Publications by authors named "Xiaoqing Zhu"

74 Publications

Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells.

Bioengineered 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiology, Affiliated Suzhou Science and Technology City Hospital of Nanjing Medical University, Suzhou, China.

Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct an AS model. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of circ_0090231, IL-1β, and IL-18 transcripts. CircRNA/ target gene interactions were predicted using StarBase and TargetScan and confirmed using an RNA pull-down assay and dual luciferase reporter assay. Further, 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to evaluate cell viability and damage in the AS model, respectively. Cell pyroptosis and protein expression were determined using flow cytometry and western blotting respectively. The treatment of HAECs with ox-LDL not only led to significant increase in the levels of circ_0090231 but also resulted in improved cell viability as well as reduced cell injury and pyroptosis as compared to that in non-treated cells. The circ_0090231 was also identified to function as a sponge for miR-635, knockdown of which reverses the effects of circ_0090231 inhibition. Furthermore, our results revealed that levels of NLRP3, a miR-635 target, are not only augmented in the AS model but its overexpression also weakens the miR-635 regulatory effects in the AS development. Taken together, the circ_0090231/miR-635/NLRP3 axis affects the development of AS by regulating cell pyroptosis, thus providing new insights into the mechanism of AS development.
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http://dx.doi.org/10.1080/21655979.2021.1989260DOI Listing
October 2021

Apple or apple polyphenol consumption improves cardiovascular disease risk factors: a systematic review and meta-analysis.

Rev Cardiovasc Med 2021 Sep;22(3):835-843

Department of Geriatrics, The First People's Hospital of Xiaoshan District, 311200 Hangzhou, Zhejiang, China.

Many fruits and vegetables have been found to have a protective effect against cardiovascular diseases. We conducted a systematic review and meta-analysis to determine the relationship between apple or apple polyphenol intake and cardiovascular disease risk. The PubMed, Embase, Cochrane, and Web of Science databases were searched up to August 4, 2020. Studies that had an intervention time of >1 week; used apple or apple polyphenols as the intervention; were designed as a randomized controlled trial; and measured blood pressure, cholesterol, and blood glucose levels were included. The meta-analysis showed that the group with apple or apple polyphenol intake had significantly higher high-density lipoprotein levels (standardized mean difference [SMD] = 0.34, 95% confidence interval [CI] [0.01, 0.67], = 0.0411, = 77%, random-effects model) and significantly lower C-reactive protein levels (SMD = -0.43, 95% CI [-0.65, -0.20], = 0.0002, = 18%, fixed-effects model) than the control group, indicating that the intervention reduced the risk of cardiovascular diseases. Apple or apple polyphenol intake is associated with a reduced risk of cardiovascular diseases. These results are consistent with the old saying that eating an apple a day can help keep the doctors away.
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http://dx.doi.org/10.31083/j.rcm2203089DOI Listing
September 2021

Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma.

BMC Pharmacol Toxicol 2021 09 6;22(1):48. Epub 2021 Sep 6.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China.

Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC.

Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI.

Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.
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http://dx.doi.org/10.1186/s40360-021-00515-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419969PMC
September 2021

Prognostic Significance of Preoperative Lymphocyte-to-C-Reactive Protein Ratio in Patients with Non-Metastatic Colorectal Cancer.

Onco Targets Ther 2021 12;14:337-346. Epub 2021 Jan 12.

Department of Gastrointestinal Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, People's Republic of China.

Background: The inflammatory indexes are attracting increasing attention as a prognostic predictor for colorectal cancer (CRC). However, the prognostic value of the preoperative lymphocyte-to-C-reactive protein ratio (LCR) in patients with non-metastatic CRC remains to be established.

Methods: A total of 955 patients from 2010 to 2014 at a single center were included. Receiver operating characteristic curves (ROC) were generated to define the optimal cutoff value of the inflammatory indexes, and the areas under the curve (AUC) were calculated to compare the predictive value among the inflammatory indexes. The Fine and Gray competing risk regression model and Cox proportional hazard model were used to determine the prognostic factors for cancer-specific survival (CSS) and overall survival (OS) by using sub-distribution hazard ratio (SHR) and hazard ratio (HR) as size effects, respectively.

Results: A ratio of 6500 was defined as the optimal cutoff value for LCR for dividing CRC patients into the high (> 6500, n = 528) and low (≤ 6500, n = 427) LCR groups. The LCR had the highest value of prognostic prediction among all inflammation-based scores. Low LCR was significant correlated with several clinicopathological features of tumor invasion and development. The patients with low LCR had poorer CSS and OS as compared to those with high LCR. Multivariate analyses showed that low LCR was independently associated with worse OS (HR = 0.61, 95% CI: 0.53-0.70) and CSS (SHR = 0.55, 95% CI: 0.43-0.71).

Conclusion: Preoperative LCR can be a useful biomarker for prognostic prediction in non-metastatic CRC patients with a better predictive value than other inflammatory indexes.
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http://dx.doi.org/10.2147/OTT.S290234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811467PMC
January 2021

The Wnt Effector TCF7l2 Promotes Oligodendroglial Differentiation by Repressing Autocrine BMP4-Mediated Signaling.

J Neurosci 2021 02 15;41(8):1650-1664. Epub 2021 Jan 15.

Department of Neurology, School of Medicine, University of California, Davis, California, 95817

Promoting oligodendrocyte (OL) differentiation represents a promising option for remyelination therapy for treating the demyelinating disease multiple sclerosis (MS). The Wnt effector transcription factor 7-like 2 (TCF7l2) was upregulated in MS lesions and had been proposed to inhibit OL differentiation. Recent data suggest the opposite yet underlying mechanisms remain elusive. Here, we unravel a previously unappreciated function of TCF7l2 in controlling autocrine bone morphogenetic protein (BMP)4-mediated signaling. Disrupting TCF7l2 in mice of both sexes results in oligodendroglial-specific BMP4 upregulation and canonical BMP4 signaling activation Mechanistically, TCF7l2 binds to gene regulatory element and directly represses its transcriptional activity. Functionally, enforced TCF7l2 expression promotes OL differentiation by reducing autocrine BMP4 secretion and dampening BMP4 signaling. Importantly, compound genetic disruption demonstrates that oligodendroglial-specific BMP4 deletion rescues arrested OL differentiation elicited by TCF7l2 disruption Collectively, our study reveals a novel connection between TCF7l2 and BMP4 in oligodendroglial lineage and provides new insights into augmenting TCF7l2 for promoting remyelination in demyelinating disorders such as MS. Incomplete or failed myelin repairs, primarily resulting from the arrested differentiation of myelin-forming oligodendrocytes (OLs) from oligodendroglial progenitor cells, is one of the major reasons for neurologic progression in people affected by multiple sclerosis (MS). Using culture systems and animal models, this study unraveled a previously unrecognized autocrine regulation of bone morphogenetic protein (BMP)4-mediated signaling by the Wnt effector transcription factor 7-like 2 (TCF7l2). We showed for the first time that TCF7l2 promotes oligodendroglial differentiation by repressing BMP4-mediated activity, which is dysregulated in MS lesions. Our study suggests that elevating TCF7l2 expression may be possible in overcoming arrested oligodendroglial differentiation as observed in MS patients.
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http://dx.doi.org/10.1523/JNEUROSCI.2386-20.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115879PMC
February 2021

High nuclear expression of APE1 correlates with unfavorable prognosis and promotes tumor growth in hepatocellular carcinoma.

J Mol Histol 2021 Apr 4;52(2):219-231. Epub 2021 Jan 4.

Department of Interventional Radiology, Affiliated Hospital of Nantong University, Nantong, 226001, China.

APE1 is a multifunctional protein that plays important roles in cancer development. However, the association between APE1 expression and the clinicopathological parameters of HCC patients has not been fully characterized. In this study, bioinformatics analysis of APE1 was performed in several databases, including the TCGA, GeneCard, Human Protein Atlas and Ualcan databases. The relationship between APE1 mRNA expression and several attributes of liver cancer patients in TCGA was investigated. Then, the protein expression of APE1 was detected by IHC analysis in 95 HCC samples and the association between APE1 expression and the clinicopathological parameters of HCC patients was explored. GSEA-KEGG analysis was performed to predict the potential signaling pathways that associated with APE1 expression. Then the siRNA-mediated knockdown model of APE1 was constructed in HCC cell line to further detect the detailed function of APE1 in HCC development in vitro and in vivo. The results of the bioinformatics analysis showed that APE1 expression was primarily located in the cell nucleus. APE1 mRNA expression was substantially correlated with pathological grade and T status in TCGA database. Elevated APE1 expression was observed in HCC samples and was associated with unfavorable survival time in liver cancer patients. IHC data demonstrated that the nuclear expression of APE1 in HCC tissues was significantly higher than that in noncancerous tissues. The expression level of the APE1 protein in HCC was strongly associated with tumor diameter and overall survival. Survival analysis indicated that APE1 nuclear expression is an independent prognostic marker for the overall survival of HCC patients. GSEA-KEGG results confirmed that APE1 associated with the base excision repair signaling pathway. The data of phenotypic experiments indicated that APE1 remarkably promoted tumor growth both in HCC cells and xenografts. The findings firstly imply that nuclear expression of APE1 is a valuable prognostic marker for HCC. APE1 significantly facilitate HCC development and targeting APE1 may be a promising strategy for HCC treatment.
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http://dx.doi.org/10.1007/s10735-020-09939-9DOI Listing
April 2021

Enhanced autophagy promotes the clearance of in diabetic rats with wounds.

Ann Transl Med 2020 Nov;8(21):1362

NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Department of Diabetic foot, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China.

Background: To investigate the effects of the () type 3 secretion system (T3SS) on diabetic wound healing and autophagy-associated proteins.

Methods: and without T3SS were used to infect back wounds in 36 rats (18 normal and 18 diabetic). Followed infection with , another 36 rats (18 normal and 18 diabetic) with back wounds were treated with autophagy inducer rapamycin or gentamicin (positive control). Wound healing, colony count, HE and Masson staining were recorded. Western blot and immunofluorescent were used to determine the expression of the autophagy markers (LC3, beclin-1 and p62) in wound tissues.

Results: The number of colonies in infected wounds began to decrease on day 3 in normal rats and on day 7 in diabetic rats. The decrease was more apparent in without T3SS. The expression of LC3-II/LC3-I and beclin-1 gradually increased, and p62 gradually decreased in the wounds in of all groups; however, the changes were more dramatic in normal rats compared with diabetic rats on day 14. Rapamycin increased LC3-II/LC3-I and beclin-1 expression, and decreased p62 expression, gentamicin had no effect on their expression of autophagy markers.

Conclusions: T3SS of inhibited the entire autophagy process in wounds. Thus inducing autophagy could enhance the clearance of in diabetic wounds and is expected to become a new method of anti- infection.
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http://dx.doi.org/10.21037/atm-20-1019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723545PMC
November 2020

A study of multinucleated giant cells in esophageal cancer.

Clin Immunol 2021 01 13;222:108600. Epub 2020 Nov 13.

Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, Guangdong, China; Jinxin Research Institute for Reproductive Medicine and Genetics, Chengdu, Jinjiang Hospital for Maternal and Child Health Care, 66 Jingxiu Road, Chengdu, China. Electronic address:

Objectives: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer.

Materials And Methods: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers.

Results: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063).

Conclusions: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.
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http://dx.doi.org/10.1016/j.clim.2020.108600DOI Listing
January 2021

An immune evasion mechanism with IgG4 playing an essential role in cancer and implication for immunotherapy.

J Immunother Cancer 2020 08;8(2)

Department of Pathology and Pathophysiology, Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Shantou University Medical College, Shantou, China

Background: Recent impressive advances in cancer immunotherapy have been largely derived from cellular immunity. The role of humoral immunity in carcinogenesis has been less understood. Based on our previous observations we hypothesize that an immunoglobulin subtype IgG4 plays an essential role in cancer immune evasion.

Methods: The distribution, abundance, actions, properties and possible mechanisms of IgG4 were investigated with human cancer samples and animal tumor models with an extensive array of techniques both in vitro and in vivo.

Results: In a cohort of patients with esophageal cancer we found that IgG4-containing B lymphocytes and IgG4 concentration were significantly increased in cancer tissue and IgG4 concentrations increased in serum of patients with cancer. Both were positively related to increased cancer malignancy and poor prognoses, that is, more IgG4 appeared to associate with more aggressive cancer growth. We further found that IgG4, regardless of its antigen specificity, inhibited the classic immune reactions of antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity against cancer cells in vitro, and these effects were obtained through its Fc fragment reacting to the Fc fragments of cancer-specific IgG1 that has been bound to cancer antigens. We also found that IgG4 competed with IgG1 in reacting to Fc receptors of immune effector cells. Therefore, locally increased IgG4 in cancer microenvironment should inhibit antibody-mediated anticancer responses and help cancer to evade local immune attack and indirectly promote cancer growth. This hypothesis was verified in three different immune potent mouse models. We found that local application of IgG4 significantly accelerated growth of inoculated breast and colorectal cancers and carcinogen-induced skin papilloma. We also tested the antibody drug for cancer immunotherapy nivolumab, which was IgG4 in nature with a stabilizing S228P mutation, and found that it significantly promoted cancer growth in mice. This may provide an explanation to the newly appeared hyperprogressive disease sometimes associated with cancer immunotherapy.

Conclusion: There appears to be a previously unrecognized immune evasion mechanism with IgG4 playing an essential role in cancer microenvironment with implications in cancer diagnosis and immunotherapy.
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http://dx.doi.org/10.1136/jitc-2020-000661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443307PMC
August 2020

Boosted Oxygen Evolution Reactivity via Atomic Iron Doping in Cobalt Carbonate Hydroxide Hydrate.

ACS Appl Mater Interfaces 2020 Sep 25;12(36):40220-40228. Epub 2020 Aug 25.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.

Cobalt carbonate hydroxide hydrate (CCHH) has long been functioning merely as a precursor to prepare compound catalysts; however, its intrinsic potential for the oxygen evolution reaction (OER) is quite limited due to its poor catalytic activity. Herein, a concept has been proposed to solve this issue by doping Fe into CCHH nanowires grown on nickel foam (denoted as Fe-CCHH/NF) for achieving efficient OER catalysis by electrochemical transformation. The obtained Fe-CCHH/NF-30 exhibits OER catalytic performance with an overpotential of only 200 mV versus the reversible hydrogen electrode (vs. RHE) at a current density of 10 mA cm and small Tafel slope of 50 mV dec in 1 M KOH. Moreover, it displays stability for over 130 h at a large current density of 55 mA cm, and no activity decline is observed after the 3000 cycle test. The performance of Fe-CCHH/NF-30 renders it one of the most promising OER catalysts. The density functional theory calculation reveals that the doped Fe can greatly enhance the OER activity by lowering the reactive energy barrier.
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http://dx.doi.org/10.1021/acsami.0c07260DOI Listing
September 2020

Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling pathways.

Nat Commun 2020 04 24;11(1):2027. Epub 2020 Apr 24.

Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children/UC Davis School of Medicine, Sacramento, CA, 95817, USA.

The mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previous in vitro data suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIFα)-activated Wnt (but not VEGF) signaling. Using in vivo genetic models, we show that HIFα in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIFα stabilization in oligodendroglia does not perturb Wnt signaling but rather activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIFα-regulated CNS angiogenesis. Blocking astroglia-derived Wnt signaling reduces astroglial HIFα-regulated CNS angiogenesis. Together, our in vivo data demonstrate that oligodendroglial HIFα regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. These findings suggest an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIFα-Wnt axis in regulating CNS vessel formation.
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http://dx.doi.org/10.1038/s41467-020-15656-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181614PMC
April 2020

Modulation of Wnt and Activin/Nodal supports efficient derivation, cloning and suspension expansion of human pluripotent stem cells.

Biomaterials 2020 08 8;249:120015. Epub 2020 Apr 8.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan, 650500, China; XiAn ChaoYue Stem Cell Co., Ltd, No. 5 Tangxing Road, Xi'An, ShanXi, 710000, China. Electronic address:

Various culture systems have been used to derive and maintain human pluripotent stem cells (hPSCs), but they are inefficient in sustaining cloning and suspension expansion of hPSCs. Through systematically modulating Wnt and Activin/Nodal signaling, we developed a defined medium (termed AIC), which enables efficient cloning and long-term expansion of hPSCs (AIC-hPSCs) through single-cell passage on feeders, matrix or in suspension (25-fold expansion in 4 days) and maintains genomic stability of hPSCs over extensive expansion. Moreover, the AIC medium supports efficient derivation of hPSCs from blastocysts or somatic cells under feeder-free conditions. Compared to conventional hPSCs, AIC-hPSCs have similar gene expression profiles but down-regulated differentiation genes and display higher metabolic activity. Additionally, the AIC medium shows a good compatibility for different hPSC lines under various culture conditions. Our study provides a robust culture system for derivation, cloning and suspension expansion of high-quality hPSCs that benefits GMP production and processing of therapeutic hPSC products.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120015DOI Listing
August 2020

Illuminating Diverse Concomitant DNA Logic Gates and Concatenated Circuits with Hairpin DNA-Templated Silver Nanoclusters as Universal Dual-Output Generators.

Adv Mater 2020 Apr 20;32(17):e1908480. Epub 2020 Mar 20.

Chinese Academy of Sciences, Changchun, Jilin, 130022, China.

Exquisite administration of a new type of hairpin DNA-templated silver nanoclusters (H-AgNCs) as universal dual-output generators in DNA-based logic systems is reported. Diverse concomitant contrary logic gates (CCLGs) with opposite functions (YES NOT, OR NOR, INHIBIT IMPLICATION, XOR XNOR, and MAJORITY MINORITY) and extended concatenated logic circuits are presented and some of them perform specific functions, such as parity generators and checkers. The introduction of H-AgNCs as noncovalent signal reporters avoids tedious and high-cost labeling procedures. Of note, the concomitant feature of CCLGs attributed to the dual-emitter AgNCs conduces to reducing the time and cost to devise multiple logic gates. As compared to previous ones, this design eliminates numerous substances (e.g., organic dyes) and unstable components (hydrogen peroxide), which not only decreases the complexity of logic performs and improves repeatability of operation, but also makes it convenient to connect distinct DNA-based logic gates. It is worthy to anticipate that the cost-effective strategy will inspire researchers to develop much more complex logic systems and contribute to the field of molecular computing.
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http://dx.doi.org/10.1002/adma.201908480DOI Listing
April 2020

KNDC1 Is a Predictive Marker of Malignant Transformation in Borderline Ovarian Tumors.

Onco Targets Ther 2020 23;13:709-718. Epub 2020 Jan 23.

Department of Gynecology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310051, People's Republic of China.

Background: Few screening markers for malignant transformation in borderline ovarian tumors (BOT) have been clearly established. The kinase noncatalytic C-lobe domain containing 1 (KNDC1), a brain-specific Ras guanine nucleotide exchange factor, negatively regulates dendrite growth. However, the biological role and underlying mechanism of KNDC1 in human cancers, including ovarian cancer (OC), remain unknown.

Methods: Gene chip screening was used to detect the expression of mRNA in normal ovarian tissues, BOT tissues, and OC tissues. And results were further validated by RT-qPCR, Western blotting and immunohistochemistry. overexpression and knockdown ovarian cancer cells were established to study the possible pathways that KNDC1 was involved. The effects of KNDC1 on the malignant behaviors of ovarian tumors were also investigated both in vitro and in vivo.

Results: We observed that the expression of mRNA and KNDC1 protein in OC was significantly downregulated compared with BOT. Subsequent investigation revealed that knockdown of enhanced the proliferation of ovarian cancer cells in vitro via induction of ERK1/2 phosphorylation, whereas reinforcing the expression of attenuated the ERK1/2 activity. Similarly, knockdown of also promoted cell proliferation in vivo. Survival analysis showed that lower predicted a poor progression-free survival (PFS) for patients.

Conclusion: Collectively, we conclude that KNDC1 might function as a tumor suppressor in ovarian tumors, inhibiting the proliferation of ovarian cells by suppressing ERK1/2 activity and hindering the malignant transformation of BOT.
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http://dx.doi.org/10.2147/OTT.S223304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986543PMC
January 2020

AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy.

Nat Commun 2020 02 25;11(1):1032. Epub 2020 Feb 25.

Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, 52074, Aachen, Germany.

The AMP-activated protein kinase (AMPK) is a master sensor of the cellular energy status that is crucial for the adaptive response to limited energy availability. AMPK is implicated in the regulation of many cellular processes, including autophagy. However, the precise mechanisms by which AMPK controls these processes and the identities of relevant substrates are not fully understood. Using protein microarrays, we identify Cyclin Y as an AMPK substrate that is phosphorylated at Serine 326 (S326) both in vitro and in cells. Phosphorylation of Cyclin Y at S326 promotes its interaction with the Cyclin-dependent kinase 16 (CDK16), thereby stimulating its catalytic activity. When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. Moreover, Cyclin Y/CDK16 is necessary for efficient AMPK-dependent activation of autophagy. This functional interaction is mediated by AMPK phosphorylating S326 of Cyclin Y. Collectively, we define Cyclin Y/CDK16 as downstream effector of AMPK for inducing autophagy.
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http://dx.doi.org/10.1038/s41467-020-14812-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042329PMC
February 2020

A General Method for Transition Metal Single Atoms Anchored on Honeycomb-Like Nitrogen-Doped Carbon Nanosheets.

Adv Mater 2020 Mar 31;32(10):e1906905. Epub 2020 Jan 31.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.

Excavating and developing highly efficient and cost-effective nonnoble metal single-atom catalysts for electrocatalytic reactions is of paramount significance but still in its infancy. Herein, reported is a general NaCl template-assisted strategy for rationally designing and preparing a series of isolated transition metal single atoms (Fe/Co/Ni) anchored on honeycomb-like nitrogen-doped carbon matrix (M -HNC-T -T , M = Fe/Co/Ni, T = 500 °C, T = 850 °C). The resulting M -HNC-500-850 with M-N active sites exhibits superior capability for oxygen reduction reaction (ORR) with the half-wave potential order of Fe -HNC-500-850 > Co -HNC-500-850 > Ni -HNC-500-850, in which Fe -HNC-500-850 shows better performance than commercial Pt/C. Density functional theory calculations reveal a choice strategy that the strong p-d-coupled spatial charge separation results the Fe-N effectively merges active electrons for elevating d-band activity in a van-Hove singularity like character. This essentially generalizes an optimal electronic exchange-and-transfer (ExT) capability for boosting sluggish alkaline ORR activity. This work not only presents a universal strategy for preparing single-atom electrocatalyst to accelerate the kinetics of cathodic ORR but also provides an insight into the relationship between the electronic structure and the electrocatalytical activity.
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http://dx.doi.org/10.1002/adma.201906905DOI Listing
March 2020

Tumor-Associated Macrophages (TAMs): A Critical Activator In Ovarian Cancer Metastasis.

Onco Targets Ther 2019 21;12:8687-8699. Epub 2019 Oct 21.

Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.

Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumor-associated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.
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http://dx.doi.org/10.2147/OTT.S216355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814357PMC
October 2019

Effects of berberine on the growth performance, antioxidative capacity and immune response to lipopolysaccharide challenge in broilers.

Anim Sci J 2019 Sep 1;90(9):1229-1238. Epub 2019 Jul 1.

College of Animal Science and Technology, Shihezi University, Xinjiang, People's Republic of China.

This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response-related genes in lipopolysaccharide (LPS)-challenged broilers. We assigned 120 one-day-old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T-SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS-induced decreases in the mRNA expression of nuclear factor-kappa B (NF-κB), TNF-α, IL-1β, inducible nitrite synthase and cyclooxygenase-2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF-κB signalling and the expression of inflammatory mediators.
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http://dx.doi.org/10.1111/asj.13255DOI Listing
September 2019

An Incremental Version of L-MVU for the Feature Extraction of MI-EEG.

Comput Intell Neurosci 2019 2;2019:4317078. Epub 2019 May 2.

Faculty of Information Technology, Beijing University of Technology, Beijing 100124, China.

Due to the nonlinear and high-dimensional characteristics of motor imagery electroencephalography (MI-EEG), it can be challenging to get high online accuracy. As a nonlinear dimension reduction method, landmark maximum variance unfolding (L-MVU) can completely retain the nonlinear features of MI-EEG. However, L-MVU still requires considerable computation costs for out-of-sample data. An incremental version of L-MVU (denoted as IL-MVU) is proposed in this paper. The low-dimensional representation of the training data is generated by L-MVU. For each out-of-sample data, its nearest neighbors will be found in the high-dimensional training samples and the corresponding reconstruction weight matrix be calculated to generate its low-dimensional representation as well. IL-MVU is further combined with the dual-tree complex wavelet transform (DTCWT), which develops a hybrid feature extraction method (named as IL-MD). IL-MVU is applied to extract the nonlinear features of the specific subband signals, which are reconstructed by DTCWT and have the obvious event-related synchronization/event-related desynchronization phenomenon. The average energy features of and waves are calculated simultaneously. The two types of features are fused and are evaluated by a linear discriminant analysis classifier. Based on the two public datasets with 12 subjects, extensive experiments were conducted. The average recognition accuracies of 10-fold cross-validation are 92.50% on Dataset 3b and 88.13% on Dataset 2b, and they gain at least 1.43% and 3.45% improvement, respectively, compared to existing methods. The experimental results show that IL-MD can extract more accurate features with relatively lower consumption cost, and it also has better feature visualization and self-adaptive characteristics to subjects. The -test results and Kappa values suggest the proposed feature extraction method reaches statistical significance and has high consistency in classification.
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http://dx.doi.org/10.1155/2019/4317078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525943PMC
January 2020

Online IMU Self-Calibration for Visual-Inertial Systems.

Sensors (Basel) 2019 Apr 4;19(7). Epub 2019 Apr 4.

Faculty of Information Technology, Beijing University of Technology, Beijing 100124, China.

Low-cost microelectro mechanical systems (MEMS)-based inertial measurement unit (IMU) measurements are usually affected by inaccurate scale factors, axis misalignments, and g-sensitivity errors. These errors may significantly influence the performance of visual-inertial methods. In this paper, we propose an online IMU self-calibration method for visual-inertial systems equipped with a low-cost inertial sensor. The goal of our method is to concurrently perform 3D pose estimation and online IMU calibration based on optimization methods in unknown environments without any external equipment. To achieve this goal, we firstly develop a novel preintegration method that can handle the IMU intrinsic parameters error propagation. Then, we frame IMU calibration problem into general factors so that we can easily integrate the factors into the current graph-based visual-inertial frameworks and jointly optimize the IMU intrinsic parameters as well as the system states in a big bundle. We evaluate the proposed method with a publicly available dataset. Experimental results verify that the proposed approach is able to accurately calibrate all the considered parameters in real time, leading to significant improvement of estimation precision of visual-inertial system (VINS) compared with the estimation results with offline precalibrated IMU measurements.
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http://dx.doi.org/10.3390/s19071624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480050PMC
April 2019

Dietary leonurine hydrochloride supplementation attenuates lipopolysaccharide challenge-induced intestinal inflammation and barrier dysfunction by inhibiting the NF-κB/MAPK signaling pathway in broilers.

J Anim Sci 2019 Apr;97(4):1679-1692

College of Animal Science and Technology, Shihezi University, Xinjiang, People's Republic of China.

This study was performed to evaluate the beneficial effects of dietary leonurine hydrochloride (LH) supplementation on intestinal morphology and barrier integrity and further illuminate its underlying antioxidant and immunomodulatory mechanisms in lipopolysaccharide (LPS)-treated broilers. A total of 120 1-d-old male broilers (Ross 308) were assigned to 4 treatment groups with 6 replicates of 5 birds per cage. The experiment was designed in a 2 × 2 factorial arrangement with LH (0 or 120 mg/kg) and LPS (injection of saline or 1.5 mg/kg body weight) as treatments. On days 14, 16, 18, and 20 of the trial, broilers were intraperitoneally injected with LPS or physiological saline. Compared with the control group, LPS-challenged broilers showed impaired growth performance (P < 0.05) from day 15 to day 21 of the trial, increased serum diamine oxidase (DAO) and D-lactic acid (D-LA) levels coupled with reduced glutathione (GSH) content and total superoxide dismutase (T-SOD) activity (duodenal and jejunal mucosa), reduced malondialdehyde (MDA) content (duodenal, jejunal, and ileal mucosa), and compromised morphological structure of the duodenum and jejunum. Additionally, LPS challenge increased (P < 0.05) the mRNA expression of proinflammatory cytokine genes and reduced tight junction (TJ) protein expression in the jejunum. However, dietary LH prevented LPS-induced reductions in average daily gain (ADG) and average daily feed intake (ADFI) in broilers. It also alleviated LPS challenge-induced increases in serum DAO levels, MDA content (duodenal and jejunal mucosa), and jejunal crypt depth (P < 0.05) but reduced villus height, GSH content (jejunal mucosa), and T-SOD activity (duodenal and jejunal mucosa) (P < 0.05). Additionally, LH supplementation significantly downregulated the mRNA expression of nuclear factor (NF)-κB, cyclooxygenase-2 (COX-2), and proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and upregulated the mRNA expression of zonula occludens-1 (ZO-1) and Occludin in the jejunal mucosa induced by LPS (P < 0.05). On the other hand, LH administration prevented LPS-induced activation of the p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) and attenuated IkB alpha (IκBα) phosphorylation and nuclear translocation of NF-κB (p65) in the jejunal mucosa. In conclusion, dietary LH supplementation attenuates intestinal mucosal disruption mainly by accelerating the expression of TJ proteins and inhibiting activation of the NF-κB/MAPK signaling pathway.
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http://dx.doi.org/10.1093/jas/skz078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447247PMC
April 2019

Fluorescent labelling of membrane fatty acid transporter CD36 (SR-B2) in the extracellular loop.

PLoS One 2019 23;14(1):e0210704. Epub 2019 Jan 23.

Department of Molecular Genetics, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.

Context: Upon palmitate oversupply, membrane fatty acid-transporter CD36 (SR-B2) permanently translocates from endosomal storage to the sarcolemma, inducing lipotoxicity. CD36 translocation results from endosomal alkalinisation elicited by palmitate-induced disattachment of the cytoplasmic V1-subcomplex from the membrane-integrated V0-subcomplex of vacuolar-type H+-ATPase.

Objective: Develop a CD36 fluorescent labeling technique as initial step towards live cell imaging.

Methods: Three human CD36 (hCD36) mutants were constructed via insertion of a tetracysteine motif at different positions within the extracellular domain. Constructs were lentivirally transduced for subsequent CD36 labeling with fluorescein-arsenical hairpin-binder (FlAsH). Cell imaging was combined with V0/V1 immunostaining and Western blotting.

Results: Transduction of hCD36-wildtype and mutants yielded corresponding proteins in HL-1 cardiomyocytes. Tetracysteine mutant-2 (hCD36-TC2) showed similar fatty acid uptake to wildtype. FlAsH staining revealed a speckled pattern reminiscent of endosomes. We found decreased V1 co-localization with CD36 upon high-palmitate culturing. Conversely, V0 consistently co-localized with CD36.

Conclusion: hCD36-TC2 is a possible candidate for application of biarsenical dyes in live imaging studies pending further investigation. Our data is compatible with V0/V1 disassembly in high-palmitate-treated cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210704PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343965PMC
October 2019

Improving Cell Survival in Injected Embryos Allows Primed Pluripotent Stem Cells to Generate Chimeric Cynomolgus Monkeys.

Cell Rep 2018 11;25(9):2563-2576.e9

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan 650500, China; Kunming Enovate Institute of Bioscience, Kunming, Yunnan 650500, China. Electronic address:

Monkeys are an optimal model species for developing stem cell therapies. We previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (dESCs). However, conventional primed pluripotent stem cells (pPSCs) lack chimera competency. Here, by altering the media in which injected morulae are cultured, we observed increased survival of cynomolgus monkey primed ESCs, induced PSCs, and somatic cell nuclear transfer-derived ESCs, thereby enabling chimeric contributions with 0.1%-4.5% chimerism into the embryonic and placental tissues, including germ cell progenitors in chimeric monkeys. Mechanically, dESCs and pPSCs belong to different cell types and similarly express epiblast ontogenic genes. The host embryonic microenvironment could reprogram injected PSCs to embryonic-like cells. However, the reprogramming level and chimerism were associated with the cell state of injected PSCs. Our findings provide a method to understand pluripotency and broaden the use of embryonic chimeras for basic developmental biology research and regenerative medicine.
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http://dx.doi.org/10.1016/j.celrep.2018.11.001DOI Listing
November 2018

The anti-inflammatory and antioxidant effects of leonurine hydrochloride after lipopolysaccharide challenge in broiler chicks.

Poult Sci 2019 Apr;98(4):1648-1657

College of Animal Science and Technology, Shihezi University, Xinjiang 832000, People's Republic of China.

This study was carried out to investigate the protective effects of leonurine hydrochloride (LH, from Leonurus sibiricus) on lipopolysaccharide (LPS)-stimulated broiler chicks. A total of 120 one-day-old male Ross broilers were randomly divided into 4 treatment groups with 6 replicates of 5 birds per cage. The experiment was designed as a 2 × 2 factorial arrangement with LH (0 or 120 mg/kg) and LPS (injection of saline or 1.5 mg/kg body weight) levels as treatments. On days 14, 16, 18, and 20 of the trial, broilers were intraperitoneally injected with LPS or saline. Blood, spleen, and liver samples were collected on days 21 and 28 for analysis. The results showed that dietary LH had no effect on growth performance or immunoglobulin concentrations in the serum. However, dietary LH prevented LPS-induced reductions in average daily gain and average daily feed intake in the broilers on days 15-21 of the trial (P > 0.05). Dietary LH supplementation dramatically attenuated the LPS-induced increases in the spleen index, reduced glutathione (GSH) activity (serum and liver) and total superoxide dismutase (T-SOD) activity (serum and spleen), and significantly reduced malondialdehyde (MDA) levels (serum, spleen, and liver) on days 21 and 28 (P < 0.05). Additionally, LH supplementation significantly mitigated the LPS-induced increases in the tumor necrosis factor (TNF)-α (serum and spleen), interleukin (IL)-1β (serum, spleen and liver), IL-2 (liver), IL-6 (serum, spleen and liver), toll-like receptor 4 (TLR4) (spleen and liver), and nuclear factor (NF)-κB (spleen and liver) levels on days 21 and 28 (P < 0.05). Therefore, this study revealed that LH could downregulate the expression of proinflammatory factors, mainly by inhibiting the expression of TLR4 and the activation of NF-κB. LH may be a potential feed additive with dual efficacy as an anti-inflammatory and antioxidant agent.
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http://dx.doi.org/10.3382/ps/pey532DOI Listing
April 2019

Rapid synthesis of CoO nanosheet arrays on Ni foam by in situ electrochemical oxidization of air-plasma engraved Co(OH) for efficient oxygen evolution.

Chem Commun (Camb) 2018 Nov;54(90):12698-12701

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China.

A novel strategy to fabricate Co3O4 nanosheet arrays for the oxygen evolution reaction (OER) was developed by electrodeposition of Co(OH)2 on nickel foam (NF) and subsequent in situ electrochemical oxidation into Co3O4 during the OER. The produced [email protected], which was further engraved with air plasma, exhibits the best performance and long-term stability.
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http://dx.doi.org/10.1039/c8cc06399kDOI Listing
November 2018

Co O /Fe Co P Interface Nanowire for Enhancing Water Oxidation Catalysis at High Current Density.

Adv Mater 2018 Nov 25;30(45):e1803551. Epub 2018 Sep 25.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.

Designing well-defined nanointerfaces is of prime importance to enhance the activity of nanoelectrocatalysts for different catalytic reactions. However, studies on non-noble-metal-interface electrocatalysts with extremely high activity and superior stability at high current density still remains a great challenge. Herein, a class of Co O /Fe Co P interface nanowires is rationally designed for boosting oxygen evolution reaction (OER) catalysis at high current density by partial chemical etching of Co(CO ) (OH)·0.11H O (Co-CHH) nanowires with Fe(CN) , followed by low-temperature phosphorization treatment. The resulting Co O /Fe Co P interface nanowires exhibit very high OER catalytic performance with an overpotential of only 215 mV at a current density of 50 mA cm and a Tafel slope of 59.8 mV dec in 1.0 m KOH. In particular, Co O /Fe Co P exhibits an obvious advantage in enhancing oxygen evolution at high current density by showing an overpotential of merely 291 mV at 800 mA cm , much lower than that of RuO (446 mV). Co O /Fe Co P is remarkably stable for the OER with negligible current loss under overpotentials of 200 and 240 mV for 150 h. Theoretical calculations reveal that Co O /Fe Co P is more favorable for the OER since the electrochemical catalytic oxygen evolution barrier is optimally lowered by the active Co- and O-sites from the Co O /Fe Co P interface.
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http://dx.doi.org/10.1002/adma.201803551DOI Listing
November 2018

The synergistic effect of propofol and ulinastatin suppressed the viability of the human lung adenocarcinoma epithelial A549 cell line.

Oncol Lett 2018 Oct 8;16(4):5191-5199. Epub 2018 Aug 8.

Department of Anesthesia, First Affiliated Hospital, Gannan Medical College, Ganzhou, Jiangxi 341000, P.R. China.

Ulinastatin and propofol (PPF) are recognized for their anticancer properties. The aim of the present study was to evaluate the synergistic antitumor effect of PPF followed by ulinastatin against A549 cells. In MTT assays, PPF (10, 20 and 30 µM) followed by 200 U/ml ulinastatin was more effective at inhibiting A549 cell viability compared with PPF (10, 20 and 30 µM) or 200 U/ml ulinastatin. PPF (10, 20 and 30 µM) followed by 200 U/ml ulinastatin treatments synergistically increased the number of S cells and synergistically reduced the number of G2/M cells associated with PPF stimulation in a dose-dependent manner. Western blot analysis demonstrated that the antitumor effect of PPF followed by 200 U/ml ulinastatin treatments were associated with the downregulated expression of extracellular signal-regulated kinase 1 and 2 phosphorylation (p-ERK1/2) and matrix metalloproteinases 2 (MMP-2). In conclusion, these data demonstrated that PPF (20 and 30 µM) followed by 200 U/ml ulinastatin treatments synergistically stimulated a significant proportion of A549 cells in S phase. Furthermore, the combination synergistically reduced a significant proportion of A549 cells in G2/M phase and synergistically suppressed the viability of A549 cells, which was possibly related regulation of the expression of p-ERK1/2 and MMP-2 in A549 cells.
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http://dx.doi.org/10.3892/ol.2018.9283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144888PMC
October 2018

Advances of exosome in the development of ovarian cancer and its diagnostic and therapeutic prospect.

Onco Targets Ther 2018 15;11:2831-2841. Epub 2018 May 15.

Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

Ovarian cancer is the leading cause of female gynecological cancer mortality. Most patients with ovarian cancer are diagnosed with advanced stage because of lack of early symptoms, physical signs, and sensitive tumor biomarkers. The standard treatment includes cytoreductive surgery and platinum-based chemotherapy (usually platinum combined with paclitaxel). Despite that postoperative adjuvant chemotherapy prolongs survival time, most patients go through relapse within 6-12 months after the treatment. Thus, elucidating the molecular mechanism in cancer development is essential to promote early diagnosis and novel treatments. The role of exosome has been highlighted in multiple research fields in recent years. Exosome has been described as nano-sized vesicle secreted by multiple mammalian cell types, carrying cargos like proteins, miRNAs, mRNAs, and lipids. It participates in the formation of tumor microenvironment and the development of tumorigenesis and drug resistance in ovarian cancer. Meanwhile, it may also play a pivotal role in diagnosis, efficacy evaluation, and prognosis. Besides, studies show that exosome and its processed products have promising value in ovarian cancer treatment. The aim of the current review is to describe the characteristics of exosome in ovarian cancer, especially focusing on its role in immune modulation and drug resistance, hoping to provide new information on its implications in cancer diagnosis and treatment.
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http://dx.doi.org/10.2147/OTT.S159829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961474PMC
May 2018

Brn2 Alone Is Sufficient to Convert Astrocytes into Neural Progenitors and Neurons.

Stem Cells Dev 2018 06 15;27(11):736-744. Epub 2018 May 15.

1 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology , Kunming, Yunnan, China .

Generating neurons or neural progenitor cells (NPCs) from astrocytes is a potential strategy for neurological repair by reprogramming. Previous study has showed that Brn2, by cooperating with other factors, participates in neurogenesis and neuronal reprogramming. However, it is still unclear whether the Brn2 alone can convert astrocytes into neurons or NPCs. Here, we explored the effect of Brn2 on reprogramming of astrocytes, and found that a single transcription factor Brn2 can convert mouse astrocytes into functional neurons. Furthermore, the Brn2-infected astrocytes can be induced into NPCs after changing culture condition. In addition, our study found that the reprogramming of astrocytes and the fate of transdifferentiated cells are closely associated with cell microenvironmental factors, such as the brain regions where the astrocytes come from, the proliferation ability of astrocytes, and culture condition of infected astrocytes. To sum up, for the first time, our results demonstrated that Brn2 alone is sufficient to convert astrocytes into neural progenitors and neurons, and the conversion is associated with cell microenvironments. This new conversion method will be a potential therapeutic approach to restore the injured diseased brain in regenerative medicine.
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http://dx.doi.org/10.1089/scd.2017.0250DOI Listing
June 2018

Imaging and Laparoscopic Findings in a Patient with Congenital Uterine Arteriovenous Malformation.

J Minim Invasive Gynecol 2019 01 21;26(1):18-20. Epub 2018 Mar 21.

Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.jmig.2018.03.008DOI Listing
January 2019
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