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Sung PH, Yeh JN, Yin TC, Chai HT, Chiang JY, Huang CR, Chen YL, Lee MS, Yip HK. Extracorporeal shockwave therapy rescued mouse critical limb ischemia via upregulating GPR120 against inflammation and promoting angiogenesis for restoring the blood flow in ischemic zone-experimental study. Int J Surg 2025; 111:2414-2429. [PMID: 39869384 DOI: 10.1097/js9.0000000000002243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/29/2024] [Indexed: 01/28/2025]
Abstract
BACKGROUND This study tested the hypothesis that extracorporeal shockwave therapy (ECSWT) effectively rescues critical limb ischemia (CLI) in mice through the upregulation of GPR120, which protects against inflammation and angiogenesis to restore blood flow in the ischemic area. METHODS AND RESULTS Compared with the control, ECSWT-induced GPR120-mediated anti-inflammatory effects significantly suppressed the expression of inflammatory signaling biomarkers (TAK1/MAPK family/NF-κB/IL-1β/IL-6/TNF-α/MCP-1) in HUVECs, and these effects were abolished by silencing GPR120 or by the GPR120 antagonist AH7614 (all P < 0.001). C57BL/6 mice ( n = 40) were equally categorized into Groups 1 (sham-operated control), 2 (CLI), 3 (CLI + ECSWT), and 4 (CLI + ECSWT + AH7614). By Days 7, 14, and 28 just prior to harvesting the quadriceps muscle, the laser Doppler results showed that the ratio of ischemia to normal blood flow (INBF) in the CLI area was highest in Group 1, lowest in Group 2, and significantly greater in Group 3 than in Group 4 (all P < 0.0001). Endothelial cell markers (CD31/vWF) and GPR120 + cells exhibited identical patterns of INBF among the groups, whereas angiogenesis biomarkers (CXCR4/SDF-1/VEGF/VEGFR2) were significantly and progressively upregulated from Groups 1 to 4 (all P < 0.0001). The protein levels of inflammation (MMP-9, IL-6, and TNF-α) and oxidative stress (NOX-1 and NOX-2) and the cellular levels of inflammation (CD68+)/DNA damage (γ-H2AX+) displayed opposite patterns, whereas the small vessel density in the CLI area displayed an identical pattern of INBF among the groups (all P < 0.0001). CONCLUSIONS ECSWT rescued CLI by increasing GPR120-mediated suppression of inflammation and enhancing angiogenesis via activation of VEGFR2.
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Affiliation(s)
- Pei-Hsun Sung
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jui-Ning Yeh
- Institute of Nephrology and Blood Purification, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of Cardiology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Tsung-Cheng Yin
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Han-Tan Chai
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - John Y Chiang
- Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Chi-Ruei Huang
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yi-Ling Chen
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Mel S Lee
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Pao-Chien Hospital, Pingtung, Taiwan
| | - Hon-Kan Yip
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
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Wang H, Shi Y. Extracorporeal shock wave treatment for post‑surgical fracture nonunion: Insight into its mechanism, efficacy, safety and prognostic factors (Review). Exp Ther Med 2023; 26:332. [PMID: 37346403 PMCID: PMC10280326 DOI: 10.3892/etm.2023.12031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 04/21/2023] [Indexed: 06/23/2023] Open
Abstract
Post-surgical fracture nonunion (PSFN) represents the failure to achieve cortical continuity at radiological examination after an orthopedic operation, which causes a considerable disease burden in patients with fractures. As one of the traditional treatment modalities, surgical therapy is associated with a high fracture union rate; however, post-surgical complications are not negligible. Therefore, less invasive therapies are needed to improve the prognosis of patients with PSFN. Extracorporeal shock wave treatment (ESWT) is a noninvasive method that presents a similar efficacy profile and favorable safety profile compared with surgical treatment. However, the application and detailed mechanism of ESWT in patients with PSFN remain unclear. The present review focuses on the mechanism, efficacy, safety and prognostic factors of ESWT in patients with PSFN, aiming to provide a theoretical basis for its application and improve the prognosis of these patients.
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Affiliation(s)
- Haoyu Wang
- Department of Orthopaedics, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Yaxuan Shi
- Department of Internal Medicine (Bone Oncology), Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
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Zhu JY, Yan J, Xiao J, Jia HG, Liang HJ, Xing GY. Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis. World J Clin Cases 2023; 11:1974-1984. [PMID: 36998970 PMCID: PMC10044968 DOI: 10.12998/wjcc.v11.i9.1974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 02/07/2023] [Accepted: 03/03/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head (ONFH), although significant adverse reactions often follow long-term use. Extracorporeal shock wave therapy (ESWT) can delay the progression of ONFH, alleviate the pain and functional limitations it causes, and avoid the adverse effects of celecoxib.
AIM To investigate the effects of individual ESWT, a treatment alternative to the use of celecoxib, in alleviating pain and dysfunction caused by ONFH.
METHODS This was a randomized, controlled, double-blinded, non-inferiority trial. We examined 80 patients for eligibility in this study; 8 patients were excluded based on inclusion and exclusion criteria. A total of 72 subjects with ONFH were randomly assigned to group A (n = 36; celecoxib + alendronate + sham-placebo shock wave) or group B (n = 36; individual focused shock wave [ESWT based on magnetic resonance imaging three-dimensional (MRI-3D) reconstruction] + alendronate). The outcomes were assessed at baseline, at the end of treatment, and at an 8-wk follow-up. The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score (HHS) (improvement of 10 points or more from the baseline was deemed sufficient). Secondary outcome measures were post-treatment HHS, visual analog scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.
RESULTS After treatment, the pain treatment efficiency of group B was greater than that of group A (69% vs 51%; 95%CI: 4.56% to 40.56%), with non-inferiority thresholds of -4.56% and -10%, respectively. Furthermore, the HHS, WOMAC, and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A (P < 0.001). After therapy, the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk (P < 0.001), although HHS was only significantly altered at the 2 wk point (P < 0.001). On the 1st d and 2nd wk after treatment, HHS and VAS scores were different between groups, with the difference in HHS lasting until week 4. Neither group had severe complications such as skin ulcer infection or lower limb motor-sensory disturbance.
CONCLUSION Individual shock wave therapy (ESWT) based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.
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Affiliation(s)
- Jun-Yu Zhu
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, The Armed Police Clinical College, Anhui Medical University, Hefei 230022, Anhui Province, China
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jun Yan
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jian Xiao
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Hai-Guang Jia
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Hao-Jun Liang
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Geng-Yan Xing
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, The Armed Police Clinical College, Anhui Medical University, Hefei 230022, Anhui Province, China
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TNFAIP3 mediates FGFR1 activation-induced breast cancer angiogenesis by promoting VEGFA expression and secretion. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2022; 24:2453-2465. [PMID: 36002765 DOI: 10.1007/s12094-022-02918-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/30/2022] [Indexed: 11/27/2022]
Abstract
PURPOSE To investigate the role and mechanism of TNF-inducible protein 3(TNFAIP3) in breast cancer angiogenesis induced by fibroblast growth factor receptor1 (FGFR1) activation. METHODS The immunohistochemical assay was used to detect the expression of vascular endothelial cell marker CD31 and CD105 in mice DCIS.COM-iFGFR1 transplanted tumor (previously established by our group). The effects of TNFAIP3 knockout/knockdown breast cancer cell lines on angiogenesis, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVEC) were detected by the tubulogenesis and Trewells assay. RNA-seq analysis of TNFAIP3 downstreams differential genes after TNFAIP3 knockdown. The expression and secretion of VEGFA after FGFR1 activation in breast cancer cells were detected by qPCR, Western blot, and ELISA. RESULTS Immunohistochemistry showed that TNFAIP3 knockout inhibited the expression of CD31 and CD105 in DCIS grafted tumors promoted by FGFR1 activation. Tubulogenesis and Trewells experiments showed that TNFAIP3 gene knockout/knockdown inhibited the angiogenesis, migration, and invasion of HUVEC cells promoted by FGFR1 activation. qPCR assay showed that VEGFA mRNA level in the TNFAIP3 knockdown cell line was significantly down-regulated (p < 0.05). qPCR, Western blot and ELISA results showed that TNFAIP3 gene knockout/knockdown could inhibit the expression and secretion of VEGFA in breast cancer cells induced by FGFR1 activation. CONCLUSION TNFAIP3 promotes breast cancer angiogenesis induced by FGFR1 activation through the expression and secretion of VEGFA.
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Translational Applications of Extracorporeal Shock Waves in Dental Medicine: A Literature Review. Biomedicines 2022; 10:biomedicines10040902. [PMID: 35453651 PMCID: PMC9030023 DOI: 10.3390/biomedicines10040902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/04/2022] [Accepted: 04/12/2022] [Indexed: 12/04/2022] Open
Abstract
Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its share of utilizing ESWT in various investigations. This review aimed to provide an up-to-date summary of ESWT use in preclinical and clinical dental medicine. There is growing interest in ESWT use stemming from its non-invasiveness, low cost, and safe qualities in addition to its proven regenerative biostimulating aspects. Targeted tissue and parameters of ESWT delivery continue to be an integral part of successful ESWT treatment to attain the clinical value of the anticipated dose’s effect.
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Peters K, Wiesmann N, Heimes D, Schwab R, Kämmerer PW, Al-Nawas B, Unger RE, Hasenburg A, Brenner W. Extracorporeal Shock Wave Therapy Improves In Vitro Formation of Multilayered Epithelium of Oral Mucosa Equivalents. Biomedicines 2022; 10:biomedicines10030700. [PMID: 35327502 PMCID: PMC8945876 DOI: 10.3390/biomedicines10030700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/14/2022] [Accepted: 03/17/2022] [Indexed: 11/16/2022] Open
Abstract
Oral mucosa is used in various surgical fields as a graft for the reconstruction of tissue defects. Tissue engineering of oral mucosa equivalents using autologous cells represents a suitable less burdensome alternative. The survival of the multilayered epithelium is essential for the functionality of the tissues in vivo. To ensure its functionality after transplantation, mucosa equivalents in vitro were subjected to extracorporeal shock wave therapy (ESWT) to determine whether this treatment stimulated the formation and differentiation of the epithelium. Mucosa equivalents treated with ESWT were examined for cellular metabolic activity using AlamarBlueTM assay. The formation of vascular structures, basement membrane, and multilayered epithelium were examined using confocal fluorescence microscopy and immunohistochemistry. The potential ingrowth in vivo was simulated using the chorioallantoic membrane model (CAM assay) in ovo. ESWT on culture day 19 of oral mucosa equivalents resulted in slightly increased cellular metabolic activity. The in vitro development of basement membrane and multilayer epithelium was stimulated by ESWT. Additionally, in the CAM assay, ESWT led to a more pronounced multilayered epithelium. Thus, ESWT stimulated the formation of a more distinct and differentiated multilayered epithelium of oral mucosa equivalents in vitro and might increase the chance of efficient ingrowth, survival, and functionality of tissue equivalents in vivo.
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Affiliation(s)
- Katharina Peters
- Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (K.P.); (R.S.); (A.H.)
| | - Nadine Wiesmann
- Department of Oral and Maxillofacial and Plastic Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (N.W.); (D.H.); (P.W.K.); (B.A.-N.)
- Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Diana Heimes
- Department of Oral and Maxillofacial and Plastic Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (N.W.); (D.H.); (P.W.K.); (B.A.-N.)
| | - Roxana Schwab
- Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (K.P.); (R.S.); (A.H.)
| | - Peer W. Kämmerer
- Department of Oral and Maxillofacial and Plastic Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (N.W.); (D.H.); (P.W.K.); (B.A.-N.)
| | - Bilal Al-Nawas
- Department of Oral and Maxillofacial and Plastic Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (N.W.); (D.H.); (P.W.K.); (B.A.-N.)
| | - Ronald E. Unger
- Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
| | - Annette Hasenburg
- Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (K.P.); (R.S.); (A.H.)
| | - Walburgis Brenner
- Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (K.P.); (R.S.); (A.H.)
- Correspondence: ; Tel.: +49-6131-17-2740
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Use of the Shock Wave Therapy in Basic Research and Clinical Applications-From Bench to Bedsite. Biomedicines 2022; 10:biomedicines10030568. [PMID: 35327369 PMCID: PMC8944950 DOI: 10.3390/biomedicines10030568] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/05/2023] Open
Abstract
Shock Waves (SW) are acoustic disturbances that propagate through a medium carrying the energy. These specific sonic pulses are composed of two phases—high positive pressure, a rise time < 10 ns, and a tensile wave. Originally Shock Waves were introduced to clinical practice as a part of the lithotripsy therapy focused on disrupting calcific deposits in the body. Since that time, shock wave therapy (SWT) has gone far beyond the original application related to the destruction of kidney stones. In this narrative Review, we present basic clinical applications of the SWT along with the potential therapeutic application in clinical practice.
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