Publications by authors named "Wenwen Lu"

21 Publications

  • Page 1 of 1

Comorbid Bipolar Disorder and Migraine: From Mechanisms to Treatment.

Front Psychiatry 2020 11;11:560138. Epub 2021 Jan 11.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods, with some patients suffering a gradual deterioration of illness and consequent cognitive deficits during the late stage. Migraine is a disease generally without abnormal medical examinations, neurological examinations or laboratory studies, and the diagnosis is made based on the retrospective demonstration of headache features and groupings of disease-associated symptoms. The epidemiology of comorbid BD and migraine is high and it is obligatory to find effective treatments to improve the prognosis. Recent investigations demonstrated that the close relationship between BD and migraine significantly increased the rapid cycling rates of both BD and migraine in patients. Although the detailed mechanism is complex and largely unclear in comorbid BD and migrain, genetic factors, neurotransmitters, altered signaling pathways, disturbances of inflammatory cytokines, and mitochondrial dysfunction are risk factors of BD and migraine. Particularly these two diseases share some overlapping mechanisms according to previous studies. To this end, we call for further investigations of the potential mechanisms, and more efforts are underway to improve the treatment of people with comorbid BD and migraine. In this review, we provide an overview of the potential mechanisms in patients with BD or migraine and we further discuss the treatment strategies for comorbid BD and migraine and it is obligatory to find effective treatments to improve the prognosis. This work will provide insights for us to know more about the mechanisms of comorbid BD and migraine, provides new therapeutic targets for the treatment and give clinicians some guidance for more appropriate and beneficial treatment.
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http://dx.doi.org/10.3389/fpsyt.2020.560138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829298PMC
January 2021

WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression.

Mol Brain 2020 11 13;13(1):155. Epub 2020 Nov 13.

Institute of Life Sciences, Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life Sciences, Hangzhou Normal University, Hangzhou, 310029, People's Republic of China.

Olig2 transcription factor is essential for the maintenance of neural progenitor cells (NPCs) in the pMN domain and their sequential specification into motor neurons (MNs) and oligodendrocyte precursor cells (OPCs). The expression of Olig2 rapidly declines in newly generated MNs. However, Olig2 expression persists in later-born OPCs and antagonizes the expression of MN-related genes. The mechanism underlying the differential expression of Olig2 in MNs and oligodendrocytes remains unknown. Here, we report that activation of WNT/β-catenin signaling in pMN lineage cells abolished Olig2 expression coupled with a dramatic increase of Ngn2 expression. Luciferase reporter assay showed that Ngn2 inhibited Olig2 promoter activity. Overexpression of Ngn2-EnR transcription repressor blocked the expression of Olig2 in ovo. Our results suggest that down-regulation of WNT-Ngn2 signaling contributes to oligodendrogenesis from the pMN domain and the persistent Olig2 expression in OPCs.
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http://dx.doi.org/10.1186/s13041-020-00696-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666497PMC
November 2020

Influence of acupuncture on the expression of VIP, SP, NKA and NKB, cAMP/cGMP and HE content and treatment of bronchial asthma in rats.

Cell Mol Biol (Noisy-le-grand) 2020 Jul 31;66(5):29-35. Epub 2020 Jul 31.

This research was set up to explore the neural mechanisms of acupuncture in the treatment of bronchial asthma in rats by detecting the content of substance P(SP), vasoactive intestinal peptide (VIP), neurokinin A(NKA), neurokinin B (NKB), cyclic adenosine monophosphate/cyclic guanosine monophosphate ratio (cAMP/cGMP) and hematoxylin-eosin (HE) staining for the pathological changes of lung tissue, in order to Institute Certain Experimental and Theoretical Foundation for Traditional Chinese Medicine (TCM) Prevention and Treatment of Bronchial Asthma. For this purpose, fifty healthy adult Wistar male rats, weighing 200-250 g, were randomly divided into 5 groups: normal control group A, asthma control group B, asthma acupuncture group C, adrenalectomy (ADX)-asthma  group D, adrenalectomy (ADX)-asthma acupuncture group E. Group A was raised with other groups at the same period; Group B was induced asthma by ovalbumin; Group C was induced asthma as Group B and then acupunctured five acupoints (bilateral Feishu, bilateral Fengmen, and Dazhui); Group D was induced asthma after adrenalectomy; group E was treated with acupuncture on the basis of group D. HE staining was performed in the lung tissue of rats from each group, and histopathologic changes were observed. SP, VIP, NKA, NKB in each rat lung tissue were measured by immunohistochemistry. cAMP/cGMP was measured with ELISA to speculate the neural mechanisms of acupuncture in the treatment of bronchial asthma. The results were as: decrease of cAMP/cGMP and VIP and increase of SP, NKA, NKB in the lung tissue are the neural mechanisms of an asthma attack. The increase of cAMP/cGMP and decrease of NKA, NKB, SP and VIP in the lung tissue of group C indicated the improvement of bronchial asthma symptoms. It is possible that the decrease of NKA and NKB, increase of cAMP/cGMP and a slight change of SP and VIP in group E were related to the reduction of glucocorticoid after ADX which influenced the effect of acupuncture. The neural regulation mechanisms of acupuncture in the treatment of bronchial asthma were related to bronchiectasis caused by stimulation of adrenergic nerve and inhibition of the vagus nerve function by acupuncture, and related to the release of inflammatory mediators.
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July 2020

Divinylsulfonamides enable the construction of homogeneous antibody-drug conjugates.

Bioorg Med Chem 2020 12 6;28(23):115793. Epub 2020 Oct 6.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai 201210, China. Electronic address:

Methods that site-specifically attach payloads to an antibody with controlled DAR (Drug-Antibody Ratio) are highly desirable for the generation of homogeneous antibody-drug conjugates (ADCs). We describe the use of N-phenyl-divinylsulfonamide scaffold as a linker platform to site-specifically construct homogeneous DAR four ADCs through a disulfide re-bridging approach. Several monomethyl auristatin E (MMAE)-linkers were synthesized and the drug-linkers that contain electron-donating groups on the phenyl of the linker showed high stability. Her2-targeted MMAE-linker-herceptin and EGFR targeted MMAE-linker-cetuximab conjugates were prepared. The conjugates demonstrated high efficacy and selectivity for killing target-positive cancer cells in vitro. The EGFR-targeted conjugates also showed significant antitumor activities in vivo.
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http://dx.doi.org/10.1016/j.bmc.2020.115793DOI Listing
December 2020

Persistent pulmonary subsolid nodules with a solid component smaller than 6 mm: what do we know?

J Thorac Dis 2020 Aug;12(8):4584-4587

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.21037/jtd-20-1972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475582PMC
August 2020

Saccharogenic refining of Ginkgo biloba leaf residues using a cost-effective enzyme cocktail prepared by the fungal strain A32 isolated from ancient ginkgo biloba tree.

Bioresour Technol 2020 Dec 8;317:123980. Epub 2020 Aug 8.

College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China.

To reduce environmental pollution and waste of biomass from Ginkgo biloba leaf residues (GBLRs), we developed a cost-effective enzyme system to hydrolyze GBLRs into available reducing sugars (RS). Biomass characteristics of GBLRs were investigated, which indicated that the acid hydrolyzed fraction was 49.43% of the dry weight of GBLRs. The fraction could be effectively converted into RS by an enzyme cocktail with high polygalacturonase activity without traditionally intricate pretreatment. The strain A32 isolated from the ancient ginkgo soil was used for the production of the enzyme cocktail, and a response surface methodology was used to optimize the enzymatic production. The enzyme cocktail released 87.2% of RS from GBLRs at 35 ℃ for 72 h with 1% (m/v) of loading, and the RS concentration arrived 8.95 ± 0.39 mg/ml with 9% of GBLRs loading. The cost-effective system of self-prepared enzyme cocktail is promising for facilitating GBLRs' bio-based industry.
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http://dx.doi.org/10.1016/j.biortech.2020.123980DOI Listing
December 2020

The transcription factor NKX2-2 regulates oligodendrocyte differentiation through domain-specific interactions with transcriptional corepressors.

J Biol Chem 2020 02 13;295(7):1879-1888. Epub 2020 Jan 13.

College of Life Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China; Institute of Life Sciences, Key Laboratory of Organ Development and Regeneration of Zhejiang Province, Hangzhou Normal University, 16 Xuelin Street, Hangzhou 311121, China. Electronic address:

The homeodomain protein NK2 homeobox 2 (NKX2-2) is a transcription factor that plays a critical role in the control of cell fate specification and differentiation in many tissues. In the developing central nervous system, this developmentally important transcription factor functions as a transcriptional repressor that governs oligodendrocyte (OL) differentiation and myelin gene expression, but the roles of various NKX2-2 structural domains in this process are unclear. In this study, using hybridization, immunofluorescence, and coimmunoprecipitation, we determined the structural domains that mediate the repressive functions of murine NKX2-2 and identified the transcriptional corepressors that interact with it in OL cells. Through electroporation in embryonic chicken spinal cords, we demonstrate that the N-terminal Tinman domain and C-terminal domain synergistically promote OL differentiation by recruiting distinct transcriptional corepressors, including enhancer of split Groucho 3 (GRG3), histone deacetylase 1 (HDAC1), and DNA methyltransferase 3 α (DNMT3A). We also observed that the NK2-specific domain suppresses the function of the C-terminal domain in OL differentiation. These findings delineate the distinct NKX2-2 domains and their roles in OL differentiation and suggest that NKX2-2 regulates differentiation by repressing gene expression via multiple cofactors and molecular mechanisms.
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http://dx.doi.org/10.1074/jbc.RA119.011163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029133PMC
February 2020

Qualitative and quantitative imaging features of pulmonary subsolid nodules: differentiating invasive adenocarcinoma from minimally invasive adenocarcinoma and preinvasive lesions.

J Thorac Dis 2019 Nov;11(11):4835-4846

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Background: To explore the role of qualitative and quantitative imaging features of pulmonary subsolid nodules (SSNs) in differentiating invasive adenocarcinoma (IAC) from minimally invasive adenocarcinoma (MIA) and preinvasive lesions.

Methods: We reviewed the clinical records of our institute from October 2010 to December 2015 and included 316 resected SSNs from 287 patients: 260 pure ground-glass nodules, 47 part-solid nodules with solid components ≤5 mm, and 9 ground-glass nodules (GGNs) with cystic airspaces. According to the pathologic review results, 307 SSNs in addition to nine GGNs with cystic airspaces were divided into two groups: A, including atypical adenomatous hyperplasia (AAH) (n=15), adenocarcinoma in situ (AIS) (n=56), and MIA (n=41); B, including 195 IACs. Univariate and binary logistic regression analyses were conducted to identify independent risk factors for IAC.

Results: Univariate analysis showed significant differences between groups regarding patient age, mean diameter, mean and relative computed tomography (CT) values, volume, mass (all P<0.001), and morphological features including lobulated sign (P<0.001), spiculated sign (P=0.028), vacuole sign/air bronchogram (P<0.001), and pleural retraction (P=0.017). Binary logistic regression and receiver operating characteristic analysis indicated the SSN mass as the only independent risk factor of IAC (odds ratio, 1.007; P<0.001), with an optimal cutoff value of 283.2 mg [area under curve (AUC): 0.859; sensitivity: 68.7%; specificity: 92.9%]. Among lepidic, acinar, and papillary adenocarcinomas, we found significant differences for the vacuole sign/air bronchogram (P=0.032) and mean and relative CT values (P<0.001). All nine GGNs with cystic airspaces were IACs.

Conclusions: The SSN mass with an optimal cutoff value of 283.2 mg may be reliable for differentiating IAC from MIA and preinvasive lesions.
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http://dx.doi.org/10.21037/jtd.2019.11.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940263PMC
November 2019

Application of ultrasonography in monitoring the complications of autologous arteriovenous fistula in hemodialysis patients.

Medicine (Baltimore) 2018 Nov;97(44):e12994

Department of Nursing, Huashan Hospital.

This study aims to evaluate the application of color Doppler ultrasound in monitoring the complications of autologous arteriovenous fistula in hemodialysis patients.Patients with maintenance hemodialysis who underwent autologous arteriovenous fistula were enrolled in this cross-sectional study. Ultrasound was used to detect fistula complications (stenosis and thrombosis), brachial artery diameter, and hemodynamic parameters. The ultrasound parameters were analyzed and screened to identify the most important indicator for monitoring complications.In all, 89 patients were included. Ultrasound showed 72 cases (80.90%) had normal fistula structure, and 17 cases (19.10%) had complications. The diameter, time-averaged mean velocity, flow volume, and diastolic peak velocity of brachial artery in complication group were significantly lower than those of noncomplication group (P < .05). The brachial artery pulsatility index and resistance index of complication group were significantly higher than those of noncomplication group (P < .05). There was no significant difference in peak flow velocity between complication and noncomplication group (P > .05). Indicators showed statistical significance were grouped based on quantiles. The incidence of complications was higher when the brachial artery diameter was ≤5.40 mm, or brachial artery flow was ≤460 mL/ min, or brachial artery pulsatility index was >1.04, or brachial artery resistance index was >0.60.Ultrasound monitoring of brachial artery diameter and hemodynamic parameters can help early detection of fistula complications. When the brachial artery diameter was ≤5.40 mm, or brachial artery flow was ≤460 mL/min, or brachial artery pulsatility index was >1.04, or brachial artery resistance index >0.60, stenosis or thrombosis should be checked to prevent fistula failure.
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http://dx.doi.org/10.1097/MD.0000000000012994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221746PMC
November 2018

The protective effect of different dialysis types on residual renal function in patients with maintenance hemodialysis: A systematic review and meta-analysis.

Medicine (Baltimore) 2018 Sep;97(37):e12325

Nursing Department, Huashan Hospital Affiliated to Fudan University, Shanghai, China.

Background: Residual renal function (RRF) is an important determinant of mortality and morbidity in patients undergoing hemodialysis. Different dialysis types may have different effects on RRF. We therefore conducted this meta-analysis to examine the RRF protective effect of different dialysis types for hemodialysis patients.

Methods: A systematic search was performed on PubMed, EMbase, Web of Science, Chinese Biomedical Literature Database, Wanfang database, and China National Knowledge Infrastructure for randomized controlled trials and cohort studies. Dialysis types included low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), hemodiafiltration (HDF), and hemodialysis and hemoperfusion (HD+HP). The mean of endogenous creatinine clearance rate (CCR) and urea clearance rate (Curea), or urine volume was used to estimate RRF [95% confidence interval (95% CI), 6.05-16.80].

Results: There were 12 articles involving 1224 patients, including 11 random controlled trials and 1 cohort study. Meta-analysis showed that the RRF protective effect of HFHD [mean difference (MD) = 1.48, 95% CI (2.11 to 0.86), P < .01] and HD+HP [MD = 0.41, 95% CI (0.69 to 0.12), P = .005] was better than that of LFHD, and the RRF decline rate was the lowest in HFHD group [MD = 0.13, 95% CI (0.17 to 0.09), P < .01]. Descriptive analysis showed that HDF could better protect RRF when compared with LFHD. However, there was no consistency among other interventions when removing LFHD due to limited data.

Conclusion: For patients undergoing maintenance hemodialysis, the HFHD, HD+HP and HDF may better protect RRF, compared with LFHD.
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http://dx.doi.org/10.1097/MD.0000000000012325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156018PMC
September 2018

The impact of chemotherapy on persistent ground-glass nodules in patients with lung adenocarcinoma.

J Thorac Dis 2017 Nov;9(11):4743-4749

Radiology Department, Dongzhimen Hospital/Beijing University of Chinese Medicine, Beijing 100700, China.

Backgrounds: To evaluate the response of persistent ground glass nodules (GGNs) in patients with lung adenocarcinoma treated with platinum-based chemotherapy on computed tomography (CT).

Methods: We retrospectively studied patients with GGNs that met the following criteria: (I) GGNs found in patients with lung adenocarcinoma, which persist for more than 3 months; (II) patients treated with platinum-based (cisplatin or carboplatin) chemotherapy for at least 2 cycles; (III) ground glass proportion ¡Ý50%. For each patient, if more than two CTs satisfied the inclusion criteria, then the baseline and last CTs were used for analysis, defined as CT1 and CT2. A total of 91 persistent pulmonary GGNs in 51 patients fulfilled the inclusion criteria. We defined growth as a nodule ¡Ý2 mm increase in diameter or showing up a solid portion. GGN response to therapy was assessed and compared with the baseline CT. Differences in CT findings were analyzed using a paired test and Pearson ¦Ö test.

Results: Between 2010 and 2015, 25 of the 51 (49%) were male and 26 of the 51 (51%) were female. The average age at time of detection of a GGN was 63.8 (range, 36-84) years. Mean follow-up duration was 24.1¡À17.9 months. During the follow-up periods, on a per-nodule basis, 94.5% of GGNs (n=86) remained unchanged in size. Only 5.5% GGNs (n=5) in 5 patients increased in size. The nodules CT feature in each lung adenocarcinoma clinical stage show no difference. No significant difference was found in the size, attenuation, volume, and mass of GGN between baseline and post-treatment measurements, regardless of the type of chemotherapy (P>0.05).

Conclusions: The clinical course of GGNs in patients with lung adenocarcinoma is predominantly indolent, and platinum-based chemotherapy may have no effect on the growth of persistent GGNs.
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http://dx.doi.org/10.21037/jtd.2017.10.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720993PMC
November 2017

Estrogen Receptor-β Modulation of the ERα-p53 Loop Regulating Gene Expression, Proliferation, and Apoptosis in Breast Cancer.

Horm Cancer 2017 08 2;8(4):230-242. Epub 2017 Jun 2.

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, IL, 61801-3704, USA.

Estrogen receptor α (ERα) is a crucial transcriptional regulator in breast cancer, but estrogens mediate their effects through two estrogen receptors, ERα and ERβ, subtypes that have contrasting regulatory actions on gene expression and the survival and growth of breast cancer cells. Here, we examine the impact of ERβ on the ERα-p53 loop in breast cancer. We found that ERβ attenuates ERα-induced cell proliferation, increases apoptosis, and reverses transcriptional activation and repression by ERα. Further, ERβ physically interacts with p53, reduces ERα-p53 binding, and antagonizes ERα-p53-mediated transcriptional regulation. ERα directs SUV39H1/H2 and histone H3 lys9 trimethylation (H3K9me3) heterochromatin assembly at estrogen-repressed genes to silence p53-activated transcription. The copresence of ERβ in ERα-positive cells abrogates the H3K9me3 repressive heterochromatin conformation by downregulating SUV39H1 and SUV39H2, thereby releasing the ERα-induced transcriptional block. Furthermore, the presence of ERβ stimulates accumulation of histone H3 lys4 trimethylation (H3K4me3) and RNA polymerase II (RNA Pol II) on ERα-repressed genes, inducing H3K4me3-associated epigenetic activation of the transcription of these repressed genes that can promote p53-based tumor suppression. ERβ also reduced corepressor N-CoR and SMRT recruitment by ERα that could attenuate the crosstalk between ERα and p53. Overall, our data reveal a novel mechanism for ERβ's anti-proliferative and pro-apoptotic effects in breast cancer cells involving p53 and epigenetic changes in histone methylation that underlie gene regulation of these cellular activities.
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http://dx.doi.org/10.1007/s12672-017-0298-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523813PMC
August 2017

Utility Evaluation Based on One-To-N Mapping in the Prisoner's Dilemma Game for Interdependent Networks.

PLoS One 2016 1;11(12):e0167083. Epub 2016 Dec 1.

Tianjin Key Laboratory of Intelligence Computing and Novel Software Technology, Tianjin University of Technology, Tianjin 300384, China.

In the field of evolutionary game theory, network reciprocity has become an important means to promote the level of promotion within the population system. Recently, the interdependency provides a novel perspective to understand the widespread cooperation behavior in many real-world systems. In previous works, interdependency is often built from the direct or indirect connections between two networks through the one-to-one mapping mode. However, under many realistic scenarios, players may need much more information from many neighboring agents so as to make a more rational decision. Thus, beyond the one-to-one mapping mode, we investigate the cooperation behavior on two interdependent lattices, in which the utility evaluation of a focal player on one lattice may not only concern himself, but also integrate the payoff information of several corresponding players on the other lattice. Large quantities of simulations indicate that the cooperation can be substantially promoted when compared to the traditionally spatial lattices. The cluster formation and phase transition are also analyzed in order to explore the role of interdependent utility coupling in the collective cooperation. Current results are beneficial to deeply understand various mechanisms to foster the cooperation exhibited inside natural, social and engineering systems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167083PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131937PMC
June 2017

Arabidopsis mitochondrial protein slow embryo development1 is essential for embryo development.

Biochem Biophys Res Commun 2016 05 22;474(2):371-376. Epub 2016 Apr 22.

Key Laboratory of Cell Proliferation and Differentiation (Ministry of Education), College of Life Sciences, Peking University, Beijing 100871, China. Electronic address:

The plant seeds formation are crucial parts in reproductive process in seed plants as well as food source for humans. Proper embryo development ensure viable seed formation. Here, we showed an Arabidopsis T-DNA insertion mutant slow embryo development1 (sed1) which exhibited retarded embryogenesis, led to aborted seeds. Embryo without SED1 developed slower compared to normal one and could be recognized at early globular stage by its white appearance. In later development stage, storage accumulated poorly with less protein and lipid body production. In vitro culture did not rescue albino embryo. SED1 encoded a protein targeted to mitochondria. Transmission electron microscopic analysis revealed that mitochondria developed abnormally, and more strikingly plastid failed to construct grana in time in sed1/sed1 embryo. These data indicated that SED1 is indispensable for embryogenesis in Arabidopsis, and the mitochondria may be involved in the regulation of many aspects of seed development.
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http://dx.doi.org/10.1016/j.bbrc.2016.04.114DOI Listing
May 2016

Total glucosides of peony ameliorates Sjögren's syndrome by affecting Th1/Th2 cytokine balance.

Exp Ther Med 2016 Mar 22;11(3):1135-1141. Epub 2016 Jan 22.

Department of Chinese Traditional Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

The present study aimed to investigate the molecular mechanisms underlying the effects of total glucosides of peony (TGP) in the treatment of Sjögren's syndrome (SS). A total of 40 mice with SS were evenly assigned into four groups, including: Control group; TGP group, receiving 1 mg TGP daily; hydroxychloroquine (HCQ) group, receiving 0.25 mg HCQ daily; and a combined group, receiving 1 mg TGP and 0.25 mg HCQ daily. After 8 weeks, quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay were used to detect the levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), Fas and FasL in each group of mice. In addition, immunohistochemical analysis was used to determine the expression levels of IFN-γ and IL-4. IFN-γ, IL-4, Fas and FasL levels were significantly increased in the control group compared with the other three groups (P<0.05). Furthermore, the expression levels of these factors were reduced in the combined group in comparison with the HCQ group (P<0.05). The ratios of IFN-γ to IL-4 were decreased in the TGP and combined groups compared with the control group (P<0.05). The present results indicate that TGP ameliorates SS by affecting the Th1/Th2 cytokine balance and decreasing the expression levels of IFN-γ, IL-4, Fas and FasL. Therefore, TGP may represent a potential novel therapeutic agent for the treatment of SS.
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http://dx.doi.org/10.3892/etm.2016.3016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774573PMC
March 2016

Diagnosis and treatment for primary small intestinal lymphoma of 59 cases: a follow-up study.

Int J Colorectal Dis 2016 Jul 5;31(7):1377-9. Epub 2016 Jan 5.

Department of Gastroenterology, The First Affiliated Hospital, Medical College of Zhejiang University, 79 Qing'chun Road, Hangzhou, Zhejiang Province, 310003, China.

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http://dx.doi.org/10.1007/s00384-015-2486-1DOI Listing
July 2016

Translational study of Alzheimer's disease (AD) biomarkers from brain tissues in AβPP/PS1 mice and serum of AD patients.

J Alzheimers Dis 2015 ;45(1):269-82

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The aim of this study was to investigate potential biomarkers of Alzheimer's disease (AD). Changes in protein expression in brain tissues from AβPP/PS1 transgenic mice were evaluated using two-dimensional gel electrophoresis combined with LC-MS/MS. A total of 23 differentially expressed proteins were successfully identified in brain tissues of which 11 were validated by western blot. Then, the levels of these differentially expressed proteins in serum from AD patients and healthy controls were examined. Of these 11 proteins, levels of 5 changed in the same direction in the serum of AD patients as they did in mouse brain: cathepsin B, VDAC1, and cofilin-2 increased, and Alix and ACAP1 decreased. Alix, cofilin-2, and ACAP1 have not been previously associated with AD. More importantly, the serum levels of Alix, cofilin-2, and ACAP1 were significantly different between AD patients and healthy controls. Furthermore, the expressions of cathepsin B, cofilin-2, VDAC1, and ACAP1 strongly correlated with the Mini-Mental State Examination scores of the AD patients. The results indicate that these proteins are putative biomarkers of AD which may be useful in its diagnosis and in the evaluation of new anti-AD drugs both in pre-clinical and clinical studies.
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http://dx.doi.org/10.3233/JAD-142805DOI Listing
February 2016

Specific changes of serum proteins in Parkinson's disease patients.

PLoS One 2014 25;9(4):e95684. Epub 2014 Apr 25.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen γ-chain (FGG) appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4) was found to exist two forms in serum. The full size (120 kDa) of the protein was increased and the fragmented ITI-H4 (35 kDa) was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85 ± 0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (∼ 26 kDa) was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ∼ 26 kDa Apo A-IV disappear would provide strong evidence for PD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095684PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000217PMC
January 2015

Sterols are required for cell-fate commitment and maintenance of the stomatal lineage in Arabidopsis.

Plant J 2013 Jun 27;74(6):1029-44. Epub 2013 Apr 27.

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

Asymmetric cell division is important for regulating cell proliferation and fate determination during stomatal development in plants. Although genes that control asymmetric division and cell differentiation in stomatal development have been reported, regulators controlling the process from asymmetric division to cell differentiation remain poorly understood. Here, we report a weak allele (fk-J3158) of the Arabidopsis sterol C-14 reductase gene FACKEL (FK) that shows clusters of small cells and stomata in leaf epidermis, a common phenomenon that is often seen in mutants defective in stomatal asymmetric division. Interestingly, the physical asymmetry of these divisions appeared to be intact in fk mutants, but the cell-fate asymmetry was greatly disturbed, suggesting that the FK pathway links these two crucial events in the process of asymmetric division. Sterol profile analysis revealed that the fk-J3158 mutation blocked downstream sterol production. Further investigation indicated that cyclopropylsterol isomerase1 (cpi1), sterol 14α-demethylase (cyp51A2) and hydra1 (hyd1) mutants, corresponding to enzymes in the same branch of the sterol biosynthetic pathway, displayed defective stomatal development phenotypes, similar to those observed for fk. Fenpropimorph, an inhibitor of the FK sterol C-14 reductase in Arabidopsis, also caused these abnormal small-cell and stomata phenotypes in wild-type leaves. Genetic experiments demonstrated that sterol biosynthesis is required for correct stomatal patterning, probably through an additional signaling pathway that has yet to be defined. Detailed analyses of time-lapse cell division patterns, stomatal precursor cell division markers and DNA ploidy suggest that sterols are required to properly restrict cell proliferation, asymmetric fate specification, cell-fate commitment and maintenance in the stomatal lineage cells. These events occur after physical asymmetric division of stomatal precursor cells.
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http://dx.doi.org/10.1111/tpj.12190DOI Listing
June 2013

The BIG gene is required for auxin-mediated organ growth in Arabidopsis.

Planta 2013 Apr 4;237(4):1135-47. Epub 2013 Jan 4.

MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, 730000, China.

Control of organ size by cell expansion and cell proliferation is a fundamental process during development, but the importance of BIG in this process is still poorly understood. Here, we report the isolation and characterization of a new allele mutant of BIG in Arabidopsis: big-j588. The mutant displayed small aerial organs that were characterized by reduced cell size in the epidermis and short roots with decreased cell numbers. The big-j588 axr1 double and big-j588 arf7 arf19 triple mutants displayed more severe defects in leaf expansion and root elongation than their parents, implying BIG is involved in auxin-dependent organ growth. Genetic analysis suggests that BIG may act synergistically with PIN1 to affect leaf growth. The PIN1 protein level decreased in both the root cells and the tips of leaf pavement cell lobes of big-j588. Further analysis showed that the auxin maxima in the roots and the leaves of big-j588 decreased. Therefore, we concluded that the small leaves and the short roots of big-j588 were associated with reduction of auxin maxima. Overall, our study suggested that BIG is required for Arabidopsis organ growth via auxin action.
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http://dx.doi.org/10.1007/s00425-012-1834-4DOI Listing
April 2013

Strain- and age-related alteration of proteins in the brain of SAMP8 and SAMR1 mice.

J Alzheimers Dis 2011 ;23(4):641-54

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

In order to discover and identify the key protein biomarkers in the aging process, we performed a differential proteomic analysis of hippocampus and cortex in 5- and 15-month old senescence-accelerated mouse prone 8 (SAMP8) as well as in control strain SAM/resistant 1 (SAMR1). Using 2-DE combined with MALDI TOF/TOF mass spectrometry, about 1700 protein spots were isolated, and three groups of differentially expressed proteins were identified. The first group contained the strain-specific and non-age-related differential proteins that were differentially expressed in SAMP8 compared with SAMR1 mice. The changes might be implicated in the genetic difference between SAMP8 and SAMR1 mice; specifically, the proteins ubiquitin carboxyl-terminal esterase L3, mitofilin, adenylate kinase 4, and an unnamed protein product (gi|12847201). The proteins in the second group were age-specific, which were differentially expressed between 5- and 15-month old SAM mice. Those proteins are particularly interesting since the changes were aging-related and some of them were previously reported to be expressed in Alzheimer's disease patients. These proteins included N-myc downstream regulated gene 2, enolase 2, Cu/Zn superoxide dismutase, myosin, and two unnamed protein products (gi|74214304 and gi|74178239). The protein in the third group was SAMP8 specific-age-related protein, which was identified as heme binding protein 1. The present study provides new information about SAMP8 specific and aging-related protein changes in brain. Further investigations will be performed to reveal the significance of these proteins in brain aging process and the potential roles as biomarkers for effective diagnosis and therapy.
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http://dx.doi.org/10.3233/JAD-2010-101389DOI Listing
March 2012