Publications by authors named "Bobo Zhang"

13 Publications

  • Page 1 of 1

IP-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion.

Nat Commun 2021 04 28;12(1):2461. Epub 2021 Apr 28.

School of Life Sciences, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China.

COP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1-CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2 mice with partially disrupted binding of IP, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP-assisted CSN-COP1 competition. Deregulation of the IP-CSN-CRL4-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.
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http://dx.doi.org/10.1038/s41467-021-22941-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080631PMC
April 2021

MiR-877 suppresses tumor metastasis via regulating FOXM1 in ovarian cancer.

J BUON 2021 Jan-Feb;26(1):229-234

Department of Oncology, Dongda Hospital, Shanxian, Heze, China.

Purpose: Ovarian cancer (OC) is a serious threat to women's life. OC is insidious and lacks early diagnosis and effective treatment. Therefore, it is vital to look for new therapeutic targets and biomarkers.

Methods: MicroRNA-877 (miR-877) expression level in OC was accessed via quantitative real-time polymerase chain reaction (qRT-PCR). Transwell assay, Matrigel assay and wound healing assay were used to analyze the ability of miR-877 on cell migration and invasion. Luciferase reporter assay was employed for verification the target of miR-877. Western blotting was taken in for the determination of the expression level of FOXM1.

Results: MiR-877 had low expression level in OC tissues and cell lines. MiR-877 over-expression induced inhibition of cell migration and invasion. FOXM1 was a direct target of miR-877. MiR-877 restrained cell migration and invasion by negatively regulating FOXM1 expression in OC.

Conclusions: Our research elucidated that miR-877 played a role of tumor suppressor in OC by negatively regulating FOXM1 which may bring a novel insight into new molecular therapeutic targets and biomarkers for OC.
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March 2021

Effects of Cellulose Nanocrystals and Cellulose Nanofibers on the Structure and Properties of Polyhydroxybutyrate Nanocomposites.

Polymers (Basel) 2019 Dec 11;11(12). Epub 2019 Dec 11.

College of Light Industry & Food Engineering, Guangxi University, Nanning 530004, China.

One of the major obstacles for polyhydroxybutyrate (PHB), a biodegradable and biocompatible polymer, in commercial applications is its poor elongation at break (~3%). In this study, the effects of nanocellulose contents and their types, including cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs) on the crystallization, thermal, and mechanical properties of PHB composites were systematically compared. We explored the toughening mechanisms of PHB by adding CNCs and cellulose CNFs. The results showed that when the morphology of bagasse nanocellulose was rod-like and its content was 1 wt %, the toughening modification of PHB was the best. Compared with pure PHB, the elongation at break and Young's modulus increased by 91.2% and 18.4%, respectively. Cellulose nanocrystals worked as heterogeneous nucleating agents in PHB and hence reduced its crystallinity and consequently improved the toughness of PHB. This simple approach could potentially be explored as a strategy to extend the possible applications of this biopolymer in packaging fields.
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http://dx.doi.org/10.3390/polym11122063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960622PMC
December 2019

Production, structure and morphology of exopolysaccharides yielded by submerged fermentation of Antrodia cinnamomea.

Carbohydr Polym 2019 Feb 28;205:271-278. Epub 2018 Oct 28.

State Key Laboratory of Food Science and Technology, Jiangnan University, WuXi 214122, China. Electronic address:

Carbon and nitrogen sources in culture medium of Antrodia cinnamomea were optimized to eliminate the interference of exterior macromolecules on exopolysaccharide (EPS) yield by submerged fermentation. The results suggested that culture medium containing 50 g/L of glucose and 20 g/L of yeast extract as the optimal carbon and nitrogen sources could produce 1.03 g/L of exopolysaccharides. After purification, two heteropolysaccharides (AC-EPS1 and AC-EPS2) were obtained and characterized to provide the basic structure information. As the main component of the produced EPS, AC-EPS2 (accounting for 89.63%) was mainly composed of galactose (87.42%) with M (molecular weight) and R.M.S. (root-mean-square) radius of 1.18 × 10 g/mol and 25.3 nm, respectively. Furthermore, the spherical and flexible chain morphologies of EPS were observed in different solvents by TEM. The structural and morphological information of purified EPS were significant for further study on their structure-activity relationship and related applications.
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http://dx.doi.org/10.1016/j.carbpol.2018.10.070DOI Listing
February 2019

A novel recombinant RANKL vaccine prepared by incorporation of an unnatural amino acid into RANKL and its preventive effect in a murine model of collagen-induced arthritis.

Int Immunopharmacol 2018 Nov 20;64:326-332. Epub 2018 Sep 20.

Department of Orthopaedics, Shenzhen University General Hospital, Shenzhen 518000, China. Electronic address:

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis, bone atrophy, and subsequent progressive destruction of articular tissue. Targeted inhibition of receptor activator of NF-kB ligand (RANKL) has been highly successful in preventing RA-mediated bone erosion in animal models and patients, suggesting that development of a RANKL vaccine might be of therapeutic value. Our previous study has shown that the recombinant RANKL vaccine YpNOPhe, generated by replacement of a single tyrosine residue (Tyr) in murine RANKL (mRANKL) with p-nitrophenylalanine (pNOPhe), induces a high titer antibody response and prevents ovariectomy (OVX)-induced bone loss in mice. This aim of this study was to further evaluate the vaccine's preventive effects in a murine model of collagen-induced arthritis. The results of this study showed that YpNOPhe not only induced a high titer antibody response and inhibited osteoclastogenesis but also significantly prevented bone erosion and ameliorated the severity of a collagen-induced arthritis (CIA) model in mice. Moreover, use of the vaccine improved the clinical situations of the CIA mice. These results suggest a potential application of an anti-RANKL vaccine in the treatment of RA-induced bone erosion.
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http://dx.doi.org/10.1016/j.intimp.2018.09.022DOI Listing
November 2018

A new vaccine targeting RANKL, prepared by incorporation of an unnatural Amino acid into RANKL, prevents OVX-induced bone loss in mice.

Biochem Biophys Res Commun 2018 05 31;499(3):648-654. Epub 2018 Mar 31.

Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China; Department of Orthopaedics, Shenzhen University General Hospital, Shenzhen 518052, China. Electronic address:

Bone homeostasis is maintained by a dynamic balance between osteoblastic bone formation and osteoclastic bone resorption. The receptor activator of nuclear-κB ligand (RANKL) is essential for the function of the bone-resorbing osteoclasts, and targeting RANKL has been proved highly successful in osteoporosis patients. This study aimed to design a novel vaccine targeting RANKL and evaluate its therapeutic effects in OVX-induced bone loss model. Anti-RANKL vaccine was generated by incorporating the unnatural amino acid p-nitrophenylalanine (pNOPhe) into selected sites in the murine RANKL (mRANKL) molecule. Specifically, mutation of a single tyrosine residue Tyr (Y234) or Tyr (Y240) of mRANKL to pNOPhe (thereafter named as YpNOPhe or YpNOPhe) induced a high titer antibody response in mice, whereas no significant antibody response was observed for the wild type mRANKL (WT mRANKL). The antiserum induced by YpNOPhe or YpNOPhe could efficiently prevent osteoclastogenesis in vitro. Moreover, immunization with YpNOPhe or YpNOPhe could also prevent OVX-induced bone loss in mice, suggesting that selected pNOPhe-substituted mRANKL may pave the way for creating a novel vaccine to treat osteoporosis.
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http://dx.doi.org/10.1016/j.bbrc.2018.03.205DOI Listing
May 2018

D-chiro-inositol enriched Fagopyrum tataricum (L.) Gaench extract alleviates mitochondrial malfunction and inhibits ER stress/JNK associated inflammation in the endothelium.

J Ethnopharmacol 2018 Mar 7;214:83-89. Epub 2017 Dec 7.

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, PR China. Electronic address:

Ethnopharmacological Relevance: Tartary buckwheat is a food medicine dual-use crop with healing effects on cardiovascular diseases and type2 diabetes. It has been proposed that endothelial dysfunction is the initial lesion in these diseases and it's associated with mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive compound of Tartary buckwheat and is always deficit in type2 diabetes. However, it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate mitochondrial dysfunction, ER stress and inflammation in the endothelium.

Material And Methods: Endothelial cells were treated with palmitic acid (PA) and mice were fed with high fat diet (HFD). The effects of DCI-enriched Tartary buckwheat bran extract (TBBE) on superoxide anion generation, dynamin-related protein 1 (Drp1), mitofusin2 (Mfn2), inositol-requiring enzyme-1α (IRE1α) and Jun n-terminal kinase (JNK) activation and inflammation in the endothelium against lipotoxicity were investigated.

Results: In endothelial cells, TBBE significantly inhibited oxidative stress. Meanwhile, in HFD-fed mice and PA-induced cells, TBBE regulated Drp1 phosphorylation and inhibited its activation, implying the protective effect of TBBE on mitochondrial morphology. As a result, TBBE protected mitochondrial function. Additionally, TBBE inhibited ER stress and reduced the production of IL-6 and VCAM-1, associated with JNK pathway, thereby inhibiting the caspase-3 activation in vivo and in vitro.

Conclusions: Taken together, this study indicated the beneficial role of TBBE in endothelial inflammation, with emphasis on mitochondrial dysfunction, ER stress and JNK activation.
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http://dx.doi.org/10.1016/j.jep.2017.12.002DOI Listing
March 2018

PhI(OCOCF)-Mediated Construction of a 2-Spiropseudoindoxyl Skeleton via Cascade Annulation of 2-Sulfonamido-N-phenylpropiolamide Derivatives.

Org Lett 2017 02 30;19(4):902-905. Epub 2017 Jan 30.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University , Tianjin 300072, P. R. China.

A cascade annulation of 2-sulfonamido-N-phenylpropiolamide derivatives leading to the construction of the 2-spiropseudoindoxyl skeleton was realized under mild conditions with phenyliodine(III) bis(trifluoroacetate) (PIFA) as the sole oxidant. This metal-free spirocyclization process is suggested to encompass a sequential C(sp)-C(sp) and C(sp)-N bond formation with the concomitant introduction of a carbonyl oxygen.
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http://dx.doi.org/10.1021/acs.orglett.7b00058DOI Listing
February 2017

d-Chiro inositol ameliorates endothelial dysfunction via inhibition of oxidative stress and mitochondrial fission.

Mol Nutr Food Res 2017 08 3;61(8). Epub 2017 Mar 3.

College of Food Science and Engineering, Northwest A&F University, YangLing, Shaanxi, China.

Scope: d-chiro inositol (DCI), an isomer of inositol, possesses anti-oxidative and endothelial protective properties. The mechanism by which DCI prevents endothelial dysfunction was investigated, with emphasis on oxidative stress.

Methods And Results: DCI was found to inhibit NOX4 induction and enhance Nrf2 activity in palmitate (PA)-stimulated cells, showing that DCI prevents oxidative stress. DCI suppressed Ser616 phosphorylation and increased Ser637 phosphorylation of Drp1 and inhibited PA-induced mitochondrial fission. Knockdown of Drp1 attenuated NOX4 over-expression and increased the inhibitory effect of DCI. In addition, DCI enhanced AMPK activity through the LKB1-dependent pathway. AMPK knockdown diminished the inhibitory effect of DCI on Drp1/NOX4 induction, indicating that AMPK is essential for Drp1 and NOX4 suppression by DCI. As a result, DCI inhibited cell apoptosis against PA insults. Consistent with the effects observed in cells, DCI reversed endothelial dysfunction in rat aorta rings under lipid-challenged conditions. In high fat-fed mice, oral administration of DCI inhibited Drp1/NOX4 induction and enhanced NO generation in the aortic endothelium, confirming its protective role in endothelial function in vivo.

Conclusion: Drp1 activation-induced mitochondrial fission and NOX4 over-expression are associated with endothelial injury. DCI prevented endothelial dysfunction by inhibiting oxidative stress and mitochondrial fission in an AMPK-dependent manner.
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http://dx.doi.org/10.1002/mnfr.201600710DOI Listing
August 2017

Induction of antroquinonol production by addition of hydrogen peroxide in the fermentation of Antrodia camphorata S-29.

J Sci Food Agric 2017 Jan 3;97(2):595-599. Epub 2016 Jun 3.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.

Background: Antroquinonol have significantly anti-tumour effects on various cancer cells. There is still lack of reports on regulation of environmental factors on antroquinonol production by Antrodia camphorata.

Results: An effective submerged fermentation method was employed to induce antroquinonol with adding H O . The production of antroquinonol was 57.81 mg L after fermentation for 10 days when adding 25 mmol L H O at day 4 of the fermentation process. Then, antroquinonol was further increased to 80.10 mg L with cell productivity of 14.94 mg g dry mycelium when the feeding rate of H O was adjusted to 0.2 mmol L h in the 7 L fermentation bioreactor. After inhibiting the generation of reactive oxygen species with the inhibitor diphenyleneiodoium, the synthesis of antroquinonol from A. camphorata was significantly reduced, and the yield was only 3.3 mg L .

Conclusion: The results demonstrated that addition of H O was a very effective strategy to induce and regulate the synthesis of antroquinonol in submerged fermentation. Reactive oxygen species generated by H O during fermentation caused oxidative stress, which induced the synthesis of antroquinonol and other chemical compounds. Moreover, it is very beneficial process to improve production and diversity of the active compounds during liquid fermentation of A. camphorata mycelium. © 2016 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.7770DOI Listing
January 2017

Wireless Falling Detection System Based on Community.

J Nanosci Nanotechnol 2015 Jun;15(6):4367-72

The elderly are more likely to suffer the aches or pains from the accidental falls, and both the physiology and psychology of patients would subject to a long-term disturbance, especially when the emergency treatment was not given timely and properly. Although many methods and devices have been developed creatively and shown their efficiency in experiments, few of them are suitable for commercial applications routinely. Here, we design a wearable falling detector as a mobile terminal, and utilize the wireless technology to transfer and monitor the activity data of the host in a relatively small community. With the help of the accelerometer sensor and the Google Mapping service, information of the location and the activity data will be send to the remote server for the downstream processing. The experimental result has shown that SA (Sum-vector of all axes) value of 2.5 g is the threshold value to distinguish the falling from other activities. A three-stage detection algorithm was adopted to increase the accuracy of the real alarm, and the accuracy rate of our system was more than 95%. With the further improvement, the falling detecting device which is low-cost, accurate and user-friendly would become more and more common in everyday life.
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http://dx.doi.org/10.1166/jnn.2015.9805DOI Listing
June 2015

Effect of cultural conditions on antrodin C production by basidiomycete Antrodia camphorata in solid-state fermentation.

Biotechnol Appl Biochem 2014 Nov-Dec;61(6):724-32. Epub 2014 May 14.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.

Antrodia camphorata is a medicinal fungus and antrodin C is one of the main bioactive components of A. camphorata in the submerged fermentation (SmF). To optimize the culture conditions, the factors influencing the production of antrodin C by A. camphorata under solid-state fermentation (SSF) were investigated in this study. Different solid substrates and external nitrogen sources were tested for their efficiency in producing antrodin C. The response surface methodology was applied to evaluate the influence of several variables, namely, the concentrations of soybean meal, initial moisture content, and inoculum density on antrodin C production in solid-state fermentation. The experimental results show that the optimum fermentation medium for antrodin C production by A. camphorata was composed of 0.578 g soybean meal, 0.05 g Na2 HPO4 , 0.05 g MgSO4 for 100 g rice, with 51.83% initial moisture content, 22 day culture time, 28 °C culture temperature, and 35.54% inoculum density. At optimized conditions, 6,617.36 ± 92.71 mg kg(-1) yield of antrodin C was achieved. Solid-state fermentation is one good cultural method to improve the production of antrodin C by A. camphorata.
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http://dx.doi.org/10.1002/bab.1220DOI Listing
August 2015

Enhanced production of pigments by addition of surfactants in submerged fermentation of Monascus purpureus H1102.

J Sci Food Agric 2013 Oct 29;93(13):3339-44. Epub 2013 May 29.

Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.

Background: The production of pigments by Monascus spp. has attracted increasing attention. Modification of the cell membrane structure by addition of surfactants has proved to be effective for the secretion of intracellular metabolites. Hence in this study the effects and underlying mechanism of surfactants on the production of pigments in submerged fermentation of Monascus purpureus H1102 were systematically investigated.

Results: Various surfactants exerted significant but different impacts on the biomass and production of pigments. The maximum production of pigment (304.3 U mL(-1) ) and highest extracellular/intracellular pigment ratio (1.46) were achieved when 15 g L(-1) Triton X-100 was added at 24 h of fermentation, corresponding to significant increases of 88.4 and 240% respectively compared with the control. Meanwhile, the concentration of citrinin (0.94 mg L(-1) ) was 20.6% lower than that of the control. A further study on the fatty acid composition of M. purpureus H1102 showed that the unsaturated/saturated fatty acid ratio and the index of unsaturated fatty acid increased significantly with the addition of Triton X-100.

Conclusion: The addition of surfactant Triton X-100 could greatly enhance the production of pigment. It was suggested that Triton X-100 facilitated the secretion of intracellular pigment and therefore enhanced pigment production accordingly.
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http://dx.doi.org/10.1002/jsfa.6182DOI Listing
October 2013