Publications by authors named "Ying Qu"

219 Publications

S-Allylmercapto-N-acetylcysteine ameliorates elastase-induced chronic obstructive pulmonary disease in mice via regulating autophagy.

Biochem Biophys Res Commun 2021 Jul 25;562:83-88. Epub 2021 May 25.

Department of Pharmaceutics, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Cheelloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, PR China; Key University Laboratory of Pharmaceutics & Drug Delivery Systems of Shandong Province, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, PR China; Pediatric Pharmaceutical Engineering Laboratory of Shandong Province, Shandong Dyne Marine Biopharmaceutical Company Limited, Rongcheng, Shandong, 264300, PR China; Chemical Immunopharmaceutical Engineering Laboratory of Shandong Province, Shandong Xili Pharmaceutical Company Limited, Heze, Shandong, 274300, PR China. Electronic address:

Autophagy-impairment is involved in the pathological process of chronic obstructive pulmonary disease (COPD), and relates to inflammation and emphysema in lung injury. This study aimed to elucidate the protective effect of S-Allylmercapto-N-acetylcysteine (ASSNAC) against COPD via regulating the autophagy. Firstly, porcine pancreatic elastase (PPE)-induced COPD model in A549 cells was established, and ASSNAC was verified to alleviate the autophagy-impairment from the results of western blotting analysis of LC3BⅡ/Ⅰ and monodansylcadaverine (MDC) staining of autophagosome. Secondly, Balb/c mice were stimulated by PPE to induce the COPD model in vivo. The histological analysis of lung tissues presented that ASSNAC could alleviate the lung injury induced by PPE. Thirdly, the secretions of NO, TNF-α and IL-1β in serum and BALF were reduced by ASSNAC compared with the PPE group. Finally, the mechanism of therapeutic effects of ASSNAC against COPD through regulating the autophagy-impairment was clarified. That is, ASSNAC inhibits the phosphorylation of PI3K/Akt/mTOR signaling pathways. In a word, this research provides a reference for ASSNAC to be an effective drug for pulmonary diseases.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.047DOI Listing
July 2021

BMI1 regulates multiple myeloma-associated macrophage's pro-myeloma functions.

Cell Death Dis 2021 May 15;12(5):495. Epub 2021 May 15.

Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.

Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MΦs (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MΦs (MM-associated macrophages) have pro-myeloma functions, and BM MM-MΦs numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MΦs, which expressed higher BMI1 levels relative to normal MΦs. In the MM tumor microenvironment, hedgehog signaling in MΦs was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MΦs, BMI1-KO (BMI1 knockout) MM-MΦs from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MΦs lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MΦs, BMI1-KO MM-MΦs lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MΦs.
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http://dx.doi.org/10.1038/s41419-021-03748-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124065PMC
May 2021

Prevalence of Infection in Military Personnel from Northeast China: A Cross-Sectional Study.

Int J Gen Med 2021 21;14:1499-1505. Epub 2021 Apr 21.

Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, People's Republic of China.

Purpose: infection is an important cause of peptic ulcer disease and gastric cancer. Current knowledge regarding epidemiology of infection in military personnel has insufficiently been updated. This cross-sectional study aimed to estimate the prevalence of infection in military personnel and to compare the prevalences in military and civilian groups.

Patients And Methods: We retrospectively enrolled the subjects who underwent C-urea breath tests at the Department of Gastroenterology of the General Hospital of Northern Theater Command between January 2017 and July 2020. Subjects were divided into military and civilian groups. infection and major endoscopic findings were reviewed.

Results: Overall, 23,496 subjects were eligible, including 2282 subjects in the military group and 21,214 subjects in the civilian group. In the overall analysis, the prevalence of infection was not significantly different between military and civilian groups (33.9% versus 34.4%, =0.592). In the population aged 17-25 years, the prevalence of infection was significantly higher in the military group than in the civilian group (35.6% versus 25.9%, =0.001). Both C-UBT and endoscopy were performed in 547 inpatients, including 83 military inpatients and 464 civilian inpatients. There was a significantly higher prevalence of in inpatients with peptic ulcer and/or gastric cancer than in those without (65.5% versus 41.4%, =0.001).

Conclusion: Among the adolescent population, infection may be more common in military personnel as compared to the civilians. Well-designed prospective studies should be required to validate such a high prevalence and to explain its potential causes.
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http://dx.doi.org/10.2147/IJGM.S308572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071091PMC
April 2021

miR-30c inhibits angiogenesis by targeting delta-like ligand 4 in liver sinusoidal endothelial cell to attenuate liver fibrosis.

FASEB J 2021 May;35(5):e21571

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Liver fibrosis is a common feature of liver dysfunction during chronic liver diseases and is frequently associated with angiogenesis, a dynamic process that forms new blood vessels from preexisting vasculature. MicroRNAs (miRNAs), which act as posttranscriptional regulators of gene expression, have been shown to regulate liver fibrosis; however, how miRNAs regulate angiogenesis and its mechanism in fibrosis are not well understood. We aimed to elucidate the role and mechanism of miR-30c in attenuating liver fibrosis. Using miRNA profiling of fibrotic murine livers, we identified differentially regulated miRNAs and discovered that miR-30c is aberrantly expressed and targets endothelial delta-like ligand 4 (DLL4) in either carbon tetrachloride-treated or bile duct ligated fibrotic mice, as well as in patients with liver fibrosis. Using CCK-8, wound healing and Matrigel tube formation assays, we found that miR-30c inhibited liver sinusoidal endothelial cell (LSEC) proliferation, migration, and angiogenesis capacity by targeting DLL4 in vitro. Importantly, nanoparticle-based delivery of miR-30c to LSECs inhibited the DLL4/Notch pathway and angiogenesis, thereby ameliorating liver fibrosis in vivo. Collectively, our findings demonstrate a protective role of miR-30c in liver fibrosis by regulating DLL4/Notch signaling and angiogenesis. Thus, miR-30c may serve as a potential treatment for chronic liver diseases.
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http://dx.doi.org/10.1096/fj.202002694RDOI Listing
May 2021

Diagnostic Performance of FibroTouch Ultrasound Attenuation Parameter and Liver Stiffness Measurement in Assessing Hepatic Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

Clin Transl Gastroenterol 2021 Apr 13;12(4):e00323. Epub 2021 Apr 13.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Introduction: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers.

Results: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index.

Discussion: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.
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http://dx.doi.org/10.14309/ctg.0000000000000323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049161PMC
April 2021

Homoharringtonine synergizes with quizartinib in FLT3-ITD acute myeloid leukemia by targeting FLT3-AKT-c-Myc pathway.

Biochem Pharmacol 2021 Jun 6;188:114538. Epub 2021 Apr 6.

Hematology Research Laboratory, Department of Hematology, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3-ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3-ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3-ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3-ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3-ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3β, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3-ITD AML.
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http://dx.doi.org/10.1016/j.bcp.2021.114538DOI Listing
June 2021

The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B.

Mediators Inflamm 2021 1;2021:6636947. Epub 2021 Mar 1.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Methods: Differential expression of five selected miRNAs (hsa-mir-1225-3p, hsa-mir-1238, hsa-miR-3162-3P, hsa-miR-4721, and hsa-miR-H7) was verified by qRT-PCR in the plasma of 83 patients and 20 healthy controls. The relative expression of these miRNAs was analyzed in different groups to screen target miRNA. A logistic regression analysis was performed to assess factors associated with fibrosis progression. The receiver operating characteristic (ROC) curve and discriminant analyses validated the ability of these predicted variables to discriminate the nonsignificant liver fibrosis group from the significant liver fibrosis group. Furthermore, the established models were compared with other prediction models to evaluate the diagnostic efficiency.

Results: These five tested miRNAs all had signature correlations with hepatic fibrotic level ( < 0.05), and the upregulation trends were consistent with miRNA microarray analysis previously. The multivariate logistic regression analysis identified that a model of five miRNAs (miR-5) had a high diagnostic accuracy in discrimination of different stages of liver fibrosis. The ROC showed that the miR-5 has excellent value in diagnosis of fibrosis, even better than the Forns score, FIB-4, S index, and APRI. GO functions of different miRNAs mainly involved in various biological processes were markedly involved in HBV and revealed signaling pathways dysregulated in liver fibrosis of CHB patients.

Conclusions: It was validated that the combination of these five miRNAs was a new set of promising molecular diagnostic markers for liver fibrosis. The diagnosis model (miR-5) can distinguish significant and nonsignificant liver fibrosis with high sensitivity and specificity.
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http://dx.doi.org/10.1155/2021/6636947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939739PMC
March 2021

Injectable Soft Tissue Nano/Micro Fillers for Facial Reconstruction.

J Biomed Nanotechnol 2021 Jan;17(1):1-17

Soft Tissue augmentation is a way to restore lost tissue and also a way to reshape confidence for patients who suffer from soft tissue loss. Materials that can realize such a function are called soft tissue fillers. Among the large number of fillers, injectable fillers have attracted widespread attention in facial cosmetic fields due to their convenience and competitive performance. Meanwhile, there is a huge demand for better injectable soft tissue fillers in medical cosmetology market. This review introduces several fillers which were once used in clinical or are now still in use. Furthermore, we update recent improvements and progress on injectable filling materials hoping to contribute to its further developments.
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http://dx.doi.org/10.1166/jbn.2021.3011DOI Listing
January 2021

Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden.

Acta Haematol 2021 Feb 25:1-9. Epub 2021 Feb 25.

Department of Hematology, Lund University, Lund, Sweden.

Introduction: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment.

Objective: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM.

Methods: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive.

Results: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007).

Conclusions: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.
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http://dx.doi.org/10.1159/000512165DOI Listing
February 2021

Acupuncture at Back-Shu and Front-Mu Acupoints Prevents Gastric Ulcer by Regulating the TLR4/MyD88/NF-B Signaling Pathway.

Evid Based Complement Alternat Med 2021 9;2021:8214052. Epub 2021 Feb 9.

Bao'an Authentic TCM Therapy Hospital, Shenzhen 518101, Guangdong, China.

Purpose: To assess the preventive effects of acupuncture at back-shu and front-mu acupoints on rats with restraint water-immersion stress (RWIS)-induced gastric ulcer.

Methods: Thirty-six rats were randomly divided into four groups for 10 days of treatment as follows: the normal group received no treatment; the model group received RWIS-induced gastric ulcer; the omeprazole group was administered omeprazole orally every 2 days; and the electroacupuncture group received electroacupuncture at the RN12 and BL21 acupoints every 2 days. After 10 days of treatment, except for the normal group, all rats were induced with gastric ulcer by RWIS for 3 h. The ulcer index (UI), ulcer inhibition rate, and histopathological score were calculated. We determined the levels of tumor necrosis factor (TNF)- and interleukin (IL)-6 in serum, and the activities of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and glutathione peroxidase (GSH-Px) in serum and gastric tissues. Protein expression of MyD88, nuclear factor (NF)-B (p65), and toll-like receptor (TLR) 4 was quantified in gastric tissues.

Results: The electroacupuncture and omeprazole groups were equivalent in terms of UI, ulcer inhibition rate, and histopathological score. The serum levels of TNF- and IL-6 were significantly lower in the electroacupuncture group compared with the omeprazole group ( < 0.05). Compared with the model group, there were significant changes in the levels of NO, MPO, GSH-Px, and MDA in all other groups, while the expression of TLR4, MyD88, and NF-B p65 in gastric tissue decreased significantly in the electroacupuncture group. The expression of TLR4 was substantially lower in the electroacupuncture group compared with the omeprazole group.

Conclusion: Acupuncture at back-shu and front-mu acupoints played a role in preventing gastric ulcer by inhibiting extracellular signals, stimulating kinases in serum and gastric tissues, and activating the inhibition of the TLR4 signaling pathway.
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http://dx.doi.org/10.1155/2021/8214052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886517PMC
February 2021

Improved model simulation of soil carbon cycling by representing the microbially derived organic carbon pool.

ISME J 2021 Feb 22. Epub 2021 Feb 22.

Key Laboratory of Geographical Processes and Ecological Security of Changbai Mountains, Ministry of Education, School of Geographical Sciences, Northeast Normal University, Changchun, China.

During the decomposition process of soil organic carbon (SOC), microbial products such as microbial necromass and microbial metabolites may form an important stable carbon (C) pool, called microbially derived C, which has different decomposition patterns from plant-derived C. However, current Earth System Models do not simulate this microbially derived C pool separately. Here, we incorporated the microbial necromass pool to the first-order kinetic model and the Michaelis-Menten model, respectively, and validated model behaviors against previous observation data from the decomposition experiments of C-labeled necromass. Our models showed better performance than existing models and the Michaelis-Menten model was better than the first-order kinetic model. Microbial necromass C was estimated to be 10-27% of total SOC in the study soils by our models and therefore should not be ignored. This study provides a novel modification to process-based models for better simulation of soil organic C under the context of global changes.
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http://dx.doi.org/10.1038/s41396-021-00914-0DOI Listing
February 2021

Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury.

Exp Mol Med 2021 Feb 10;53(2):168-188. Epub 2021 Feb 10.

Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD, 20892, USA.

Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE-alcohol-adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.
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http://dx.doi.org/10.1038/s12276-021-00561-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080618PMC
February 2021

Nose-to-brain delivery of disulfiram nanoemulsion in situ gel formulation for glioblastoma targeting therapy.

Int J Pharm 2021 Mar 22;597:120250. Epub 2021 Jan 22.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). In this work, we designed a DSF loaded ion-sensitive nanoemulsion in situ gel (DSF-INEG) that was delivered intranasally along with Cu to the rat brains for the GBM treatment. The developed DSF-INEG nanomedicine showed a suitable particle size of 63.4 ± 1.1 nm and zeta potential of -23.5 ± 0.2 mV with a favorable gelling ability and prolonged DSF release. The results in vitro indicate DSF-INEG/Cu effectively inhibited the proliferation of both C6 and U87 cells. Besides, the excellent brain-targeting efficacy via nose-to-brain delivery was proved by the highest fluorescence signal of Cy5.5-INEG in the rat brains. Moreover, GFP imaging showed enhanced tumor growth inhibition of the rats by the DSF-INEG/Cu treatment, and their median survival time was 1.6 and 1.2 folds than those of the rats in the control and DSF/Cu treated groups, respectively, with no obvious histopathological damage to normal tissues. Overall, DSF-INEG/Cu could be a promising intranasal nanomedicine for effective GBM treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120250DOI Listing
March 2021

Gene expression comparison between primary estrogen receptor-positive and triple-negative breast cancer with paired axillary lymph node metastasis.

Breast J 2021 May 19;27(5):432-440. Epub 2021 Jan 19.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.
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http://dx.doi.org/10.1111/tbj.14119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137535PMC
May 2021

Advances in the Application of Injectable Thermosensitive Hydrogel Systems for Cancer Therapy.

J Biomed Nanotechnol 2020 Oct;16(10):1427-1453

Systemic administration of anticancer therapeutic agents remains a crucial strategy for clinical cancer therapy. However, poor drug accumulation at tumor sites and severe side effects to normal tissues induced by off-target effects lower their therapeutic efficiency and limit their deep application in clinical settings. How to overcome these issues has continuously raised concerns. Reportedly, injectable thermosensitive hydrogels are good carriers for local drug delivery systems, demonstrating a flowable and injectable sol state at room temperature, easily loading therapeutic agents with large loading contents. Under normal body temperature, these hydrogels are stimulated to undergo a phase transition to an immobile gel state, which serves as a drug reservoir at local injection sites. After intratumoral or peritumoral injection, the localized hydrogel reservoir shows a slow and sustained drug release behavior, and can also targeted deliver therapeutic agents to cancer cells instead of normal cells, improving the therapeutic efficiency and reducing systemic side effects. This review summarizes the development of injectable thermosensitive hydrogel systems, reviews the research application advances of these systems in different therapy strategies for cancer, discusses the present issues and awaits their future in clinical applications.
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http://dx.doi.org/10.1166/jbn.2020.2988DOI Listing
October 2020

Prior-Based Tensor Approximation for Anomaly Detection in Hyperspectral Imagery.

IEEE Trans Neural Netw Learn Syst 2020 Dec 9;PP. Epub 2020 Dec 9.

The key to hyperspectral anomaly detection is to effectively distinguish anomalies from the background, especially in the case that background is complex and anomalies are weak. Hyperspectral imagery (HSI) as an image-spectrum merging cube data can be intrinsically represented as a third-order tensor that integrates spectral information and spatial information. In this article, a prior-based tensor approximation (PTA) is proposed for hyperspectral anomaly detection, in which HSI is decomposed into a background tensor and an anomaly tensor. In the background tensor, a low-rank prior is incorporated into spectral dimension by truncated nuclear norm regularization, and a piecewise-smooth prior on spatial dimension can be embedded by a linear total variation-norm regularization. For anomaly tensor, it is unfolded along spectral dimension coupled with spatial group sparse prior that can be represented by the l2,1-norm regularization. In the designed method, all the priors are integrated into a unified convex framework, and the anomalies can be finally determined by the anomaly tensor. Experimental results validated on several real hyperspectral data sets demonstrate that the proposed algorithm outperforms some state-of-the-art anomaly detection methods.
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http://dx.doi.org/10.1109/TNNLS.2020.3038659DOI Listing
December 2020

The fragility of a structurally diverse duplication block triggers recurrent genomic amplification.

Nucleic Acids Res 2021 01;49(1):244-256

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12-21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors. KRTAP-1 carries numerous tandemly-duplicated segments that exhibit diversity within the human population. We evaluated the fragility of the block by cytogenetically measuring the distances between the flanking regions and found that spontaneous distance outliers (i.e DNA breaks) appear more frequently at KRTAP-1 than at the representative common fragile site (CFS) FRA16D. Unlike CFSs, KRTAP-1 is not sensitive to aphidicolin. The exonuclease activity of DNA repair protein Mre11 protects KRTAP-1 from breaks, whereas CtIP does not. Breaks at KRTAP-1 lead to the palindromic duplication of the ERBB2 locus and trigger Breakage-Fusion-Bridge cycles. Our results indicate that an insufficiently investigated area of the human genome is fragile and could play a crucial role in cancer genome evolution.
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http://dx.doi.org/10.1093/nar/gkaa1136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797068PMC
January 2021

Novel Gene Signature Reveals Prognostic Model in Acute Myeloid Leukemia.

Front Genet 2020 28;11:566024. Epub 2020 Oct 28.

Department of Hematology, The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, China.

Background: Acute myeloid leukemia (AML) is a clonal malignant disease with poor prognosis and a low overall survival rate. Although many studies on the treatment and detection of AML have been conducted, the molecular mechanism of AML development and progression has not been fully elucidated. The present study was designed to pursuit the molecular mechanism of AML using a comprehensive bioinformatics analysis, and build an applicable model to predict the survival probability of AML patients in clinical use.

Methods: To simplify the complicated regulatory networks, we performed the gene co-expression and PPI network based on WGCNA and STRING database using modularization design. Two machine learning methods, A least absolute shrinkage and selector operation (LASSO) algorithm and support vector machine-recursive feature elimination (SVM-RFE), were used to filter the common hub genes by five-fold cross-validation. The candidate hub genes were used to build the predictive model of AML by the cox-proportional hazards analysis, and validated in The Cancer Genome Atlas (TCGA) cohort and ohsu cohort, which were reliable in the experimental verification by qRT-PCR and western blotting in mRNA and protein levels.

Results: Three hub genes, FLT3, CD177 and TTPAL were used to build a clinically applicable model to predict the survival probability of AML patients and divided them into high and low groups. To compare the survival ability of the model with the classical clinical features, we generated the nomogram. The model displayed the most risk points contrast to other clinical characteristics, which was compatible with the data of cox multivariate regression.

Conclusion: This study reveal the novel molecular mechanism of AML, and construct a clinical model significantly related to AML patient prognosis. We showed the integrated roles of critical pathways, hub genes associated, which provide potential targets and new research ideas for the treatment and early detection of AML.
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http://dx.doi.org/10.3389/fgene.2020.566024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655922PMC
October 2020

Therapeutic effect of disulfiram inclusion complex embedded in hydroxypropyl-β-cyclodextrin on intracranial glioma-bearing male rats via intranasal route.

Eur J Pharm Sci 2021 Jan 13;156:105590. Epub 2020 Oct 13.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 West Wenhua Road, Jinan, Shandong, 250012, China.

The unique environment of brain poses a huge challenge for drug development aimed at combatting glioblastoma (GBM) due to poor organ targeting. Intranasal administration is often considered as an attractive route directly into brain by not only circumventing the blood brain barrier and but also avoiding the hepatic first-pass effect. Disulfiram (DSF) is an old alcohol-aversion drug that has anti-tumor activities against diverse cancer types such as GBM in preclinical studies, especially when it is combined with cupper ion (Cu). In this study, DSF was embedded in hydroxypropyl-β-cyclodextrin (HP-β-CD) to prepare a DSF inclusion complex with the enhanced solubility, anti-GBM activity and high safety in vitro. The highest fluorescence signal of Cy5.5/HP-β-CD in the male rat brains showed the strong brain-targeting of nose-to-brain drug delivery. Therapeutic effects of DSF/HP-β-CD combined with Cu (DSF/HP-β-CD/Cu) on intracranial glioma-bearing male rats via different drug delivery routes were then investigated. DSF/HP-β-CD/Cu administrated by the intranasal route effectively inhibited tumor growth and migration, promoted apoptosis, and achieved 36.8% and 18.2% prolonged median survival time comparing to those of model rats by oral and intravenous administrations, respectively. Moreover, no obvious histopathological damage to normal tissues was observed by H&E staining. Overall, DSF/HP-β-CD/Cu could be a promising intranasal formulation for the effective GBM treatment.
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http://dx.doi.org/10.1016/j.ejps.2020.105590DOI Listing
January 2021

Effects of Exogenous Putrescine on Delaying Senescence of Cut Foliage of .

Front Plant Sci 2020 10;11:566824. Epub 2020 Sep 10.

College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, China.

Senescence is the main limitation for cut foliage display in vase. Naturally occurring polyamines such as putrescine (Put) have been considered effective anti-senescence agents. However, effect of Put on cut foliage in vase in a realistic indoor environment has not yet been revealed. In the present study, effects of Put spraying on the postharvest performance of cut foliage of L. were investigated. Cut fronds sprayed with deionized water (Put0) showed visible injuries after 10 days in vase. Meanwhile, chlorophyll (Chl), soluble protein (Sp), and proline (Pro) content were decreased by 60.15, 57.93, and 73.09% respectively, photochemical activity reflected by Chl fluorescence parameters was inhibited, whereas electrolyte leakage (EL), contents of soluble sugar (Ss), malondialdehyde (MDA), and hydrogen peroxide (HO) were increased (+194.29, +44.83, +34.06, and +178.01%, respectively). Put spraying extended the vase life of the cut foliage and the 2.0 mM Put had a longer vase life (21 days) than 0.2 mM (15 days). Leaf spraying of 2.0 mM Put for 10 days significantly ameliorated the losses of Chl, Sp, and Pro content (-10.72, -26.29, and -42.64%, respectively), followed by 0.2 mM Put (-27.36, -36.24, and -60.55%, respectively). Put spraying also improved photochemical capability and prevented membrane impairment as well as visible injury in comparison with Put0. In addition, 2.0 mM Put had a better mitigating ability than that of 0.2 mM. Leaf spraying of 2.0 mM Put greatly reduced the decline of the effective quantum yield of photochemical energy conversion in PSII (ΦPSII), the maximal quantum yield of PSII photochemistry measured in the dark-adapted state (Fv/Fm) and electron transport rate (ETR) (-7.89, -12.91, and -10.06%, respectively), and also inhibited the increases of EL, MDA, Ss, and HO (+31.87, +6.43, +16.22, and +49.40%, respectively). Overall, Put played important roles in deterring the degradation of Chl, Ss, and Pro, detoxifying the HO, weakening the sugar signaling, mitigating the decline of photochemical activity, and eventually postponing the leaf senescence. The present study gives new insights into effects of Put on leaf senescence and provides a strategy for preserving post-harvest cut foliage.
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http://dx.doi.org/10.3389/fpls.2020.566824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511530PMC
September 2020

A Retrospective Study from 2 Centers in China on the Effects of Continued Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients with Hypertension and COVID-19.

Med Sci Monit 2020 Sep 24;26:e926651. Epub 2020 Sep 24.

Department of Congenital Heart Disease, General Hospital of Northern Theater Command, Shenyang, China (mainland).

BACKGROUND Use of renin-angiotensin-aldosterone system inhibitors in coronavirus disease 2019 (COVID-19) patients lacks evidence and is still controversial. This study was designed to investigate effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on clinical outcomes of COVID-19 patients and to assess the safety of ACEIs/ARBs medication. MATERIAL AND METHODS COVID-19 patients with hypertension from 2 hospitals in Wuhan, China, from 17 Feb to 18 Mar 2020 were retrospectively screened and grouped according to in-hospital medication. We performed 1: 1 propensity score matching (PSM) analysis to adjust for confounding factors. RESULTS We included 210 patients and allocated them to ACEIs/ARBs (n=81; 46.91% males) or non-ACEIs/ARBs (n=129; 48.06% males) groups. The median age was 68 [interquartile range (IQR) 61.5-76] and 66 (IQR 59-72.5) years, respectively. General comparison showed mortality in the ACEIs/ARBs group was higher (8.64% vs. 3.88%) but the difference was not significant (P=0.148). ACEIs/ARBs was associated with significantly more cases 7-categorical ordinal scale >2 at discharge, more cases requiring Intensive Care Unit (ICU) stay, and increased values and ratio of days that blood pressure (BP) was above normal range (P<0.05). PSM analysis showed no significant difference in mortality, cumulative survival rate, or other clinical outcomes such as length of in-hospital/ICU stay, BP fluctuations, or ratio of adverse events between groups after adjustment for confounding parameters on admission. CONCLUSIONS We found no association between ACEIs/ARBs and clinical outcomes or adverse events, thus indicating no evidence for discontinuing use of ACEIs/ARBs in the COVID-19 pandemic.
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http://dx.doi.org/10.12659/MSM.926651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523417PMC
September 2020

Effect of Qinbai Qingfei Concentrated Pellets on substance P and neutral endopeptidase of rats with post-infectious cough.

BMC Complement Med Ther 2020 Sep 22;20(1):289. Epub 2020 Sep 22.

Department of Emergency, Nangang Branch of Heilongjiang Academy of Traditional Chinese Medicine, Harbin, 150001, China.

Background: In recent years, it has been reported that Qinbai Qingfei Concentrated Pellet (QQCP) has the effect of relieving cough and reducing sputum. However, the therapeutic potentials of QQCP on post-infectious cough (PIC) rat models has not been elucidated. So the current study was aimed to scientifically validate the efficacy of QQCP in post infectious cough.

Methods: All rats were exposed to sawdust and cigarette smokes for 10 days, and intratracheal lipopolysaccharide (LPS) and capsaicin aerosols. Rats were treated with QQCP at dose of 80, 160, 320 mg/kg. Cough frequency was monitored twice a day for 10 days after drug administration. Inflammatory cell infiltration was determined by ELISA. Meanwhile, the histopathology of lung tissue and bronchus in rats were evaluated by hematoxylin-eosin staining (H&E). Neurogenetic inflammation were measured by ELISA and qRT-PCR.

Results: QQCP dose-dependently decreased the cough frequency and the release of pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, but exerted the opposite effects on the secretion of anti-inflammatory cytokines IL-10 and IL-13 in BALF and serum of PIC rats. The oxidative burden was effectively ameliorated in QQCP-treated PIC rats as there were declines in Malondialdehyde (MDA) content and increases in Superoxide dismutase (SOD) activity in the serum and lung tissue. In addition, QQCP blocked inflammatory cell infiltration into the lung as evidenced by the reduced number of total leukocytes and the portion of neutrophils in the broncho - alveolar lavage fluid (BALF) as well as the alleviated lung damage. Furthermore, QQCP considerable reversed the neurogenetic inflammation caused by PIC through elevating neutral endopeptidase (NEP) activity and reducing Substance P (SP) and Calcitonin gene related peptide (CGRP) expression in BALF, serum and lung tissue.

Conclusions: Our study indicated that QQCP demonstrated a protective role of PIC and may be a potential therapeutic target of PIC.
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http://dx.doi.org/10.1186/s12906-020-03081-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507634PMC
September 2020

Corrigendum to "Mild photothermal therapy/photodynamic therapy/chemotherapy of breast cancer by Lyp-1 modified docetaxel/IR820 co-loaded micelles"[Biomaterials, 106 (2016) 119-133].

Biomaterials 2021 Feb 18;269:120375. Epub 2020 Sep 18.

State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Sichuan, China. Electronic address:

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http://dx.doi.org/10.1016/j.biomaterials.2020.120375DOI Listing
February 2021

[Effect of Schizonepetae Herba and Saposhnikoviae Radix on expression of AQP4 and AQP8 in colonic mucosa of rats with ulcerative colitis].

Zhongguo Zhong Yao Za Zhi 2020 Aug;45(15):3719-3725

Department of Anorectal Surgery, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Beijing 100700, China.

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200220.401DOI Listing
August 2020

Design, synthesis and biological evaluation of dual-function inhibitors targeting NMDAR and HDAC for Alzheimer's disease.

Bioorg Chem 2020 10 21;103:104109. Epub 2020 Jul 21.

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China. Electronic address:

Histone deacetylases (HDACs) have been indicated important roles in neurodegenerative disorders including Alzheimer's disease (AD). Herein, a series of novel compounds that contain a memantine moiety were designed to target HDACs and N-methyl-d-aspartate receptor (NMDAR) which are related to the treatment of AD. Biological characterization established that compound 9d exhibited a balanced inhibitory activity on NMDAR and HDACs. This compound is relatively selective to HDAC6 with IC of 0.18 μM and also maintains comparable activity on NMDAR (K = 0.59 μM) as memantine. Functionally, treatment with 9d increased the level of AcTubulin in MV4-11 cells and rescued PC-12 cells from HO-induced cytotoxicity with EC of 0.94 μM. Studies in mice also demonstrated that compound 9d efficiently penetrates the blood brain barrier to reach the brain tissue. Collectively, the results strongly encourage further development of 9d as a potential therapeutic agent for AD.
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http://dx.doi.org/10.1016/j.bioorg.2020.104109DOI Listing
October 2020

[Network pharmacological study of Schizonepetae Herba and Saposhnikoviae Radix in treatment of ulcerative colitis].

Zhongguo Zhong Yao Za Zhi 2019 Dec;44(24):5465-5472

Beijing University of Traditional Chinese Medicine Beijing 100029,China.

The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190929.402DOI Listing
December 2019

Toxic effects of dechlorane plus on the common carp (Cyprinus carpio) embryonic development.

Chemosphere 2020 Jun 17;249:126481. Epub 2020 Mar 17.

College of Life Science, Henan Normal University, Xinxiang, 453007, PR China. Electronic address:

Dechlorane Plus (DP) is a widely used chlorinated flame retardant, which has been extensively detected in the environment. Although DP content in the surface water is low, it can pose a continuous exposure risk to aquatic organisms due to its strong bioaccumulation. Considering that the related studies on the toxicity mechanism of DP exposure are limited, the effect of DP on carp embryo development was evaluated. In the present work, carp embryos were exposed to different concentrations (0, 30, 60, and 120 μg/L) of DP at 3 h post-fertilization (hpf). The expression levels of neural and skeletal development-associated genes, such as sox2, sox19a, Mef2c and BMP4, were detected with quantitative PCR, and the changes in different developmental toxicity endpoints were observed. Our results demonstrated that the expression levels of sox2, sox19a, Mef2c and BMP4 were significantly altered and several developmental abnormalities were found in DP-exposed carp embryos, such as DNA damage, increased mortality rate, delayed hatching time, reduced hatching rate, decreased body length, and increased morphological deformities. In addition, the activities of reactive oxygen species and malondialdehyde were remarkably higher in 60 and 120 μg/L DP exposure groups than in control group. These results suggest that DP can exhibit a unique modes of action, which lead to aberration occurrence in the early development stage of common carps, which may be related to some gene damage and oxidative stress. Besides, the parameters evaluated here can be used as tools to access the environmental risk for biota and humans exposed to DP.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126481DOI Listing
June 2020

Ultrasmall [email protected] nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

Theranostics 2020 1;10(4):1500-1513. Epub 2020 Jan 1.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.

Mesenchymal stem cell (MSC)-based therapies have been used in skin regeneration due to their ability to differentiate into many cells, promote cytokine secretion and participate in collagen deposition. In this study, we concluded that a [email protected] nanoparticles exhibited similar potential in inducing MSCs differentiation to fibroblasts as Cu ions for wound healing. : First, we verified the photothermal efficiency of [email protected] and and had no cytotoxicity for MSCs when the temperature was controlled at 42 °C by adjusting the power of irradiation at 980 nm. And then we detected the expression of vimentin in MSCs, which further directed the MSCs to fibroblasts through Western blotting and Immunofluorescence when treated with [email protected] or pre-heat at 42 °C. In addition, we implanted MSCs into the Matrigel or electrospun PLA nanofiber membrane to evaluating the effect of heating or [email protected] on the morphological change of MSCs by SEM. Finally, we evaluated improving skin regeneration by the combination of preheated-MSCs and [email protected] nanoparticles that were encapsulated in Matrigel. : The [email protected] nanoparticles have good photothermal conversion efficiency. Not only CuS nanoparticles itself or after irradiation at 980 nm stimulated the expressioin of vimentin in MSCs. Besides, the [email protected] can promote cell proliferation as Cu ion through the expression of ERK. The combination of the [email protected] nanoparticles and thermal treatment synergistically improved the closure of an injured wound in an injured wound model. : MSCs combined with [email protected] are a promising wound dressing for the reconstruction of full-thickness skin injuries.
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http://dx.doi.org/10.7150/thno.39471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993219PMC
April 2021

Roles of biochar media and oxygen supply strategies in treatment performance, greenhouse gas emissions, and bacterial community features of subsurface-flow constructed wetlands.

Bioresour Technol 2020 Apr 25;302:122890. Epub 2020 Jan 25.

Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650091, China.

Biochar-based subsurface-flow constructed wetlands (CWs) with intermittent aeration (IA) or tidal flow (TF) oxygen supply strategies were established to treat domestic wastewater. The results showed that biochar achieved higher nutrient removal and lower greenhouse gas (GHG) emissions than ceramsite while supporting more diverse bacterial communities and higher abundances of functional taxa. Both IA and TF effectively enhanced nutrient removal, though the latter was more efficient and practical, and aeration conditions greatly influenced nutrient removal efficiency. GHG emissions were decreased by IA but were slightly increased by TF. Both oxygen supply methods significantly shaped the biofilm microbial communities and influenced biodiversity and richness, with observably higher proportions of potential nitrifiers and denitrifiers present in aerated CWs. Overall, biochar-based CWs operated with oxygen supply strategies provide superior treatment of decentralized wastewater.
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http://dx.doi.org/10.1016/j.biortech.2020.122890DOI Listing
April 2020

Dnmt3a loss and Idh2 neomorphic mutations mutually potentiate malignant hematopoiesis.

Blood 2020 03;135(11):845-856

Department of Molecular and Human Genetics and.

Mutations in the epigenetic regulators DNMT3A and IDH1/2 co-occur in patients with acute myeloid leukemia and lymphoma. In this study, these 2 epigenetic mutations cooperated to induce leukemia. Leukemia-initiating cells from Dnmt3a-/- mice that express an IDH2 neomorphic mutant have a megakaryocyte-erythroid progenitor-like immunophenotype, activate a stem-cell-like gene signature, and repress differentiated progenitor genes. We observed an epigenomic dysregulation with the gain of repressive H3K9 trimethylation and loss of H3K9 acetylation in diseased mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). HDAC inhibitors rapidly reversed the H3K9 methylation/acetylation imbalance in diseased mouse HSPCs while reducing the leukemia burden. In addition, using targeted metabolomic profiling for the first time in mouse leukemia models, we also showed that prostaglandin E2 is overproduced in double-mutant HSPCs, rendering them sensitive to prostaglandin synthesis inhibition. These data revealed that Dnmt3a and Idh2 mutations are synergistic events in leukemogenesis and that HSPCs carrying both mutations are sensitive to induced differentiation by the inhibition of both prostaglandin synthesis and HDAC, which may reveal new therapeutic opportunities for patients carrying IDH1/2 mutations.
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http://dx.doi.org/10.1182/blood.2019003330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068035PMC
March 2020