Publications by authors named "Haiping Zheng"

19 Publications

  • Page 1 of 1

Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury.

Biomaterials 2021 Aug 27;277:121103. Epub 2021 Aug 27.

Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China. Electronic address:

Radiation-induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic cancer radiotherapy. However, effective therapeutic agents for this condition are limited. Here, we describe a novel strategy to exert additive effects of a non-erythropoietic EPO derivative (ARA290), along with a free radical scavenger, superoxide dismutase (SOD), using a bioengineered nanoreactor ([email protected]). ARA290-chimeric nanoreactor makes SOD present in a confined reaction space by encapsulation into its interior to heighten stability against denaturing stimuli. In a RILI mouse model, intratracheal administration of [email protected] was shown to significantly ameliorate acute radiation pneumonitis and pulmonary fibrosis. Our investigations revealed that [email protected] performs its radioprotective effects by protecting against radiation induced alveolar epithelial cell apoptosis and ferroptosis, suppressing oxidative stress, inhibiting inflammation and by modulating the infiltrated macrophage phenotype, or through a combination of these mechanisms. In conclusion, [email protected] is a potential therapeutic agent for RILI, and given its multifaceted roles, it may be further developed as a translational nanomedicine for other related disorders.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121103DOI Listing
August 2021

In Situ biomimetic Nanoformulation for metastatic cancer immunotherapy.

Acta Biomater 2021 Jul 27. Epub 2021 Jul 27.

Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, P.R. China. Electronic address:

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8 T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. STATEMENT OF SIGNIFICANCE: Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields.
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http://dx.doi.org/10.1016/j.actbio.2021.07.055DOI Listing
July 2021

Tubule-specific protein nanocages potentiate targeted renal fibrosis therapy.

J Nanobiotechnology 2021 May 26;19(1):156. Epub 2021 May 26.

Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, People's Republic of China.

Background: Despite the dramatic advances in modern medicine, efficient therapeutic measures for renal fibrosis remain limited. Celastrol (CLT) is effective in treating renal fibrosis in rat models, while causing severe systemic toxicity. Thus, we designed a tubule-specific nanocage (K3-HBc NCs) that effectively deliver CLT to tubular epithelial cell in a virus-like manner. The targeting ligand (K3) to tubular epithelial cells was displayed on the surface of Hepatitis B core protein (HBc) NCs by genetic fusion to the major immunodominant loop region. Ultra-small CLT nanodots were subtly encapsulated into the cavity through electrostatic interaction with the disassembly and reassembly of K3-HBc NCs, to yield K3-HBc/CLT complex. The efficacy of K3-HBc/CLT NCs were demonstrated in Unilateral ureteral obstruction (UUO)-induced renal fibrosis.

Results: The self-assembled K3-HBc/CLT could specifically target tubular epithelial cells via affinity with K3 ligand binding to the megalin receptor, significantly attenuating renal fibrosis. Remarkably, K3-HBc/CLT NCs significantly increased therapeutic efficacy and reduced the systemic toxicity in comparison with free CLT in UUO-induced mouse renal fibrosis model. Importantly, analysis of RNA sequencing data suggested that the anti-fibrotic effect of K3-HBc/CLT could be attributed to suppression of premature senescence in tubular epithelial cells via p21 and p16 pathway.

Conclusion: The tubule-specific K3-HBc/CLT represented a promising option to realize precise treatment for renal fibrosis.
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http://dx.doi.org/10.1186/s12951-021-00900-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157627PMC
May 2021

Berberine Prolongs Mouse Heart Allograft Survival by Activating T Cell Apoptosis the Mitochondrial Pathway.

Front Immunol 2021 25;12:616074. Epub 2021 Feb 25.

Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Organ Transplantation Institute, Xiamen University, Xiamen, China.

Berberine, which is a traditional Chinese medicine can inhibit tumorigenesis by inducing tumor cell apoptosis. However, the immunoregulatory of effects berberine on T cells remains poorly understood. Here, we first examined whether berberine can prolong allograft survival by regulating the recruitment and function of T cells. Using a major histocompatibility complex complete mismatch mouse heterotopic cardiac transplantation model, we found that the administration of moderate doses (5 mg/kg) of berberine significantly prolonged heart allograft survival to 19 days and elicited no obvious berberine-related toxicity. Compared to that with normal saline treatment, berberine treatment decreased alloreactive T cells in recipient splenocytes and lymph node cells. It also inhibited the activation, proliferation, and function of alloreactive T cells. Most importantly, berberine treatment protected myocardial cells by decreasing CD4 and CD8 T cell infiltration and by inhibiting T cell function in allografts. and assays revealed that berberine treatment eliminated alloreactive T lymphocytes the mitochondrial apoptosis pathway, which was validated by transcriptome sequencing. Taken together, we demonstrated that berberine prolongs allograft survival by inducing apoptosis of alloreactive T cells. Thus, our study provides more evidence supporting the potential use of berberine in translational medicine.
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http://dx.doi.org/10.3389/fimmu.2021.616074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959711PMC
June 2021

Relationship Between Pregnancy and Acute Disseminated Encephalomyelitis: A Single-Case Study.

Front Immunol 2020 1;11:609476. Epub 2021 Feb 1.

Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.

The relationship between pregnancy and autoimmune diseases is unclear. This study investigated the possible role of local immune changes and the activation state of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal-fetal interface during pregnancy in the pathogenesis of acute disseminated encephalomyelitis (ADEM). Clinical data and blood samples of a patient with ADEM were collected to observe the dynamic changes in lymphocyte populations after an abortion. The expression of HMGB1, TLR4, Nf-κB, AQP4, IL-2, IL-4, IL-6, and TNF-α in the fetal membrane and placenta was compared between the patient with pregnancy-related ADEM and a woman with a normal pregnancy using Real-time qPCR and western blotting (WB). The patient was diagnosed with ADEM in the early stage of pregnancy after showing limb weakness symptoms. In the third month of gestation, the symptoms worsened, with a disturbance of consciousness and breathing. After the abortion, the patient relapsed with vertigo and visual rotation. Analysis of lymphocyte subsets by flow cytometry showed that B lymphocytes increased, while natural killer T lymphocytes decreased. WB and Real-time qPCR showed that the expression levels of HMGB1, TLR4, Nf-κB, AQP4, and IL-6 in the fetal membrane and placenta were higher in the patient with pregnancy-related ADEM than in the woman with a normal pregnancy, while those of IL-2 were lower in the patient than in the woman with a normal pregnancy. The local immune changes and the activation of the HMGB1/TLR4/Nf-κB/IL-6 pathway at the maternal-fetal interface may be related to the pathogenesis of ADEM.
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http://dx.doi.org/10.3389/fimmu.2020.609476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882727PMC
June 2021

Genomic Mutations of Primary and Metastatic Lung Adenocarcinoma in Chinese Patients.

J Oncol 2020 8;2020:6615575. Epub 2020 Dec 8.

Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Lung cancer is still the leading cause of cancer-related death worldwide. Of lung cancer, lung adenocarcinoma (LUAD) is the most common subtype. Most patients with LUAD would develop into metastasis, which limits the available treatment. Targeted therapy and immunotherapy provided options for those advanced patients. But they also broached up challenges to identify the appropriate patients. This study aims to reveal the landscapes of genomic mutations in primary and metastatic LUAD and their actionability. This study enrolled 636 patients with LUAD, of whom 85 and 551 were from patients with and without metastasis, respectively. Next-generation sequencing technology was used to retrieve their genomic information. Genomic mutations including short nucleotide variation, long variation, copy number variations, and fusions were called. The corresponding actionability was revealed. A comparison of genomic mutations and actionability between primary and metastatic LUAD was performed. In primary tumors, BRCA2 and FAT3 were significantly mutated in older patients; while in metastases, ALK and NOTCH2 were significantly mutated in younger patients. Primary tumors in male patients were significantly mutated in LRP1B and KRAS. Compared to primary tumors, metastases harbored less short nucleotide variations but more copy number variations and fusions. In metastases, chromosome 1 and chromosome 9 had less short nucleotide variations and more CNV than in primary tumors. Genomic variations of activated dendritic cells were more frequently mutated in metastases. EGFR genomic variations were negatively associated with PD-L1 and TMB. Patients with EGFR inhibitor treatment tend to have lower PD-L1 expression. The revealed discrepancy between primary and metastatic lung cancer could help guide the treatment strategies and the development of novel drugs.
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http://dx.doi.org/10.1155/2020/6615575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787720PMC
December 2020

A Carrier Strategy for Mass Cytometry Analysis of Small Numbers of Cells.

Methods Mol Biol 2020 ;2111:21-33

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.

The recent launch of mass cytometry or cytometry by time of flight (CyTOF) has revolutionized flow cytometry. Similar to fluorescence flow cytometry, a key challenge for CyTOF is to analyze samples of limited amount or very rare cell populations under various experimental settings. Here we describe a carrier strategy that significantly reduces the required sample amount without losing analytical resolution. We were able to detect as few as 5 × 10 human peripheral blood mononuclear cells (PBMCs) using this method. This simple method thus enables the maximal usage of valuable clinical samples.
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http://dx.doi.org/10.1007/978-1-0716-0266-9_2DOI Listing
January 2021

Bioengineered Nanocage from HBc Protein for Combination Cancer Immunotherapy.

Nano Lett 2019 03 11;19(3):1719-1727. Epub 2019 Feb 11.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences , Xiamen University , Xiamen , Fujian 361102 , China.

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Naïve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.nanolett.8b04722DOI Listing
March 2019

Association between Parkinson's disease and risk of prostate cancer in different populations: An updated meta-analysis.

Sci Rep 2017 10 18;7(1):13449. Epub 2017 Oct 18.

Department of Neurology, Second Xiangya Hospital, Hunan, P. R. China.

Recently, growing evidence has revealed a significant association between Parkinson's disease (PD) and cancer. However, controversy still exists concerning the association between PD and prostate cancer. A comprehensive article search for relevant published studies was performed using the online databases PubMed, Web of Science and Embase up to January 1, 2017. The pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using the method of inverse variance with a random-effects model. Fifteen studies comprising 346,153 PD patients were included in this study. The results of the present study showed that PD was significantly associated with a decreased risk of prostate cancer in the Western population (RR: 0.83, 95% CI: 0.72-0.95, P < 0.01), while an increased risk of prostate cancer was shown in the Asian population (RR: 1.80, 95% CI: 1.52-2.13, P < 0.001). In the subgroup analysis, the reduced risk of prostate cancer in PD patients from Western populations was consistent regardless of study design or study quality. In conclusion, PD was significantly associated with a reduced risk of prostate cancer in the Western population. The relationship between those conditions in the Asian population needs to be confirmed by future studies.
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http://dx.doi.org/10.1038/s41598-017-13834-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647429PMC
October 2017

MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase.

Oncol Res 2017 Sep 23;25(8):1231-1243. Epub 2017 Jan 23.

MicroRNAs (miRs) have been demonstrated to be involved in the development and progression of osteosarcoma (OS), but the molecular mechanism still remains to be fully investigated. The present study investigated the function of miR-148a in OS, as well as its underlying mechanism. Our data showed that miR-148a was significantly downregulated in OS tissues compared to their matched adjacent normal tissues, and also in OS cell lines compared to normal human osteoblast cells. Low expression of miR-148a was significantly associated with tumor progression and a poor prognosis for OS patients. Rho-associated coiled-coil kinase 1 (ROCK1) was then identified as a target of miR-148a in Saos-2 and U2OS cells, and the expression of ROCK1 was significantly increased in OS tissues and cell lines. Moreover, the protein expression of ROCK1 was markedly reduced in miR-148a-overexpressing Saos-2 and U2OS cells, but significantly increased in miR-148a-downregulated Saos-2 and U2OS cells. Further investigation indicated that miR-148a had a suppressive effect on the proliferative, migratory, and invasive capacities of Saos-2 and U2OS cells. Moreover, overexpression of ROCK1 attenuated the inhibitory effects of miR-148a upregulation on the malignant phenotypes of Saos-2 and U2OS cells. In addition, overexpression of miR-148a significantly inhibited the tumor growth of U2OS cells in nude mice. Taken together, these data demonstrate that miR-148a acts as a tumor suppressor in OS, at least partly, via targeting ROCK1. Therefore, the miR-148a/ROCK1 axis may become a potential therapeutic target for OS.
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http://dx.doi.org/10.3727/096504017X14850134190255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841117PMC
September 2017

Effects of Lycium barbarum polysaccharides on the damage to human endometrial stromal cells induced by hydrogen peroxide.

Mol Med Rep 2017 Feb 28;15(2):879-884. Epub 2016 Dec 28.

Department of Nephrology, Affiliated Hospital of Hebei Engineering University, Handan, Hebei 056002, P.R. China.

Previous studies have shown that Lycium barbarum polysaccharides (LBPs) serve an important role in antioxidant activity to protect the cells and tissues. However, the specific mechanism of LBPs in the prevention of endometrial damage remains to be elucidated. Using morphological observation, cell proliferation assay, the detection of superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) in cell culture supernatant fluid, the detection by western blot analysis and reverse transcription-quantitative polymerase chain reaction of the mRNA and protein expression levels of caspase‑3 and Bcl‑2 in endometrial stromal cells (ESCs), it was demonstrated that, in vitro, hydrogen peroxide (H2O2)-induced death of ESCs, increased the content of MDA and decreased the activity of SOD, and decreased the expression of Bcl-2 and increased the expression of caspase‑3. LBPs can inhibit H2O2‑induced cell death of ESCs, decrease the content of MDA in ESCs and increase the activity of SOD, as well as increasing the expression of Bcl‑2 and decreasing the expression levels of caspase‑3. These findings suggested that LBPs can inhibit H2O2‑induced apoptosis of EECs and that LBPs are able to offer a significant protection against oxidative stress to ESCs.
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http://dx.doi.org/10.3892/mmr.2016.6080DOI Listing
February 2017

Mechanism and Therapy of Brain Edema after Intracerebral Hemorrhage.

Cerebrovasc Dis 2016 26;42(3-4):155-69. Epub 2016 Apr 26.

Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Intracerebral hemorrhage (ICH) is a subtype of stroke with a severe high mortality and disability rate and accounts for about 10-15% of all strokes. The oppression and destruction by hematoma to brain tissue cause the primary brain injury. The inflammation and coagulation response after ICH would accelerate the formation of brain edema around hematoma, resulting in a more severe and durable injury. Currently, treatments for ICH are focusing on the primary injury including reducing intracranial hypertension, blood pressure control, and rehabilitation. There is a short-of-effective medical treatment for secondary inflammation and reducing brain edema in ICH patients. So, it is very important to study on the relationship between brain edema and ICH.

Summary: Many molecular and cellular mechanisms contribute to the formation and progress of brain edema after ICH; inhibition of brain edema provides favorable outcome of ICH.

Key Messages: This review mainly discusses the pathology and mechanism of brain edema, the effects of brain edema on ICH, and the methods of treating brain edema after ICH.
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http://dx.doi.org/10.1159/000445170DOI Listing
November 2017

[Effect of the Combination of Xiyanping and Cefazolin on the Function of Neutrophils in Mice].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2015 Oct;32(5):1079-82

Xiyanping is used to treat infectious diseases with antibiotics in clinic. The aim of this study is to investigate the mechanism of Xiyanping through studying the effect of the combination of Xiyanping with Cefazolin on the chemotaxis and phagocytic function of peripheral blood neutrophils in mice. Ten healthy mice were in control group. Forty healthy mice in experimental group were infected with staphylococcus aureus, and were randomly divided further into four groups, i. e. model group, Xiyanping group, Cefazolin group and combination group (Xiyanping with Cefazolin). Mice in the control group and model group were given normal saline (NS) through abdomen while those in other groups were given Xiyanping, Cefazolin, and Xiyanping with Cefazolin, respectively. The chemotaxis of peripheral blood neutrophils was detected with the transwell method, and the phagocytic function of peripheral blood neutrophils was analyzed with flow cytometry (FCM). In the present study, there was no significance on the chemotactic index of peripheral blood neutrophils in all the groups (P > 0.05). The actual phagocytotic rate and index of peripheral blood neutrophils in the blank group, Xiyanping group, and the combination group were significantly higher than those of the model group and Cefazolin group (P < 0.05). However, those were not significant in the blank group, Xiyanping group, and the combination group (P > 0.05) or between the model group and Cefazolin group (P> 0.05). Our results suggested the combination of Xiyanping and Cefazolin could enhance the therapeutic effect by improving the phagocytic function of peripheral blood neutrophils.
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October 2015

Functional diversity and properties of multiple xylanases from Penicillium oxalicum GZ-2.

Sci Rep 2015 Jul 30;5:12631. Epub 2015 Jul 30.

National Engineering Research Center for Organic-based Fertilizers, Jiangsu Collaborative Innovation Center for Solid Organic Waste Utilization, Nanjing Agricultural University, Nanjing, 210095, China.

A multiple xylanase system with high levels of xylanase activity produced from Penicillium oxalicum GZ-2 using agricultural waste as a substrate has been previously reported. However, the eco-physiological properties and origin of the multiplicity of xylanases remain unclear. In the present study, eight active bands were detected using zymography, and all bands were identified as putative xylanases using MALDI-TOF-MS/MS. These putative xylanases are encoded by six different xylanase genes. To evaluate the functions and eco-physiological properties of xylanase genes, xyn10A, xyn11A, xyn10B and xyn11B were expressed in Pichia pastoris. The recombinant enzymes xyn10A and xyn10B belong to the glycoside hydrolase (GH) family 10 xylanases, while xyn11A and xyn11B belong to GH11 xylanases. Biochemical analysis of the recombinant proteins revealed that all enzymes exhibited xylanase activity against xylans but with different substrate specificities, properties and kinetic parameters. These results demonstrated that the production of multiple xylanases in P. oxalicum GZ-2 was attributed to the genetic redundancy of xylanases and the post-translational modifications, providing insight into a more diverse xylanase system for the efficient degradation of complex hemicelluloses.
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http://dx.doi.org/10.1038/srep12631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519791PMC
July 2015

Identification and comparative analysis of microRNAs in barnyardgrass (Echinochloa crus-galli) in response to rice allelopathy.

Plant Cell Environ 2015 Jul 23;38(7):1368-81. Epub 2015 Jan 23.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fujian Agriculture and Forestry University, Fuzhou, 35002, China.

Rice allelopathy is a hot topic in the field of allelopathy, and behaviour of donor allelopathic rice has been well documented. However, few study addresses response of receiver barnyardgrass (BYG). We found that expression of miRNAs relevant to plant hormone signal transduction, nucleotide excision repair and the peroxisome proliferator-activated receptor and p53 signalling pathways was enhanced in BYG co-cultured with the allelopathic rice cultivar PI312777, the expression levels of these miRNAs in BYG plants were positively correlated with allelopathic potential of the co-cultured rice varieties. Treatment of BYG plants with rice-produced phenolic acids also increased miRNA expression in BYG, while treatment with rice-produced terpenoids had no obvious effect on miRNA expression. In the hydroponic system, the largest number of Myxococcus sp. was found in the growth medium containing rice with the highest allelopathic potential. The addition of phenolic acids in the hydroponic medium also increased the number of Myxococcus sp. More interestingly, inoculation with Myxococcus xanthus significantly increased miRNA expression in the treated BYG. Jointed treatments of ferulic acid and M. xanthus led to strongest growth inhibition of BYG. The results suggest that there exist involvement of Myxococcus sp. and mediation of miRNA expression in rice allelopathy against BYG.
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http://dx.doi.org/10.1111/pce.12492DOI Listing
July 2015

A new acidophilic thermostable endo-1,4-β-mannanase from Penicillium oxalicum GZ-2: cloning, characterization and functional expression in Pichia pastoris.

BMC Biotechnol 2014 Oct 28;14:90. Epub 2014 Oct 28.

Jiangsu Collaborative Innovation Center for Solid Organic Waste Utilization, College of Resources and Environmental Science, Nanjing Agricultural University, Nanjing, 210095, China.

Background: Endo-1,4-β-mannanase is an enzyme that can catalyze the random hydrolysis of β-1, 4-mannosidic linkages in the main chain of mannans, glucomannans and galactomannans and has a number of applications in different biotechnology industries. Penicillium oxalicum is a powerful hemicellulase-producing fungus (Bioresour Technol 123:117-124, 2012); however, few previous studies have focused on the cloning and expression of the endo-1,4-β-mannanase gene from Penicillium oxalicum.

Results: A gene encoding an acidophilic thermostable endo-1,4-β-mannanase (E.C. 3.2.1.78) from Penicillium oxalicum GZ-2, which belongs to glycoside hydrolase family 5, was cloned and successfully expressed in Pichia pastoris GS115. A high enzyme activity (84.4 U mL(-1)) was detected in the culture supernatant. The recombinant endo-1,4-β-mannanase (rPoMan5A) was tagged with 6 × His at its C-terminus and purified using a Ni-NTA Sepharose column to apparent homogeneity. The purified rPoMan5A showed a single band on SDS-PAGE with a molecular mass of approximately 61.6 kDa. The specific activity of the purified rPoMan5A was 420.9 U mg(-1) using locust bean gum as substrate. The optimal catalytic temperature (10 min assay) and pH value for rPoMan5A are 80 °C and pH 4.0, respectively. The rPoMan5A is highly thermostable with a half-life of approximately 58 h at 60 °C at pH 4.0. The K m and V max values for locust bean gum, konjac mannan, and guar gum are 7.6 mg mL(-1) and 1425.5 μmol min(-1) mg(-1), 2.1 mg mL(-1) and 154.8 μmol min(-1) mg(-1), and 2.3 mg mL(-1) and 18.9 μmol min(-1) mg(-1), respectively. The enzymatic activity of rPoMan5A was not significantly affected by an array of metal ions, but was inhibited by Fe(3+) and Hg(2+). Analytical results of hydrolytic products showed that rPoMan5A could hydrolyze various types of mannan polymers and released various mannose and manno-oligosaccharides, with the main products being mannobiose, mannotriose, and mannopentaose.

Conclusion: Our study demonstrated that the high-efficient expression and secretion of acid stable and thermostable recombinant endo-1, 4-β-mannanase in Pichia pastoris is suitable for various biotechnology applications.
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http://dx.doi.org/10.1186/s12896-014-0090-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219100PMC
October 2014

Does clopidogrel with aspirin after acute minor stroke or transient ischemic attack increase the risk of cerebral hemorrhage?

Chin Med J (Engl) 2014 ;127(18):3352-3

Department of Neurology, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Email:

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May 2016

Chorea-ballism associated with ketotic hyperglycemia.

Neurol Sci 2014 Dec 28;35(12):1851-5. Epub 2014 Sep 28.

Department of Neurology, Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People's Republic of China.

Chorea-ballism is a rare movement disorder characterized by irregular, poorly patterned, and involuntary movements, which are usually unilateral but may be bilateral or involve the extremities. The most common metabolic cause of transient chorea-ballism is nonketotic or ketotic hyperglycemia (NKHG or KHG, respectively). A meta-analysis and several reviews have identified clinical characteristics of NKHG-associated chorea-ballism; however, the characteristics of KHG-associated chorea-ballism remain unknown. We performed a search for studies of patients with KHG-associated chorea-ballism, published in MEDLINE between 1960 and May 2014, and identified 13 studies of 15 patients. Despite the limited number of cases, we identified some significant differences in the clinical and radiological characteristics between patients with KHG- or NKHG-induced chorea-ballism. Patients with KHG were significantly younger than patients with NKHG, and a higher percentage of patients with KHG had atypical or negative brain imaging findings for chorea-ballism compared to patients with NKHG. We recommend that blood glucose levels be tested on admission as a key diagnostic measure, to improve the early diagnosis of chorea-ballism. The best treatment for KHG-induced chorea-ballism is rapid glucose control with an insulin drip and, possibly, neuroleptics. The mechanisms of the disease are unclear, although the GABA theory, cerebrovascular insufficiency, and alterations of dopaminergic activity in the striatum might play important roles.
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http://dx.doi.org/10.1007/s10072-014-1968-1DOI Listing
December 2014

Statins and intracerebral hemorrhage.

Chin Med J (Engl) 2014 ;127(13):2531-6

Department of Neurology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Email:

Objective: To briefly review the literature regarding the impact of statins on the prevention and treatment of stroke, especially on intracerebral hemorrhage (ICH). We described statins' effects, mechanism of ICH, serum total cholesterol and ICH, and the relationship between statins and ICH.

Data Sources: All articles used in this review were mainly searched from the PubMed database with no limitations of language and year of publication.

Study Selection: Randomized controlled studies, prospective cohort studies, animal experiments, and meta-analysis articles related to this topic in the past decade were selected.

Results: Statins play an important role in the primary and secondary prevention of cardiovascular diseases and also have an impact on the treatment of vascular diseases. There still exist controversies about the relationship between statins and ICH. More clinical and experimental trials indicate that statins do not increase the risk of ICH.

Conclusion: A low or a regular dose of statins would not increase the risk of ICH.
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April 2015
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