Distinctive Roles of Wnt Signaling in Chondrogenic Differentiation of BMSCs under Coupling of Pressure and Platelet-Rich Fibrin

Cheng Baixiang,Feng Fan,Shi Fan,Huang Jinmei,Zhang Songbai,Quan Yue,Tu Teng,Liu Yanli,Wang Junjun,Zhao Ying,Zhang Min 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.4

BACKGROUND: Although newly formed constructs of feasible pressure-preadjusted bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) showed biomechanical flexibility and superior capacity for cartilage regeneration, it is still not very clear how BMSCs and seed cells feel mechanical stimuli and convert them into biological signals, and the difference in signal transduction underlying mechanical and chemical cues is also unclear. METHODS: To determine whether mechanical stimulation (hydrostatic pressure) and chemical cues (platelet-rich fibrin, PRF) activate canonical or noncanonical Wnt signaling in BMSCs, BMSCs cocultured with PRF were subjected to hydrostatic pressure loading, and the activation of the Wnt signaling molecules and expression of cartilage-associated proteins and genes were determined by western blotting and polymerase chain reaction (PCR). Inhibitors of canonical or noncanonical Wnt signaling, XVX-939 or L690,330, were adopted to investigate the role of Wnt signaling molecules in mechanically promoted chondrogenic differentiation of BMSCs. RESULTS: Hydrostatic pressure of 120 kPa activated both Wnt/b-catenin signaling and Wnt/Ca2? signaling, with the the maximum promotion effect at 60 min. PRF exerted no synergistic effect on Wnt/b-catenin signaling activation. However, the growth factors released by PRF might reverse the promotion effects of pressure on Wnt/Ca2? signaling. Real-time PCR and Western blotting results showed that pressure could activate the expression of Col-II, Sox9, and aggrecan in BMSCs cocultured with PRF. Blocking experiment found a positive role of Wnt/b-catenin signaling, and a negative role of Wnt/ Ca2? signaling in chondrogenic differentiation of the BMSCs. Mutual inhibition exists between canonical and noncanonical Wnt signaling in BMSCs under pressure. CONCLUSION: Wnt signaling participates in the pressure-promoted chondrogenesis of the BMSCs co-cultured with PRF, with canonical and noncanonical pathways playing distinct roles during the process.

Facile Synthesis of Block Copolymers from a Cinnamate Derivative by Combination of AGET ATRP and Click Chemistry

Chuanjie Cheng,Xiongxiong Bai,Xu Zhang,Ming Chen,Qinghua Huang,Zhongyu Hu,Yuanming Tu 한국고분자학회 2014 Macromolecular Research Vol.22 No.12

An azido- and bromo-containing compound derived from naturally occurring ethyl cinnamate was usedsuccessfully to prepare block copolymers by a combination of ‘activator generated by electron transfer atom transferradical polymerization’ (AGET ATRP) and Huisgen “click” reactions in emulsion. First, azido-end poly(methyl methacrylate)and alkyne-end polystyrene were prepared under AGET ATRP conditions, then, poly(methyl methacrylate) blockpolystyrene (PMMA-b-PS) diblock copolymer was formed by Huisgen 1,3-dipolar cycloaddition. Finally, polystyreneblock poly(methyl methacrylate) block polystyrene (PS-b-PMMA-b-PS) triblock copolymer was synthesizedvia simultaneous AGET ATRP and click reactions, catalyzed by the same copper-based catalyst. The polymers werecharacterized by 1H nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC),which confirmed the successful synthesis of the corresponding polymers.

Suture Repair in Endoscopic Surgery for Craniovertebral Junction

Mei-Yin Yeh,Wen-Cheng Huang,Jau-Ching Wu,Chao-Hung Kuo,Hsuan-Kan Chang,Tsung-Hsi Tu,Peng-Yuan Chang,Yu-Shu Yen,Henrich Cheng 대한척추신경외과학회 2019 Neurospine Vol.16 No.2

Objective: Endoscopic approaches to the craniovertebral junction (CVJ) have been established as viable and effective surgical treatments in the past decade. One of the major complications is leakage of the cerebrospinal fluid (CSF). This study aimed to investigate the efficacy and feasibility of suture closure at the nasopharyngeal mucosa upon durotomy. Methods: A series of consecutive patients who underwent different endoscopic approaches to the CVJ were retrospectively reviewed. The pathologies, surgical corridors, neurological and functional outcomes, radiological evaluations, and complications were analyzed. Different strategies of repair for the intraoperative CSF leakage were described and compared. Results: A total of 22 patients covering 13 years were analyzed. There were 12, 2, and 8 patients who underwent transnasal, transoral, and combined approaches, respectively. There were 8 patients (36.4%) who experienced intraoperative CSF leakage, and were grouped into 2: 4 in the nonsuture (NS) group and 4 in the suture-repaired (SR) group. The NS group had 3 (75%) persistent CSF leakages postoperation that caused 1 mortality, whereas patients of the SR group had only 1 minor CSF rhinorrhea that healed spontaneously within days. Conclusion: In this series of 22 patients who required anterior endoscopic resection of pathologies at the CVJ, there was 1 (4.5%) serious complication related to CSF leakage. For patients who had no durotomy, the mucosal incision at the nasopharynx usually healed rapidly and there were few procedure-related complications. For patients with intraoperative CSF leakage, suture closure was technically challenging but could significantly lower the risks of postoperative complications.

Correlation of the size and shape of the solid particles in synovial fluid and knee joint disease

Zhen-Gang Zha,Cheng-Can Yao,Mei Tu,Yao-Xiong Huang 한국물리학회 2007 Current Applied Physics Vol.7 No.s1

The shape and size of solid particles and their distribution in synovial uid were observed and determined as functions of knee jointdiseases by using a multi-dimensional microscope. The results show that there is a close correlation between them, so that the measurement of the parameters might offer a reliable method for diagnosing joint diseases at an early stage and their prognosis.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson’s Disease

Hung-Li Wang,Chin-Song Lu,Tu-Hsueh Yeh,Yu-Ming Shen,Yi-Hsin Weng,Ying-Zu Huang,Rou-Shayn Chen,Yu-Chuan Liu,Yi-Chuan Cheng,Hsiu-Chen Chang,Ying-Ling Chen,Yu-Jie Chen,Yan-Wei Lin,Chia Chen Hsu,Huang-Li 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose It is essential to develop a reliable predictive serum biomarker for Parkinson’s disease (PD). Te accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. Te purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. Methods Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. Results The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutof age than in the group above the cutof age. Conclusions Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

Acidic Fibroblast Growth Factor in Spinal Cord Injury

Chin-Chu Ko,Tsung-Hsi Tu,Jau-Ching Wu,Wen-Cheng Huang,Henrich Cheng 대한척추신경외과학회 2019 Neurospine Vol.16 No.4

Spinal cord injury (SCI), with an incidence rate of 246 per million person-years among adults in Taiwan, remains a devastating disease in the modern day. Elderly men with lower socioeconomic status have an even higher risk for SCI. Despite advances made in medicine and technology to date, there are few effective treatments for SCI due to limitations in the regenerative capacity of the adult central nervous system. Experiments and clinical trials have explored neuro-regeneration in human SCI, encompassing cell- and molecule-based therapies. Furthermore, strategies have aimed at restoring connections, including autologous peripheral nerve grafts and biomaterial scaffolds that theoretically promote axonal growth. Most molecule-based therapies target the modulation of inhibitory molecules to promote axonal growth, degrade glial scarring obstacles, and stimulate intrinsic regenerative capacity. Among them, acidic fibroblast growth factor (aFGF) has been investigated for nerve repair; it is mitogenic and pluripotent in nature and could enhance axonal growth and mitigate glial scarring. For more than 2 decades, the authors have conducted multiple trials, including human and animal experiments, using aFGF to repair nerve injuries, including central and peripheral nerves. In these trials, aFGF has shown promise for neural regeneration, and in the future, more trials and applications should investigate aFGF as a neurotrophic factor. Focusing on aFGF, the current review aimed to summarize the historical evolution of the utilization of aFGF in SCI and nerve injuries, to present applications and trials, to summarize briefly its possible mechanisms, and to provide future perspectives.

The Synthesis and Preliminary Activity Assay In Vitro of Peptide-like Derivatives as APN Inhibitors

Li, Shao-Hua,Li, Gang,Huang, Hui-Ming,Xiong, Fang,Liu, Cheng-Mei,Tu, Guo-Gang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

Both the aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential metallopeptidases in the development of tumor invasion and angiogenesis. A series of novel peptide-like derivatives were designed and synthesized as antitumor agents. Their structures were confirmed by IR, MS, and $^1H$-NMR. These compounds exhibited potent inhibitory activities against APN and low activity against MMP in vitro. The derivatives with methoxy group show better activities than those with other substituted group and could be used as lead compounds for exploring new APN inhibitors in the future.

A Hybrid Dynamic Stabilization and Fusion System in Multilevel Lumbar Spondylosis

Li-Yu Fay,Chih-Chang Chang,Hsuan-Kan Chang,Tsung-Hsi Tu,Tzu-Yun Tsai,Ching-Lan Wu,Wen-Cheng Huang,Jau-Ching Wu,Henrich Cheng 대한척추신경외과학회 2018 Neurospine Vol.15 No.3

Objective: The Dynesys-Transition-Optima (DTO) hybrid system was designed to achieve arthrodesis and stabilization in patients with lumbar degeneration. Satisfactory outcomes were demonstrated previously. However, no study has evaluated the effects of using the DTO system in patients with lumbar spondylolisthesis or stenosis. Methods: This retrospective study included 35 consecutive patients with multilevel lumbar degeneration with or without spondylolisthesis who underwent surgery using the DTO system. Imaging studies included pre- and postoperative radiography, magnetic resonance imaging, and computed tomography. The clinical outcomes were measured by Japanese Orthopedic Association (JOA) scores, Oswestry Disability Index (ODI) scores, and a visual analogue scale (VAS) for back and leg pain. Results: Thirty patients (85.7%) with a mean age of 61.9 years completed the follow-up, with a mean duration of 35.1 months. There were 21 patients in the spondylolisthesis group and 9 in the stenosis group. The spondylolisthesis group had worse functional scores than the stenosis group preoperatively. After DTO surgery, all patients showed significant improvements in clinical outcomes, including VAS for back and leg pain, ODI, and JOA scores (p<0.05). There were no significant differences in clinical outcomes between the 2 groups. At a 2-year follow-up, lumbar alignment was well maintained in both groups (p=0.116). There were no significant differences in lumbar alignment between the 2 groups. Conclusion: During a follow-up period of over 2 years, both patients with spondylolisthesis and those with stenosis showed improvements and similar disability and pain scores after surgery using the DTO system. Lumbar alignment was also well maintained.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

Hai-Feng Zhang,Mao-Xiong Wu,Yong-Qing Lin,Shuang-Lun Xie,Tu-Cheng Huang,Pin-Ming Liu,Ru-Qiong Nie,Qin-Qi Meng,Nian-Sang Luo,Yang-Xin Chen,Jing-Feng Wang 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and sitespecific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the − 2000 to − 1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the − 1997 to − 1700 and − 1091 to − 811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

Comparison of Cortical Bone Trajectory to Pedicle-Based Dynamic Stabilization: An Analysis of 291 Patients

Chih-Chang Chang,Hsuan-Kan Chang,Chin-Chu Ko,Ching-Lan Wu,Yi-Hsuan Kuo,Tsung-Hsi Tu,Wen-Cheng Huang,Jau-Ching Wu 대한척추신경외과학회 2023 Neurospine Vol.20 No.1

Objective: Pedicle-based dynamic stabilization (DS) has gained popularity outside of America. Although pedicle screw (PS) loosening has always been a concern, it is reportedly innocuous. Cortical bone trajectory (CBT) screw is an emerging option with less invasiveness and similar effectiveness to PS in short-segment lumbar fusion. This study aimed to verify the use of CBT for DS by comparing the outcomes between pedicle- and CBT-based DS. Methods: Consecutive patients with lumbar spondylosis or low-grade spondylolisthesis who underwent 1- or 2-level DS between L3–5 with a minimum follow-up of 24 months were reviewed. Screw loosening was determined by computed tomography and the incidences were compared. Results: A total of 291 patients who underwent Dynesys DS (235 pedicle- and 56 CBT-based, respectively) were compared. The demographics and preoperative conditions were similar. All the clinical outcomes improved at 24-month postoperation, while the CBT-based group had less operation time and blood loss than the pedicle-based group. The rates of screw loosening were lower in the CBT-based (5.4% per screw and 12.5% per patient) than the pedicle-based group (9% per screw and 26.4% per patient). Furthermore, there were no differences in the clinical outcomes and complication profiles. Conclusion: The CBT-based DS for 1- or 2-level lumbar degeneration demonstrated equivalent clinical improvement as the pedicle-based DS. The adaption of CBT-based screws for DS could be a less invasive approach (shorter operation time and less blood loss), with lower chances of screw loosening than the conventional PS-based DS.