org/10.1007/s10637-020-01053-7DOI Listing
June 2021

Bisphenol A promotes breast cancer cell proliferation by driving miR-381-3p-PTTG1-dependent cell cycle progression.

Chemosphere 2021 Apr 15;268:129221. Epub 2020 Dec 15.

Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, China. Electronic address:

Bisphenol A (BPA) is a high-production-volume industrial chemical that facilitates the development of breast cancer. However, the molecular mechanism associated with BPA-induced breast cancer cell proliferation and migration remains elusive. In our study, we exposed MCF-7 cells to different concentrations of BPA (0.1, 1 and 10 μM) for 24, 48, or 72 h. We found that BPA exposure significantly promoted MCF-7 cell proliferation and migration but not invasion. To elucidate the mechanisms, the differentially expressed genes between the BPA and control groups were investigated with the Gene Expression Omnibus (GEO) database through GEO2R. Kyoto Encyclopedia of Genes and Genomes (KEGG) and pathway action network analyses demonstrated the important role of the cell cycle pathway in the effects of BPA exposure on MCF-7 cells. Importantly, analysis with the cytoHubba plugin of Cytoscape software coupled with analysis of enriched genes in the cell cycle pathway identified PTTG1 and CDC20 (two hub genes) as key targets associated with BPA-induced MCF-7 cell proliferation and migration. Interestingly, BPA significantly increased the protein expression levels of PTTG1 but not CDC20. Knockdown of PTTG1 inhibited the BPA-induced increase in proliferation and maintained cell cycle progression. In addition, we confirmed that the increased expression of PTTG1 upon BPA exposure was caused by miR-381-3p inhibition. Moreover, we verified that miR-381-3p expression was low and inversely correlated with PTTG1 expression in breast cancer tissues. Together, these findings demonstrate that BPA promotes high PTTG1 expression and alters the cell cycle to enhance MCF-7 cell proliferation by inhibiting miR-381-3p expression.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129221DOI Listing
April 2021

Long-term bisphenol A exposure exacerbates diet-induced prediabetes via TLR4-dependent hypothalamic inflammation.

J Hazard Mater 2021 01 14;402:123926. Epub 2020 Sep 14.

Department of Environmental Medicine, and Department of Emergency Medicine of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. Electronic address:

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has been revealed associated with metabolic disorders such as obesity, prediabetes, and type 2 diabetes (T2D). However, its underlying mechanisms are still not fully understood. Here, we provide new evidence that BPA is a risk factor for T2D from a case-control study. To explore the detailed mechanisms, we used two types of diet models, standard diet (SD) and high-fat diet (HFD), to study the effects of long-term BPA exposure on prediabetes in 4-week-old mice. We found that BPA exposure for 12 weeks exacerbated HFD-induced prediabetic symptoms. Female mice showed increased body mass, serum insulin level, and impaired glucose tolerance, while male mice only exhibited impaired glucose tolerance. No change was found in SD-fed mice. Besides, BPA exposure enhanced astrocyte-dependent hypothalamic inflammation in both male and female mice, which impaired proopiomelanocortin (POMC) neuron functions. Moreover, eliminating inflammation by toll-like receptor 4 (TLR4) knockout significantly abolished the effects of BPA on the hypothalamus and diet-induced prediabetes. Taken together, our data establish a key role for TLR4-dependent hypothalamic inflammation in regulating the effects of BPA on prediabetes.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123926DOI Listing
January 2021

Docking-based virtual screening of TβR1 inhibitors: evaluation of pose prediction and scoring functions.

BMC Chem 2020 Dec 14;14(1):52. Epub 2020 Aug 14.

College of Pharmacy, Chongqing Medical University, Chongqing, 400016 China.

To improve the reliability of virtual screening for transforming growth factor-beta type 1 receptor (TβR1) inhibitors, 2 docking methods and 11 scoring functions in Discovery Studio software were evaluated and validated in this study. LibDock and CDOCKER protocols were performed on a test set of 24 TβR1 protein-ligand complexes. Based on the root-mean-square deviation (RMSD) values (in Å) between the docking poses and co-crystal conformations, the CDOCKER protocol can be efficiently applied to obtain more accurate dockings in medium-size virtual screening experiments of TβR1, with a successful docking rate of 95%. A dataset including 281 known active and 8677 inactive ligands was used to determine the best scoring function. The receiver operating characteristic (ROC) curves were used to compare the performance of scoring functions in attributing best scores to active than inactive ligands. The results show that Ludi 1, PMF, Ludi 2, Ludi 3, PMF04, PLP1, PLP2, LigScore2, Jain and LigScore1 are better scoring functions than the random distribution model, with AUC of 0.864, 0.856, 0.842, 0.812, 0.776, 0.774, 0.769, 0.762, 0.697 and 0.660, respectively. Based on the pairwise comparison of ROC curves, Ludi 1 and PMF were chosen as the best scoring functions for virtual screening of TβR1 inhibitors. Further enrichment factors (EF) analysis also supports PMF and Ludi 1 as the top two scoring functions.
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http://dx.doi.org/10.1186/s13065-020-00704-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427878PMC
December 2020

Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress.

Toxicol Res (Camb) 2019 Nov 27;8(6):918-927. Epub 2019 Sep 27.

Department of Cell Biology , School of Life Sciences and School of Medicine , Guangxi University , Nanning 530004 , China . Email:

Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (Δ ) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.
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http://dx.doi.org/10.1039/c9tx00186gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399654PMC
November 2019

MiR-17 Knockdown Promotes Vascular Smooth Muscle Cell Phenotypic Modulation Through Upregulated Interferon Regulator Factor 9 Expression.

Am J Hypertens 2020 12;33(12):1119-1126

Department of Pharmacy, The First Hospital of Nanchang, Nanchang, China.

Background: MiR-17 is a small noncoding RNA that plays an important role in the development of tumorgenesis, which recently has emerged to be involved in regulation of inflammatory responses and angiogenesis. However, the effect and underlying mechanism of miR-17 on vascular smooth muscle cell (VSMC) phenotypic modulation have not been investigated.

Methods And Results: In the current study, we observed that miR-17 expression tested by real-time polymerase chain reaction (RT-PCR) was downregulated in VSMCs administrated with platelet-derived growth factor-BB stimulation and carotid arteries subjected to wire injury, which were accompanied with decreased VSMC differentiation markers. Loss-of-function strategy demonstrated that miR-17 knockdown promoted VSMC phenotypic modulation characterized as decreased VSMC differentiation marker genes, increased proliferated and migrated capability of VSMC examined by RT-PCR and western blot analysis. Mechanistically, the bioinformatics analysis and luciferase assay demonstrated that miR-17 directly targeted Interferon Regulator Factor 9 (IRF9) and the upregulated IRF9 expression was responsible for the promoted effect miR-17 knockdown on VSMC phenotypic modulation.

Conclusions: Taken together, our results demonstrated that miR-17 knockdown accelerated VSMC phenotypic modulation partially through directly targeting to IRF9, which suggested that miR-17 may act as a novel therapeutic target for intimal hyperplasia management.
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http://dx.doi.org/10.1093/ajh/hpaa087DOI Listing
December 2020

An Experimental Study of Effects of Media Implication on Self-Report Symptoms Related With MP Use.

Front Public Health 2020 13;8:175. Epub 2020 May 13.

Department of Occupational Health, Key Laboratory of Medical Protection for Electromagnetic Radiation, Ministry of Education, Third Military Medical University, Chongqing, China.

Along with gradually increases in mobile phone (MP) use, the mass media has played a vital role in informing the public regarding the potential health hazards of MP use. These media warnings have prompted public worries about health. The aim of the present study is to investigate the effects of media warnings about the possible health hazards of MP use on self-reported symptoms. Participants were 703 undergraduate students who volunteered to take part in an experimental study between August 2013 and July 2015. After completing baseline questionnaires containing information on demographics, MP usage and possible confounding variables, the participants were randomly clustered assigned to a video treatment group (watching a 5-min video about the possible health hazards of MP use) or a control group. Then, they completed another set of questionnaires containing 6 self-reported physical symptoms and the Beck Depression Inventory (BDI). Chi-squared tests, Mann-Whitney -tests and logistic regression models were applied in the data analysis. Participants in the video group reported significantly more frequent headache ( = 0.01), fatigue ( = 0.00), memory loss ( = 0.03), inattention ( = 0.00), and higher level of depression ( = 0.05) than those in the control group. Additionally, the prevalence of memory loss (β = 0.071, = 0.03) and inattention (β = 0.110, = 0.00) were significantly higher in participants with higher level of depression who watched the video. Media warnings about the possible health hazards of MP use promote people to report physical symptoms and psychological problems. Considering this tendency, more moderate and scientific media information is needed to alleviate public worries about MP use.
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http://dx.doi.org/10.3389/fpubh.2020.00175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237582PMC
May 2021

KIF5A-dependent axonal transport deficiency disrupts autophagic flux in trimethyltin chloride-induced neurotoxicity.

Autophagy 2021 04 30;17(4):903-924. Epub 2020 Mar 30.

Department of Environmental Medicine, and Department of Emergency Medicine of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Trimethyltin chloride (TMT) is widely used as a constituent of fungicides and plastic stabilizers in the industrial and agricultural fields, and is generally acknowledged to have potent neurotoxicity, especially in the hippocampus; however, the mechanism of induction of neurotoxicity by TMT remains elusive. Herein, we exposed Neuro-2a cells to different concentrations of TMT (2, 4, and 8 μM) for 24 h. Proteomic analysis, coupled with bioinformatics analysis, revealed the important role of macroautophagy/autophagy-lysosome machinery in TMT-induced neurotoxicity. Further analysis indicated significant impairment of autophagic flux by TMT via suppressed lysosomal function, such as by inhibiting lysosomal proteolysis and changing the lysosomal pH, thereby contributing to defects in autophagic clearance and subsequently leading to nerve cell death. Mechanistically, molecular interaction networks of Ingenuity Pathway Analysis identified a downregulated molecule, KIF5A (kinesin family member 5A), as a key target in TMT-impaired autophagic flux. TMT decreased KIF5A protein expression, disrupted the interaction between KIF5A and lysosome, and impaired lysosomal axonal transport. Moreover, overexpression restored axonal transport, increased lysosomal dysfunction, and antagonized TMT-induced neurotoxicity . Importantly, in TMT-administered mice with seizure symptoms and histomorphological injury in the hippocampus, TMT inhibited KIF5A expression in the hippocampus. Gene transfer of enhanced autophagic clearance in the hippocampus and alleviated TMT-induced neurotoxicity . Our results are the first to demonstrate KIF5A-dependent axonal transport deficiency to cause autophagic flux impairment via disturbance of lysosomal function in TMT-induced neurotoxicity; manipulation of KIF5A may be a therapeutic approach for antagonizing TMT-induced neurotoxicity.: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin beta; AGC: automatic gain control; ATG: autophagy-related; ATP6V0D1: ATPase H transporting lysosomal V0 subunit D1; ATP6V1E1: ATPase H transporting lysosomal V1 subunit E1; CA: cornu ammonis; CQ: chloroquine; CTSB: cathepsin B; CTSD: cathepsin D; DCTN1: dynactin subunit 1; DG: dentate gyrus; DYNLL1: dynein light chain LC8-type 1; FBS: fetal bovine serum; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; IPA: Ingenuity Pathway Analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIF5A: kinesin family member 5A; LAMP: lysosomal-associated membrane protein; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PBS: phosphate-buffered saline; PFA: paraformaldehyde; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PRM: parallel reaction monitoring; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; SYP: synaptophysin; TAX1BP1: Tax1 binding protein 1; TMT: trimethyltin chloride; TUB: tubulin.
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http://dx.doi.org/10.1080/15548627.2020.1739444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078766PMC
April 2021

Building an anti-interfering DNAzyme-powered micromachine resistant to being inhibited by biological matrices.

Chem Commun (Camb) 2020 Feb;56(17):2658-2661

Biliary Surgical Department of West China Hospital, Sichuan University, Chengdu, Sichuan 610064, China.

A DNAzyme-powered micromachine with anti-interfering properties and displaying resistance to being inhibited by biological matrices was built. This micromachine was able to respond to a specific target in high-concentration serum or whole blood.
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http://dx.doi.org/10.1039/c9cc08515gDOI Listing
February 2020

[Effects of drought on leaf growth and chlorophyll fluorescence kinetics parameters in Cyclobalanopsis glauca seedlings of Karst areas].

Ying Yong Sheng Tai Xue Bao 2019 Dec;30(12):4071-4081

Key Laboratory Breeding Base for the Protection and Utilization of Rare Economic Species in Southeastern Guangxi, Yulin Normal University, Yulin 537000, Guangxi, China.

To uncover adaptation mechanism of Cyclobalanopsis glauca to the arid environment of Karst areas, current-year seedlings of C. glauca were potted and grown under four soil water conditions: Normal water supply (-0.1 MPa), light drought stress (-0.5 MPa), moderate drought stress (-0.9 MPa), and severe drought stress (-1.5 MPa). We measured leaf growth and parameters of fast chlorophyll fluorescence induction dynamics after treated by 15, 30, 45, 60 and 90 days. With the increase of drought stress intensity, leaf area, number of green leaves, leaf water content, the contents of chlorophyll a+b and carotenoids, the maximum fluorescence, maximum photochemical quantum yield and potential photochemical efficiency significantly decreased, while the number of dead leaves and the initial fluorescence significantly increased. There was no significant difference in these parameters between light drought and normal water treatments. There were no significant difference in the absorption flux per reaction center (ABS/RC), captured light energy used to restore q (TR/RC), number of active reaction centers per unit area (RC/CS), light energy captured per unit area (TR/CS) and light energy used for electron transfer per unit area (ET/CS) between light drought and normal water treatments. Among these parameters, RC/CS was slightly higher under light drought treatment than that of normal water treatment. TR/CS and ET/CS reached peaks at the 45th day, being 606.12 and 440.78, respectively. Leaf ABS/RC, TR/RC, ET/RC, DIR/RC, RC/CS, TR/CS and ET/CS of C. glauca seedlings under mode-rate drought and severe drought treatment were lower than those of normal water treatment, and the parameters under severe drought stress decreased more significantly with the extension of drought stress time. With increasing intensity and duration of drought stress, the maximum quantum efficiency, probability of other electron acceptors, and quantum ratio of electron transfer decreased, but quantum yield for energy dissipation increased. These results demonstrated that C. glauca seedlings under light drought condition showed some degree of adaptability and resistance to drought. Mode-rate drought treatment caused a decline in chlorophyll fluorescence and photosynthetic pigments, leading to slow growth of seedlings. Severe drought had a serious impact on growth of C. glauca seedlings, but did not lead to seedling death. Therefore, C. glauca seedlings showed strong drought tolerance, which were suitable for the application of vegetation restoration and reforestation projects in Karst areas.
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http://dx.doi.org/10.13287/j.1001-9332.201912.001DOI Listing
December 2019

8-Formylophiopogonanone Antagonizes Paraquat-Induced Hepatotoxicity by Suppressing Oxidative Stress.

Front Pharmacol 2019 24;10:1283. Epub 2019 Oct 24.

Department of Cell Biology, School of Life Sciences and School of Medicine, Guangxi University, Nanning, China.

Flavonoids are some of the most important natural products with a variety of physiological activities. 8-Formylophiopogonanone B (8-FOB) is a naturally existing homoisoflavonoid in Ophiopogon japonicus. Paraquat (PQ) has been widely used as a potent herbicide and has high toxicity in humans. The goal of the present study was to investigate whether 8-FOB could protect against PQ-induced hepatotoxicity in vitro and in vivo. We first tested the protective effects of 8-FOB on PQ-induced cytotoxicity in L02 cells by determining cell viability, intracellular oxidative stress levels, mitochondrial function, and apoptosis in vitro. To verify the protective effects of 8-FOB, we pretreated mice with 8-FOB and assessed liver function, hepatic oxidative stress, and histopathological changes after PQ administration. Our results revealed that 8-FOB could antagonize PQ-induced hepatotoxicity in vitro and in vivo. The antagonistic effects could be attributed to suppressing oxidative stress, preserving mitochondrial function, and inhibiting apoptosis. The present study is the first to document that 8-FOB, a homoisoflavonoid compound, is an effective antioxidant for antagonizing PQ-induced hepatotoxicity.
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http://dx.doi.org/10.3389/fphar.2019.01283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821879PMC
October 2019

Transcriptomic insight into cadmium-induced neurotoxicity in embryonic neural stem/progenitor cells.

Toxicol In Vitro 2020 Feb 12;62:104686. Epub 2019 Oct 12.

Department of Environmental Medicine, School of Public Health, and Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, China. Electronic address:

Cadmium exposure has raised great public concern. Extensive studies have revealed the neurotoxic effects of cadmium exposure during brain development. However, more evidence is still needed to reach a consistent conclusion and uncover the underlying mechanisms. Here, we used primary mouse embryonic neural stem/progenitor cells (NSPCs) as a cell model and exposed the cells to 0, 1, 2 or 4 μM cadmium. High-throughput mRNA-seq technology was used to explore the global transcriptome changes in NSPCs after exposure to 2 μM cadmium. We found that cadmium exposure remarkably influenced the expression of genes involved in cell growth, proliferation, cell cycle and survival. Pathway-Act-Network analysis revealed that these altered genes were targeted to the P53, PI3K-AKT, MAPK, calcium, and NF-kappa B signaling pathways. In vitro experiments using cultured NSPCs verified that cadmium exposure reduced cell viability, proliferation, neurosphere formation and caused cell cycle arrest at low concentrations (≤ 2 μM), while induced cell apoptosis at high concentrations (≥ 4 μM). Real-time PCR results confirmed the concentration-dependent effects of cadmium exposure on the expression of critical genes in the above signaling pathways. Together, our results provide transcriptomic insight into cadmium-induced developmental neurotoxic effects and the underlying mechanisms.
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http://dx.doi.org/10.1016/j.tiv.2019.104686DOI Listing
February 2020
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