Publications by authors named "Jianya Ling"

12 Publications

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Dynamic content changes of cordycepin and adenosine and transcriptome in Cordyceps kyushuensis Kob at different fermentation stages.

Bioprocess Biosyst Eng 2021 Mar 30. Epub 2021 Mar 30.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.

20% (w/w) Astragali radix was added to the rice medium to cultivate C. kyushuensis Kob. The fermentation product was collected at mycelium stage, coloring stage, stromata-forming initial stage and fruiting body stage of C. kyushuensis Kob. The dynamic content changes of cordycepin and adenosine were detected at different fermentation stages. In the rice medium with Astragalus radix, both cordycepin and adenosine reached the highest content value on the 30th day of fermentation, 17.31 mg/g and 0.94 mg/g, respectively, which were 8.6 times and 2.0 times of that in rice medium at the same stage. At the same time, transcriptomics technology was used to analyze C. kyushuensis Kob during these four periods.
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http://dx.doi.org/10.1007/s00449-021-02561-3DOI Listing
March 2021

Immunomodulatory and Antioxidant Effects of Polysaccharides from the Parasitic Fungus .

Biomed Res Int 2020 29;2020:8257847. Epub 2020 Aug 29.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, China.

The ascomycete Cordyceps genus has been used as valued traditional Chinese medicine. is a unique species of Cordyceps, which parasitizes on the larvae of Walker, and its major component cordycepin and aqueous extract are known to have many pharmacological effects. However, the physiological function of water-soluble polysaccharides has not been explored in detail. In this study, to resolve these doubts, we extracted and separated Cordyceps-derived polysaccharides and then evaluated the immunomodulatory and antioxidant activities. Four polysaccharide fractions were purified from Cordyceps-cultured stroma by DEAE-cellulose 23 and Sephadex G-150 column chromatography. Basic structural information was elucidated on the basis of physicochemical property and spectroscopic evidences. The antioxidant activities were evaluated by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method and protective effect of DNA damage. The qualified immunologic activities were also determined and . The polysaccharides could stimulate the proliferation of mouse splenocytes whether concanavalin A (ConA) and lipopolysaccharide (LPS) existed or not, strengthen peritoneal macrophages to devour neutral red, and increase the content of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-) in serum. The research provides the corresponding evidence for Cordyceps polysaccharides as a potential candidate for functional foods and therapeutic agents.
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http://dx.doi.org/10.1155/2020/8257847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475740PMC
May 2021

Cordycepin and pentostatin biosynthesis gene identified through transcriptome and proteomics analysis of Cordyceps kyushuensis Kob.

Microbiol Res 2019 Jan 17;218:12-21. Epub 2018 Sep 17.

State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China. Electronic address:

Cordyceps kyushuensis is the only species of cordyceps growing on the larvae of Clanis bilineata Walker, and has been demonstrated that there are lots of pharmacological components including cordycepin. Cordycepin shows lots of pharmacological action but it could be converted to 3'-deoxyinosine by adenosine deaminase in vivo, which weakens the efficiency of cordycepin. That pentostatin, which has been reported to inhibit adenosine deaminase, combining cordycepin could enhance the efficiency of cordycepin in vivo. During transcriptome and proteomics analysis of Cordyceps kyushuensis, a single gene cluster including four genes we named ck1-ck4 which can synthesis both cordycepin and pentostatin has been identified using BLAST. Meanwhile, KEGG, KOG, GO analysis and differentially expressed genes were analyzed in transcriptome and proteomics. This study first sequenced transcriptome and proteomics of C. kyushuensis, and demonstrated that there is a single gene cluster related to biosynthesis of cordycepin and pentostatin, which can be employed to improve the yield of cordycepin and find more functional proteins.
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http://dx.doi.org/10.1016/j.micres.2018.09.005DOI Listing
January 2019

Genome shuffling improved the nucleosides production in Cordyceps kyushuensis.

J Biotechnol 2017 Oct 4;260:42-47. Epub 2017 Sep 4.

State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address:

Genome shuffling was first applied to improve the production of nucleosides in Cordyceps kyushuensis. Six improved strains were selected for genome shuffling by UV and HNO mutagenesis. Ten improved genome shuffling strains with good genetic stability were obtained, among which, the production of cordycepin in R6 was 9.624 times higher than that of the ancestor. While in R18 and R19, the yield of cordycepin, adenosine, guanosine and uridine were all increased greatly compared with the ancestor. Based on the four phenotypes of the content of cordycepin, adenosine, guanosine and uridine, hierarchical clustering analysis (HCA) and principal component analysis (PCA) were applied to infer the relationships between genome shuffling strains and mutants.
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http://dx.doi.org/10.1016/j.jbiotec.2017.08.021DOI Listing
October 2017

Cordycepin induces autophagy-mediated c-FLIPL degradation and leads to apoptosis in human non-small cell lung cancer cells.

Oncotarget 2017 Jan;8(4):6691-6699

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, China.

Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8. And ectopic expression of c-FLIPL dramatically prevented cordycepin-caused apoptosis. Meanwhile, cordycepin stimulated autophagy through suppressing mTOR signaling pathway in lung cancer cells. When autophagy was blocked by Atg5 siRNA or PI3K inhibitor LY294002, the levels of apoptosis caused by cordycepin were obviously attenuated. In addition, suppression of autophagy could also elevate the level of c-FLIPL which indicated cordycepin-triggered autophagy promoted the degradation of c-FLIPL. Therefore, we conclude that cordycepin induces apoptosis through autophagy-mediated downregulation of c-FLIPL in human NSCLC cells. Taken together, our findings provide a novel prospect on the anti-tumor property of cordycepin, which may further prompt cordycepin to serve as a promising therapeutic approach in NSCLC treatment.
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http://dx.doi.org/10.18632/oncotarget.14262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351663PMC
January 2017

Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells.

Cell Cycle 2015 ;14(5):761-71

a Key Laboratory of Systems Biomedicine (Ministry of Education); Shanghai Center for Systems Biomedicine ; Shanghai Jiao Tong University ; Shanghai , China.

Cordycepin, an adenosine analog derived from Cordyceps militaris has been shown to exert anti-tumor activity in many ways. However, the mechanisms by which cordycepin contributes to the anti-tumor still obscure. Here our present work showed that cordycepin inhibits cell growth in NB-4 and U937 cells by inducing apoptosis. Further study showed that cordycepin increases the expression of p53 which promotes the release of cytochrome c from mitochondria to the cytosol. The released cytochrome c can then activate caspase-9 and trigger intrinsic apoptosis. Cordycepin also blocks MAPK pathway by inhibiting the phosphorylation of ERK1/2, and thus sensitizes the apoptosis. In addition, our results showed that cordycepin inhibits the expression of cyclin A2, cyclin E, and CDK2, which leads to the accumulation of cells in S-phase. Moreover, our study showed that cordycepin induces DNA damage and causes degradation of Cdc25A, suggesting that cordycepin-induced S-phase arrest involves activation of Chk2-Cdc25A pathway. In conclusion, cordycepin-induced DNA damage initiates cell cycle arrest and apoptosis which leads to the growth inhibition of NB-4 and U937 cells.
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http://dx.doi.org/10.1080/15384101.2014.1000097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615139PMC
November 2015

Physicochemical characteristics of epichlorohydrin, pyridine and trimethylamine functionalized cotton stalk and its adsorption/desorption properties for perchlorate.

J Colloid Interface Sci 2015 Feb 12;440:219-28. Epub 2014 Nov 12.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100, PR China.

Amine-impregnated cotton stalk (AICS) prepared by the reaction of cotton stalk with epichlorohydrin, pyridine and trimethylamine was used as the effective adsorbent for perchlorate removal. Solid-state (13)C NMR spectra, FT-IR, BET principle and element analysis provided evidence that amine groups have been successfully introduced onto the surface of AICS. The adsorption capacity of perchlorate by AICS was about 83.8 mg g(-1) at 20 °C. It was decreased to 80.6 mg g(-1) as the temperature was increased to 40 °C, which implied an exothermic nature for this adsorption process. Perchlorate adsorption capacity in fixed-bed column was optimum at neutral condition (pH: 6.0, 70.8 mg g(-1)) with bed depth of 2.7 cm and flow rate of 5 ml min(-1). In addition, chemical regeneration by HCl or NaOH (0.1 mol L(-1)) achieved more than 95% of regeneration efficiency. Biological regeneration of the saturated AICS with mixed bacteria has shown its merit with regeneration and biological perchlorate destruction simultaneously although its regeneration efficiency was only 56.8-74.8%.
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http://dx.doi.org/10.1016/j.jcis.2014.10.045DOI Listing
February 2015

Column adsorption of perchlorate by amine-crosslinked biopolymer based resin and its biological, chemical regeneration properties.

Carbohydr Polym 2015 Jan 16;115:432-8. Epub 2014 Sep 16.

Key Laboratory of Water Pollution Control and Recycling (Shandong), School of Environmental Science and Engineering, Shandong University, Jinan 250100, PR China.

Column adsorption of perchlorate by amine-crosslinked biopolymer based resin was investigated by considering the bed depth, stream flow rate and influent pH. The empty bed contact time (EBCT) increased with the growth of bed depths, meanwhile rising flow rate at constant bed depth (3.4 cm) decreased the breakthrough time. It was observed that perchlorate adsorption capacity was optimum at neutral condition (pH: 6.0, 170.4 mg/g), and decreased at acidic (pH: 3.0, 96.4 mg/g) or alkalic (pH: 12.0, 72.8 mg/g) influents. The predominant strains of the acclimated sludge for resin biological regeneration were the β-subclass of Proteobacteria. Biological regeneration of the saturated amine-crosslinked biopolymer based resin with mixed bacteria have shown its merit with regeneration and biological perchlorate destruction simultaneously, although its regeneration efficiency was only 61.2-84.1% by contrast to chemical regeneration with efficiency more than 95%.
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http://dx.doi.org/10.1016/j.carbpol.2014.09.010DOI Listing
January 2015

Determination of essential and toxic elements in Cordyceps kyushuensis Kawam by inductively coupled plasma mass spectrometry.

J Pharm Biomed Anal 2013 Jan 16;72:172-6. Epub 2012 Aug 16.

State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.

In this study, a total of 20 elements (essential, non-essential and toxic): lithium (Li), sodium (Na), potassium (K), gallium (Ga), magnesium (Mg), zinc (Zn), iron (Fe), copper (Cu), manganese (Mn), vanadium (V), chromium (Cr), nickel (Ni), cobalt (Co), molybdenum (Mo), selenium (Se), barium (Ba), tin (Sn), arsenic (As), lead (Pb) cadmium (Cd) and mercury (Hg) in natural and cultured Cordyceps kyushuensis have been determined by means of inductively coupled plasma mass spectrometry (ICP-MS). Cultured stroma, natural stroma and natural worm were digested by microwave-assisted method before analysis. The proposed ICP-MS method was validated by analyzing a certified reference material (CRM) GBW10015 (spinach). The results of one-way analysis of variance (ANOVA) revealed that the element concentrations in the three kinds of samples were significantly different (p<0.05). Except for Mg, Zn, Cu, the values of other elemental contents were the highest in the stroma of natural C. kyushuensis. In comparison with the worm, the concentrations of determined elements in wild stroma were higher. The remarkable difference of elemental contents between cultured and natural stroma may be caused by distinct growing environment. This finding highlighted the usefulness of ICP-MS elemental analysis and enhanced the value of C. kyushuensis as a candidate for nourishing food based on its composition.
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http://dx.doi.org/10.1016/j.jpba.2012.08.007DOI Listing
January 2013

Isolation and characterization of a novel pyrene-degrading Bacillus vallismortis strain JY3A.

Sci Total Environ 2011 Apr 2;409(10):1994-2000. Epub 2011 Mar 2.

State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.

The PAHs-degrading bacterium strain JY3A was newly isolated from the polluted soil in the Jinan Oil Refinery Factory, Shandong Province of China. The isolate was identified as Bacillus vallismortis with respect to its 16S rDNA sequence, DNA-DNA relatedness and fatty acid profiles, as well as various physiological characteristics. The strain was Gram-positive, motile, endospore forming, aerobic, oxidase and catalase-positive. The cells were 0.8-1.0μm wide and 2.0-2.5μm long, single or in pairs and sometimes in chains. Bacillus vallismortis strain JY3A could utilize naphthalene, phenanthrene, anthracene, pyrene, fluorene, benzene, toluene, phenol, methanol, ethanol, Tween 80, cyclohexane or catechol as sole carbon source. The strain alone removed 90.5% of pyrene at an initial concentration of 150ppm in 15days in the presence of 0.5% (w/w) Tween 80. However, in co-culture with Phanerochaete chrysosporium, JY3A reduced the concentration of pyrene by nearly 55.4% after 7days of incubation.
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http://dx.doi.org/10.1016/j.scitotenv.2011.02.020DOI Listing
April 2011

Enediyne antitumor antibiotic maduropeptin biosynthesis featuring a C-methyltransferase that acts on a CoA-tethered aromatic substrate.

J Am Chem Soc 2010 Sep;132(36):12534-6

Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.

The enediyne antitumor antibiotic maduropeptin (MDP) is produced by Actinomadura madurae ATCC 39144. The biosynthetic pathway for the 3,6-dimethylsalicylic acid moiety of the MDP chromophore is proposed to be comprised of four enzymes: MdpB, MdpB1, MdpB2, and MdpB3. Based on the previously characterized biosynthesis of the naphthoic acid moiety of neocarzinostatin (NCS), we expected a biosynthetic pathway featuring carboxylic acid activation by the MdpB2 CoA ligase immediately before its coupling to an enediyne core intermediate. Surprisingly, the MDP aromatic acid biosynthetic pathway employs an unusual logic in which MdpB2-catalyzed CoA activation occurs before MdpB1-catalyzed C-methylation, demonstrating that MdpB1 is apparently unique in its ability to C-methylate a CoA-tethered aromatic acid. MdpB2 is a promiscuous CoA ligase capable of activating a variety of salicylic acid analogues, a property that could be potentially exploited to engineer MDP analogues.
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http://dx.doi.org/10.1021/ja1050814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935939PMC
September 2010

[Comparison of supercritical fluid extraction and steam distillation methods for the extraction of essential oils from Schizonepeta tenuifolia Briq].

Se Pu 2005 Nov;23(6):646-50

School of Environmental Science and Engineering, Shandong University, Jinan 250100, China.

Essential oil was extracted from Schizonepeta tenuifolia Briq. by supercritical fluid extraction (SFE) and steam distillation (SD). The components extracted were determined by gas chromatography with area normalization method and identified by gas chromatography-mass spectrometry (GC-MS). The optimal chromatographic conditions were: capillary column, SE-54 (30 m x 0.25 mm i.d., 0.25 microm); column temperature, 50 degrees C (3 min) --> (5 degrees c/min) 180 degrees C (2 min --> (10 degrees C/ min) 260 degrees C 50 min); split injection, split ratio 1: 50; injector temperature, 280 degrees C. Fifty-four components were identified for the essential oils extracted by SFE, and its main components were found to be pulegone, menthone, linoleic acid chloride etc. Thirty-nine components were identified for the essential oil obtained by SD, and its main components were found to be pulegone, menthone, limonene etc. The SFE method is better than the SD method in reliability stability and reproducibility, and is thus well suitable for similar applications involving for extraction of other traditional Chinese herbal medicines.
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November 2005