Publications by authors named "Yishan Chen"

32 Publications

Underwater Crawling Robot With Hydraulic Soft Actuators.

Front Robot AI 2021 26;8:688697. Epub 2021 Aug 26.

Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen, China.

Benthic operation plays a vital role in underwater applications, where crawling robots have advantages compared with turbine-based underwater vehicles, in locomotion accuracy, actuation efficiency, current resistance, and in carrying more payloads. On the other hand, soft robots are quickly trending in underwater robotic design, with their naturally sealed body structure and intrinsic compliance both desirable for the highly unstructured and corrosive underwater environment. However, the limitations resulting directly from the inherent compliance, in structural rigidity, actuation precision, and limited force exertion capability, have also restricted soft robots in underwater applications. To date soft robots are adopted mainly as grippers and manipulators for atraumatic sampling, rather than as locomotion platforms. In this work, we present a soft-robotic approach to designing underwater crawling robots, with three main innovations: 1) using rigid structural components to strategically reinforce the otherwise omni-directionally flexible soft actuators, drastically increasing their loading capability and actuation precision; 2) proposing a rigid-soft hybrid multi-joint leg design, with quasi-linear motion range and force exertion, while maintaining excellent passive impact compliance by exploiting the inherent flexibility of soft actuators; 3) developing a novel valve-free hydraulic actuation system with peristaltic pumps, achieving a compact, lightweight, and untethered underwater crawling robot prototype with a 5:1 payload-to-weight ratio and multi-gait capability. The prototype was tested for design verification and showcasing the advantages of the proposed hybrid mechanism and actuation approach.
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http://dx.doi.org/10.3389/frobt.2021.688697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427137PMC
August 2021

Influence of Polymorphisms on Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis (rs1800566 and rs10517).

Cardiovasc Ther 2021 12;2021:5534946. Epub 2021 Aug 12.

Department of General Medicine, The Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, China.

This meta-analysis was conducted to analyze the effect of polymorphism on the warfarin maintenance dosage. Using strict inclusion and exclusion criteria, we searched PubMed, EMBASE, and the Cochrane Library for eligible studies published prior to July 7, 2021. The required data were extracted, and experts were consulted when necessary. Review Manager Version 5.4 software was used to analyze the relationship between polymorphisms and the warfarin maintenance dosage. Four articles involving 757 patients were included in the meta-analysis. Patients who were rs10517 G carriers (AG carriers or GG carriers) required a 48% higher warfarin maintenance dose than those who were AA carriers. Patients with CT carriers required a 13% higher warfarin dose than those who were CC carriers, with no associations observed with the other comparisons of the genotypes. However, the results obtained by comparing the rs1800566 genotypes require confirmation, as significant changes in the results were found in sensitivity analyses. Our meta-analysis suggests that the rs10517and rs1800566 variant statuses affect the required warfarin maintenance dose.
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http://dx.doi.org/10.1155/2021/5534946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376459PMC
August 2021

Preoperative and perioperative intervention reduces the risk of recurrence of endometriosis in mice caused by either incomplete excision or spillage and dissemination.

Reprod Biomed Online 2021 Apr 29. Epub 2021 Apr 29.

Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China. Electronic address:

Research Question: Can preoperative or perioperative intervention reduce the risk of recurrence of endometriosis caused by either incomplete excision or spillage and dissemination?

Design: A mouse model of endometriosis recurrence caused by spillage and dissemination was first established using 24 female Balb/c mice. The spillage and dissemination model was used to test the efficacy of preoperative use of ketorolac, perioperative use of aprepitant and combined use of propranolol and andrographolide in a prospective, randomized mouse experiment involving 75 mice. The efficacy of these preoperative and perioperative interventions in a mouse recurrence model caused by incomplete excision was also tested using 72 mice. In all experiments, the baseline body weight and hotplate latency of all mice were measured and recorded before the induction of endometriosis, before the primary surgery and before sacrifice. In addition, all lesions were excised, weighed and processed for quantification and immunohistochemistry analysis of E-cadherin, α-SMA, VEGF, ADRB2 and putative markers of recurrence PR-B, p-p65, as well as Masson trichrome staining.

Results: All interventions substantially and significantly suppressed the outgrowth of endometriotic lesions and reduced the risk of recurrence caused by either spillage and dissemination or incomplete excision (P = 0.0007 to 0.042). These interventions also significantly attenuated the generalized hyperalgesia, inhibited the staining of α-SMA, p-p65, VEGF and ADRB2 but increased staining of E-cadherin and PR-B, resulting in reduced fibrosis.

Conclusion: Given the excellent safety profiles of these drugs, these data strongly suggest that preoperative and perioperative intervention may potentially reduce the risk of endometriosis recurrence effectively.
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http://dx.doi.org/10.1016/j.rbmo.2021.04.017DOI Listing
April 2021

Soft Origami Optical-Sensing Actuator for Underwater Manipulation.

Front Robot AI 2020 10;7:616128. Epub 2021 Mar 10.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China.

Soft robots are ideal for underwater manipulation in sampling and other servicing applications. Their unique features of compliance, adaptability, and being naturally waterproof enable robotic designs to be compact and lightweight, while achieving uncompromized dexterity and flexibility. However, the inherent flexibility and high nonlinearity of soft materials also results in combined complex motions, which creates both soft actuator and sensor challenges for force output, modeling, and sensory feedback, especially under highly dynamic underwater environments. To tackle these limitations, a novel Soft Origami Optical-Sensing Actuator (SOSA) with actuation and sensing integration is proposed in this paper. Inspired by origami art, the proposed sensorized actuator enables a large force output, contraction/elongation/passive bending actuation by fluid, and hybrid motion sensing with optical waveguides. The SOSA design brings two major novelties over current designs. First, it involves a new actuation-sensing mode which enables a superior large payload output and a robust and accurate sensing performance by introducing the origami design, significantly facilitating the integration of sensing and actuating technology for wider applications. Secondly, it simplifies the fabrication process for harsh environment application by investigating the boundary features between optical waveguides and ambient water, meaning the external cladding layer of traditional sensors is unnecessary. With these merits, the proposed actuator could be applied to harsh environments for complex interaction/operation tasks. To showcase the performance of the proposed SOSA actuator, a hybrid underwater 3-DOFs manipulator has been developed. The entire workflow on concept design, fabrication, modeling, experimental validation, and application are presented in detail as reference for wider effective robot-environment applications.
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http://dx.doi.org/10.3389/frobt.2020.616128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988097PMC
March 2021

Intermolecular interactions between the heavy alkenes HSi = TH (T = C, Si, Ge, Sn, Pb) and acetylene.

J Mol Model 2021 Mar 20;27(4):110. Epub 2021 Mar 20.

School of Chemistry & Environmental Science, Qujing Normal University, Qujing, 655011, Yunnan, China.

The intermolecular interactions between the heavy alkenes HSi = TH (T = C, Si, Ge, Sn, Pb) and CH have been calculated at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level, and the nature of these complexes has been investigated by natural bond orbital. The four types (type-A, type-B, type-C and type-D) of complexes can be located for HSi = TH···CH system. The complexes involving HSi = TH···CF and HSi = TH···C(CN) have also been examined to explore the substituent effects. Some complexes which are stable for HSi = TH···CH system become unstable for HSi = TH···CF or HSi = TH···C(CN) system, while other complexes which are unstable for HSi = TH···CH system become stable for HSi = TH···CF or HSi = TH···C(CN) system.
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http://dx.doi.org/10.1007/s00894-021-04738-9DOI Listing
March 2021

Protective effects of resveratrol liposomes on mitochondria in substantia nigra cells of parkinsonized rats.

Ann Palliat Med 2021 Mar 7;10(3):2458-2468. Epub 2021 Feb 7.

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Background: Parkinson's disease (PD) is a central nervous system degenerative disease. The progressive death of dopaminergic neurons is closely correlated to mitochondrial dysfunction. Resveratrol contains three hydroxyl groups, and has a strong neuroprotective effect. This study aimed to investigate the protective effect of resveratrol liposome on mitochondria of substantia nigra cells in Parkinsonized rats through experiment.

Methods: The investigators used 6-hydroxydopamine to establish the Parkinsonized rat model, and used resveratrol liposome from Polygonum cuspidatum (20 mg·kg-1) for gavage, up to a total volume of 1 mL, once-daily, for two weeks. After treatment, the levels of mitochondrial membrane potential, mitochondrial complexes I-IV, mitochondrial cytochrome C, apoptosis-inducing factor (AIF), PTEN-induced putative kinase 1 (PINK1), tumor necrosis factor-receptor-associated protein 1 (TRAP1) and phosphorylated TRAP1 in rat mesencephalic cells were detected according to the operation instructions of the kits.

Results: After two weeks of treatment, resveratrol liposomes could significantly enhance the activity of mitochondrial electron transfer chain complex I in the substantia nigra cells of Parkinsonized model rats, promote the expression of complex I subcomponent MT-ND1-37kD, improve mitochondrial membrane potential, inhibit the release of mitochondrial cytochrome C and apoptotic inducible factor, enhance the expression of mitochondrial functional protein PINK1, increase the phosphorylated TRAP1 level, and elevate the phosphorylated TRAP1/TRAP1 ratio.

Conclusions: Resveratrol liposome has positive effects on mitochondria in substantia nigra cells of Parkinsonized rats, and may be one of its pharmacological mechanisms.
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http://dx.doi.org/10.21037/apm-19-426DOI Listing
March 2021

Intermolecular Interactions Involving Heavy Alkenes HSi=TH (T = C, Si, Ge, Sn, Pb) with HO and HCl: Tetrel Bond and Hydrogen Bond.

ACS Omega 2020 Nov 12;5(46):30210-30225. Epub 2020 Nov 12.

School of Chemistry & Environmental Science, Qujing Normal University, Qujing 655011, Yunnan, China.

The intermolecular interactions between the heavy alkenes HSi=TH (T = C, Si, Ge, Sn, Pb) and HO or HCl have been explored at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level. The various hydrogen bond (HB) and tetrel bond (TB) complexes can be located on the basis of molecular electrostatic potential maps of the isolated monomers. The competition between TB and HB interactions has been investigated through the relaxed potential energy surface scan. The results indicate that the HB complexes become more and more unstable relative to the TB complexes with the increase of the T atomic number, and cannot even retain as a minimum in some cases, for HSi=TH2···HO systems. In contrast, the HB complexes are generally more stable than TB complexes, and the TB complexes exhibit rather weak binding strength, for HSi=TH···HCl systems. The majority of the TB complexes formed between HSi=TH and HO possesses very strong binding strength with covalent characteristics. The noncovalent TB complexes can be divided into two types on the basis of the orbital interactions: π-hole complexes, with binding angles ranging from 91 to 111°, and hybrid σ/π-hole complexes, with binding angles ranging from 130 to 165°. The interplay between different molecular interactions has been explored, and an interesting result is that the covalent TB interaction is significantly abated and becomes noncovalent because of the competitive effect.
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http://dx.doi.org/10.1021/acsomega.0c04682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689927PMC
November 2020

Sodium lactate promotes stemness of human mesenchymal stem cells through KDM6B mediated glycolytic metabolism.

Biochem Biophys Res Commun 2020 11 3;532(3):433-439. Epub 2020 Sep 3.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou, China; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China. Electronic address:

Mesenchymal stem cells (MSCs) are an important cell source for tissue homeostasis and repair due to their stemness characteristic. Lots of intrinsic signaling pathways have been reported to regulate MSC stemness, but the extrinsic signals such as sodium lactate, particularly in physiological conditions, are poorly understood. Herein, we evaluated the effect of sodium lactate on human MSC stemness regulation by examining colony-forming ability, energy metabolism, multi-lineage differentiation ability, and pluripotent gene and protein expression. The underlying mechanism was further investigated with gene knockdown as well as small molecule interference and rescue experiments. We found that: (1) low concentration (1 mM) of sodium lactate promoted the stemness of human MSCs; (2) the upregulation of glycolysis was responsible for the MSC stemness promotion; (3) lysine demethylase 6B (KDM6B) was the key regulator which mediated sodium lactate-induced glycolysis and human MSC stemness enhancement. This study indicated that sodium lactate played an important role in human MSC stemness maintenance in physiological conditions, which could be related to KDM6B mediated metabolic regulation. It would provide new insight into stem cell biology, and contribute to cell transplantation and tissue regeneration strategies.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.061DOI Listing
November 2020

Diagnosing Deep Endometriosis Using Transvaginal Elastosonography.

Reprod Sci 2020 07 24;27(7):1411-1422. Epub 2020 Apr 24.

Shanghai OB/GYN Hospital, Fudan University, Shanghai, 200090, China.

Transvaginal ultrasound (TVUS) and MRI are currently two mainstream imaging techniques used to diagnose deep endometriosis (DE) with comparable accuracy, but there is still ample room for improvement. As endometriotic lesions progress to fibrosis concomitant with the increase in tissue stiffness, transvaginal elastosonography (TVESG) is well-suited for diagnosing DE. To test the hypothesis that lesional stiffness as measured by TVESG correlates with the extent of lesional fibrosis, the markers of progression, hormonal receptor expression, and vascularity, we recruited 30 patients suspected to have DE who went through pelvic examination, TVUS and/or MRI, and TVESG and were ultimately diagnosed by histology. Their lesional tissue samples were subjected to immunohistochemistry analysis of markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), estrogen and progesterone receptors (ERβ and PR), microvessel density (MVD), and vascularity, as well as quantification of lesional fibrosis. We found that pelvic examination, TVUS, and MRI detected 83.3%, 66.7%, and 83.3% of all DE cases, respectively, while TVESG detected them all. The lesions missed by pelvic exam, TVUS and MRI were significantly smaller than those detected but nonetheless had higher lesional stiffness. Lesional stiffness correlated closely and positively with the extent of lesional fibrosis, negatively with the markers of EMT, MVD, vascularity, and PR expression, but positively with the marker for FMT and ERβ. Thus, through the additional use of information on differential stiffness between DE lesions and their surrounding tissues, TVESG improves diagnostic accuracy, provides a ballpark estimate on the developmental stage of the lesions, and may help clinicians choose the best treatment modality.
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http://dx.doi.org/10.1007/s43032-019-00108-2DOI Listing
July 2020

Evidence in Support for the Progressive Nature of Ovarian Endometriomas.

J Clin Endocrinol Metab 2020 07;105(7)

Shanghai OB/GYN Hospital, Fudan University, Shanghai, China.

Context: Whether endometriosis is a progressive disease is a highly contentious issue. While progression is reported to be unlikely in asymptomatic deep endometriosis, progression in symptomatic deep endometriosis has recently been reported, especially in menstruating women. However, pathophysiological reasons for these differences are unclear.

Objective: This study was designed to investigate whether ovarian endometrioma (OE) is progressive or not.

Setting, Design, Patients, Intervention And Main Outcome Measures: Thirty adolescent patients, aged 15 to 19 years, and 32 adult patients, aged 35 to 39 years, all laparoscopically and histologically diagnosed with OE, were recruited into this study after informed consent. Their demographic and clinical information were collected. Their OE tissue samples were collected and subjected to immunohistochemical analysis for E-cadherin, α-smooth muscle actin (α-SMA), desmin, and adrenergic receptor β2 (ADRB2), as well as quantification of lesional fibrosis by Masson trichrome staining.

Results: OE lesions from the adolescent and adult patients are markedly different, with the latter exhibiting more extensive and thorough progression and more extensive fibrosis, suggesting that lesions in adults progressed to a more advanced stage. Adult lesions and higher staining level of α-SMA and ADRB2 are positively associated with the extent of lesional fibrosis, while the lesion size and the E-cadherin staining are negatively associated.

Conclusions: Our data provide a more definitive piece of evidence suggesting that OE is a progressive disease, since the adult lesions have had a longer time to progress. In addition, the pace of progression depends on lesional age as well as the severity of endometriosis-associated dysmenorrhea, if any.
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http://dx.doi.org/10.1210/clinem/dgaa189DOI Listing
July 2020

High-Resolution Dissection of Chemical Reprogramming from Mouse Embryonic Fibroblasts into Fibrocartilaginous Cells.

Stem Cell Reports 2020 03 20;14(3):478-492. Epub 2020 Feb 20.

Department of Orthopaedic Surgery, Second Affiliated Hospital and Zhejiang University-University of Edinburgh Institute and School of Basic Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310058, China. Electronic address:

Articular cartilage injury and degeneration causing pain and loss of quality-of-life has become a serious problem for increasingly aged populations. Given the poor self-renewal of adult human chondrocytes, alternative functional cell sources are needed. Direct reprogramming by small molecules potentially offers an oncogene-free and cost-effective approach to generate chondrocytes, but has yet to be investigated. Here, we directly reprogrammed mouse embryonic fibroblasts into PRG4+ chondrocytes using a 3D system with a chemical cocktail, VCRTc (valproic acid, CHIR98014, Repsox, TTNPB, and celecoxib). Using single-cell transcriptomics, we revealed the inhibition of fibroblast features and activation of chondrogenesis pathways in early reprograming, and the intermediate cellular process resembling cartilage development. The in vivo implantation of chemical-induced chondrocytes at defective articular surfaces promoted defect healing and rescued 63.4% of mechanical function loss. Our approach directly converts fibroblasts into functional cartilaginous cells, and also provides insights into potential pharmacological strategies for future cartilage regeneration.
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http://dx.doi.org/10.1016/j.stemcr.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066361PMC
March 2020

Targeting downstream subcellular YAP activity as a function of matrix stiffness with Verteporfin-encapsulated chitosan microsphere attenuates osteoarthritis.

Biomaterials 2020 02 26;232:119724. Epub 2019 Dec 26.

School of Basic Medical Sciences and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China. Electronic address:

Changes in the stiffness of chondrocyte extracellular matrix (ECM) are involved in the pathological progression of osteoarthritis (OA). However, the downstream responses of cartilage ECM stiffness are still unclear. YAP (Yes-associated protein) has been extensively studied as a mechanotransducer, we thus hypothesized that by targeting the downstream molecule activity of ECM stiffness could maintain chondrocyte phenotype and prevent cartilage degeneration in OA. Here, we showed that human cartilage matrix stiffened during pathological progression of OA, and the chondrocyte YAP activity was associated with ECM stiffness. We then mimicked the physiological and pathological stiffness of human cartilage by using PDMS-based substrates, and found that YAP was activated in chondrocytes seeded on stiff substrate, gradually losing their phenotype. In addition, it was observed that YAP was also significantly activated in mice OA development, and conditional knockout (cKO) of YAP in mice preserved collagen II expression and protected cartilage from degeneration in the OA model. Furthermore, intra-articular injection of YAP-selective inhibitor, Verteporfin, significantly maintained cartilage homeostasis in mice OA model. This study indicates that the application of mechanotransducer-targeted drugs could be a potential therapeutic approach for cartilage repair in OA.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119724DOI Listing
February 2020

Ezh2 Ameliorates Osteoarthritis by Activating TNFSF13B.

J Bone Miner Res 2020 05 3;35(5):956-965. Epub 2020 Feb 3.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Epigenetic regulation is highly correlated with osteoarthritis (OA) development, whereas its role and detailed mechanisms remain elusive. In this study, we explored the expression of EZH2, an H3K27me3 transferase, in human OA cartilages and its roles in regulating OA pathogenesis. Here, we found EZH2 was highly expressed in both mice and human OA cartilage samples by using histological analysis and RNA sequencing (RNA-Seq). The medial meniscectomy (MMx) OA model results indicated the conditional knockout of Ezh2 deteriorated OA pathological conditions. Furthermore, we showed the positive role of Ezh2 in cartilage wound healing and inhibition of hypertrophy through activating TNFSF13B, a member of the tumor necrosis factor superfamily. Further, we also indicated that the effect of TNFSF13B, increased by Ezh2, might boost the healing of chondrocytes through increasing the phosphorylation of Akt. Taken together, our results uncovered an EZH2-positive subpopulation existed in OA patients, and that EZH2-TNFSF13B signaling was responsible for regulating chondrocyte healing and hypertrophy. Thus, EZH2 might act as a new potential target for OA diagnosis and treatment. © 2020 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3952DOI Listing
May 2020

Synergistic and antagonistic interplay between tetrel bond and pnicogen bond in complexes involving ring compounds.

J Mol Model 2019 Nov 20;25(12):351. Epub 2019 Nov 20.

School of Chemistry & Environmental Science, Qujing Normal University, Qujing, 655011, Yunnan, China.

The binary and ternary complexes composed of GeHF, AsHF and ring compounds (benzene, borazine and cyclopentadienyl anion) have been studied by theoretical calculations to understand the interplay between the tetrel bond and pnicogen bond interactions. The bonding strength of intermolecular interactions in these complexes is analyzed by means of atoms in molecules (AIM), natural bond orbital (NBO) and noncovalent interaction (NCI) index methods. The binary tetrel-bonded and pnicogen-bonded complexes can be classified as an n-type or π-type complex according to the orbital interactions involved in the complexes. Three binding modes can be distinguished according to the interplay between interactions for the ternary complexes. The binding mode A is characterized by the interplay between π-type tetrel bond and n-type pnicogen bond; binding mode B is characterized by the interplay between π-type pnicogen bond and n-type tetrel bond, and binding mode C is characterized by the interplay between π-type tetrel bond and π-type pnicogen bond. The binding modes A and B exhibit the synergistic interplay effect, while the antagonistic effect is reflected in mode C. The synergistic effect in binding modes A and B is stronger than antagonistic effect in mode C, and the synergistic effect in binding mode B is stronger than that in mode A.
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http://dx.doi.org/10.1007/s00894-019-4206-1DOI Listing
November 2019

Nano genome altas (NGA) of body wide organ responses.

Biomaterials 2019 06 15;205:38-49. Epub 2019 Mar 15.

Clinical Research Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, PR China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, Zhejiang, 310058, PR China; Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regeneration Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, PR China. Electronic address:

Nanoparticles are widely developed and utilized in the pharmaceutical and medicine industry, as they can be easily distributed and infiltrated throughout the whole body once administered; however, the body wide effect of nanoparticles infiltration is still unclear. In this study, we developed a new strategy of Nano Genome Altas (NGA) of multi-tissues to study the acute Body-wide-Organ-Transcriptomic response to nanomaterials. Hydroxyapatite(HA)-Nanoparticles (HANPs) was applied in this study as an example both in vitro and in vivo. Results showed that the effect of HANPs is organ specific and mainly related to immune responses in spleen and muscle, proliferation in spleen and bone, stress and apoptosis in spleen and PBMC, ion transport in spleen, kidney, and liver tissues, metabolism in heart, spleen, and muscle, as well as tissue specific epigenetic and signal pathways. In vitro experiments also confirmed that the effects of HANPs on different tissue stem cells were tissue specific. Thus, Nano Genome Altas can provide a body-wide view of the transcriptomic response of multiple organs and tissue specific stem cells to HANPs; it could also be useful for optimizing HANPs and other nano-delivery systems.
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http://dx.doi.org/10.1016/j.biomaterials.2019.03.019DOI Listing
June 2019

Airflow-Assisted 3D Bioprinting of Human Heterogeneous Microspheroidal Organoids with Microfluidic Nozzle.

Small 2018 09 21;14(39):e1802630. Epub 2018 Aug 21.

State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China.

Hydrogel microspheroids are widely used in tissue engineering, such as injection therapy and 3D cell culture, and among which, heterogeneous microspheroids are drawing much attention as a promising tool to carry multiple cell types in separated phases. However, it is still a big challenge to fabricate heterogeneous microspheroids that can reconstruct built-up tissues' microarchitecture with excellent resolution and spatial organization in limited sizes. Here, a novel airflow-assisted 3D bioprinting method is reported, which can print versatile spiral microarchitectures inside the microspheroids, permitting one-step bioprinting of fascinating hydrogel structures, such as the spherical helix, rose, and saddle. A microfluidic nozzle is developed to improve the capability of intricate cell encapsulation with heterotypic contact. Complex structures, such as a rose, Tai chi pattern, and single cell line can be easily printed in spheroids. The theoretical model during printing is established and process parameters are systematically investigated. As a demonstration, a human multicellular organoid of spirally vascularized ossification is reconstructed with this method, which shows that it is a powerful tool to build mini tissues on microspheroids.
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http://dx.doi.org/10.1002/smll.201802630DOI Listing
September 2018

Gefitinib for Epidermal Growth Factor Receptor Activated Osteoarthritis Subpopulation Treatment.

EBioMedicine 2018 Jun 11;32:223-233. Epub 2018 Jun 11.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Hangzhou, Zhejiang 310058, China; Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China; China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310058, China. Electronic address:

Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward personalized precision medicine. In the present study, we identified a subpopulation of OA patients displaying high activation level of epidermal growth factor receptor (EGFR). With Col2a1-creER; Egfr mice, it was found that the activation of EGFR, indicated by EGFR phosphorylation (pEGFR), led to the destruction of joints. Excitingly, EGFR inhibition prohibited cartilage matrix degeneration and promoted cartilage regeneration. The Food and Drug Administration (FDA)-approved drug gefitinib could efficiently inhibit EGFR functions in OA joints and restore cartilage structure and function in the mouse model as well as the clinical case report. Overall, our findings suggested the concept of the EGFR activated OA subpopulation and illustrated the mechanism of EGFR signaling in regulating cartilage homeostasis. Gefitinib could be a promising disease-modifying drug for this OA subpopulation treatment.
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http://dx.doi.org/10.1016/j.ebiom.2018.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020860PMC
June 2018

Significant benefit of Nivolumab treating PD-L1 positive metastatic pulmonary carcinosarcoma: a case report and literature review.

Oncotarget 2017 Nov 7;8(56):96453-96459. Epub 2017 Jul 7.

Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China.

Immunotherapy has recently become a new focus for the treatment of malignant tumors following the surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Nivolumab, a human monoclonal antibody, is the first programmed cell death protein-1 (PD-1) inhibitor, which can prohibit the interaction of its ligand (PD-L1), restoring the immune response of T cells, and enhancing the recognition of tumor cells by the immune system. Pulmonary carcinosarcoma is an uncommon but highly aggressive tumor type with a poor prognosis. We described a case of pulmonary carcinosarcoma, with the positive expression of PD-L1, obtained a significant benefit from Nivolumab treatment in a 64-year-old Chinese man, which give us a clue that patients with pulmonary carcinosarcoma may benefit fromanti-PD-1 immunotherapy.
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http://dx.doi.org/10.18632/oncotarget.19089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707114PMC
November 2017

Analysis of biofilm bacterial communities under different shear stresses using size-fractionated sediment.

Sci Rep 2017 05 2;7(1):1299. Epub 2017 May 2.

State Key Laboratory of Hydro-science and Engineering, Department of Hydraulic Engineering, Tsinghua University, Beijing, 100084, China.

Microorganisms are ubiquitous in aqueous environments and are crucial for biogeochemical processes, but their community structures and functions remain poorly understood. In this paper, a rotating reactor was designed to study the effects of substrata and flow conditions on sediment bacterial communities using 16S rRNA gene sequencing, assaying three groups of size-fractionated sediments and three different levels of applied shear stress. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla of the microbial communities, with more anaerobic bacteria and opportunistic pathogens being detected under static water conditions, while more aerobic bacteria were detected under dynamic water flow conditions. Most of the top 10 genera were present in all the samples; however, there were significant differences in the species abundance. Paludibacter and Comamonadaceae_unclassified were the most abundant genera under static and dynamic conditions, respectively. Under static water conditions, the medium-grained sediment had the highest microbial diversity, followed by the fine and coarse sediments. Under dynamic water flow conditions, a higher flow velocity corresponded to a greater microbial diversity. Overall, there was no significant difference in the community richness or diversity between the static and dynamic water flow conditions. This study is beneficial for further understanding the heterogeneities of microbial communities in natural aquatic ecosystems.
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http://dx.doi.org/10.1038/s41598-017-01446-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431010PMC
May 2017

Kdm6b regulates cartilage development and homeostasis through anabolic metabolism.

Ann Rheum Dis 2017 Jul 17;76(7):1295-1303. Epub 2017 Mar 17.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Zhejiang, China.

Objectives: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms.

Methods: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic . RNA-Seq was applied to explore the underlying changes in chondrocytes upon knockdown of Kdm6b. Experimental OA in mice was induced by destabilisation of the medial meniscus in C57BL/6J (wild type, and ) mice, either with intra-articular injection of shKdm6b lentivirus or after tamoxifen treatment. Mouse joints and human cartilage samples were used for histological analysis.

Results: Kdm6b expression was significantly increased during cartilage development. mice displayed obvious skeletal abnormalities at E16.5 and E18.5 with intraperitoneal injection of tamoxifen at E12.5. RNA-Seq and qRT-PCR analyses revealed decreased expression of chondrocyte anabolic genes in chondrocytes. The histological OA score was significantly higher in mice injected with Kdm6b short hairpin RNA lentivirus. mice exhibited accelerated OA development at 8 and 12 weeks following surgical induction. The number of Kdm6b-positive chondrocytes was lower in both mice and human OA cartilage samples.

Conclusions: These findings indicate that knockdown of Kdm6b in chondrocytes leads to abnormal cartilage development and accelerated OA progression via inhibition of the anabolic metabolism of chondrocytes. Understanding the epigenetic mechanism of joint cartilage development and homeostasis would be useful for development of new therapeutic modalities for OA.
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http://dx.doi.org/10.1136/annrheumdis-2016-210407DOI Listing
July 2017

The effects of lactate and acid on articular chondrocytes function: Implications for polymeric cartilage scaffold design.

Acta Biomater 2016 09 23;42:329-340. Epub 2016 Jun 23.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, China; Department of Sports Medicine, School of Medicine, Zhejiang University, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003 Hangzhou, China. Electronic address:

Unlabelled: Poly (lactic-co-glycolic acid) (PLGA) and poly-l-lactate acid (PLLA) are biodegradable polymers widely utilized as scaffold materials for cartilage tissue engineering. Their acid degradation products have been widely recognized as being detrimental to cell function. However, the biological effects of lactate, rather than lactic acid, on chondrocytes have never been investigated. This is the major focus of this study. The amounts of lactate and the pH value (acid) of the PLGA and PLLA degradation medium were measured. The effects of PLGA and PLLA degradation medium, as well as different lactate concentrations and timing of exposure on chondrocytes proliferation and cartilage-specific matrix synthesis were investigated by various techniques including global gene expression profiling and gene knockdown experiments. It was shown that PLGA and PLLA degradation medium differentially regulated chondrocyte proliferation and matrix synthesis. Acidic pH caused by lactate inhibited chondrocyte proliferation and matrix synthesis. The effect of lactate on chondrocyte matrix synthesis was both time and dose dependent. A lactate concentration of 100mM and exposure duration of 8h significantly enhanced matrix synthesis. Lactate could also inhibit expression of cartilage matrix degradation genes in osteoarthritic chondrocytes, such as the major aggrecanase ADAMTS5, whilst promoting matrix synthesis simultaneously. Pulsed addition of lactate was shown to be more efficient in promoting COL2A1 expression. Global gene expression data and gene knock down experiments demonstrated that lactate promote matrix synthesis through up-regulation of HIF1A. These observed differential biological effects of lactate on chondrocytes would have implications for the future design of polymeric cartilage scaffolds.

Statement Of Significance: Lactic acid is a widely used substrate for polymers synthesis, PLGA and PLLA in particular. Although physical and biological modifications have been made on these polymers to make them be better cartilage scaffolds, little concern has been given on the biological effect of lactic acid, the main degradation product of these polymers, on chondrocytes. Our finding illustrates the differential biological function of lactate and acid on chondrocytes matrix synthesis. These results can facilitate future design of lactate polymers-based cartilage scaffolds.
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http://dx.doi.org/10.1016/j.actbio.2016.06.029DOI Listing
September 2016

Mobility of phosphorus induced by sediment resuspension in the Three Gorges Reservoir by flume experiment.

Chemosphere 2015 Sep 15;134:374-9. Epub 2015 May 15.

School of Engineering, University of Liverpool, Liverpool L69 3GQ, UK.

The mobility of phosphorus (P) induced by sediment resuspension have been examined in a circulated flume. During the flume run, the water level and velocity were monitored, and water samples were taken for measurement of sediment and P concentrations. Peak values of both the P and sediment concentrations existed at x=4m, and then decreased slightly along the flume due to deposition. A faster P release was observed for coarser sediment, while a more sustained P release for finer sediment. Combining with the measured data from Yangtze River and sorption experiment, the relation between the load of total P (LTP) and sediment load (Qs) was estimated, and the expressions of distribution coefficient Kd and the concentration of particulate P (PP) were obtained. This study established a bridge between the small-scale sorption experiment and the field observation of natural scale, providing references for the management of contaminated sediment in natural rivers.
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http://dx.doi.org/10.1016/j.chemosphere.2015.05.009DOI Listing
September 2015

Down-regulation of Rac GTPase-activating protein OCRL1 causes aberrant activation of Rac1 in osteoarthritis development.

Arthritis Rheumatol 2015 May;67(8):2154-63

Zhejiang University School of Medicine, Hangzhou, China.

Objective: Chondrocyte hypertrophy and mineralization are considered to be important pathologic factors in osteoarthritis (OA). We previously reported that Rac1 was aberrantly activated to promote chondrocyte hypertrophy, mineralization, and expression of matrix metalloproteinase 13 and ADAMTS in OA. However, the underlying mechanism of aberrant Rac1 activation in OA is unclear. The present study was undertaken to identify the specific molecular regulator controlling Rac1 activity in OA, as well as to investigate its function in chondrocyte hypertrophy, mineralization, and OA development.

Methods: Expression levels of 28 upstream regulators of Rac1 activity, including 8 GTPase-activating proteins (GAPs) and 20 guanine nucleotide exchange factors, in OA and normal cartilage were assessed by quantitative polymerase chain reaction. Chondrocytes were transduced with lentiviral vectors encoding OCRL1, GAP, non-GAP, CA-Rac1, and DN-Rac1, either alone or in combination. Alkaline phosphatase staining was used as a marker of chondrocyte hypertrophy. Rac1 activity was analyzed by pulldown assay. Finally, OA was established in mice by surgical transection of the anterior cruciate ligament and cutting of the medial meniscus. The mice were injected intraarticularly with OCRL1-encoding lentivirus, and whole joints were assessed histologically 6 weeks after surgery.

Results: OCRL1 was abundantly expressed in normal cartilage and was the only significantly down-regulated RacGAP in OA cartilage. Overexpression of OCRL1 inhibited interleukin-1β-induced Rac1 activity, chondrocyte hypertrophy, and expression of hypertrophy-related genes. Conversely, knockdown of OCRL1 elevated Rac1 activity and promoted chondrocyte hypertrophy and mineralization. Further, OCRL1 modulated Rac1 activity via its GAP domain. Finally, intraarticular injection of OCRL1-encoding lentivirus protected against destruction and degeneration of cartilage in the mouse OA model.

Conclusion: OCRL1 acts as a RacGAP in cartilage to impede chondrocyte hypertrophy and OA development through modulating Rac1 activity. This regulatory pathway might provide potential targets for the development of new therapies for OA.
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http://dx.doi.org/10.1002/art.39174DOI Listing
May 2015

Theoretical study of interactions between electron-deficient arenes and coinage metal anions.

J Mol Model 2015 Mar 8;21(3):38. Epub 2015 Feb 8.

School of Chemistry & Chemical Engineering, Qujing Normal University, Qujing, 655011, Yunnan, China,

The binding behavior of coinage metal anions with some electron-deficient arenes has been investigated by MP2 calculations, and the character of interactions in these complexes has been examined by NBO analysis. The results indicate that coinage metal anions can interact with electron-deficient arenes to form anion-π, strong σ-type and hydrogen-bonding complexes. The σ-type structure is the global minimum for triazine, trifluorotriazine, hexafluorobenzene and tricyanobenzene, and the hydrogen-bonding structure is the global minimum for trifluorobenzene. There exist some differences in the stability of anion-π complexes for coinage metal anions: the anion-π complexes of Au(-) are minima expect for triazine complex; the anion-π complexes of Ag(-) are minima expect for tricyanobenzene complex; and the anion-π complexes of Cu(-) are not minima expect for trifluorobenzene complex. The binding strength of anion-π and hydrogen-bonding complexes for Au(-) is larger than that for Ag(-) and Cu(-), but the binding strength of σ complex displays a different sequence: Cu(-) > Au(-) > Ag(-). The binding behavior of coinage metal anions is more similar to that of F(-) than that of Cl(-) and Br(-). The relaxed potential energy surface scans for some selected systems have been performed to help understand the interactions between coinage metal anions with electron-deficient arenes.
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http://dx.doi.org/10.1007/s00894-015-2584-6DOI Listing
March 2015

Polymeric micelles encapsulating fisetin improve the therapeutic effect in colon cancer.

ACS Appl Mater Interfaces 2015 Jan 24;7(1):534-42. Epub 2014 Dec 24.

State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041, P. R. China.

The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolonged in vitro release behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As for in vivo studies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection of Ki-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG-PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.
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http://dx.doi.org/10.1021/am5066893DOI Listing
January 2015

Theoretical study of X⁻ · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂): noncovalently electron-withdrawing effects on anion-arene interactions.

J Mol Model 2014 Jan 25;20(1):2076. Epub 2014 Jan 25.

School of Chemistry & Chemical Engineering, Qujing Normal University, Qujing, 655011, Yunnan, China,

The ternary complexes X(-) · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH2 and AsH2) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X(-)), both weak σ-type and anion-π complexes can be formed for Cl(-) and Br(-), but only anion-π complex can be formed for I(-). Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl(-) and Br(-). Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl(-) and Br(-) in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl(-) and Br(-) can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I(-) is different from that for Cl(-) and Br(-) in two aspects. First, the anion-π complex for I(-) can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I(-) is the global minimum when it can retain as a stable structure.
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http://dx.doi.org/10.1007/s00894-014-2076-0DOI Listing
January 2014

Theoretical study of interactions between halogen-substituted s-triazine and halide anions.

Authors:
Yishan Chen

J Phys Chem A 2013 Aug 13;117(33):8081-90. Epub 2013 Aug 13.

School of Chemistry & Chemical Engineering, Qujing Normal University, Qujing 655011, Yunnan, China.

The interactions between halogen-substituted s-trazine (C3H2N3X) and halide anions (Y(-)) have been investigated at the MP2/aug-cc-pVDZ (aug-cc-pVDZ-PP) level. C3H2N3X can interact with halide anions to form five types of complexes (C3H2N3X·Y(-)): a strong σ-type interaction complex, a weak σ-type interaction complex, an anion-π interaction complex, a hydrogen-bonding complex, and a halogen-bonding complex. The binding energies, structures, and bonding characteristics of these complexes have been discussed. The local details of potential energy surfaces around the binding sites for some selected complexes have been depicted. The results indicate that the binding behavior of F(-) is quite different from that of Cl(-), Br(-), and I(-). The potential energy surface is separated into two parts, the HB-σ-π region and the XB region, by a relatively high energy barrier for complexes C3H2N3Cl·Cl(-), C3H2N3Br·Cl(-), and C3H2N3I·Cl(-). The HB-σ-π region is characterized by the flat potential energy surface, indicating that the binding strength is retained when the anion is held over the HB-σ-π region. The XB region is characterized by the steeper potential energy surface, indicating that the binding strength is more sensitive to the anion position in this region. The binding strength of the HB-σ-π region is stronger than that of the XB region for C3H2N3Cl·Cl(-) and C3H2N3Br·Cl(-), whereas the binding strength of the XB region is stronger than that of the HB-σ-π region for C3H2N3I·Cl(-).
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http://dx.doi.org/10.1021/jp4069015DOI Listing
August 2013

Curcumin loaded polymeric micelles inhibit breast tumor growth and spontaneous pulmonary metastasis.

Int J Pharm 2013 Feb 31;443(1-2):175-82. Epub 2012 Dec 31.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

This work aims to develop curcumin (Cur) loaded biodegradable self-assembled polymeric micelles (Cur-M) to overcome poor water solubility of Cur and to meet the requirement of intravenous administration. Cur-M were prepared by solid dispersion method, which was simple and easy to scale up. Cur-M had a small particle size of 28.2 ± 1.8 nm and polydisperse index (PDI) of 0.136 ± 0.050, and drug loading and encapsulation efficiency of Cur-M were 14.84 ± 0.11% and 98.91 ± 0.70%, respectively. Besides, in vitro release profile showed a significant difference between rapid release of free Cur and much slower and sustained release of Cur-M. Cytotoxicity study showed that the encapsulated Cur remained its potent anti-tumor effect. Furthermore, Cur-M were more effective in inhibiting tumor growth and spontaneous pulmonary metastasis in subcutaneous 4T1 breast tumor model, and prolonged survival of tumor-bearing mice. In addition, immunofluorescent and immunohistochemical studies also showed that tumors of Cur-M-treated mice had more apoptosis cells, fewer microvessels, and fewer proliferation-positive cells. In conclusion, polymeric micelles encapsulating Cur were developed with enhanced anti-tumor and anti-metastasis activity on breast tumor, and Cur-M is excellent water-based formulation of Cur which may serve as a candidate for breast cancer therapy.
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http://dx.doi.org/10.1016/j.ijpharm.2012.12.032DOI Listing
February 2013

Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles.

Biomaterials 2013 Jan 17;34(4):1413-32. Epub 2012 Nov 17.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.

For developing aqueous formulation and improving anti-tumor activity of curcumin (Cur), we prepared Cur encapsulated MPEG-PCL micelles by solid dispersion method without using any surfactants or toxic organic solvent. Cur micelles could be lyophilized into powder form without any cryoprotector or excipient, and the re-dissolved Cur micelles are homogenous and stable. Molecular modeling study suggested that Cur tended to interact with PCL serving as a core embraced by PEG as a shell. After Cur was encapsulated into polymeric micelles, cytotoxicity and cellular uptake were both increased. Cur micelles had a stronger inhibitory effect on proliferation, migration, invasion, and tube formation of HUVECs than free Cur. Besides, Cur micelles showed a sustained in vitro release behavior and slow extravasation from blood vessels in transgenic zebrafish model. Embryonic angiogenesis and tumor-induced angiogenesis were both dramatically inhibited by Cur micelles in transgenic zebrafish model. Furthermore, Cur micelles were more effective in inhibiting tumor growth and prolonged survival in both subcutaneous and pulmonary metastatic LL/2 tumor models. In pharmacokinetic and tissue distribution studies, Cur micelles showed higher concentration and longer retention time in plasma and tumors. Our findings suggested that Cur micelles may have promising applications in pulmonary carcinoma therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2012.10.068DOI Listing
January 2013

Influence of Paeonia lactiflora roots extract on cAMP-phosphodiesterase activity and related anti-inflammatory action.

J Ethnopharmacol 2011 Sep 18;137(1):914-20. Epub 2011 Jul 18.

Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing 102206, PR China.

Background: Paeonia lactiflora root (baishao in Chinese) is a commonly used herb in TCM. Research has shown baishao to have positive pharmacological actions, including, particularly, anti-inflammatory properties. In this paper we studied the influence of baishao extract on cAMP-phosphodiesterase (PDE) activity and related anti-inflammatory action to identify new pharmacologic action for its clinically widespread use.

Methods: PDE activity was calculated by cAMP change examined with HPLC, respiratory burst of neutrophils was detected with method of cytochrome C reduction, elastase release was indicated with the substrate reduction, rat arthritis model was caused by complete Freund's adjuvant, mouse capillary permeability model was made by acetic acid, and chemical constituents of baishao extract was identified by HPLC, mass spectroscopy and NMR spectrum.

Results: Baishao extract had significant inhibition on cAMP-PDE activity (p<0.01), had dose dependent restraint on neutrophils respiratory burst (p<0.001), had inhibition at low concentration and promotion at high concentration on elastase release (p<0.05), and had obvious restraint on local inflammation of animal model (p<0.01). Analysis of HPLC, mass spectroscopy and NMR spectrum showed baishao extract mainly had five components (identified as gallic acid, paeoniflorin sulfonate, albiflorin, paeoniflorin and benzoic acid), among which gallic acid had the largest inhibition on cAMP-PDE activity.

Conclusion: The anti-inflammatory effects of baishao may be mediated, at least in part, through its gallic acid content, and this effect may be regulated in part by an inhibition on cAMP-PDE.
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http://dx.doi.org/10.1016/j.jep.2011.07.020DOI Listing
September 2011
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