Publications by authors named "Xiaohua Yu"

75 Publications

Serum sex hormone-binding globulin is associated with symptomatic late-onset hypogonadism in aging rural males: a community-based study.

Sex Health 2021 May;18(2):156-161

Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China; and Corresponding authors. Emails:

Background To investigate whether serum levels of sex hormone-binding globulin (SHBG) and testosterone are associated with symptomatic late-onset hypogonadism (SLOH) in middle-aged and elderly rural Chinese males.

Methods: A population-based cross-sectional study was conducted in Zhejiang rural communities. A total of 965 men (aged 40-80 years) were admitted to the aging males' symptoms (AMS) scale and related physical examinations including body mass index (BMI) and waist circumference were conducted. Serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG) and serum lipid levels were measured separately. Serum level of bioavailable testosterone (Bio-T) was calculated.

Results: A total of 965 participants were divided into two groups, symptomatic late-onset hypogonadism (SLOH) group (n = 202) (AMS score ≥27) and control group (n = 763), according to total AMS score. Men in the SLOH group were older (61.57±9.06 vs 54.95±8.27 years) and had a smaller waist circumference (81.06±6.89 vs 82.54±6.60 cm) than those in the control group. Moreover, a relatively higher level of SHBG and lower levels of FT, Bio-T, triglyceride (TG) and total cholesterol (T-CHOL) were found in the SLOH group compared with that in the control group (P < 0.05). Receiver operating characteristic curves (ROC) analysis showed that age (AUC = 0.702, P < 0.001) and SHBG (AUC = 0.617, P < 0.001) were potential predictive indicators for SLOH diagnosis, with the best cut-off values of 59 years for age and 44.40 nmol/L for SHBG.

Conclusions: SHBG might be a potential predictor in men with hypogonadism, whereas BMI had no proportionality to the measurement of AMS. Age and SHBG should be used for SLOH diagnosis.
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http://dx.doi.org/10.1071/SH20201DOI Listing
May 2021

Association of hypogonadism symptoms and serum hormones in aging males.

Andrologia 2021 Feb 18:e14013. Epub 2021 Feb 18.

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

The association between hypogonadism symptoms and the levels of serum hormones are still in debate. To investigate the relationship between hypogonadism symptoms and serum hormones in middle-aged and elderly Chinese men, this community-based cross-sectional study was conducted based on a total of 965 ageing men. The ageing males' symptom (AMS) scale, International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS) questionnaires and related variables were assessed. Blood tests for total testosterone (TT), sex hormone-binding globulin (SHBG) and luteinising hormone (LH) were performed. Serum level of free testosterone (FT) and bioavailable testosterone (Bio-T) was calculated. The mean age was 56.34 ± 8.85 years. Total AMS score was significantly associated with all five serum hormones (LH: p < 0.001; SHBG: p < 0.001; TT: p =.043; FT: p = 0.007; Bio-T: p < 0.001). We identified sexual and somatic symptoms were obviously related to five serum hormones, while psychological symptoms seemed to have no association with serum hormones. After adjusting for age and BMI, multiple linear regression analysis indicated that LH had positive correlations with total AMS score, somatic and sexual symptom score (p < 0.05). In conclusion, LH and SHBG had the strongest correlation hypogonadism and might be used as early predictors for symptomatic hypogonadism in the near future.
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http://dx.doi.org/10.1111/and.14013DOI Listing
February 2021

A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle.

Bioact Mater 2021 Jul 10;6(7):1853-1866. Epub 2020 Dec 10.

Department of Orthopedics, Centre for Orthopaedic Research, Orthopedics Research Institute of Zhejiang University, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, PR China.

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles. However, ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc. As these incidents could easily introduce new microbial pathogens in/onto the implants. Herein, we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning, could effectively eradicate bacterial infection at various stages of implantation. Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating. Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating. Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model . Finally, the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc, which maintained a strong antibacterial ability against both and even after the removal of top layer coating. Moreover, sustained release of Sr and Zn during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.
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http://dx.doi.org/10.1016/j.bioactmat.2020.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732879PMC
July 2021

Utility of Air Bladder-Derived Nanostructured ECM for Tissue Regeneration.

Front Bioeng Biotechnol 2020 15;8:553529. Epub 2020 Oct 15.

Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

Exploration for ideal bone regeneration materials still remains a hot research topic due to the unmet clinical challenge of large bone defect healing. Bone grafting materials have gradually evolved from single component to multiple-component composite, but their functions during bone healing still only regulate one or two biological processes. Therefore, there is an urgent need to develop novel materials with more complex composition, which convey multiple biological functions during bone regeneration. Here, we report an naturally nanostructured ECM based composite scaffold derived from fish air bladder and combined with dicalcium phosphate (DCP) microparticles to form a new type of bone grafting material. The DCP/acellular tissue matrix (DCP/ATM) scaffold demonstrated porous structure with porosity over 65% and great capability of absorbing water and other biologics. cell culture study showed that DCP/ATM scaffold could better support osteoblast proliferation and differentiation in comparison with DCP/ADC made from acid extracted fish collagen. Moreover, DCP/ATM also demonstrated more potent bone regenerative properties in a rat calvarial defect model, indicating incorporation of ECM based matrix in the scaffolds could better support bone formation. Taken together, this study demonstrates a new avenue toward the development of new type of bone regeneration biomaterial utilizing ECM as its key components.
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http://dx.doi.org/10.3389/fbioe.2020.553529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594528PMC
October 2020

Single-dose mRNA therapy via biomaterial-mediated sequestration of overexpressed proteins.

Sci Adv 2020 Jul 1;6(27). Epub 2020 Jul 1.

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.

Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA's short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single mRNA dose via an "overexpress and sequester" mechanism, whereby mRNA-transfected cells locally overexpress a growth factor that is then sequestered within the biomaterial to sustain the biologic response over time. In a murine diabetic wound model, this strategy demonstrated improved wound healing compared to delivery of a single mRNA dose alone or recombinant protein. In addition, codelivery of anti-inflammatory proteins using this biomaterial eliminated the need for mRNA chemical modification for in vivo therapeutic efficacy. The results support an approach that may be broadly applicable for single-dose delivery of mRNA without chemical modification.
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http://dx.doi.org/10.1126/sciadv.aba2422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458450PMC
July 2020

Interleukin-5 promotes ATP-binding cassette transporter A1 expression through miR-211/JAK2/STAT3 pathways in THP-1-dervied macrophages.

Acta Biochim Biophys Sin (Shanghai) 2020 Aug;52(8):832-841

Department of Cardiology, The Second Affiliated Hospital of University of South China, Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang 421001, China.

Interleukin-5 (IL-5) is manifested as its involvement in the process of atherosclerosis, but the mechanism is still unknown. In this study, we explored the effect of IL-5 on lipid metabolism and its underlying mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction (qPCR) and western blot analysis results showed that IL-5 significantly up-regulated ATP-binding cassette transporter A1 (ABCA1) expression in a dose-dependent and time-dependent manner. [3H]-labeled cholesterol was used to assess the levels of cholesterol efflux, and the results showed that IL-5 increased ABCA1-mediated cholesterol efflux. A high-performance liquid chromatography assay indicated that cellular cholesterol content was decreased by IL-5 treatment in THP-1-derived macrophages. The selective inhibitor and small interfering RNA were used to block the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway. The results of the qPCR and western blot analysis showed that IL-5 activated JAK2/STAT3 pathway to up-regulate ABCA1 expression. Meanwhile, IL-5 reduced the expression level of miR-211. Furthermore, we found that JAK2 is a target gene of miR-211 and miR-211 mimic inhibited the expression of JAK2 and reduced the levels of p-STAT3 and ABCA1 as revealed by luciferase reporter assay, qPCR and western blot analysis. In summary, these findings indicated that IL-5 promotes ABCA1 expression and cholesterol efflux through the miR-211/JAK2/STAT3 signaling pathway in THP-1-derived macrophages.
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http://dx.doi.org/10.1093/abbs/gmaa071DOI Listing
August 2020

RIC-seq for global in situ profiling of RNA-RNA spatial interactions.

Nature 2020 06 6;582(7812):432-437. Epub 2020 May 6.

Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Highly structured RNA molecules usually interact with each other, and associate with various RNA-binding proteins, to regulate critical biological processes. However, RNA structures and interactions in intact cells remain largely unknown. Here, by coupling proximity ligation mediated by RNA-binding proteins with deep sequencing, we report an RNA in situ conformation sequencing (RIC-seq) technology for the global profiling of intra- and intermolecular RNA-RNA interactions. This technique not only recapitulates known RNA secondary structures and tertiary interactions, but also facilitates the generation of three-dimensional (3D) interaction maps of RNA in human cells. Using these maps, we identify noncoding RNA targets globally, and discern RNA topological domains and trans-interacting hubs. We reveal that the functional connectivity of enhancers and promoters can be assigned using their pairwise-interacting RNAs. Furthermore, we show that CCAT1-5L-a super-enhancer hub RNA-interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Our study demonstrates the power and applicability of RIC-seq in discovering the 3D structures, interactions and regulatory roles of RNA.
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http://dx.doi.org/10.1038/s41586-020-2249-1DOI Listing
June 2020

Cell-modified bioprinted microspheres for vascular regeneration.

Mater Sci Eng C Mater Biol Appl 2020 Jul 23;112:110896. Epub 2020 Mar 23.

Department of Cardiology, Cardiovascular Key Lab of Zhejiang Province, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310000, China. Electronic address:

Cell therapy is a promising strategy in which living cells or cellular materials are delivered to treat a variety of diseases. Here, we developed an electrospray bioprinting method to rapidly generate cell-laden hydrogel microspheres, which limit the migration of the captured cells and provide an immunologically privileged microenvironment for cell survival in vivo. Currently, therapeutic angiogenesis aims to induce collateral vessel formation after limb ischemia. However, the clinical application of gene and cell therapy has been impeded by concerns regarding its inefficacy, as well as the associated risk of immunogenicity and oncogenicity. In this study, hydrogel microspheres encapsulating VEGF-overexpressing HEK293T cells showed good safety via subcutaneously injecting into male C57BL/6 mice. In addition, these cell-modified microspheres effectively promoted angiogenesis in a mouse hind-limb ischemia model. Therefore, we demonstrated the great therapeutic potential of this approach to induce angiogenesis in limb ischemia, indicating that bioprinting has a bright future in cell therapy.
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http://dx.doi.org/10.1016/j.msec.2020.110896DOI Listing
July 2020

The antiatherogenic function of kallistatin and its potential mechanism.

Acta Biochim Biophys Sin (Shanghai) 2020 Jun;52(6):583-589

Department of Cardiology, The First Affiliated Hospital of University of South China, Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, University of South China, Hengyang 421001, China.

Atherosclerosis is the pathological basis of most cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Kallistatin, originally discovered in human serum, is a tissue-kallikrein-binding protein and a unique serine proteinase inhibitor. Upon binding to its receptor integrin β3, lipoprotein receptor-related protein 6, nucleolin, or Krüppel-like factor 4, kallistatin can modulate various signaling pathways and affect multiple biological processes, including angiogenesis, inflammatory response, oxidative stress, and tumor growth. Circulating kallistatin levels are significantly decreased in patients with coronary artery disease and show an inverse correlation with its severity. Importantly, both in vitro and in vivo experiments have demonstrated that kallistatin reduces atherosclerosis by inhibiting vascular inflammation, antagonizing endothelial dysfunction, and improving lipid metabolism. Thus, kallistatin may be a novel biomarker and a promising therapeutic target for atherosclerosis-related diseases. In this review, we focus on the antiatherogenic function of kallistatin and its potential mechanism.
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http://dx.doi.org/10.1093/abbs/gmaa035DOI Listing
June 2020

Biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum for accelerating bone regeneration.

Mater Sci Eng C Mater Biol Appl 2020 May 14;110:110670. Epub 2020 Jan 14.

Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Periosteum as an important component in the construct of bone is mainly responsible for providing nourishment and regulating osteogenic differentiation. When bone defect happens, the functionality of periosteum will also be influenced, furthermore, it will finally hamper the process of bone regeneration. However, fabrication of an artificial periosteum with the capabilities in accelerating angiogenesis and osteogenesis in the defect area is still a challenge for researchers. In this study, we fabricated an organic-inorganic hybrid biomimetic periosteum by electrospinning, which can induce mineralization in situ and control the ions release for long-term in local area. Further, this system exhibited potential capabilities in promoting in vitro, which means the potentiality in accelerating bone regeneration in vivo. Calcium phosphate nanoparticles (CaPs) were fabricated by emulsion method, then CaPs were further incorporated with gelatin-methacryloyl (GelMA) by electrospinning fibers to construct the hybrid hydrogel fibers. The fibers exhibited satisfactory morphology and mechanical properties, additionally, controlled ions release could be observed for over 10 days. Further, significant mineralization was proved on the surface of hybrid fibers after 7 days and 14 days' co-incubation with simulated body fluid (SBF). Then, favorable biocompatibility of the hybrid fibers was approved by co-cultured with MC3T3-E1 cells. Finally, the hybrid fibers exhibited potential capabilities in promoting angiogenesis and osteogenesis by co-culture with HUVECs and MC3T3-E1 cells. This biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum provided a promising strategy to develop periosteum biomaterials with angiogenesis and osteogenesis capabilities.
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http://dx.doi.org/10.1016/j.msec.2020.110670DOI Listing
May 2020

Programmed Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 and Inorganic Ion Composite Hydrogel as Artificial Periosteum.

ACS Appl Mater Interfaces 2020 Feb 30;12(6):6840-6851. Epub 2020 Jan 30.

Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute , Soochow University , Suzhou , Jiangsu 215007 , P. R. China.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioceramic are the widely used bioactive factors in treatment of bone defects, but these easily cause side effects because of uncontrollable local concentration. In this study, rhBMP-2 was grafted on the surface of mesoporous bioglass nanoparticles (MBGNs) with an amide bond and then photo-cross-linked together with methacrylate gelatin (GelMA); in this way, a GelMA/MBGNs-rhBMP-2 hydrogel membrane was fabricated to release rhBMP-2 in a controllable program during the early bone regeneration period and then release calcium and silicon ions to keep promoting osteogenesis instead of rhBMP-2 in a long term. In this way, rhBMP-2 can keep releasing for 4 weeks and then the ions keep releasing after 4 weeks; this process is matched to early and late osteogenesis procedures. In vitro study demonstrated that the early release of rhBMP-2 can effectively promote local cell osteogenic differentiation in a short period, and then, the inorganic ions can promote cell adhesion not only in the early stage but also keep promoting osteogenic differentiation for a long period. Finally, the GelMA/MBGNs-rhBMP-2 hydrogel shows a superior capacity in long-term osteogenesis and promoting bone tissue regeneration in rat calvarial critical size defect. This GelMA/MBGNs-rhBMP-2 hydrogel demonstrated a promising strategy for the controllable and safer use of bioactive factors such as rhBMP-2 in artificial periosteum to accelerate bone repairing.
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http://dx.doi.org/10.1021/acsami.9b18496DOI Listing
February 2020

IgM natural antibody T15/E06 in atherosclerosis.

Clin Chim Acta 2020 May 25;504:15-22. Epub 2020 Jan 25.

Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, Department of Cardiology, The First Affiliated Hospital of University of South China, University of South China, Hengyang, Hunan 421001, China. Electronic address:

Atherosclerosis is regarded as a lipid-driven chronic inflammatory disease. A variety of immune cells, including B1 cells, play an important role in the occurrence and development of atherosclerosis. T15/E06 is an IgM Nab secreted by B1 cells. The concentration of T15/E06 is significantly decreased in animal models of atherosclerosis. Accumulating evidence has shown that T15/E06 can protect against atherosclerosis by blocking macrophage lipid uptake, inhibiting vascular inflammation, and promoting apoptotic cell clearance. In this review, we describe the structure, functions and regulation of T15/E06 and summarize the latest advance regarding its atheroprotective effect.
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http://dx.doi.org/10.1016/j.cca.2020.01.024DOI Listing
May 2020

Controllable Fabrication and Li Storage Kinetics of 1 D Spinel LiMn O Positive Materials for Li-ion Batteries: An Exploration of Critical Diameter.

ChemSusChem 2020 Feb 21;13(4):803-810. Epub 2020 Jan 21.

National and Local Joint Engineering Laboratory for Lithium-ion Batteries and Materials Preparation Technology, Key Laboratory of Advanced Battery Materials of Yunnan Province, Faculty of Materials Science and Engineering, Kunming University of Science and Technology, Kunming, 650093, P.R. China.

The morphology and size of nanoelectrode materials determine their properties. Compared to the bulk structure electrodes, 1 D electrode materials for Li-ion batteries have been intensively studied owing to their excellent Li diffusion kinetics. It is generally accepted that smaller-sized electrode materials lead to better Li storage kinetics. In this study, this is found to not be the case in 1 D LiMn O positive materials. A facile strategy of manipulating the KMnO concentration is introduced to precisely fabricate 1 D LiMn O nanorods with four distinct diameter gradients from 30 to 170 nm. The role of 1 D crystal size in effecting interface chemical species and electrochemical performance is elucidated by comparative characterization methods. X-ray photoelectron spectroscopy (XPS) Ar-ion etching technology shows that the Mn is electrochemically inactive on the surface of the sample, which explains the adverse effects observed on LiMn O nanorods with the minimum diameter of 30-40 nm, such as decreased discharge capacity. The LiMn O nanorod with a critical diameter of approximately 70-80 nm displays the highest discharge capacity and promising cycling performance. This work clarifies an important property that has previously been neglected and deepens the understanding for design of Mn-based positive materials.
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http://dx.doi.org/10.1002/cssc.201902846DOI Listing
February 2020

The ERK signaling pathway is involved in cardiotrophin-1-induced neural differentiation of human umbilical cord blood mesenchymal stem cells in vitro.

Cytotechnology 2019 Oct 5;71(5):977-988. Epub 2019 Sep 5.

Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, China.

Central nervous system diseases remain the most challenging pathologies, with limited or even no therapeutic possibilities and a poor prognosis. This study aimed to investigate the differentiation properties of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transfected with recombinant adenovirus expressing enhanced green fluorescence protein cardiotrophin-1 (Adv-EGFP-CT-1) and the possible mechanisms involved. Cells were isolated, and MSC immunophenotypes were confirmed. The resulting differentiated cells treated with Adv-EGFP-CT-1 and cultured in neural induction medium (NIM) expressed higher levels of Nestin, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) markers than cells in other treatments. Expression of glycoprotein 130/leukemia inhibitory factor receptor β (gp130/LiFRβ), Raf-1, phosphorylated Raf-1 (p-Raf-1), extracellular signal-regulated kinase 1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) increased gradually within 72 h after transfection with Adv-EGFP-CT-1 and NIM culture. Additionally, inhibition of extracellular signal-regulated kinase kinase (MEK) abrogated expression of p-ERK1/2, Nestin, GFAP and NeuN. Thus, the ERK1/2 pathway may contribute to CT1-stimulated neural differentiation of hUCB-MSCs.
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http://dx.doi.org/10.1007/s10616-019-00339-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787130PMC
October 2019

A microparticle approach for non-viral gene delivery within 3D human mesenchymal stromal cell aggregates.

Acta Biomater 2019 09 18;95:408-417. Epub 2019 Apr 18.

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA; AO Foundation Collaborative Research Center, Davos, Switzerland. Electronic address:

Three-dimensional (3D) multicellular aggregates, in comparison to two-dimensional monolayer culture, can provide tissue culture models that better recapitulate the abundant cell-cell and cell-matrix interactions found in vivo. In addition, aggregates are potentially useful building blocks for tissue engineering. However, control over the interior aggregate microenvironment is challenging due to inherent barriers for diffusion of biological mediators (e.g. growth factors) throughout the multicellular aggregates. Previous studies have shown that incorporation of biomaterials into multicellular aggregates can support cell survival and control differentiation of stem cell aggregates by delivering morphogens from within the 3D construct. In this study, we developed a highly efficient microparticle-based gene delivery approach to uniformly transfect human mesenchymal stromal cells (hMSC) within multicellular aggregates and cell sheets. We hypothesized that release of plasmid DNA (pDNA) lipoplexes from mineral-coated microparticles (MCMs) within 3D hMSC constructs would improve transfection in comparison to standard free pDNA lipoplex delivery in the media. Our approach increased transfection efficiency 5-fold over delivery of free pDNA lipoplexes in the media and resulted in homogenous distribution of transfected cells throughout the 3D constructs. Additionally, we found that MCMs improved hMSC transfection by specifically increasing macropinocytosis-mediated uptake of pDNA. Finally, we showed up to a three-fold increase of bone morphogenetic protein-2 (BMP-2) expression and enhanced calcium deposition within 3D hMSC constructs following MCM-mediated delivery of a BMP-2 encoding plasmid and culture in osteogenic medium. The technology described here provides a valuable tool for achieving efficient and homogenous transfection of 3D cell constructs and is therefore of particular value in tissue engineering and regenerative medicine applications. STATEMENT OF SIGNIFICANCE: This original research describes a materials-based approach, whereby use of mineral-coated microparticles improves the efficiency of non-viral gene delivery in three-dimensional human mesenchymal stromal cell constructs. Specifically, it demonstrates the use of mineral-coated microparticles to enable highly efficient transfection of human mesenchymal stromal cells in large, 3D culture formats. The manuscript also identifies specific endocytosis pathways that interact with the mineral coating to afford the improved transfection efficiency, as well as demonstrates the utility of this approach toward improving differentiation of large cell constructs. We feel that this manuscript will impact the current understanding and near-term development of materials for non-viral gene delivery in broad tissue engineering and biofabrication applications, and therefore be of interest to a diverse biomaterials audience.
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http://dx.doi.org/10.1016/j.actbio.2019.04.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888862PMC
September 2019

Overweight and obesity standards and subjective well-being: Evidence from China.

Econ Hum Biol 2019 05 1;33:144-148. Epub 2019 Mar 1.

School of Agricultural Economics and Rural Development, Renmin University of China, Haidian Dis Beijing, 100872, China; Department of Agricultural Economics and Rural Development, University of Goettingen, Platz der Goettinger Sieben 5, 37073, Goettingen, Germany. Electronic address:

The adult BMI cutoffs for overweight and obesity standards set by the Working Group on Obesity in China are exerting growing influence over daily life. Using the regression discontinuity design method, this paper confirms the existence of a statistically significant discontinuity in subjective well-being at the overweight and obesity cutoffs, respectively. The overweight standard causes a significant decrease in subjective well-being (SWB) by approximate 0.10 units, and the obesity standard by 0.14 units, both sizable. Thus the standard setting has profound social, economic and welfare impacts beyond the health scope.
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http://dx.doi.org/10.1016/j.ehb.2019.02.006DOI Listing
May 2019

VEGF-loaded mineral-coated microparticles improve bone repair and are associated with increased expression of epo and RUNX-2 in murine non-unions.

J Orthop Res 2019 04 28;37(4):821-831. Epub 2019 Mar 28.

Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany.

A poor vascular supply of the fracture gap is a key factor for the development of atrophic non-unions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF). Hence, we investigated whether VEGF-loaded MCM improve bone repair in non-unions. For this purpose, we analyzed binding and release kinetics of MCM for VEGF in vitro. Moreover, we applied VEGF-loaded or -unloaded MCM in a murine non-union model in vivo and studied the process of bone healing by means of biomechanical, radiological, histomorphometric, and Western blot techniques. MCM-free non-unions served as controls. The binding efficiency of MCM for VEGF was 46 ± 3% and the release profile revealed an initial minor burst release followed by a sustained release over a 50-day study period, thus, mimicking the physiological expression profile of VEGF during bone healing. In vivo, bone defects treated with VEGF-loaded MCM exhibited a higher bending stiffness, a higher fraction of bone volume/tissue volume and a larger callus area on days 14 and 70 when compared to the other groups. Western blot analyses on day 14 revealed a higher expression of VEGF, erythropoietin (EPO), and runt-related transcription factor 2, but not of EPO-receptor in bone defects treated with VEGF-loaded MCM. These findings demonstrate that the use of MCM for VEGF delivery shows great potential due to the ability to maintain protein stability and functionality in vivo. Moreover, the application of VEGF-loaded MCM represent a promising strategy for the treatment of non-unions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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http://dx.doi.org/10.1002/jor.24267DOI Listing
April 2019

Phosphatase activity of small C-terminal domain phosphatase 1 (SCP1) controls the stability of the key neuronal regulator RE1-silencing transcription factor (REST).

J Biol Chem 2018 10 14;293(43):16851-16861. Epub 2018 Sep 14.

From the Departments of Molecular Biosciences and

The RE1-silencing transcription factor (REST) is the major scaffold protein for assembly of neuronal gene silencing complexes that suppress gene transcription through regulating the surrounding chromatin structure. REST represses neuronal gene expression in stem cells and non-neuronal cells, but it is minimally expressed in neuronal cells to ensure proper neuronal development. Dysregulation of REST function has been implicated in several cancers and neurological diseases. Modulating REST gene silencing is challenging because cellular and developmental differences can affect its activity. We therefore considered the possibility of modulating REST activity through its regulatory proteins. The human small C-terminal domain phosphatase 1 (SCP1) regulates the phosphorylation state of REST at sites that function as REST degradation checkpoints. Using kinetic analysis and direct visualization with X-ray crystallography, we show that SCP1 dephosphorylates two degron phosphosites of REST with a clear preference for phosphoserine 861 (pSer-861). Furthermore, we show that SCP1 stabilizes REST protein levels, which sustains REST's gene silencing function in HEK293 cells. In summary, our findings strongly suggest that REST is a substrate for SCP1 and that SCP1 phosphatase activity protects REST against degradation. These observations indicate that targeting REST via its regulatory protein SCP1 can modulate its activity and alter signaling in this essential developmental pathway.
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http://dx.doi.org/10.1074/jbc.RA118.004722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204920PMC
October 2018

The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes.

Cell Res 2018 10 24;28(10):981-995. Epub 2018 Aug 24.

Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.

Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) to diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in the genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3), that is both required and sufficient to define AID-binding sites genome-wide in activated B cells. ROD1 interacts with AID via an ultraconserved loop, which proves to be critical for the recruitment of AID to ssDNA using bi-directionally transcribed nascent RNAs as stepping stones. Strikingly, AID-specific mutations identified in human patients with hyper-IgM syndrome type 2 (HIGM2) completely disrupt the AID interacting surface with ROD1, thereby abolishing the recruitment of AID to immunoglobulin (Ig) loci. Together, our results suggest that bi-directionally transcribed RNA traps the RNA-binding protein ROD1, which serves as a guiding system for AID to load onto specific genomic loci to induce DNA rearrangement during immune responses.
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http://dx.doi.org/10.1038/s41422-018-0076-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170407PMC
October 2018

TiO2 NPs Alleviates High-Temperature Induced Oxidative Stress in Silkworms.

J Econ Entomol 2018 04;111(2):879-884

School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, Jiangsu, P.R. China.

Silkworm, Bombyx mori (L.; Lepidoptera: Bombycidae), is an economically important insect, which is sensitive to the environment and susceptible to oxidative damages at high temperature. Low concentrations of TiO2 NPs (titanium dioxide nanoparticles) can scavenge reactive oxygen species (ROS) produced by oxidative damages in vivo. To explore whether TiO2 NPs could alleviate oxidative damages of high temperature, the effects of TiO2 NPs treatment on silkworm growth, the levels of ROS and H2O2, as well as the transcription level of antioxidant-related genes were studied at 30°C. These results showed that TiO2 NPs treatment increased silkworm body weight by 6.0% and reduced the occurrence of irregular cocoon at 30°C. TiO2 NPs treatment at 30°C decreased ROS levels in fat body and increased expression of Hsp70, SOD by 5.70-fold at 48 h, TPx by 1.61-fold, CAT by 1.81-fold. These results indicated that TiO2 NPs treatment at 30°C could promote the expression of antioxidant genes and reduce oxidative stress and provide a new method to alleviate high-temperature induced oxidative stress to silkworm.
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http://dx.doi.org/10.1093/jee/toy002DOI Listing
April 2018

Dual non-viral gene delivery from microparticles within 3D high-density stem cell constructs for enhanced bone tissue engineering.

Biomaterials 2018 04 3;161:240-255. Epub 2018 Jan 3.

Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA; Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA; The National Center for Regenerative Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA; School of Dentistry, Kyung Hee University, Seoul, South Korea. Electronic address:

High-density mesenchymal stem cell (MSC) aggregates can be guided to form bone-like tissue via endochondral ossification in vitro when culture media is supplemented with proteins, such as growth factors (GFs), to first guide the formation of a cartilage template, followed by culture with hypertrophic factors. Recent reports have recapitulated these results through the controlled spatiotemporal delivery of chondrogenic transforming growth factor-β1 (TGF-β1) and chondrogenic and osteogenic bone morphogenetic protein-2 (BMP-2) from microparticles embedded within human MSC aggregates to avoid diffusion limitations and the lengthy, costly in vitro culture necessary with repeat exogenous supplementation. However, since GFs have limited stability, localized gene delivery is a promising alternative to the use of proteins. Here, mineral-coated hydroxyapatite microparticles (MCM) capable of localized delivery of Lipofectamine-plasmid DNA (pDNA) nanocomplexes encoding for TGF-β1 (pTGF-β1) and BMP-2 (pBMP-2) were incorporated, alone or in combination, within MSC aggregates from three healthy porcine donors to induce sustained production of these transgenes. Three donor populations were investigated in this work due to the noted MSC donor-to-donor variability in differentiation capacity documented in the literature. Delivery of pBMP-2 within Donor 1 aggregates promoted chondrogenesis at week 2, followed by an enhanced osteogenic phenotype at week 4. Donor 2 and 3 aggregates did not promote robust glycosaminoglycan (GAG) production at week 2, but by week 4, Donor 2 aggregates with pTGF-β1/pBMP-2 and Donor 3 aggregates with both unloaded MCM and pBMP-2 enhanced osteogenesis compared to controls. These results demonstrate the ability to promote osteogenesis in stem cell aggregates through controlled, non-viral gene delivery within the cell masses. These findings also indicate the need to screen donor MSC regenerative potential in response to gene transfer prior to clinical application. Taken together, this work demonstrates a promising gene therapy approach to control stem cell fate in biomimetic 3D condensations for treatment of bone defects.
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http://dx.doi.org/10.1016/j.biomaterials.2018.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826638PMC
April 2018

Linc-RAM is required for FGF2 function in regulating myogenic cell differentiation.

RNA Biol 2018 03 9;15(3):404-412. Epub 2018 Feb 9.

a The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences , Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College , 5 Dong Dan San Tiao, Beijing , China.

Myogenic differentiation of skeletal muscle stem cells, also known satellite cells, is tightly orchestrated by extrinsic and intrinsic regulators. Basic fibroblast growth factor (FGF2) is well documented to be implicated in satellite cell self-renewal and differentiation by repressing MyoD. We recently identified a MyoD-regulated and skeletal muscle-specifically expressed long non-coding RNA Linc-RAM which enhances myogenic differentiation by facilitating MyoD/Baf60c/Brg1 complex assembly. Herein, we investigated the transcriptional regulation and intracellular signaling pathway in mediating Linc-RAM gene expression during muscle cell differentiation. Firstly, we demonstrate Linc-RAM is negatively regulated by FGF2 via Ras/Raf/Mek/Erk signaling pathway in muscle cells. Overexpression of MyoD significantly attenuates repression of Linc-RAM promoter activities in C2C12 cells treated with FGF2. Knockout of MyoD abolishes FGF2-mediated repression of Linc-RAM gene transcription in satellite cells sorted from skeletal muscle of MyoD;Pax7-nGFP mice, suggesting inhibition of MyoD is required for FGF2-mediated expression of Linc-RAM. For the functional significance, we show that overexpression of Linc-RAM rescues FGF2-induced inhibition of C2C12 cell differentiation, indicating inhibition of Linc-RAM is required for FGF2-mediated suppression of myogenic differentiation. Consistently, we are able to further corroborate the requirement of Linc-RAM inhibition for FGF2-modulated repression of myogenic differentiation by using an ex vivo cultured single fiber system and satellite cells sorted from Linc-RAM;Pax7-nGFP knockout mice. Collectively, the present study not only reveals the intracellular signaling in FGF2-mediated Linc-RAM gene expression but also demonstrate the functional significance of Linc-RAM in FGF2-mediated muscle cell differentiation.
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http://dx.doi.org/10.1080/15476286.2018.1431494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927723PMC
March 2018

Functionalization of microparticles with mineral coatings enhances non-viral transfection of primary human cells.

Sci Rep 2017 10 27;7(1):14211. Epub 2017 Oct 27.

Department of Biomedical Engineering-University of Wisconsin-Madison, Madison, WI, USA.

Gene delivery to primary human cells is a technology of critical interest to both life science research and therapeutic applications. However, poor efficiencies in gene transfer and undesirable safety profiles remain key limitations in advancing this technology. Here, we describe a materials-based approach whereby application of a bioresorbable mineral coating improves microparticle-based transfection of plasmid DNA lipoplexes in several primary human cell types. In the presence of these mineral-coated microparticles (MCMs), we observed up to 4-fold increases in transfection efficiency with simultaneous reductions in cytotoxicity. We identified mechanisms by which MCMs improve transfection, as well as coating compositions that improve transfection in three-dimensional cell constructs. The approach afforded efficient transfection in primary human fibroblasts as well as mesenchymal and embryonic stem cells for both two- and three-dimensional transfection strategies. This MCM-based transfection is an advancement in gene delivery technology, as it represents a non-viral approach that enables highly efficient, localized transfection and allows for transfection of three-dimensional cell constructs.
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http://dx.doi.org/10.1038/s41598-017-14153-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660152PMC
October 2017

Uptake and translocation of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by maize from soil irrigated with wastewater.

Sci Rep 2017 09 22;7(1):12165. Epub 2017 Sep 22.

School of Environment, Tsinghua University, Beijing, 100084, PR China.

By investigating the uptake of 16 priority polycyclic aromatic hydrocarbons (PAHs) and five heavy metals from soils to maize at the farmlands with industrial wastewater irrigation, this study revealed the effects of heavy metals on PAHs uptake in terms of co-contamination. The results of 15 investigated soils showed medium contamination level and the vertical PAHs distribution in soils indicated that 2-3 rings PAHs with low octanol-water partition coefficient (log K < 4.5) were easier to transport in soils, causing a great potential risk immigrating to the groundwater. The 3-ring PAHs were most likely to be taken up by maize roots whereas 2- and 4-6 ring PAHs had the lower likelihood. The translocation of PAHs in maize tissues has positive relationship with log K less than 4.5, while negatively correlated otherwise. Redundancy analysis indicated the unexpected results that, except for soil PAHs concentration, the PAHs translocation by maize was reduced by Pb uptake, but not significantly affected by soil organic matters, pH or the other four heavy metals (Cr, Cu, Ni and Zn). This study for the first time provides the restricted factors of PAHs and heavy metal acropetal translocation by maize when they co-exist at wastewater irrigation sites.
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http://dx.doi.org/10.1038/s41598-017-12437-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610240PMC
September 2017

Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.

Adv Mater 2017 Sep 4;29(33). Epub 2017 Jul 4.

Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA.

Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrate enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect is attributed to the maintenance of protein conformational structure, which is closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintains its biological activity for weeks during release, while it maintains activity for less than 7 d during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor using a mineral coated surgical suture significantly improves functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a two fold improvement in mechanical properties. The findings of this study demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine.
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http://dx.doi.org/10.1002/adma.201701255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628619PMC
September 2017

Endochondral Ossification in Critical-Sized Bone Defects via Readily Implantable Scaffold-Free Stem Cell Constructs.

Stem Cells Transl Med 2017 07 8;6(7):1644-1659. Epub 2017 Jun 8.

Biomedical Engineering.

The growing socioeconomic burden of musculoskeletal injuries and limitations of current therapies have motivated tissue engineering approaches to generate functional tissues to aid in defect healing. A readily implantable scaffold-free system comprised of human bone marrow-derived mesenchymal stem cells embedded with bioactive microparticles capable of controlled delivery of transforming growth factor-beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) was engineered to guide endochondral bone formation. The microparticles were formulated to release TGF-β1 early to induce cartilage formation and BMP-2 in a more sustained manner to promote remodeling into bone. Cell constructs containing microparticles, empty or loaded with one or both growth factors, were implanted into rat critical-sized calvarial defects. Micro-computed tomography and histological analyses after 4 weeks showed that microparticle-incorporated constructs with or without growth factor promoted greater bone formation compared to sham controls, with the greatest degree of healing with bony bridging resulting from constructs loaded with BMP-2 and TGF-β1. Importantly, bone volume fraction increased significantly from 4 to 8 weeks in defects treated with both growth factors. Immunohistochemistry revealed the presence of types I, II, and X collagen, suggesting defect healing via endochondral ossification in all experimental groups. The presence of vascularized red bone marrow provided strong evidence for the ability of these constructs to stimulate angiogenesis. This system has great translational potential as a readily implantable combination therapy that can initiate and accelerate endochondral ossification in vivo. Importantly, construct implantation does not require prior lengthy in vitro culture for chondrogenic cell priming with growth factors that is necessary for current scaffold-free combination therapies. Stem Cells Translational Medicine 2017;6:1644-1659.
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http://dx.doi.org/10.1002/sctm.16-0222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689752PMC
July 2017

Cardiotrophin-1 stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through PI3K/Akt-dependent signaling pathways.

Cytotechnology 2017 Dec 10;69(6):933-941. Epub 2017 Jun 10.

Department of Pediatric, First Affiliated Hospital, Zunyi Medical College, Zunyi, 563003, Guizhou Province, China.

Cardiotrophin-1 (CT1) plays an important role in the differentiation, development, and survival of neural stem cells. In this study, we analyzed its effects on the stimulation of human umbilical cord blood-derived mesenchymal stem cells in terms of their potential to differentiate into neuron-like cells, their survival characteristics, and the molecular mechanisms involved. The treatment of cells with neural induction medium (NIM) and CT1 generated more cells that were neuron-like and produced stronger expression of neural-lineage markers than cells treated with NIM and without CT1. Bcl-2 and Akt phosphorylation (p-Akt) expression levels increased significantly in cells treated with both NIM and CT1. This treatment also effectively blocked cell death following neural induction and decreased Bax, Bak and cleaved-caspase 3 expression compared with cells treated with NIM without CT1. In addition, the inhibition of phosphatidylinositol 3-kinase (PI3K) abrogated p-Akt and Bcl-2 expression. Thus, PI3K/Akt contribute to CT1-stimulated neural differentiation and to the survival of differentiated cells.
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http://dx.doi.org/10.1007/s10616-017-0103-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660737PMC
December 2017

Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells.

Acta Biochim Biophys Sin (Shanghai) 2017 Jun;49(6):530-540

Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.

Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.
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http://dx.doi.org/10.1093/abbs/gmx038DOI Listing
June 2017

Mineral binding peptides with enhanced binding stability in serum.

Biomater Sci 2017 Mar;5(4):663-668

Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. and Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53792, USA and Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.

Although calcium phosphate (CaP) binding peptides are used to link orthobiologics to orthopedic biomaterials, their binding stability in physiological environment is still unknown. In this study, we investigate the binding capability of a series of CaP-binding peptides and their binding stability in serum solutions, which are selected to resemble physiological conditions. The findings in this study may be applicable for designing robust orthobiologic delivery systems.
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http://dx.doi.org/10.1039/c6bm00928jDOI Listing
March 2017

Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD.

Nat Commun 2017 01 16;8:14016. Epub 2017 Jan 16.

The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Department of Biochemistry and Molecular Biology, School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.

Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells. Mechanistically, Linc-RAM regulates expression of myogenic genes by directly binding MyoD, which in turn promotes the assembly of the MyoD-Baf60c-Brg1 complex on the regulatory elements of target genes. Collectively, our findings reveal the functional role and molecular mechanism of a lineage-specific Linc-RAM as a regulatory lncRNA required for tissues-specific chromatin remodelling and gene expression.
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http://dx.doi.org/10.1038/ncomms14016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241866PMC
January 2017