Publications by authors named "Yunyun Luo"

18 Publications

  • Page 1 of 1

A flexible electrostatic nanogenerator and self-powered capacitive sensor based on electrospun polystyrene mats and graphene oxide films.

Nanotechnology 2021 Jul 14;32(40). Epub 2021 Jul 14.

State Key Laboratory for Manufacturing Systems Engineering, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Xi'an Jiaotong University, Xi'an, Shannxi 710049, People's Republic of China.

Electrostatic nanogenerators or capacitive sensors that leverage electrostatic induction for power generation or sensing, has attracted significant interests due to their simple structure, ease of fabrication, and high device stability. However, in order for such devices to work, an additional power source or a post-charging process is necessary to activate the electrostatic effect. In this work, an electrostatic nanogenerator is fabricated using electrospun polystyrene (PS) mats and dip-coated graphene oxide (GO) films as the self-charged components. The electret performances of the PS mats and GO films are characterized via the electrostatic force microscopy phase shift and surface potential measurements. With a multilayer device structure that consists of top electrodes/GO films/spacer/electrospun PS mats/bottom electrodes, the resultant device acts as an electrostatic generator that operates in the noncontact mode. The nanogenerator can output a peak voltage of ca. 6.41 V and a peak current of ca. 6.57 nA at a rate of 1 Hz of mechanical compression, and with no attenuation of electrical outputs even after 50 000 cycles over a 13 h period. Furthermore, this as-prepared device is also capable of serving as a self-powered capacitive sensor for detection of tiny mechanical impacts and measurement of human finger bending. This results of this work provides a new avenue to easily fabricate electrostatic nanogenerators with high durability and self-powered capacitive sensors for the detection of small impacts.
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http://dx.doi.org/10.1088/1361-6528/ac1019DOI Listing
July 2021

Treatment of Short Stature with Aromatase Inhibitors: A Systematic Review and Meta-Analysis.

Horm Metab Res 2021 Jun 21;53(6):391-401. Epub 2021 Jun 21.

Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China.

The objective of the study is to determine the risks and benefits of treating idiopathic short stature (ISS) with aromatase inhibitors (AIs). We comprehensively searched PubMed, Embase, and the China National Knowledge Infrastructure between establishment year and January 31, 2020. Mean difference (MD)/Standardized mean differences (SMD) with 95% confidence intervals (CI) of individual studies were pooled using fixed or random effects models. Subgroup and sensitivity analyses were also performed. Publication bias was estimated using funnel plots and Egger tests. Fourteen studies including 388 participants were included. The meta-analysis results showed that AIs significantly increased final height (MD=2.46, 95% CI: 0.8-4.12) and predicted adult height (MD=0.34, 95% CI: 0.11-0.57). Changes in bone age (MD=-0.1, 95% CI: -0.86-0.66) and bone mineral density (MD=-0.05, 95% CI: -0.19-0.1) were not different between intervention and control group. AI significantly increased testosterone level (SMD=2.01, 95% CI: 0.8-3.23) and reduced estradiol level (SMD=-1.13, 95% CI: -1.87 to -0.40); The intervention and control group had no significant differences in the levels of high-density lipoprotein-cholesterol (SMD=-0.31, 95%CI: -0.68-0.06) and IGF-1 (SMD=0.7, 95% CI: -0.66-2.06) levels. Adverse events were more frequent in the intervention group than in the control group (odds ratio=3.12, 95% CI: 1.44-6.73). In conclusion, both AI monotherapy and AI combination therapy can increase predicted adult height and testosterone levels.
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http://dx.doi.org/10.1055/a-1492-2841DOI Listing
June 2021

A thin-film temperature sensor based on a flexible electrode and substrate.

Microsyst Nanoeng 2021 1;7:42. Epub 2021 Jun 1.

State Key Laboratory for Mechanical Manufacturing Systems Engineering, Xi'an Jiaotong University, 710049 Xi'an, China.

Accurate temperature measurements can efficiently solve numerous critical problems and provide key information. Herein, a flexible micro-three-dimensional sensor, with a combination of platinum and indium oxide to form thermocouples, is designed and fabricated by a microfabrication process to achieve in situ real-time temperature measurements. The stability and reliability of the sensor are greatly improved by optimizing the process parameters, structural design, and preparation methods. A novel micro-three-dimensional structure with better malleability is designed, which also takes advantage of the fast response of a two-dimensional thin film. The as-obtained flexible temperature sensor with excellent stability and reliability is expected to greatly contribute to the development of essential components in various emerging research fields, including bio-robot and healthcare systems. The model of the application sensor in a mask is further proposed and designed to realize the collection of health information, reducing the number of deaths caused by the lack of timely detection and treatment of patients.
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http://dx.doi.org/10.1038/s41378-021-00271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166532PMC
June 2021

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis.

J Orthop Traumatol 2021 Mar 9;22(1):10. Epub 2021 Mar 9.

Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev Hovedgade 207, 2730, Herlev, Denmark.

Background: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study is to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation.

Materials And Methods: The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n = 106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n = 147). Risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.

Results: In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared with subjects with high PRO-C2. Mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 (1.4-8.6)-fold higher risk of progression. There was no significant effect of sCT treatment, compared with placebo, on JSN over 2 years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared with the moderate/high group (Chi squared = 6.5, p = 0.011).

Conclusion: Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.

Level Of Evidence: Level III post hoc exploratory analysis of one longitudinal cohort and a sub-study from one phase III clinical trial.
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http://dx.doi.org/10.1186/s10195-021-00572-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943687PMC
March 2021

Effects of growth hormone on cognitive, motor, and behavioral development in Prader-Willi syndrome children: a meta-analysis of randomized controlled trials.

Endocrine 2021 02 22;71(2):321-330. Epub 2020 Nov 22.

Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Research Center for Behavior Medicine in Growth and Development, Beijing, China.

Purpose: The benefits of growth hormone (GH) therapy in Prader-Willi syndrome (PWS) children are well established, but there is still considerable controversy regarding whether GH treatment can improve cognitive, motor, and behavioral development in PWS children. The objectives of this meta-analysis were to quantitatively evaluate the effects of GH on cognitive, motor function, and behavioral development in PWS children.

Methods: Randomized controlled trials (RCTs) examining the effects of GH on cognitive, motor, and behavioral development in PWS children were identified by searching the MEDLINE, EMBASE, and Cochrane Library databases. Intervention effects were represented by Hedges'g and pooled to calculate effect sizes using a random-effects model.

Results: Ten relevant studies comprising data from 302 participants were finally included. We observed no significant difference in cognitive performance between the GH treatment group and the control group (p = 0.197). GH treatment was shown to remarkably improve motor development in PWS children compared with the control treatment (p < 0.001), with moderate positive treatment effects (Hedges'g [95% CI] = 0.71 [0.38, 1.03]). There were no significant differences between the GH group and the control group based on objective assessments of behavioral development (p = 0.53).

Conclusions: The meta-analysis suggested that GH treatment had a significantly positive effect on motor development, with moderate treatment effects in PWS children; however, there was no evidence of effects on cognitive or behavioral development.
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http://dx.doi.org/10.1007/s12020-020-02547-3DOI Listing
February 2021

The Radial Piezoelectric Response from Three-Dimensional Electrospun PVDF Micro Wall Structure.

Materials (Basel) 2020 Mar 18;13(6). Epub 2020 Mar 18.

State Key Laboratory for Manufacturing Systems Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

The ability of electrospun polyvinylidene fluoride (PVDF) fibers to produce piezoelectricity has been demonstrated for a while. Widespread applications of electrospun PVDF as an energy conversion material, however, have not materialized due to the random arrangement of fibers fabricated by traditional electrospinning. In this work, a developed 3D electrospinning technique is utilized to fabricate a PVDF micro wall made up of densely stacked fibers in a fiber-by-fiber manner. Results from X-ray diffraction (XRD) and Fourier transform infrared spectra (FTIR) demonstrate that the crystalline structure of this PVDF wall is predominant in the β phase, revealing the advanced integration capability of structural fabrication and piezoelectric poling with this 3D electrospinning. The piezoelectric response along the radial direction of these PVDF fibers is measured while the toppled micro wall, comprised of 60 fibers, is sandwich assembled with a pair of top/bottom electrodes. The measured electrical output is ca. 0.48 V and 2.7 nA. Moreover, after constant mechanical compression happening over 10,000 times, no obvious reduction in the piezoelectric response has been observed. The combined merits of high-precision 3D fabrication, in situ piezoelectric poling, and high mechanical robust make this novel structure an attractive candidate for applications in piezoelectric energy harvesting and sensing.
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http://dx.doi.org/10.3390/ma13061368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143062PMC
March 2020

Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.

J Gastrointestin Liver Dis 2019 Jun 1;28:175-182. Epub 2019 Jun 1.

Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.

Background And Aims: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot.

Methods: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin.

Results: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively.

Conclusion: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.
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http://dx.doi.org/10.15403/jgld-178DOI Listing
June 2019

Is awake physiological confirmation necessary for DBS treatment of Parkinson's disease today? A comparison of intraoperative imaging, physiology, and physiology imaging-guided DBS in the past decade.

Brain Stimul 2019 Jul - Aug;12(4):893-900. Epub 2019 Mar 7.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China. Electronic address:

Background: Deep brain stimulation (DBS) is a well-established surgical therapy for Parkinson's disease (PD). Intraoperative imaging (IMG), intraoperative physiology (PHY) and their combination (COMB) are the three mainstream DBS guidance methods.

Objective: To comprehensively compare the use of IMG-DBS, PHY-DBS and COMB-DBS in treating PD.

Methods: PubMed, Embase, the Cochrane Library and OpenGrey were searched to identify PD-DBS studies reporting guidance techniques published between January 1, 2010, and May 1, 2018. We quantitatively compared the therapeutic effects, surgical time, target error and complication risk and qualitatively compared the patient experience, cost and technical prospects. A meta-regression analysis was also performed. This study is registered with PROSPERO, number CRD42018105995.

Results: Fifty-nine cohorts were included in the main analysis. The three groups were equivalent in therapeutic effects and infection risks. IMG-DBS (p < 0.001) and COMB-DBS (p < 0.001) had a smaller target error than PHY-DBS. IMG-DBS had a shorter surgical time (p < 0.001 and p = 0.008, respectively) and a lower intracerebral hemorrhage (ICH) risk (p = 0.013 and p = 0.004, respectively) than PHY- and COMB-DBS. The use of intraoperative imaging and microelectrode recording correlated with a higher surgical accuracy (p = 0.018) and a higher risk of ICH (p = 0.049).

Conclusions: The comparison of COMB-DBS and PHY-DBS showed intraoperative imaging's superiority (higher surgical accuracy), while the comparison of COMB-DBS and IMG-DBS showed physiological confirmation's inferiority (longer surgical time and higher ICH risk). Combined with previous evidence, the use of intraoperative neuroimaging techniques should become a future trend.
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http://dx.doi.org/10.1016/j.brs.2019.03.006DOI Listing
December 2019

GPDPLQ-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro.

Sci Rep 2019 02 28;9(1):3050. Epub 2019 Feb 28.

Nordic Bioscience, Herlev, Denmark.

C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe the GPDPLQ ELISA which targets the EKGPDPLQ↓ neo-epitope, an elongated version of the CTX-II neo-epitope (EKGPDP↓), speculated to be a blood-precursor of CTX-II generated by the cysteine protease cathepsin K. Human osteoclast cartilage resorption cultures as well as oncostatin M and tumour necrosis factor α-stimulated bovine cartilage explant cultures were used to validate GPDPLQ biologically by treating the cultures with the cysteine protease inhibitor E-64 and/or the matrix metalloproteinase (MMP) inhibitor GM6001 to assess the potential contributions of these two protease classes to GPDPLQ release. Cartilage resorption-derived GPDPLQ release was inhibited by E-64 (72.1% inhibition), GM6001 (75.5%), and E-64/GM6001 (91.5%), whereas CTX-II release was inhibited by GM6001 (87.0%) but not by E-64 (5.5%). Cartilage explant GPDPLQ and CTX-II release were both fully inhibited by GM6001 but were not inhibited by E-64. No clinically relevant GPDPLQ reactivity was identified in human serum, plasma, or urine from healthy donors or arthritis patients. In conclusion, the GPDPLQ biomarker is released during osteoclast-derived cysteine protease- and MMP-mediated cartilage degradation in vitro, whereas CTX-II release is mediated by MMPs and not by cysteine proteases, as well as from MMP-mediated cartilage degradation under a pro-inflammatory stimulus. These findings suggest that GPDPLQ may be relevant in diseases with pathological osteoclast activity and cartilage degradation. Further studies are required to validate the neo-epitope in human samples.
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http://dx.doi.org/10.1038/s41598-019-39803-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395810PMC
February 2019

A novel microsensor for measuring thermal conductivity of fluid based on three omega method.

Rev Sci Instrum 2019 Jan;90(1):015002

State Key Laboratory for Manufacturing Systems Engineering, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies, Collaborative Innovation Center of Suzhou Nano Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

A novel microsensor has been designed for the measurement of thermal conductivity of fluids based on the three omega (3ω) method. First, we theoretically analyzed the heat conduction using the 3ω method to demonstrate the mechanism of the microsensor to measure the thermal conductivity of a fluid. For the main structure of the microsensor, a heater was supported by the thin dielectric layers. In order to obtain the optimal parameters, we used the finite element method to simulate the working condition of the microsensor. In the simulation model, the effects of the thicknesses of the heater and dielectric layers on the thermal conductivity λ of the fluid were analyzed. The simulation results confirmed the validity and accuracy of conventional analytical calculations. Based on the simulation and theoretical calculation, a microsensor was optimally designed and fabricated to measure the thermal conductivity of fluids. Experimental data are consistent with those reported in the literature and demonstrate that the proposed sensor is effective for measuring thermal conductivity of fluids, including conductive ones.
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http://dx.doi.org/10.1063/1.5053835DOI Listing
January 2019

A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation.

Int J Mol Sci 2018 Nov 6;19(11). Epub 2018 Nov 6.

Department of Rheumatology, Nordic Bioscience, Biomarkers and Research, 2730 Herlev, Denmark.

N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utility of PIIBNP as a marker in preclinical and clinical settings has not been fully investigated yet. In this study, we aimed to characterize an antibody targeting human PIIBNP and to develop an immunoassay assessing type II collagen synthesis in human blood samples. A high sensitivity electrochemiluminescence immunoassay, hsPRO-C2, was developed using a well-characterized antibody against human PIIBNP. Human cartilage explants from replaced osteoarthritis knees were cultured for ten weeks in the presence of growth factors, insulin-like growth factor 1 (IGF-1) or recombinant human fibroblast growth factor 18 (rhFGF-18). The culture medium was changed every seven days, and levels of PIIBNP, PIIANP, and matrix metalloproteinase 9-mediated degradation of type II collagen (C2M) were analyzed herein. Serum samples from a cross-sectional knee osteoarthritis cohort, as well as pediatric and rheumatoid arthritis samples, were assayed for PIIBNP and PIIANP. Western blot showed that the antibody recognized PIIBNP either as a free fragment or attached to the main molecule. Immunohistochemistry demonstrated that PIIBNP was predominately located in the extracellular matrix of the superficial and deep zones and chondrocytes in both normal and osteoarthritic articular cartilage. In addition, the hsPRO-C2 immunoassay exhibits acceptable technical performances. In the human cartilage explants model, levels of PIIBNP, but not PIIANP and C2M, were increased (2 to 7-fold) time-dependently in response to IGF-1. Moreover, there was no significant correlation between PIIBNP and PIIANP levels when measured in knee osteoarthritis, rheumatoid arthritis, and pediatric serum samples. Serum PIIBNP was significantly higher in controls (KL0/1) compared to OA groups (KL2/3/4, = 0.012). The hsPRO-C2 assay shows completely different biological and clinical patterns than PIIANP ELISA, suggesting that it may be a promising biomarker of cartilage formation.
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http://dx.doi.org/10.3390/ijms19113485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275061PMC
November 2018

Erratum: Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rats.

Am J Transl Res 2017 15;9(11):5180. Epub 2017 Nov 15.

Nordic Bioscience (Beijing) Ltd.Beijing, China.

[This corrects the article on p. 3517 in vol. 9, PMID: 28804568.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714801PMC
November 2017

Acupuncture May Improve Quality of Life in Menopausal Women: A Meta-Analysis of Randomized Controlled Trials.

Complement Med Res 2018 12;25(3):183-190. Epub 2017 Oct 12.

Objective: This analysis aims to identify, on the basis of the results of randomized controlled trials (RCTs), whether acupuncture therapy can alleviate menopausal symptoms and promote health-related quality of life.

Methods: We included RCTs that directly compared any type of acupuncture with sham acupuncture in treating menopause-related symptoms and which were published from January 1, 2010 to December 31, 2016 in 6 electronic databases. Two authors performed this work independently; 'risk-of-bias' assessment and data extraction were also independently performed by these 2 review authors. The outcomes are presented as scores of the menopause rating scale (MRS), which represents the self-assessment of patients.

Results: Six studies were included. Our analysis found that acupuncture can reduce the MRS score in menopausal women by the end of the treating period (2-3 months, on average) and even in the follow-up period (1-3 months), not only in the total score but also in each subscale score. But the grade of evidence is very low.

Conclusions: Both the total score and the subgroup analysis strongly indicated that acupuncture can alleviate menopause-related symptoms. However, the evidence is not very strong. Thus, further studies about the efficiency of acupuncture on menopausal symptoms based on well-designed trials are needed.
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http://dx.doi.org/10.1159/000479630DOI Listing
September 2019

Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rats [corrected].

Am J Transl Res 2017 15;9(7):3517-3527. Epub 2017 Jul 15.

Nordic Bioscience (Beijing) Ltd.Beijing, China.

The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-Dawley rats each were subjected to ovariectomized (OVX) or sham surgery and treated orally once daily with herbal extracts or vehicle. Body weight was recorded weekly, and blood samples were collected from fasting animals at different time points. Biochemical markers of bone resorption and cartilage degradation were analyzed. Changes in bone mineral density and calcium content were determined in the femoral center and femoral telocentric end of rats. Out of 56 TCM herbs/roots extracts, only kudzu root demonstrated consistent joint protective effects. OVX resulted in a marked increase in bone resorption and cartilage degradation, which could be significantly reversed by kudzu after three weeks of treatment. Compared to vehicle, kudzu induced a significant increase in bone mineral density in the femoral center and femoral telocentric end, and calcium content. The results show that kudzu exerts direct effects on articular cartilage in the OVX rat and can effectively prevent the acceleration of cartilage degradation induced by ovariectomy. Moreover, kudzu has demonstrated positive effects on metabolic health (cause a weight reduction) and may represent a possible treatment for OP and OA with high body mass index. Further studies are needed to investigate the potential effects of kudzu root in postmenopausal women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527265PMC
July 2017

Investigation of the inhibitory potential of phospholipase A inhibitor gamma from Sinonatrix annularis to snake envenomation.

Toxicon 2017 Oct 23;137:83-91. Epub 2017 Jul 23.

Department of Biochemistry, College of Basic Medical Science, Nanchang University, Nanchang, 330006, China; Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology, Nanchang University, Nanchang, 330006, China. Electronic address:

SaPLIγ is a novel gamma phospholipase A inhibitor (PLI) recently isolated from Sinonatrix annularis, a Chinese endemic non-venomous snake. To explore the neutralization effects of saPLIγ in snakebite envenomation, a dose equivalent to LD of Deinagkistrodon acutus, Agkistrodon halys and Naja atra venom with/without saPLIγ was inoculated into the gastrocnemius muscle of female Kunming mice. The ability of saPLIγ to inhibit myonecrosis and systemic toxicity were evaluated through investigations of muscle histopathology, and determination of the serum levels of creatine kinase (CK), lactate dehydrogenase isoenzyme1 (LDH1) and aspartate transferase (AST). Edema of the gastrocnemius muscle was evaluated by calculating the width difference between the inoculated limb and the contralateral leg. Desmin loss in the gastrocnemius muscle was determined by Western blot analysis. Co-immunoprecipitation and shotgun LC-MS/MS analyses were performed to identify venom proteins that interact with saPLIγ. All the envenomed mice had significantly elevated serum CK, LDH1 and AST levels, whereas the levels were decreased significantly in the presence of saPLIγ. Histopathological evaluation of gastrocnemius muscle sections showed severe snake venom-induced damage, characterized by leukocyte infiltration and erythrocyte leakage, leading to local edema. Myonecrosis, hemorrhage and desmin loss were significantly attenuated by saPLIγ. SaPLIγ interacted with a wide range of venom proteins, including PLAs, metalloproteinases and C type lectins, which may contribute to broad anti-venom effects.
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http://dx.doi.org/10.1016/j.toxicon.2017.07.019DOI Listing
October 2017

The minor collagens in articular cartilage.

Protein Cell 2017 Aug 17;8(8):560-572. Epub 2017 Feb 17.

Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.
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http://dx.doi.org/10.1007/s13238-017-0377-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546929PMC
August 2017

MMP mediated degradation of type VI collagen is highly associated with liver fibrosis--identification and validation of a novel biochemical marker assay.

PLoS One 2011 14;6(9):e24753. Epub 2011 Sep 14.

Nordic Bioscience A/S, Herlev, Denmark.

Background And Aims: During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragments, so-called neo-epitopes, may be specific biochemical marker of liver fibrosis. The aim of this study was to develop an ELISA detecting a fragment of type VI collagen generated by MMP-2 and MMP-9, and evaluate this assay in two preclinical models of liver fibrosis.

Methods: Mass spectrometric analysis of cleaved type VI collagen revealed a large number of protease-generated neo-epitopes. A fragment unique to type VI collagen generated by MMP-2 and MMP-9 was selected for ELISA development. The CO6-MMP assay was evaluated in two rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetrachloride (CCl4)-treated rats.

Results: Intra- and inter-assay variation was 4.1% and 10.1% respectively. CO6-MMP levels were significantly elevated in CCl(4)-treated rats compared to vehicle-treated rats at weeks 12 (mean 30.9 ng/mL vs. 12.8 ng/mL, p = 0.002); week 16 (mean 34.0 ng/mL vs. 13.7 ng/mL, p = 0.0018); and week 20 (mean 35.3 ng/mL vs. 13.3 ng/mL, p = 0.0033) with a tight correlation between hepatic collagen content and serum levels of CO6-MMP (R(2) = 0.58, p<0.0001) in CCl(4)- treated rats. In BDL rats, serum levels of CO6-MMP were significantly elevated compared to the levels in sham-operated animals both at 2 weeks (mean 29.5 ng/mL vs. 14.2 ng/mL, p = 0.0001) and 4 weeks (mean 33.0 ng/mLvs. 11.8 ng/mL, p = 0.0003).

Conclusions: This novel ELISA is the first assay enabling assessment of MMP degraded type VI collagen, allowing quantification of type VI collagen degradation, which would be relevant for different pathologies. The marker was highly associated with liver fibrosis in two liver fibrosis animal models, suggesting type VI turnover to be a central player in fibrogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024753PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173456PMC
February 2012

Muscarinic cholinergic modulation of synaptic transmission and plasticity in rat hippocampus following chronic lead exposure.

Naunyn Schmiedebergs Arch Pharmacol 2009 Jan 21;379(1):37-45. Epub 2008 Aug 21.

Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People's Republic of China.

The cholinergic system is believed to be associated with learning and memory functions. Lead (Pb2+) is a well-known neurotoxic metal that causes irreversible damage to the central nervous system (CNS). To investigate whether Pb2+ interferes with cholinergic modulation, we examined the effects of carbachol (CCh), a muscarinic cholinergic agonist, on synaptic transmission and plasticity in the CA1 area of the hippocampus of developmentally Pb2+-exposed rats. The results showed that: (1) In both control and Pb2+-exposed rats, 0.1 microM CCh significantly enhanced tetanus-induced long-term potentiation (LTP), while 5 microM CCh induced a reversible depression of field excitatory postsynaptic potentials (fEPSPs). However, both the enhancement of LTP and depression of fEPSPs were significantly smaller in Pb2+-exposed rats than in controls, suggesting that the extent of the effect of CCh on the cholinergic system was depressed by Pb2+. (2) In Pb2+-exposed rats, the enhancement of LTP induced by 0.1 microM CCh was attenuated by pirenzepine, a M1AChR antagonist, but was not affected by methoctramine tetrahydrochloride (M-105), a M2/4AChR antagonist. The depression of fEPSPs induced by 5 microM CCh was reduced by either pirenzepine or M-105. (3) Furthermore, paired-pulse facilitation (PPF) was not affected by 0.1 microM CCh in control and Pb2+-exposed rats but was increased by 5 microM CCh in either group; the increase in PPF was less pronounced in Pb2+-treated when compared to control rats. These results suggested that cholinergic modulation could be impaired by Pb2+, and this kind of impairment might occur via different mAChR subtypes. Our study delineated the effects of Pb2+ on muscarinic modulation, and this might be one of the underlying mechanisms by which Pb2+ impairs learning and memory.
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http://dx.doi.org/10.1007/s00210-008-0344-1DOI Listing
January 2009
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