Publications by authors named "Yonghua Yang"

59 Publications

Design, synthesis and biological evaluation of anilide (dicarboxylic acid) shikonin esters as antitumor agents through targeting PI3K/Akt/mTOR signaling pathway.

Bioorg Chem 2021 Mar 29;111:104872. Epub 2021 Mar 29.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC = 4.52 ± 0.28 μM; SK: IC = 7.62 ± 0.26 μM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/β-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure-activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.
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http://dx.doi.org/10.1016/j.bioorg.2021.104872DOI Listing
March 2021

The chromosome-scale assembly of the willow genome provides insight into Salicaceae genome evolution.

Hortic Res 2020 Apr 1;7(1):45. Epub 2020 Apr 1.

Key Laboratory for Tree Breeding and Germplasm Improvement, Southern Modern Forestry Collaborative Innovation Center, College of Forestry, Nanjing Forestry University, Nanjing, 210037, China.

Salix suchowensis is an early-flowering shrub willow that provides a desirable system for studies on the basic biology of woody plants. The current reference genome of S. suchowensis was assembled with 454 sequencing reads. Here, we report a chromosome-scale assembly of S. suchowensis generated by combining PacBio sequencing with Hi-C technologies. The obtained genome assemblies covered a total length of 356 Mb. The contig N50 of these assemblies was 263,908 bp, which was ~65-fold higher than that reported previously. The contiguity and completeness of the genome were significantly improved. By applying Hi-C data, 339.67 Mb (95.29%) of the assembled sequences were allocated to the 19 chromosomes of haploid willow. With the chromosome-scale assembly, we revealed a series of major chromosomal fissions and fusions that explain the genome divergence between the sister genera of Salix and Populus. The more complete and accurate willow reference genome obtained in this study provides a fundamental resource for studying many genetic and genomic characteristics of woody plants.
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http://dx.doi.org/10.1038/s41438-020-0268-6DOI Listing
April 2020

Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis.

PeerJ 2021 7;9:e10675. Epub 2021 Jan 7.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, China.

Background: Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC.

Methods: In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight.

Results: Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues.

Conclusions: Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.
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http://dx.doi.org/10.7717/peerj.10675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797173PMC
January 2021

Video-based Detection of Generalized Tonic-clonic Seizures Using Deep Learning.

IEEE J Biomed Health Inform 2021 Jan 6;PP. Epub 2021 Jan 6.

Timely detection of seizures is crucial to implement optimal interventions, and may help reduce the risk of sudden unexpected death in epilepsy (SUDEP) in patients with generalized tonic-clonic seizures (GTCSs). While video-based automated seizure detection systems may be able to provide seizure alarms in both in-hospital and at-home settings, earlier studies have primarily employed hand-designed features for such a task. In contrast, deep learning-based approaches do not rely on prior feature selection and have demonstrated outstanding performance in many data classification tasks. Despite these advantages, neural network-based video classification has rarely been attempted for seizure detection. We here assessed the feasibility and efficacy of automated GTCSs detection from videos using deep learning. We retrospectively identified 76 GTCS videos from 37 participants who underwent long-term video-EEG monitoring (LTM) along with interictal video data from the same patients, and 10 full-night seizure-free recordings from additional patients. Using a leave-one-subject-out cross-validation approach (LOSO-CV), we evaluated the performance to detect seizures based on individual video frames (convolutional neural networks, CNNs) or video sequences [CNN+long short-term memory (LSTM) networks]. CNN+LSTM networks based on video sequences outperformed GTCS detection based on individual frames yielding a mean sensitivity of 88% and mean specificity of 92% across patients. The average detection latency after presumed clinical seizure onset was 22 seconds. Detection performance increased as a function of training dataset size. Collectively, we demonstrated that automated video-based GTCS detection with deep learning is feasible and efficacious. Deep learning-based methods may be able to overcome some limitations associated with traditional approaches using hand-crafted features, serve as a benchmark for future methods and analyses, and improve further with larger datasets.
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http://dx.doi.org/10.1109/JBHI.2021.3049649DOI Listing
January 2021

Impact of a G2-EPSPS & GAT Dual Transgenic Glyphosate-Resistant Soybean Line on the Soil Microbial Community under Field Conditions Affected by Glyphosate Application.

Microbes Environ 2020 ;35(4)

Institute for Plant Molecular Biology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University.

In the past thirty years, the biosafety of the aboveground part of crops, including horizontal gene transferal through pollen dispersal and hybridization, has been the focus of research; however, microbial communities in the underground part are attracting increasing attention. In the present study, the soybean root-associated bacterial communities of the G2-EPSPS plus GAT transgenic soybean line Z106, its recipient variety ZH10, and Z106 treated with glyphosate (Z106J) were compared at the seedling, flowering, and seed filling stages by high-throughput sequencing of the V4 hypervariable regions of 16S rRNA gene amplicons using Illumina MiSeq. The results obtained showed no significant differences in the alpha/beta diversities of root-associated bacterial communities at the three stages among ZH10, Z106, and Z106J under field growth conditions; however, the relative abundance of four main nitrogen-fixing bacterial genera significantly differed among ZH10, Z106, and Z106J. Ternary plot results indicated that in the root compartment, the proportional contributions of rhizobial nitrogen-fixing Ensifer fredii and Bradyrhizobium elkanii, which exhibit an extremely broad nodulation host range, markedly differed among the three treatments at the three stages. Thus, the present results indicate that transgenic G2-EPSPS and GAT soybean may induce different changes in functional bacterial species in soil, such as E. fredii and B. elkanii, from ZH10, which were compensated for/enriched at the flowering and seed filling stages, respectively, to some extent through as of yet unknown mechanisms by transgenic soybean treated with glyphosate.
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http://dx.doi.org/10.1264/jsme2.ME20056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734404PMC
January 2020

The effect of family doctor policy practice on primary health-care workers' health in Hongkou District of Shanghai, China: varied by occupational divisions?

BMC Fam Pract 2020 09 30;21(1):205. Epub 2020 Sep 30.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: A key component of the 2009 medical reform in China was the change to family doctor (FD) policy practice. However, this led to an increased workload for primary health-care workers (PHCWs) at community health service centres. Their increasing workload may play a significant role in affecting PHCWs' health.

Methods: A questionnaire survey was conducted in Hongkou district of Shanghai amongst PHCWs including family doctors (FDs), family nurses (FNs), public health doctors (PHDs), and other PHCWs in early 2019. Ordered logistic regression models (Models 1 to 3) were performed to explore the differing health status amongst PHCWs, and their respective influential factors were also tested (Models 4 to 7).

Results: Five hundred sixty-two valid questionnaires were collected with a response rate of 96.4%. Other PHCWs' (OR = 2.03; 95% CI: 1.163-3.560) and FNs' (OR = 1.98; 95% CI: 1.136-3.452) self-rated health (SRH) were significantly better than that of FDs. In terms of FNs, the OR of SRH for those who strongly perceived the extra workload brought by FD-contracted services was only 12.0% (95% CI: 0.018-0.815) of that of the no-pressure group. Similarly, FNs with stronger work pressure had worse SRH, i.e., compared with "no" pressure, the SRH ORs for "neutral," "strong," and "very strong" evaluations of work pressure were 0.002 (95% CI: 0.000-0.055), 0.001 (95% CI: 0.000-0.033), and 0.000 (95% CI: 0.000-0.006), respectively. Information technology (IT) systems and performance incentives were suggested to improve SRH for FNs, while the former was found to be negatively correlated with other PHCWs. After one unit increase in the PHDs' team/department support, their OR was 10.7 times (95% CI: 1.700-67.352) higher. In addition, policy support had a negative effect on SRH for PHDs. The OR of "good" assessments of cultural environments was 25.98 times (95% CI: 1.391-485.186) higher than that of "very poor" for Other PHCWs.

Conclusions: The influences of FD policy practice on FNs' SRH were the most significant amongst PHCWs, rather than FDs' as expected. The significant factors of SRH were varied over different occupational categories, that is team/department support and policy support (though negative) for PHDs, IT system and incentive for FNs, facility and equipment for FDs, and culture environment for other PHCWs respectively.
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http://dx.doi.org/10.1186/s12875-020-01275-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529512PMC
September 2020

The chromosome-scale assembly of the willow genome provides insight into Salicaceae genome evolution.

Hortic Res 2020 1;7:45. Epub 2020 Apr 1.

1Key Laboratory for Tree Breeding and Germplasm Improvement, Southern Modern Forestry Collaborative Innovation Center, College of Forestry, Nanjing Forestry University, Nanjing, 210037 China.

is an early-flowering shrub willow that provides a desirable system for studies on the basic biology of woody plants. The current reference genome of was assembled with 454 sequencing reads. Here, we report a chromosome-scale assembly of generated by combining PacBio sequencing with Hi-C technologies. The obtained genome assemblies covered a total length of 356 Mb. The contig N50 of these assemblies was 263,908 bp, which was ~65-fold higher than that reported previously. The contiguity and completeness of the genome were significantly improved. By applying Hi-C data, 339.67 Mb (95.29%) of the assembled sequences were allocated to the 19 chromosomes of haploid willow. With the chromosome-scale assembly, we revealed a series of major chromosomal fissions and fusions that explain the genome divergence between the sister genera of and . The more complete and accurate willow reference genome obtained in this study provides a fundamental resource for studying many genetic and genomic characteristics of woody plants.
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http://dx.doi.org/10.1038/s41438-020-0268-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109076PMC
April 2020

SbWRKY30 enhances the drought tolerance of plants and regulates a drought stress-responsive gene, SbRD19, in sorghum.

J Plant Physiol 2020 Mar - Apr;246-247:153142. Epub 2020 Feb 22.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. Electronic address:

WRKY transcription factors have been suggested to play important roles in response and adaptation to drought stress. However, how sorghum WRKY transcription factors function in drought stress is still unclear. Here, we identify a WRKY transcription factor of sorghum, SbWRKY30, which is induced significantly by drought stress. SbWRKY30 is mainly expressed in sorghum taproot and leaf. SbWRKY30 has transcriptional activation activity and functions in the nucleus. Heterologous expression of SbWRKY30 confers tolerance to drought stress in Arabidopsis (Arabidopsis thaliana) and rice by affecting root architecture. In addition, SbWRKY30 transgenic Arabidopsis and rice plants have higher proline contents and SOD, POD, and CAT activities but lower MDA contents than wild-type plants after drought stress. As a homologous gene of the drought stress-responsive gene RD19 of Arabidopsis, SbRD19 overexpression in Arabidopsis improved the drought tolerance of plants relative to wild-type plants. Further analysis demonstrated that SbWRKY30 could induce SbRD19 expression through binding to the W-box element in the promoter of SbRD19. These results suggest that SbWRKY30 functions as a positive regulator in response to drought stress. Therefore, SbWRKY30 may serve as a promising candidate gene for molecular breeding to generate drought-tolerant crops.
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http://dx.doi.org/10.1016/j.jplph.2020.153142DOI Listing
August 2020

Identification of Genes Underlying the Resistance to in an Gene Supercluster of the Genome.

Plant Dis 2020 Apr 12;104(4):1133-1143. Epub 2020 Feb 12.

The Key Laboratory for Poplar Breeding and Germplasm Improvement, The Southern Modern Forestry Collaborative Innovation Center, College of Forestry, Nanjing Forestry University, Nanjing 210037, China.

Identification of the particular genes in an genes supercluster underlying resistance to the rust fungus in poplar genome remains challenging. Based on the de novo assembly of the genome, all of the detected major genetic loci conferring resistance to were confined to a 3.5-Mb region on chromosome 19. The transcriptomes of the resistant and susceptible genotypes were sequenced for a timespan from 0 to 168 hours postinoculation. By mapping the differentially expressed genes to the target genomic region, we identified two constitutive expression genes and one inducible expression gene that might confer resistance to . Nucleotide variations were predicted based on the reconstructed haplotypes for each allele of the candidate genes. We also confirmed that salicylic acid was the phytohormone mediating signal transduction pathways, and was identified as a key gene inhibiting rust reproduction. Finally, quantitative reverse transcription PCR assay revealed consistent expressions with the RNA-sequencing data for the detected key genes. This study presents an efficient approach for the identification of particular genes underlying phenotype of interest by the combination of genetic mapping, transcriptome profiling, and candidate gene sequences dissection. The identified key genes would be useful for host resistance diagnosis and for molecular breeding of elite poplar cultivars exhibiting resistance to infection. The detected genes are also valuable for testing whether the combination of individual genes can induce durable quantitative resistance.
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http://dx.doi.org/10.1094/PDIS-08-19-1699-REDOI Listing
April 2020

Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy.

Mol Cell Biochem 2019 Dec 31;462(1-2):115-122. Epub 2019 Aug 31.

Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.

Rasal2, a Ras-GTPase-activating protein (RasGAP), is a tumor suppressor in Luminal B breast cancer, frequently metastatic and recurrent. Exosomes (Exos) are small membrane vesicles secreted by various cell types, including tumor cells, recognized as vehicles for cell-to-cell communication. Our study aimed to investigate whether Rasal2 regulates breast cancer cell growth via affecting this process. In this paper, we described that Rasal2 knockout (KO) in MCF-7 cells enhanced exosomal release and increased autophagy-related proteins in exosomal fraction, while attenuated by exosome release inhibitor GW4869. Moreover, MCF-7 cells with chloroquine (CQ) treatment boosted Rasal2 KO-induced secretory autophagy. In addition, we presented that exosomes derived from KO MCF-7 cells (KO-exo) significantly promoted breast cancer cell proliferation compared to those from MCF-7 cells transfected with an empty crispr-cas9 plasmid serving as controls (sgNT-exo); however, exosomes purified from KO MCF-7 cells co-cultured with 3-methyladenine ((3-MA + KO)-exo)/CQ ((CQ + KO)-exo) dramatically inhibited/facilitated MCF-7 cell proliferation in contrast to KO-exo group, separately. In conclusion, our findings revealed a new mechanism of Rasal2 in the regulation of breast cancer cell proliferation via autophagy-exo-mediated pathway.
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http://dx.doi.org/10.1007/s11010-019-03615-7DOI Listing
December 2019

Effect of RSK4 on biological characteristics of colorectal cancer.

World J Surg Oncol 2018 Dec 22;16(1):240. Epub 2018 Dec 22.

Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, 434000, Hubei, China.

Background: This study aimed to investigate the expression of P90 Ribosomal Protein S6 kinase 4 (RSK4) in colorectal cancer cells and its biological function.

Methods: We selected early SW480 and HCT116 colorectal cancer cell lines, using Lipofectamine™ 2000 transfection reagent carrying RSK4 gene transfected into cells to establish the colorectal cancer cell lines with high expression of RSK4. RT-PCR and western blot (WB) analysis confirmed RSK4 expression in SW480 and HCT116 cancer cell lines. We used methylthiazoltetrazolium (MTT) assay and flow cytometry to detect the proliferation of colorectal cancer cells. After transfection of RSK4, the effect of RSK4 on the RNA levels associated with epithelial-mesenchymal transition (EMT) of colorectal cancer cells was analyzed by real-time fluorescence quantitative PCR and the expression of EMT-related protein was detected by WB analysis.

Results: After transfection of RSK4 overexpression, the MTT assay detected that RSK4 could significantly inhibit the growth of colorectal cancer cells in vitro; flow cytometry detected that S-phase cells decreased significantly, and G0/1 cells increased significantly (P < 0.05). The invasion ability of SW480 and HCT116 cells transfected with RSK4 was markedly lower than that in the control group, and the difference was statistically significant (P < 0.05). Fluorescent quantitative PCR and WB analysis showed that the expression of EMT-associated molecular E-cadherin was remarkably increased and the expression of Snail was significantly decreased (P < 0.01).

Conclusion: RSK4 gene in colorectal cancer cell lines with low expression of RSK4 after transfection can inhibit the growth and invasion of tumor cells. RSK4 gene may inhibit EMT and inhibit metastasis of colorectal cancer cells, may be a potential tumor suppressor gene and inhibit tumor distant metastasis, and may provide the biological basis for new therapeutic targets.
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http://dx.doi.org/10.1186/s12957-018-1474-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303929PMC
December 2018

Vincristine ablation of Sirt2 induces cell apoptosis and mitophagy via Hsp70 acetylation in MDA-MB-231 cells.

Biochem Pharmacol 2019 04 21;162:142-153. Epub 2018 Oct 21.

Department of Pharmacology and Biochemistry, School of Pharmacy Fudan University, Shanghai 201203, China. Electronic address:

Cancer cells are continuously challenged by adverse environmental stress and adopt diverse strategies to survive. Hsp70 plays pivotal roles in invasion, migration, drug resistance, and the survival of tumor cells. Hsp70 functions as molecular chaperone to protect tumor cells from stress-induced cell death. Hsp70 acetylation alters its chaperone activity in cell death pathways, but its relevance in the process of cell death and the underlying mechanisms involved are not well understood. In this study, we demonstrated that vincristine induces mitophagy via the disruption of Hsp70 binding with Sirt2, leading to Hsp70 acetylation at K126 and elevated sequestration of Bcl2 by Hsp70 for autophagosome creation. Acetylation at K126 significantly changes the physiological function of Hsp70 compared to acetylation at other sites. It also attenuates the protein folding and renaturation function of Hsp70 by altering the binding co-chaperones. In addition, acetylation at K126 inhibits Hsp70-mediated tumor cell invasion and migration, and the binding of Hsp70 to AIF1 and Apaf1 for promoting mitochondrial-mediated apoptosis. In conclusion, this study describes the molecular mechanism of vincristine induction of cell apoptosis and mitophagy via ablation of Sirt2 induced Hsp70 acetylation at K126 in MDA-MB-231 cells.
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http://dx.doi.org/10.1016/j.bcp.2018.10.021DOI Listing
April 2019

Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer.

Cancer Sci 2018 Oct 26;109(10):3272-3284. Epub 2018 Aug 26.

Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, China.

Acetylation plays an important role in regulating the chaperone activity of heat shock protein 90 (Hsp90) during malignant transformation through the stabilization and conformational maturation of oncogenic proteins. However, the functional acetylation sites, potential anticancer drug targets, are still emerging. We found that acetylation at K292 in Hsp90α is critical for the development and treatment of breast cancer. Acetylation at K292 not only augments the affinity of Hsp90 to ATP, cochaperones, and client proteins but it also promotes cancer cell colony formation, migration, and invasion in vitro as well as tumor growth in vivo. Importantly, K292-acetylated Hsp90 has been validated as an exciting anticancer drug target by interfering with the complex formation between K292-acetylated Hsp90 and cochaperone Cdc37, leading to diminishment of kinase client maturation and proteasome-dependent degradation of kinase substrates. Furthermore, we showed that simvastatin prevented, whereas LBH589 promoted, the progression of Hsp90 chaperone cycling and client maturation, resulting in an increment of cell apoptosis by the combination of simvastatin and LBH589 in a mouse xenograft model. These data suggest that simvastatin is a novel Hsp90 inhibitor to disrupt the formation of the K292-acetylated Hsp90/Cdc37 complex in triple-negative breast cancer cells. The combination of simvastatin with LBH589 could be used as a novel therapeutic strategy for triple-negative breast cancer.
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http://dx.doi.org/10.1111/cas.13748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172049PMC
October 2018

lincROR influences the stemness and crizotinib resistance in EML-ALK non-small-cell lung cancer cells.

Onco Targets Ther 2018 22;11:3649-3657. Epub 2018 Jun 22.

Department of Pharmacy, The 161th Hospital of PLA, Wuhan 430010, Hubei Province, China.

Introduction: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase () is identified as an important pathogenic factor in patients with non-small-cell lung cancer (NSCLC) and could induce a stem-like phenotype in NSCLC cells. Crizotinib is commonly used for EML4-ALK NSCLC treatment, but its acquired resistance results in tumor recurrence. Long intergenic noncoding RNA, regulator of reprogramming (lincROR) is related to the acquisition and maintenance of self-renewal and stemness features of cancer stem cells. It has been documented that lincROR is implicated in chemoresistance. However, the correlations of lincROR and in stem cell-like properties and of lincROR and crizotinib resistance in NSCLC cells are yet to be elucidated.

Patients And Methods: In the present study, we investigated the expression profile of lincROR in EML-ALK NSCLC tissues, and the potential role of lincROR in prognosis was then analyzed. Subsequently, its association with stem cell-like properties of EML-ALK NSCLC cells was determined. Furthermore, the correlation of lincROR with crizotinib and the effects of lincROR and crizotinib on cell viability of EML4-ALK NSCLC cells were all explored.

Results: The results showed that lincROR expression was upregulated in EML4-ALK NSCLC tissues relative to EML4-ALK NSCLC tissues. Low-expressed lincROR was related to a favorable prognosis of patients with EML-ALK NSCLC. lincROR overexpression could enhance the stemness features of EML-ALK NSCLC cells which were repressed by ALK knockdown.

Conclusion: We found that lincROR expression was significantly inhibited because of the increased concentration of crizotinib in EML4-ALK NSCLC cells. Furthermore, lincROR overexpression increased cell viability of EML4-ALK NSCLC cells, which was impaired by crizotinib. Conjointly, these results suggested the important role of lincROR in EML-ALK NSCLC. lincROR may serve as a potential therapeutic target to overcome chemotherapy resistance in EML-ALK NSCLC.
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http://dx.doi.org/10.2147/OTT.S165290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018841PMC
June 2018

Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

Medicine (Baltimore) 2018 May;97(19):e0632

Department of Oncology Department of Surgical Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.

Background: Lung cancer is the most common cause of cancer death. About 80% of patients are diagnosed at stage III in the non-small cell lung cancer (NSCLC). It is extremely important to understand the progression of this disease which has low survival times despite the advancing treatment modalities. We aimed to investigate the relationship between early tumor shrinkage (ETS) after initial concurrent chemoradiotherapy (C-CRT) and survival outcome in patients with stage III (NSCLC).

Methods: A retrospective review of 103 patients with stage III NSCLC who had received C-CRT from January 2006 to October 2011 was performed. Patients were treated with systemic chemotherapy regimen of Cisplatin/Vp-16 and concurrent thoracic radiotherapy at a median dose of 66 Gy (range 60-70 Gy). All patients received a computed tomography (CT) examination before treatment. Also subsequently, chest CT scans were performed with the same imaging parameters at approximately 5 weeks after the initiation of treatment. ETS is here stratified by a decrease in tumor size ≥30% and <30% in the longest dimension of the target lesion within 5 weeks.

Results: Of the 103 patients, 59 ones showed a 30% decrease in tumor size, and the rest displayed a decrease of <30%. ETS showed no significant correlation with age, T classification, N classification, histological classification, smoking status, G classification, EGFR status, or acute pulmonary toxicity. In the current retrospective clinical study, Kaplan-Meier curves showed that patients with ETS ≥ 30% had a better progression-free survival and overall survival. The univariate and multivariate Cox regression analyses indicated that ETS < 30% was associated with a significantly increased risk of cancer-related death (P < .05) in stage IIINSCLC.

Conclusions: ETS may be served as a useful prognostic factor to predict the outcome of stage III NSCLC patients treated with CCRT.
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http://dx.doi.org/10.1097/MD.0000000000010632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959434PMC
May 2018

Glyphosate application increased catabolic activity of gram-negative bacteria but impaired soil fungal community.

Environ Sci Pollut Res Int 2018 May 14;25(15):14762-14772. Epub 2018 Mar 14.

NJU-NJFU Institute of Plant Molecular Biology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Glyphosate is a non-selective organophosphate herbicide that is widely used in agriculture, but its effects on soil microbial communities are highly variable and often contradictory, especially for high dose applications. We applied glyphosate at two rates: the recommended rate of 50 mg active ingredient kg soil and 10-fold this rate to simulate multiple glyphosate applications during a growing season. After 6 months, we investigated the effects on the composition of soil microbial community, the catabolic activity and the genetic diversity of the bacterial community using phospholipid fatty acids (PLFAs), community level catabolic profiles (CLCPs), and 16S rRNA denaturing gradient gel electrophoresis (DGGE). Microbial biomass carbon (C) was reduced by 45%, and the numbers of the cultivable bacteria and fungi were decreased by 84 and 63%, respectively, under the higher glyphosate application rate. According to the PLFA analysis, the fungal biomass was reduced by 29% under both application rates. However, the CLCPs showed that the catabolic activity of the gram-negative (G-) bacterial community was significantly increased under the high glyphosate application rate. Furthermore, the DGGE analysis indicated that the bacterial community in the soil that had received the high glyphosate application rate was dominated by G- bacteria. Real-time PCR results suggested that copies of the glyphosate tolerance gene (EPSPS) increased significantly in the treatment with the high glyphosate application rate. Our results indicated that fungi were impaired through glyphosate while G- bacteria played an important role in the tolerance of microbiota to glyphosate applications.
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http://dx.doi.org/10.1007/s11356-018-1676-0DOI Listing
May 2018

Solitary duodenum metastasis from breast cancer with 8 years' latency: A case report.

Medicine (Baltimore) 2018 Jan;97(2):e9550

Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan Department of Breast Surgery, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.

Rationale: Advanced breast cancer frequently metastasizes to the lungs, liver, and bones. Metastatic involvement of the duodenal bulb is extremely rare and difficult to detect by endoscopy.

Patient Concerns: A 51-year-old menopausal woman presented with abdominal fullness and obstructive symptoms, and was diagnosed with adenocarcinoma in the duodenal bulb. The patient had undergone modified radical mastectomy of the left breast for infiltrating ductal carcinoma (IDC) 8 years previously.

Diagnosis: Metastatic infiltration of the duodenal bulb originating from IDC was proven histologically and immunohistochemically.

Interventions: She received chemotherapy with docetaxel and capecitabine followed by hormone maintenance therapy with letrozole after operation.

Outcomes: After treatment, the patient recovered well. She is currently being followed up.

Lessons: Patients with known breast cancer history with the IDC histological type and presenting with nonspecific abdominal symptoms or signs, such as abdominal fullness, nausea, and vomiting, should undergo endoscopy with histopathological examination in order to detect possible gastrointestinal metastasis of the primary breast tumor. This report intends to alert people to heed this type of breast cancer metastasis and not treat it as a primary gastrointestinal tumor.
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http://dx.doi.org/10.1097/MD.0000000000009550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943893PMC
January 2018

Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.

Mol Plant 2018 05 1;11(5):678-690. Epub 2018 Feb 1.

State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China. Electronic address:

Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes. The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi. However, the biological importance of Golgi-mediated mannose trimming is not fully understood. Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis. In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming. However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant. Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity. Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress. Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2. Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
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http://dx.doi.org/10.1016/j.molp.2018.01.006DOI Listing
May 2018

Vorinostat and Simvastatin have synergistic effects on triple-negative breast cancer cells via abrogating Rab7 prenylation.

Eur J Pharmacol 2017 Oct 19;813:161-171. Epub 2017 Aug 19.

Department of Biological Sciences, Oakland University, 2200 N. Squirrel Road, Rochester, MI 48309, USA.

Since the lack of targeted treatment, triple-negative breast cancer (TNBC) has poor outcomes. Histone deacetylase inhibitors (HDACi) blocking the activity of specific HDACs have emerged as cancer therapeutic agents. However, the therapeutic efficiency is still not satisfactory for patients with solid tumor. We thus performed screening for the synergistic agents of Vorinostat (SAHA). The resulting candidate Simvastatin was obtained. The efficacy and mechanism of combination have been studied in TNBC cells. The synergism of SAHA and Simvastatin was evaluated by IC of proliferation and combination index (CI). The antitumor activities of combination were further evaluated in TNBC cells. The pro-apoptotic effects were determined by flow cytometry and Western blot. Autophagosome-lysosome fusion was monitored using confocal microscope. The underlying mechanism was further studied by over-expressing of wild-type or inactive (C205S/C207S) Rab7 in compounds treated cells. The in vivo efficacy was also evaluated in mice. The combination of SAHA and Simvastatin had potent synergism in apoptosis of TNBC cells. It exerted pro-apoptosis effect by compromising the fusion between autophagosome and lysosome. Over-expressing of wild-type, but not inactive Rab7 rescued cells from apoptosis induced by the combinatory treatments. Mevalonate supplementation also decreased the combinatory treatment-induced apoptosis. These results indicate that the combinatory treatment enhances the apoptosis of TNBC cells by interrupting Rab7 prenylation and obstructing autophagosome-lysosome fusion. Combination between SAHA and Simvastatin could also significantly decrease the tumor growth in xenografted mice by inducing apoptosis and inhibiting Rab7 prenylation. Rab7 is a potential target for the combined effects of Simvastatin and SAHA.
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http://dx.doi.org/10.1016/j.ejphar.2017.08.022DOI Listing
October 2017

Down-regulation of long noncoding RNA RP11-713B9.1 contributes to the cell viability in non‑small cell lung cancer (NSCLC).

Mol Med Rep 2017 Sep 17;16(3):3694-3700. Epub 2017 Jul 17.

Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China.

Early diagnosis is essential to reduce lung cancer-associated morbidity and mortality rates; however the lack of diagnostic biomarkers for lung cancer has made this difficult. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) serve important roles in cancer occurrence and progression. The present study investigated the novel lncRNA RP11‑713B9.1, which is the antisense transcript of tumor suppressor in lung cancer 1 (TSLC1). The expression levels of RP11‑713B9.1 and TSLC1 in non‑small cell lung cancer were determined using reverse‑transcription quantitative polymerase chain reaction, which revealed that the expression of RP11‑713B9.1 and TSLC1 was significantly downregulated in tumor tissue compared with that in adjacent normal tissue samples. In addition, the expression of RP11‑713B9.1 was identified to be positively correlated with the expression of tumor suppressors TSLC1, CYLD lysine 63 deubiquitinase and APC WNT signaling pathway regulator, and negatively correlated with B‑Raf proto‑oncogene serine/threonine kinase expression. Furthermore, the overexpression of RP11‑713B9.1 resulted in significant upregulation of TSLC1 and inhibition of H460 cell viability, while the opposite effects were observed following the knockdown of RP11‑713B9.1 in A549 cells. Taken together, the results of the current study suggest that lncRNA RP11‑713B9.1 serves as a promising biomarker and potential therapeutic target for non‑small cell lung cancer.
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http://dx.doi.org/10.3892/mmr.2017.7026DOI Listing
September 2017

Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.

Biomed Pharmacother 2017 Sep 5;93:636-645. Epub 2017 Jul 5.

State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.
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http://dx.doi.org/10.1016/j.biopha.2017.06.076DOI Listing
September 2017

Plant-mediated resource partitioning by coexisting parasitoids.

Ecology 2017 Jun 15;98(6):1660-1670. Epub 2017 May 15.

Department of Ecology, School of Life Science, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.

Although it has been frequently suggested that resource partitioning of species coexisting at the same trophic level can be mediated by interactions with species at non-adjacent trophic levels, empirical evidence supporting this claim is scarce. Here we demonstrate that plants may mediate resource partitioning for two parasitoids that share the same herbivorous host. The tephritid fly Tephritis femoralis is the primary pre-dispersal seed predator of two Asteraceae species, Saussurea nigrescens and Anaphalis flavescens, both of which dominate the plant community in the alpine meadows of the Tibetan Plateau. Field surveys and molecular barcoding analyses showed that the identity of the fly's main predator depended on the plant in which the fly developed. Tephritid flies that developed in S. nigrescens were preyed upon mainly by the parasitoid wasp Pteromalus albipennis, while the parasitoid Mesopolobus sp. was the main predator of flies that developed in A. flavescens. Microcosm experiments revealed that P. albipennis could not exploit the host flies within the capitula of A. flavescens due to food limitation (capitula are too small), while Mesopolobus sp. could not exploit the host flies within the capitula of S. nigrescens due to its inability to reach the host with its ovipositor (capitula are too large). Such bottom-up control of plant species traits may facilitate the coexistence of parasitoid wasps sharing a common host in this system. We suggest that interactions between non-adjacent trophic levels may potentially promote species coexistence and diversity in biological communities.
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http://dx.doi.org/10.1002/ecy.1834DOI Listing
June 2017

Calcium-dependent protein kinase CPK31 interacts with arsenic transporter AtNIP1;1 and regulates arsenite uptake in Arabidopsis thaliana.

PLoS One 2017 15;12(3):e0173681. Epub 2017 Mar 15.

State Key Laboratory for Pharmaceutical Biotechnology, Nanjing University-Nanjing Forestry University Joint Institute for Plant Molecular Biology, College of Life Sciences, Nanjing University, Nanjing, China.

Although arsenite [As(III)] is non-essential and toxic for plants, it is effectively absorbed through various transporters into the roots. Here we identified a calcium-dependent protein kinase (CPK31) response for As(III) tolerance in Arabidopsis. We identified CPK31 as an interacting protein of a nodulin 26-like intrinsic protein (NIP1;1), an aquaporin involved in As(III) uptake. Similarly to the nip1;1 mutants, the loss-of-function mutants of CPK31 improved the tolerance against As(III) but not As(V), and accumulated less As(III) in roots than that of the wild-type plants. The promoter-β-glucuronidase and quantitative Real-Time PCR analysis revealed that CPK31 displayed overlapping expression profiles with NIP1;1 in the roots, suggesting that they might function together in roots. Indeed, the cpk31 nip1;1 double mutants exhibited stronger As(III) tolerance than cpk31 mutants, but similar to nip1;1 mutants, supporting the idea that CPK31 might serve as an upstream regulator of NIP1;1. Furthermore, transient CPK31 overexpression induced by dexamethasone caused the decrease in As(III) tolerance of transgenic Arabidopsis lines. These findings reveal that CPK31 is a key factor in As(III) response in plants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173681PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351991PMC
September 2017

Mevastatin blockade of autolysosome maturation stimulates LBH589-induced cell death in triple-negative breast cancer cells.

Oncotarget 2017 Mar;8(11):17833-17848

Department of Pharmacology and Biochemistry, School of Pharmacy Fudan University, Shanghai 201203, China.

Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, and combining a HDACi with other agents is an attractive therapeutic strategy in solid tumors. We report here that mevastatin increases HDACi LBH589-induced cell death in triple-negative breast cancer (TNBC) cells. Combination treatment inhibited autophagic flux by preventing Vps34/Beclin 1 complex formation and downregulating prenylated Rab7, an active form of the small GTPase necessary for autophagosome-lysosome fusion. This means that co-treatment with mevastatin and LBH589 activated LKB1/AMPK signaling and subsequently inhibited mTOR. Co-treatment also led to cell cycle arrest in G2/M phase and induced corresponding expression changes of proteins regulating the cell cycle. Co-treatment also increased apoptosis both in vitro and in vivo, and reduced tumor volumes in xenografted mice. Our results indicate that disruption of autophagosome-lysosome fusion likely underlies mevastatin-LBH589 synergistic anticancer effects. This study confirms the synergistic efficacy of, and demonstrates a potential therapeutic role for mevastatin plus LBH589 in targeting aggressive TNBC, and presents a novel therapeutic strategy for further clinical study. Further screening for novel autophagy modulators could be an efficient approach to enhance HDACi-induced cell death in solid tumors.
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http://dx.doi.org/10.18632/oncotarget.14868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392290PMC
March 2017

Transgenic studies reveal the positive role of LeEIL-1 in regulating shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.

BMC Plant Biol 2016 05 26;16(1):121. Epub 2016 May 26.

State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210046, People's Republic of China.

Background: The phytohormone ethylene (ET) is a key signaling molecule for inducing the biosynthesis of shikonin and its derivatives, which are secondary metabolites in Lithospermum erythrorhizon. Although ETHYLENE INSENSITIVE3 (EIN3)/EIN3-like proteins (EILs) are crucial transcription factors in ET signal transduction pathway, the possible function of EIN3/EIL1 in shikonin biosynthesis remains unknown. In this study, by targeting LeEIL-1 (L. erythrorhizon EIN3-like protein gene 1) at the expression level, we revealed the positive regulatory effect of LeEIL-1 on shikonin formation.

Results: The mRNA level of LeEIL-1 was significantly up-regulated and down-regulated in the LeEIL-1-overexpressing hairy root lines and LeEIL-1-RNAi hairy root lines, respectively. Specifically, LeEIL-1 overexpression resulted in increased transcript levels of the downstream gene of ET signal transduction pathway (LeERF-1) and a subset of genes for shikonin formation, excretion and/or transportation (LePAL, LeC4H-2, Le4CL-1, HMGR, LePGT-1, LeDI-2, and LePS-2), which was consistent with the enhanced shikonin contents in the LeEIL-1-overexpressing hairy root lines. Conversely, LeEIL-1-RNAi dramatically repressed the expression of the above genes and significantly reduced shikonin production.

Conclusions: The results revealed that LeEIL-1 is a positive regulator of the biosynthesis of shikonin and its derivatives in L. erythrorhizon hairy roots. Our findings gave new insights into the molecular regulatory mechanism of ET in shikonin biosynthesis. LeEIL-1 could be a crucial target gene for the genetic engineering of shikonin biosynthesis.
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http://dx.doi.org/10.1186/s12870-016-0812-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880835PMC
May 2016

Transgenic analysis reveals LeACS-1 as a positive regulator of ethylene-induced shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.

Plant Mol Biol 2016 Mar 18;90(4-5):345-58. Epub 2016 Jan 18.

State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China.

The phytohormone ethylene (ET) is a crucial signaling molecule that induces the biosynthesis of shikonin and its derivatives in Lithospermum erythrorhizon shoot cultures. However, the molecular mechanism and the positive regulators involved in this physiological process are largely unknown. In this study, the function of LeACS-1, a key gene encoding the 1-aminocyclopropane-1-carboxylic acid synthase for ET biosynthesis in L. erythrorhizon hairy roots, was characterized by using overexpression and RNA interference (RNAi) strategies. The results showed that overexpression of LeACS-1 significantly increased endogenous ET concentration and shikonin production, consistent with the up-regulated genes involved in ET biosynthesis and transduction, as well as the genes related to shikonin biosynthesis. Conversely, RNAi of LeACS-1 effectively decreased endogenous ET concentration and shikonin production and down-regulated the expression level of above genes. Correlation analysis showed a significant positive linear relationship between ET concentration and shikonin production. All these results suggest that LeACS-1 acts as a positive regulator of ethylene-induced shikonin biosynthesis in L. erythrorhizon hairy roots. Our work not only gives new insights into the understanding of the relationship between ET and shikonin biosynthesis, but also provides an efficient genetic engineering target gene for secondary metabolite production in non-model plant L. erythrorhizon.
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http://dx.doi.org/10.1007/s11103-015-0421-zDOI Listing
March 2016

Widely distributed hot and cold spots in meiotic recombination as shown by the sequencing of rice F2 plants.

New Phytol 2015 Jun 9;206(4):1491-502. Epub 2015 Feb 9.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, China.

Numerous studies have argued that environmental variations may contribute to evolution through the generation of novel heritable variations via meiotic recombination, which plays a crucial role in crop domestication and improvement. Rice is one of the most important staple crops, but no direct estimate of recombination events has yet been made at a fine scale. Here, we address this limitation by sequencing 41 rice individuals with high sequencing coverage and c. 900 000 accurate markers. An average of 33.9 crossover (c. 4.53 cM Mb(-1) ) and 2.47 non-crossover events were detected per F2 plant, which is similar to the values in Arabidopsis. Although not all samples in the stress treatment group showed an increased number of crossover events, environmental stress increased the recombination rate in c. 28.5% of samples. Interestingly, the crossovers showed a highly uneven distribution among and along chromosomes, with c. 13.9% of the entire genome devoid of crossovers, including 11 of the 12 centromere regions, and c. 0.72% of the genome containing large numbers of crossovers (> 50 cM Mb(-1) ). The gene ontology (GO) categories showed that genes clustered within the recombination hot spot regions primarily tended to be involved in responses to environmental stimuli, suggesting that recombination plays an important role for adaptive evolution in rapidly changing environments.
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http://dx.doi.org/10.1111/nph.13319DOI Listing
June 2015

Faecalibacterium prausnitzii inhibits interleukin-17 to ameliorate colorectal colitis in rats.

PLoS One 2014 2;9(10):e109146. Epub 2014 Oct 2.

Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background And Aims: It has been shown that Faecalibacterium prausnitzii (F. prausnitzii), one of the dominant intestinal bacterial flora, may protect colonic mucosa against the development of inflammation and subsequent inflammatory bowel disease (IBD), with the underlying mechanisms being unclear.

Methods: The impacts of F. prausnitzii and its metabolites on IL-23/Th17/IL-17 pathway markers were determined in human monocytes and a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid. F. prausnitzii and its culture medium (containing complete metabolites) were used to treat the rats in vivo, as well as rat splenocytes and human monocytes in vitro. Inflammatory cytokines were measured in colon tissue, plasma and cell culture medium.

Results: The culture supernatant of F. prausnitzii increased plasma anti-Th17 cytokines (IL-10 and IL-12)and suppressed IL-17 levels in both plasma and colonic mucosa, with ameliorated colonic colitis lesions. This inhibition of IL-17 release has also been observed in both rat splenocytes and human venous monocytes in vitro. The culture supernatant of F. prausnitzii also suppressed Th17 cell differentiation induced by cytokines (TGF-ß and IL-6) and bone marrow-derived dendritic cells (BMDCs) in vitro. The metabolites of F. prausnitzii in the culture supernatant exert a stronger anti-inflammatory effect than the bacterium itself. F. prausnitzii protected the colon mucosa against the development of IBD by its metabolites, suggesting a promising potential for the use of F. prausnitzii and its metabolic products in the treatment of IBD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109146PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183556PMC
December 2015

Radiation pneumonitis after radiotherapy of neck lymphoma.

Case Rep Pulmonol 2014 28;2014:614984. Epub 2014 Aug 28.

Department of Oncology, First Affiliated Hospital of Yangtz University, Hubei, Jingzhou 434000, China.

Radiotherapy is still one of the effective means for treatment of malignant tumors up to now. Particularly, it is an indispensable effective measure for treatment of some lymphoma patients. In routine work, radiation pneumonitis (RP) is the most significant complication of acute treatment-related toxicities in lung cancer; however, serious radioactive pneumonia is rare for the radiotherapy of neck lymphoma because the volume of the lungs affected by radiation dose was very small. We report a lymphoma case, where the patient had undergone radiotherapy for the bilateral neck and bilateral supraclavicular/infraclavicular area. Following completion of radiotherapy, the patient developed severe radiation pneumonitis.
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http://dx.doi.org/10.1155/2014/614984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164395PMC
September 2014

The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size.

Dev Biol 2014 Sep 25;393(1):93-108. Epub 2014 Jun 25.

Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA. Electronic address:

Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes. Cysts in unicellular tubes are enlargements of the apical lumen, whereas cysts in intracellular tubes are cytoplasmic vacuole-like compartments. The cyst phenotype in expansion mutants is similar to, but weaker than, that observed in double mutants of Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E and Ptp10D negatively regulate the receptor tyrosine kinase (RTK) pathways, especially epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor/breathless (FGFR, Btl) signaling to maintain the proper size of unicellular and intracellular tubes. We show Exp genetically interacts with RTK signaling, the downstream targets of RPTPs. Cyst size and number in expansion mutants is enhanced by increased RTK signaling and suppressed by reduced RTK signaling. Genetic interaction studies strongly suggest that Exp negatively regulates RTK (EGFR, Btl) signaling to ensure proper tube sizes. Smad proteins generally function as intermediate components of the transforming growth factor-β (TGF-β, DPP) signaling pathway. However, no obvious genetic interaction between expansion and TGF-β (DPP) signaling was observed. Therefore, Expansion does not function as a typical Smad protein. The expansion phenotype demonstrates a novel role for Smad-like proteins in epithelial tube formation.
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http://dx.doi.org/10.1016/j.ydbio.2014.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134752PMC
September 2014