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Zhang BB, Xu L, Zhang QB, Wang Y, Chen C, Zhang JN, Rao XL, Zhu BJ, Li XM, Zhu DT, Kan XL, Mao J, Zhang R, Zhou Y. Anti-fibrosis effect and its mechanism of atractylenolide III on post-traumatic extending knee joint contracture in rats. Exp Gerontol 2025; 201:112708. [PMID: 39929325 DOI: 10.1016/j.exger.2025.112708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/13/2025] [Accepted: 02/07/2025] [Indexed: 02/24/2025]
Abstract
OBJECTIVES Atractylenolide III (ATL III) is the major bioactive component found in Atractylodes macrocephala, which has shown a range of benefits in pharmacological studies, including neuroprotection, anti-neuroinflammatory properties, antioxidant effects, anti-allergic effects, anti-cancer properties and antifibrotic abilities. Here, we investigated the therapeutic potential and underlying mechanisms of ATL III in the treatment of post-traumatic joint contracture (PTJC) in rat knees. METHODS The rat PTJC model and TGF-β1-induced a primary synovial fibroblast model were used to observe several fibrotic markers (α-SMA、TGF-β1、FGF2、COL1A1and COL3A1) using histological staining, immunofluorescence and western blot. Additionally, the effects of ATL III on synovial fibroblasts in vitro were evaluated through CCK-8 assays and migration assays to ascertain both cell viability and migratory behaviors. Furthermore, molecular docking studies were performed to elucidate the potential binding affinity of ATL III for Silent information regulator of transcription 1 (Sirt1), thereby providing insights into the underlying molecular mechanisms implicated in fibrosis modulation. RESULTS ATL III treatment was observed to reduce proliferating cells, inflammatory cells and collagen accumulation in a rat model of traumatic rat knee fibrosis. In vitro, ATL III treatment was found to significantly reduce fibrosis and collagen-associated protein expression and inhibit synovial fibroblast proliferation and migration. Molecular docking identified Sirt1 as a potential target of ATL III. Interestingly, Sirt1 and Smad3 can interact and act to deacetylate Smad3, and in vitro and in vivo ATL III treatment significantly reduced Smad3 acetylation levels. CONCLUSION ATL III produces a therapeutic effect on knee fibrosis probably because Sirt1 deacetylates Smad3 and thus relieves knee fibrosis in rats.
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Affiliation(s)
- Bin-Bin Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Department of Rehabilitation Medicine, The First Affiliated Hospital of Bengbu Medical University, No.287 Changhuai Road, Bengbu 233000, China
| | - Lei Xu
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Bengbu Medical University, No.287 Changhuai Road, Bengbu 233000, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Yan Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Chen Chen
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Department of Joint Surgery, The Tongling People's Hospital, No. 468, Bijiashan Road, Tongling 244009, China
| | - Jin-Niu Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Xian-Liang Rao
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University (Anhui Public Health Clinical Center), NO.100 Huaihai Road, Hefei, China
| | - Bing-Jing Zhu
- The Second Clinical College of Anhui Medical University, NO.81 Meishan Road, Hefei, China
| | - Xue-Ming Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - De-Ting Zhu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Xiu-Li Kan
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Jing Mao
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Run Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China; Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, NO.678 Furong Road, Economic and Technological Development Zone, Hefei 230601, China.
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Tsavaris NJ, Lomis MJ, Gordon S, Vaughan P, Schneider S. Extensor Hallucis Longus Contracture Following Intramedullary Nailing for a Pilon Fracture. Cureus 2025; 17:e78195. [PMID: 40026937 PMCID: PMC11870295 DOI: 10.7759/cureus.78195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Extensor hallucis longus (EHL) fibrosis is an uncommon complication following a pilon fracture. This is caused by compartment syndrome from fracture immobilization followed by adhesion of muscle or tendon. Only a few cases of EHL fibrosis secondary to a post-traumatic lower leg fracture have been reported. This paper reports on a rare case of isolated EHL tendon fibrosis after a pilon fracture. It will outline the treatment received and the current prognosis of the patient, while also discussing methods for prevention of this complication.
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Affiliation(s)
- Nicholas J Tsavaris
- Orthopedic Surgery, Augusta University Medical College of Georgia, Athens, USA
| | - Mitchell J Lomis
- Orthopedic Surgery, Augusta University Medical College of Georgia, Athens, USA
| | - Sean Gordon
- Orthopedic Surgery, Augusta University Medical College of Georgia, Athens, USA
| | - Parker Vaughan
- Orthopedic Surgery, Augusta University Medical College of Georgia, Athens, USA
| | - Scarlett Schneider
- Sports Medicine, Augusta University/University of Georgia Medical Partnership, Athens, USA
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Maimaiti P, Shu J, Miao T, Keqike N, Tuersun A, Ruiqi Yang, Wang N. Aerobic Training and Ointment Effect on range of motion, von Willebrand factor, vascular endothelial factor and Femoral Artery Hemodynamics in Joint Contracture: A Rat Model. Biol Res Nurs 2025; 27:17-27. [PMID: 39141917 DOI: 10.1177/10998004241274290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
OBJECTIVE Using a rat model, we investigated the effect of multidisciplinary rehabilitation, including aerobic training and ointment, on the ROM, vWF, VEGF content, and femoral artery hemodynamics in rats with joint contracture. METHODS A total of 44 Wistar rats were divided into the normal control group (NC, eight rats) and the experimental group (EG). A joint contracture model was established for the rats in the EG group by an external fixator. After fixator removal, 32 rats are further divided into the MC, SC, RE, and SR groups (n = 8). Before and after the 42 day intervention, the ROM, vWF, VEGF, PS, ED, and RI were measured using X-ray imaging, ELISA, and color Doppler ultrasound, respectively. RESULTS After fixator removal, ROM for EG group was lower than that of the NC group (p < .01). After the intervention, ROM for the SR, RE, and SC groups was improved. The ROM for the SR group reached a similar value for NC group. vWF and VEGF levels in SR group were lower than in the MC, SC, and RE groups (p < .05), and had a similar value to the NC groups. PS value for SR and RE groups was higher than the MC and SC groups. The RI value for SR group was higher than that of NC and MC groups. CONCLUSION Multidisciplinary rehabilitation used in this study can treat joint contracture synergistically. It improves the ROM of the joint, reduces the content of vWF and VEGF, and improves the femoral artery hemodynamics.
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Affiliation(s)
| | - Jiaojiao Shu
- Nursing School, Xinjiang Medical University, Urumqi, China
| | - Tianyu Miao
- Nursing School, Xinjiang Medical University, Urumqi, China
| | - Nuerbiya Keqike
- Department of Nursing, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | | | - Ruiqi Yang
- Nursing School, Xinjiang Medical University, Urumqi, China
| | - Ningning Wang
- Nursing School, Xinjiang Medical University, Urumqi, China
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Kong L, Liang Y, Hou J, Zhang W, Jiang S. Target NF-κB p65 for preventing posttraumatic joint contracture in rats. J Orthop Res 2024; 42:2172-2180. [PMID: 38751161 DOI: 10.1002/jor.25877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 04/24/2024] [Accepted: 05/02/2024] [Indexed: 10/19/2024]
Abstract
RelA/p65 is as a crucial component of the nuclear factor κB (NF-κB) signaling pathway that has a significant impact on various fibrotic diseases. However, its role in the fibrosis of tissues surrounding the joint after traumatic injury remains unclear. In this study, rats were divided into three groups: non-operated control (NC) group, p65-siRNA treated (siRNA-p65) group, and negative siRNA treated (siRNA-neg) group. Then, 10 μL (10 nmol) of p65-siRNA was injected into the joint of the siRNA-p65 group. Meanwhile, 10 μL of negative siRNA was administered to the knee joint of the operated siRNA-neg group for comparison. The rats in the NC group did not receive surgery or drug intervention. After 4 weeks of right knee fixation in each group, X-ray measurements revealed significantly reduced degree of knee flexion contracture following p65-siRNA treatment (siRNA-neg: 77.73° ± 2.799°; siRNA-p65: 105.7° ± 2.629°, p < 0.0001). Histopathological examination revealed that the number of dense fibrous connective tissues decreased following p65-siRNA inhibition. Western blot analysis revealed significantly different expression levels of fibrosis-related proteins between the siRNA-p65 and siRNA-neg groups. Immunohistochemical analysis revealed a reduction in the average number of myofibroblasts in the siRNA-p65 group compared with that in the siRNA-neg group. Thus, intra-articular p65-siRNA injection could attenuate fibroblast activation and fibrosis-related protein production, suppress periarticular tissue fibrosis, and prevent joint contracture by downregulating the NF-κB p65 pathway. Statement of clinical significance: Intra-articular injection of p65-siRNA could reduce myofibroblast proliferation and fibrosis-related protein expression by downregulating the NF-κB p65 pathway, inhibit periarticular tissue fibrosis, and prevent joint adhesion, which represents a potential therapy in the prevention of joint fibrosis following traumatic injury.
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Affiliation(s)
- Lingpeng Kong
- Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuqing Liang
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jing Hou
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Weiying Zhang
- Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Shichao Jiang
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Nakao G, Kodesho T, Yamagata K, Watanabe K, Ohsaki Y, Katayose M, Taniguchi K. Validity of Elastic Imaging Evaluation of Hamstring Muscles With Knee Contracture Using Ultrasound Shear Wave Elastography. Cureus 2024; 16:e68343. [PMID: 39355060 PMCID: PMC11442639 DOI: 10.7759/cureus.68343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2024] [Indexed: 10/03/2024] Open
Abstract
PURPOSE This study used ultrasound shear wave elastography (SWE) to evaluate the mechanical properties of hamstring muscles from cadaveric specimens with knee flexion contractures. METHODS Hamstring muscles for tensile testing were harvested from Thiel soft-embalmed cadavers with and without knee flexion contracture. Muscle specimens were mounted on a testing machine. The initial load detected when a tensile load was applied to the distal end was used as the slack length. The cross-sectional areas of the muscle at slack length were measured at the proximal and distal sites using B-mode ultrasonography. Subsequently, the muscle specimen was elongated from the slack length to 8% strain, with the shear modulus measured using SWE. Young's modulus (stress/strain) was calculated based on the displacement and tensile force obtained from the tensile test. RESULTS Regression analysis showed a significant positive linear relationship between the Young's and shear moduli for all specimens at all the sites (P < 0.01 and coefficient of determination: 0.95-0.99). The Young's and average shear moduli at the proximal and distal sites were higher in all hamstring muscles with contractures than in those without contractures. CONCLUSIONS SWE can be used to estimate Young's moduli of hamstring muscles with contractures. Muscle specimens with contractures exhibited higher resistance to elongation, thereby indicating that their mechanical properties differed from those of muscles without contractures.
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Affiliation(s)
- Gakuto Nakao
- Graduate School of Health Sciences, Sapporo Medical University, Sapporo, JPN
- Department of Physical Therapy, Sapporo Medical Technology, Welfare and Dentistry Professional Training College of Nishino Gakuen School Foundation, Sapporo, JPN
| | - Taiki Kodesho
- Department of Sport Science and Research, Japan Institute of Sports Sciences (JISS), Tokyo, JPN
| | - Kazuma Yamagata
- Graduate School of Health Sciences, Sapporo Medical University, Sapporo, JPN
| | - Kota Watanabe
- Department of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, JPN
| | - Yuki Ohsaki
- Department of Anatomy, School of Medicine, Sapporo Medical University, Sapporo, JPN
| | - Masaki Katayose
- Department of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, JPN
| | - Keigo Taniguchi
- Department of Physical Therapy, School of Health Sciences, Sapporo Medical University, Sapporo, JPN
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Zhang J, Lai S, Li J, Zhang C, Yao L, Zhang Y, Chen K, Cai W, Li J, Li Q. Early Postoperative Rapid Rehabilitation Yields More Favorable Short-term Outcomes in Patients Undergoing Patellar Realignment Surgery for Recurrent Patellar Dislocation: A Prospective Randomized Controlled Study. Am J Sports Med 2024; 52:2205-2214. [PMID: 38884318 DOI: 10.1177/03635465241254524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
BACKGROUND Use of a rapid rehabilitation protocol for postoperative recovery after recurrent patellar dislocation (RPD) has gradually gained attention; nonetheless, evidence of its safety and effectiveness is lacking. PURPOSE To compare the short-term postoperative outcomes of early rapid rehabilitation with those of conservative rehabilitation in patients with RPD. STUDY DESIGN Randomized controlled trial; Level of evidence, 2. METHODS A total of 50 patients with RPD who underwent tibial tubercle osteotomy combined with medial patellofemoral ligament reconstruction were enrolled between January 2018 and February 2019. Postoperatively, the patients were randomly assigned to either the early rapid group (rapid group; n = 25 patients) or the conservative group (control group; n = 25 patients) for rehabilitation training. The rapid group underwent faster progression in weightbearing and range of motion (ROM) training. Knee joint functional scores, ROM, bilateral thigh circumference differences, and imaging data were recorded preoperatively and at 6 weeks and 3, 6, 12, and 24 months postoperatively for comparison. Postoperative complications were recorded over the 24-month follow-up period. RESULTS The baseline data did not significantly differ between the 2 groups. Postoperatively, compared with the control group, the rapid group had higher Tegner scores at 6 weeks and 3 months; higher Lysholm scores at 3 and 6 months; higher International Knee Documentation Committee scores at 6 weeks, 3 months, and 12 months; better ROM; and smaller bilateral thigh circumference differences at 24 months (P < .05 for all). However, no differences were observed in the Tegner, Lysholm, and International Knee Documentation Committee scores at 24 months postoperatively. At the 6-week and subsequent follow-up visits, the Caton and Insall indices were lower in the control group than in the rapid group (P < .01 for all). Moreover, compared with the control group, the rapid group had a lower incidence of patella baja at 24 months (0% vs 17%) and fewer complications during the whole follow-up period (P < .01). CONCLUSION Early rapid postoperative rehabilitation appears to be safe and effective for patients who undergo tibial tubercle osteotomy combined with medial patellofemoral ligament reconstruction to treat RPD. In the short term, this approach was shown to be more advantageous than conservative rehabilitation in improving functional scores, allowing an earlier return to daily activities, although the lack of difference at 24 months implies no long-term benefits. In addition, it potentially helped to prevent the occurrence of complications, including patella baja. REGISTRATION ChiCTR1800014648 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Jiayao Zhang
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Sike Lai
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Junqiao Li
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chenghao Zhang
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Lei Yao
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yuyan Zhang
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Kunhao Chen
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wufeng Cai
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jian Li
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qi Li
- Sports Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Orthopedics and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China
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Ahmed HS, Jayaram PR. Anesthetic considerations for joint replacement surgery in hemophilic arthropathy: a comprehensive review. Anesth Pain Med (Seoul) 2024; 19:194-208. [PMID: 39069647 PMCID: PMC11317322 DOI: 10.17085/apm.24047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/21/2024] [Accepted: 06/18/2024] [Indexed: 07/30/2024] Open
Abstract
Managing hemophilia in patients undergoing joint replacement surgery requires a comprehensive approach encompassing preoperative assessment, meticulous intraoperative care, and tailored postoperative management. Evaluation of joint integrity, bleeding history, and inhibitor presence guides surgical planning and hemostatic therapy selection to optimize outcomes. During surgery, careful attention to factor replacement, antibiotic prophylaxis, anesthetic techniques, and orthopedic strategies minimizes bleeding risk and enhances surgical success. Postoperatively, effective pain management, continued hemostatic therapy, and individualized rehabilitation programs are vital for facilitating recovery and preventing complications. Close monitoring for potential complications, such as periprosthetic joint infection and recurrent hemarthrosis, allows for prompt intervention when necessary. Overall, a collaborative approach involving hematologists, orthopedic surgeons, anesthesiologists, and rehabilitation specialists ensures comprehensive care tailored to the unique needs of patients with hemophilia undergoing joint replacement surgery, ultimately optimizing outcomes and improving quality of life. This holistic approach addresses the multifaceted challenges posed by hemophilia and joint replacement surgery, providing patients with the best possible chance for successful outcomes and long-term joint function. By integrating specialized expertise from multiple disciplines and implementing evidence-based strategies, healthcare providers can effectively manage hemophilia in the context of joint replacement surgery, mitigating risks and maximizing benefits for patients.
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Affiliation(s)
- H Shafeeq Ahmed
- Bangalore Medical College and Research Institute, Bangalore, India
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Lee CH, Kwon Y, Park S, Kim T, Kim MS, Kim EJ, Jung JI, Min S, Park KH, Jeong JH, Choi SE. The Impact of Ulmus macrocarpa Extracts on a Model of Sarcopenia-Induced C57BL/6 Mice. Int J Mol Sci 2024; 25:6197. [PMID: 38892385 PMCID: PMC11172872 DOI: 10.3390/ijms25116197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/24/2024] [Accepted: 05/29/2024] [Indexed: 06/21/2024] Open
Abstract
Aging leads to tissue and cellular changes, often driven by oxidative stress and inflammation, which contribute to age-related diseases. Our research focuses on harnessing the potent anti-inflammatory and antioxidant properties of Korean Ulmus macrocarpa Hance, a traditional herbal remedy, to address muscle loss and atrophy. We evaluated the effects of Ulmus extract on various parameters in a muscle atrophy model, including weight, exercise performance, grip strength, body composition, muscle mass, and fiber characteristics. Additionally, we conducted Western blot and RT-PCR analyses to examine muscle protein regulation, apoptosis factors, inflammation, and antioxidants. In a dexamethasone-induced muscle atrophy model, Ulmus extract administration promoted genes related to muscle formation while reducing those associated with muscle atrophy. It also mitigated inflammation and boosted muscle antioxidants, indicating a potential improvement in muscle atrophy. These findings highlight the promise of Ulmus extract for developing pharmaceuticals and supplements to combat muscle loss and atrophy, paving the way for clinical applications.
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Affiliation(s)
- Chan Ho Lee
- Department of Forest Biomaterials Engineering, Kangwon National University, Chuncheon 24341, Republic of Korea;
| | - Yeeun Kwon
- Dr.Oregonin Inc., #802 Bodeum Hall, Kangwondaehakgil 1, Chuncheon 24341, Republic of Korea; (Y.K.); (S.P.); (T.K.); (M.S.K.)
| | - Sunmin Park
- Dr.Oregonin Inc., #802 Bodeum Hall, Kangwondaehakgil 1, Chuncheon 24341, Republic of Korea; (Y.K.); (S.P.); (T.K.); (M.S.K.)
| | - TaeHee Kim
- Dr.Oregonin Inc., #802 Bodeum Hall, Kangwondaehakgil 1, Chuncheon 24341, Republic of Korea; (Y.K.); (S.P.); (T.K.); (M.S.K.)
| | - Min Seok Kim
- Dr.Oregonin Inc., #802 Bodeum Hall, Kangwondaehakgil 1, Chuncheon 24341, Republic of Korea; (Y.K.); (S.P.); (T.K.); (M.S.K.)
| | - Eun Ji Kim
- Industry Coupled Cooperation Center for Bio Healthcare Materials, Hallym University, Chuncheon 24252, Republic of Korea; (E.J.K.); (J.I.J.)
| | - Jae In Jung
- Industry Coupled Cooperation Center for Bio Healthcare Materials, Hallym University, Chuncheon 24252, Republic of Korea; (E.J.K.); (J.I.J.)
| | - Sangil Min
- Division of Transplantation and Vascular Surgery, Department of Surgery, Seoul National University Hospital, Seoul 03080, Republic of Korea;
| | - Kwang-Hyun Park
- Department of Emergency Medical Rescue, Nambu University, Gwangju 62271, Republic of Korea;
| | - Jae Hun Jeong
- Department of Food Science & Biotechnology, Jeonnam State University, Damyang 57337, Republic of Korea;
| | - Sun Eun Choi
- Department of Forest Biomaterials Engineering, Kangwon National University, Chuncheon 24341, Republic of Korea;
- Dr.Oregonin Inc., #802 Bodeum Hall, Kangwondaehakgil 1, Chuncheon 24341, Republic of Korea; (Y.K.); (S.P.); (T.K.); (M.S.K.)
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Suwankanit K, Shimizu M. Effects of Neuromuscular Electrical Stimulation and Therapeutic Ultrasound on Quadriceps Contracture of Immobilized Rats. Vet Sci 2024; 11:158. [PMID: 38668425 PMCID: PMC11054819 DOI: 10.3390/vetsci11040158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 03/27/2024] [Accepted: 03/27/2024] [Indexed: 04/29/2024] Open
Abstract
Quadriceps contracture is a condition where the muscle-tendon unit is abnormally shortened. The treatment prognosis is guarded to poor depending on the progress of the disease. To improve the prognosis, we investigated the effectiveness of therapeutic ultrasound and NMES in treating quadriceps contracture in an immobilized rat model. Thirty-six Wistar rats were randomized into control, immobilization alone, immobilization and spontaneous recovery, immobilization and therapeutic ultrasound, immobilization and NMES, and immobilization and therapeutic ultrasound and NMES combination groups. The continuous therapeutic ultrasound (frequency, 3 MHz, intensity 1 W/cm2) and NMES (TENS mode, frequency 50 Hz; intensity 5.0 ± 0.8 mA) were performed on the quadriceps muscle. On Day 15, immobilization-induced quadriceps contracture resulted in a decreased ROM of the stifle joint, reduction in the sarcomere length, muscle atrophy, and muscle fibrosis. On Day 43, therapeutic ultrasound, NMES, and combining both methods improved muscle atrophy and shortening and decreased collagen type I and III and α-SMA protein. The combination of therapeutic ultrasound and NMES significantly reduced the mRNA expression of IL-1β, TGF-β1, and HIF-1α and increased TGF-β3. Therefore, the combination of therapeutic ultrasound and NMES is the most potent rehabilitation program for treating quadriceps contracture.
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Affiliation(s)
- Kanokwan Suwankanit
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-0054, Tokyo, Japan;
- Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Miki Shimizu
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-0054, Tokyo, Japan;
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Suwankanit K, Shimizu M, Suzuki K, Kaneda M. Usefulness of Ultrasound Shear Wave Elastography for Detection of Quadriceps Contracture in Immobilized Rats. Animals (Basel) 2023; 14:76. [PMID: 38200807 PMCID: PMC10778017 DOI: 10.3390/ani14010076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 12/15/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
Quadriceps contracture is an abnormal pathological shortening of the muscle-tendon unit. To improve the prognosis of quadriceps contracture, improvement of its diagnostic method is needed. In this study, we evaluated the diagnostic utility of ultrasound shear wave elastography in a rat model of quadriceps contracture induced by immobilization. Fifty Wistar rats were randomly divided into control and immobilization groups. During up to 4 weeks of joint immobilization, the quadriceps elastic modulus, muscle hardness, creatinine phosphokinase levels, joint range of motion, histopathologic parameters, and levels of fibrosis-associated mRNA expression were measured every week in the immobilization and control groups and compared. In the immobilization group, the elastic modulus gradually but significantly increased (p < 0.05) throughout the immobilization period. However, muscle hardness and serum creatinine phosphokinase levels only increased at 1 and 2 weeks after the start of immobilization, respectively. Muscle atrophy and shortening progressed throughout the immobilization group. Collagen type I and III, α-SMA protein, and mRNA expression of IL-1β and TGF-β1 significantly increased (p < 0.05) throughout in the immobilization group. Ultrasound shear wave elastography is the most useful method for clinical assessment of muscle contracture.
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Affiliation(s)
- Kanokwan Suwankanit
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-0054, Japan;
- Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Miki Shimizu
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-0054, Japan;
| | - Kazuhiko Suzuki
- Laboratory of Veterinary Toxicology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-0054, Japan;
| | - Masahiro Kaneda
- Laboratory of Veterinary Anatomy, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-8509, Japan;
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Yuan H, Wang K, Zhang QB, Wang F, Zhou Y. The effect of extracorporeal shock wave on joint capsule fibrosis based on A 2AR-Nrf2/HO-1 pathway in a rat extending knee immobilization model. J Orthop Surg Res 2023; 18:930. [PMID: 38057890 DOI: 10.1186/s13018-023-04420-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 11/28/2023] [Indexed: 12/08/2023] Open
Abstract
Joint capsule fibrosis, a common complication of joint immobilization, is mainly characterized by abnormal collagen deposition. The present study aimed to investigate the effect of extracorporeal shock wave therapy (ESWT) on reduced collagen deposition in the joint capsule during immobilization-induced joint capsule fibrosis. Additionally, the potential involvement of the adenosine A2A receptor (A2AR)-Neurotrophic factor e2-related factor 2 (Nrf2)/Haem oxygenase-1 (HO-1) pathway was explored. Thirty 3-month-old male Sprague-Dawley rats were randomly assigned to five groups: control (C), immobilization model (IM), natural recovery (NR), ESWT intervention (EI), and ESWT combined with A2AR antagonist SCH 58261 intervention (CI). After the left knee joints of rats in the IM, NR, EI and CI groups were immobilized using a full-extension fixation brace for 4 weeks, the EI and CI groups received ESWT twice a week for 4 weeks. The CI group was also treated with ESWT following intraperitoneal injection of SCH 58261 (0.01 mg/kg) for 4 weeks. The range of motion of the left knee joint was measured, and the protein levels of collagens I and III, A2AR, phosphorylated-protein kinase A/protein kinase A (p-PKA/PKA), p-Nrf2/Nrf2, and HO-1 were analysed by Western blotting. The IM and NR groups showed significantly greater arthrogenic contracture than the C group (P < 0.05). Compared to the NR group, the EI and CI groups exhibited significant improvement in arthrogenic contracture (P < 0.05). Conversely, the EI group showed lower contracture than the CI group (P < 0.05). Similar results were observed for collagen deposition and the protein levels of collagens I and III. The intervention groups (EI and CI groups) showed higher levels of p-Nrf2/Nrf2 and HO-1 than the NR group (P < 0.05). Moreover, the EI group exhibited higher levels of p-PKA/PKA, p-Nrf2/Nrf2, and HO-1 than the CI group (P < 0.05). However, no significant difference was found in the A2AR levels among the five groups (P > 0.05). ESWT may activate A2AR, leading to the phosphorylation of PKA. Subsequently, Nrf2 may be activated, resulting in the upregulation of HO-1, which then reduces collagen deposition and alleviates immobilization-induced joint capsule fibrosis.
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Affiliation(s)
- Hai Yuan
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, China
- Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Rehabilitation Medicine, The Second People's Hospital of Hefei City, Hefei, China
| | - Kui Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, China
- Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, China
- Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, China
- Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Economic and Technological Development Zone, Hefei, 230601, China.
- Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
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Zhou T, Zhou CX, Zhang QB, Wang F, Zhou Y. LIPUS Alleviates Knee Joint Capsule Fibrosis in Rabbits by Regulating SOD/ROS Dynamics and Inhibiting the TGF-β1/Smad Signaling Pathway. ULTRASOUND IN MEDICINE & BIOLOGY 2023; 49:2510-2518. [PMID: 37714800 DOI: 10.1016/j.ultrasmedbio.2023.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 08/15/2023] [Accepted: 08/16/2023] [Indexed: 09/17/2023]
Abstract
OBJECTIVE The aim of the work described here was to investigate the efficacy and potential mechanisms of low-intensity pulsed ultrasound (LIPUS) for the treatment of arthrogenic contracture induced by immobilization in rabbits. METHODS The left knee joint of rabbits was immobilized for 6 wk to establish the model of extending knee joint contracture. The rabbits were divided into a control group (C), a group immobilized for 6 wk (IM-6w), a group remobilized for 1 wk (RM-1w), a group subjected to LIPUS intervention for 1 wk (LIPUS-1w), a group remobilized for 2 wk (RM-2w) and a group subjected to LIPUS intervention for 2 wk (LIPUS-2w). The degrees of arthrogenic contracture and joint capsule fibrosis were assessed, as were the levels of reactive oxygen species (ROS) and the activation status of the TGF-β1/Smad signaling pathway in the joint capsule. RESULTS After immobilization for 6 wk, the degrees of arthrogenic contracture and joint capsule fibrosis increased. The ROS level increased, as evidenced by an increase in malondialdehyde content and a decrease in superoxide dismutase content. In addition, the TGF-β1/Smad signaling pathway was significantly activated. The degrees of knee joint contracture increased in the first week after remobilization and decreased in the second week. Furthermore, joint capsule fibrosis continued to develop during the 2 wk of remobilization, and the ROS level increased, while the TGF-β1/Smad signaling pathway was significantly activated. LIPUS effectively reduced the level of ROS in the joint capsule, which further inhibited activation of the TGF-β1/Smad signaling pathway, thereby improving joint capsule fibrosis and reducing arthrogenic contracture. CONCLUSION The high ROS levels and overactivation of the TGF-β1/Smad signaling pathway may be reasons why immobilization induces knee joint capsule fibrosis. LIPUS can alleviate the degree of knee joint capsule fibrosis induced by immobilization by inhibiting the production of ROS and the activation of the TGF-β1/Smad signaling pathway.
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Affiliation(s)
- Ting Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chen Xu Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Quan Bing Zhang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Feng Wang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
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Zhou CX, Wang F, Zhou Y, Fang QZ, Zhang QB. Formation process of extension knee joint contracture following external immobilization in rats. World J Orthop 2023; 14:669-681. [PMID: 37744718 PMCID: PMC10514713 DOI: 10.5312/wjo.v14.i9.669] [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: 04/27/2023] [Revised: 06/30/2023] [Accepted: 08/21/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Current research lacks a model of knee extension contracture in rats.
AIM To elucidate the formation process of knee extension contracture.
METHODS We developed a rat model using an aluminum external fixator. Sixty male Sprague-Dawley rats with mature bones were divided into the control group (n = 6) and groups that had the left knee immobilized with an aluminum external fixator for 1, 2, and 3 d, and 1, 2, 3, 4, 6, and 8 wk (n = 6 in each group). The passive extension range of motion, histology, and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.
RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization. After 2 wk, the contracture gradually changed from myogenic to arthrogenic. The arthrogenic contracture progressed slowly during the 1st week, rapidly progressed until the 3rd week, and then showed a steady progression until the 4rd week. Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time. Correspondingly, the level of transforming growth factor beta 1 (TGF-β1) and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2) in the anterior joint capsule also increased with the immobilization time. Over time, the cross-sectional area of muscle fibers gradually decreased, while the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was increased. Unexpectedly, the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was decreased during the late stage of immobilization (6-8 wk). The myogenic contracture was stabilized after 2 wk of immobilization, whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.
CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.
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Affiliation(s)
- Chen-Xu Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Qiao-Zhou Fang
- The Second Clinical Medicine College, Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Wang F, Zhou T, Zhou CX, Zhang QB, Wang H, Zhou Y. The worsening of skeletal muscle atrophy induced by immobilization at the early stage of remobilization correlates with BNIP3-dependent mitophagy. BMC Musculoskelet Disord 2023; 24:632. [PMID: 37542244 PMCID: PMC10401904 DOI: 10.1186/s12891-023-06759-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 07/26/2023] [Indexed: 08/06/2023] Open
Abstract
BACKGROUND Recent studies have shown that immobilization enhances reactive oxygen species (ROS) production and mitophagy activity in atrophic skeletal muscle. However, there are relatively few studies examining the biological changes and underlying mechanisms of skeletal muscle during remobilization. In this study, we aimed to investigate the effects of remobilization on skeletal muscle and explore the role of BNIP3-dependent mitophagy in this process. METHODS Thirty rats were randomly divided into six groups based on immobilization and remobilization time: control (C), immobilization for two weeks (I-2w), and remobilization for one day (R-1d), three days (R-3d), seven days (R-7d), and two weeks (R-2w). At the end of the experimental period, the rectus femoris muscles were removed and weighed, and the measurements were expressed as the ratio of muscle wet weight to body weight (MWW/BW). Sirius Red staining was performed to calculate the values of cross-sectional area (CSA) of rectus femoris. Oxidative fluorescent dihydroethidium was used to evaluate the production of ROS, and the levels of superoxide dismutase (SOD) were also detected. The morphological changes of mitochondria and the formation of mitophagosomes in rectus femoris were examined and evaluated by transmission electron microscope. Immunofluorescence was employed to detect the co-localization of BNIP3 and LC3B, while Western blot analysis was performed to quantify the levels of proteins associated with mitophagy and mitochondrial biogenesis. The total ATP content of the rectus femoris was determined to assess mitochondrial function. RESULTS Within the first three days of remobilization, the rats demonstrated decreased MWW/BW, CSA, and ATP concentration, along with increased ROS production and HIF-1α protein levels in the rectus femoris. Results also indicated that remobilization triggered BNIP3-dependent mitophagy, supported by the accumulation of mitophagosomes, the degradation of mitochondrial proteins (including HSP60 and COX IV), the elevation of BNIP3-dependent mitophagy protein markers (including BNIP3, LC3B-II/LC3B-I, and Beclin-1), and the accumulation of puncta representing co-localization of BNIP3 with LC3B. Additionally, PGC-1α, which is involved in the regulation of mitochondrial biogenesis, was upregulated within the first seven days of remobilization to counteract this adverse effect. CONCLUSION Our findings suggested that BNIP3-denpendent mitophagy was sustained activated at the early stages of remobilization, and it might contribute to the worsening of skeletal muscle atrophy.
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Affiliation(s)
- Feng Wang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Hefei, 230601, China
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Ting Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Hefei, 230601, China
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Chen Xu Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Hefei, 230601, China
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Quan Bing Zhang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Hefei, 230601, China
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Hua Wang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, 230032, China
- Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, 230032, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Anhui Medical University, No.678 Furong Road, Hefei, 230601, China.
- Research Center for Translational Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
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Zhang QB, Liu AY, Fang QZ, Wang F, Wang H, Zhou Y. Effect of Electrical Stimulation on Disuse Muscular Atrophy Induced by Immobilization: Correlation With Upregulation of PERK Signal and Parkin-Mediated Mitophagy. Am J Phys Med Rehabil 2023; 102:692-700. [PMID: 36630294 DOI: 10.1097/phm.0000000000002182] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES The aims of the study are to investigate the effect of electrical stimulation on disuse muscular atrophy induced by immobilization (IM) and to explore the role of PERK signal and Parkin-dependent mitophagy in this process. DESIGN In the first subexperiment, 24 rabbits were divided into four groups, which underwent different periods of IM. In the second subexperiment, 24 rabbits were divided into four groups on average in accordance with different kinds of interventions. To test the time-dependent changes of rectus femoris after IM, and to evaluate the effect of electrical stimulation, the wet weights, cross-sectional area and fat deposition of rectus femoris were assessed in this study, along with the protein levels of atrogin-1, p-PERK, Parkin, and COXIV. RESULTS The wet weights and cross-sectional area decreased, and the fat deposition increased in rectus femoris after IM, along with the elevated protein levels of atrogin-1, p-PERK, Parkin, and decreased protein levels of COXIV. The above histomorphological and molecular changes can be partially ameliorated by electrical stimulation. CONCLUSIONS Immobilization of unilateral lower limb could induce rectus femoris atrophy, which can be partially rectified by electrical stimulation. PERK signal and Parkin-mediated mitophagy may be the mechanisms by which electrical stimulation can play a significant role.
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Affiliation(s)
- Quan-Bing Zhang
- From the Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Q-BZ, FW, YZ); The Center for Scientific Research of the First Affiliated Hospital of Anhui Medical University, Hefei, China (A-YL); The Second Clinical Medicine College of Anhui Medical University, Hefei, China (Q-ZF); Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei, China (HW); and Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China (HW)
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Shui XP, Ye F, Li CY, Zhang X, Wang MJ, Li B, Chen K, Liao YY. Effects of millimeter-wave for preventing joint stiffness in the immobilized knee rat model. Knee 2023; 42:236-245. [PMID: 37086540 DOI: 10.1016/j.knee.2023.03.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 03/14/2023] [Accepted: 03/30/2023] [Indexed: 04/24/2023]
Abstract
AIM To explore the effects and mechanism of millimeter-wave treatment on the development of joint stiffness in the immobilized knee rat model. METHODS Twenty-four Sprague-Dawley (SD) rats were randomly divided into the control group (O, n = 8), the surgical control group (OC, n = 8), and the millimeter-wave treatment group (MO, n = 8). After immobilized knee modeling, the knee mobility and quadriceps diameter was measured at the 6th week. Hematoxylin and eosin and Masson staining were performed to detect the pathology and fibrous lesions of the knee joint. Furthermore, the expression of TGF-β1 and Collagen I was quantified by immunohistochemical assay in the knee capsule, and Western blotting was performed to quantify the protein expression of NF-κB and MuRF1 in skeletal muscle. RESULTS Compared with the O group, knee mobility, and quadriceps diameter was decreased (P < 0.01), and articular capsule fibrosis and quadriceps atrophy occurred in all rats with fixed knee joints. Compared with the OC group, millimeter-wave treatment significantly increased articular mobility and the quadriceps diameter; and improved the fibrotic lesions of the joint capsule and quadriceps atrophy. Moreover, levels of TGF-β1, Collagen I, and MuRF1 were upregulated (P < 0.01) by knee immobilization, and collagen fiber content in the articular capsule was also increased (P < 0.01). However, millimeter-wave treatment reversed it. The most noteworthy result was that NF-κB expression was not significantly different in all groups. CONCLUSION Millimeter-wave treatment reversed joint contracture and quadriceps atrophy caused by joint fixation, inhibited TGF-β1 and Collagen I protein expression of the joint capsule and reduced MuRF1 expression of the quadriceps muscle, thereby inhibiting the development of joint stiffness.
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Affiliation(s)
- Xiao-Ping Shui
- Department of Acupuncture and Massage, Sichuan College of Traditional Chinese Medicine, Mian-yang 621000, Sichuan, China; Department of Rehabilitation, Mian-yang Orthopedic Hospital, Mian-yang 621000, Sichuan, China.
| | - Feng Ye
- Department of Acupuncture and Massage, Sichuan College of Traditional Chinese Medicine, Mian-yang 621000, Sichuan, China
| | - Chun-Ying Li
- Department of Geriatric Medicine, Mian-yang Hospital of Traditional Chinese Medicine, Mian-yang 621000, Sichuan, China
| | - Xin Zhang
- Department of Rehabilitation Medicine, Sichuan Provincial Orthopedic Hospital, Chengdu 610000, Sichuan, China
| | - Min-Jia Wang
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610000, Sichuan, China
| | - Bin Li
- Department of Rehabilitation, Mian-yang Orthopedic Hospital, Mian-yang 621000, Sichuan, China
| | - Ke Chen
- Department of Rehabilitation Medicine, Sichuan Provincial Orthopedic Hospital, Chengdu 610000, Sichuan, China
| | - Ying-Ying Liao
- Department of Rehabilitation Medicine, Sichuan Provincial Orthopedic Hospital, Chengdu 610000, Sichuan, China
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Ghoseiri K, Zucker-Levin A. Long-term locked knee ankle foot orthosis use: A perspective overview of iatrogenic biomechanical and physiological perils. FRONTIERS IN REHABILITATION SCIENCES 2023; 4:1138792. [PMID: 37214128 PMCID: PMC10192684 DOI: 10.3389/fresc.2023.1138792] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/03/2023] [Indexed: 05/24/2023]
Abstract
A knee ankle foot orthosis (KAFO) may be prescribed to the person with severe neuromusculoskeletal impairment of the lower limb to promote walking stability. The locked knee ankle foot orthosis (L-KAFO) is among the KAFO's routinely prescribed; however, long-term use of the L-KAFO is associated with musculoskeletal (arthrogenic and myogenic) and integumentary changes, and gait asymmetry with increased energy expenditure. Consequently, the risk of developing low back pain, osteoarthritis of the lower limbs and spinal joints, skin dermatitis, and ulceration increases, all of which impact quality of life. This article synthesizes the iatrogenic biomechanical and physiological perils of long-term L-KAFO use. It promotes using recent advances in rehabilitation engineering to improve daily activities and independence for proper patient groups.
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Lechner R, Brugger H, Paal P, Hüfner K, Agazzi G, Butler F, Gordon L, Darocha T, Zafren K. Survival in a Collapsed Stable for 37 Days After Avalanche Burial in 1755. Wilderness Environ Med 2023; 34:113-119. [PMID: 36526516 DOI: 10.1016/j.wem.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/20/2022] [Accepted: 10/26/2022] [Indexed: 12/15/2022]
Abstract
In 1755 in Bergemoletto, Italy, an avalanche buried 4 people (2 women, a girl, and a boy) and several animals in a stable. After 37 d in a pitch-dark confined space, 3 of the 4 people were rescued alive. The 3 survivors had only goat milk, a few chestnuts, a few kg of raw kid meat, and meltwater for nutrition. We describe the longest-known survival in an avalanche burial and discuss the medical and psychological problems of the survivors. The boy died. When they were extricated, all 3 survivors were exhausted, cachectic, and unable to stand or walk. They were severely malnourished and were experiencing tingling, tremors, and weakness in the legs; constipation; changes in taste; and amenorrhea. One of the women had persistent eye problems and developed symptoms consistent with post-traumatic stress disorder. The survivors were given slow refeeding. It took from 1 to 6 wk before they could walk. We compare this case to other long-duration burials, especially mining accidents, and describe the rescue and patient care after long-duration burials. This case demonstrates that people can overcome extremely adverse conditions and survive.
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Affiliation(s)
- Raimund Lechner
- Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine, and Pain Therapy, Military Hospital, Ulm, Germany.
| | - Hermann Brugger
- Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy; Department of Anesthesiology and Intensive Care Medicine, the Medical University of Innsbruck, Innsbruck, Austria; International Commission for Mountain Emergency Medicine (ICAR MedCom), Zürich, Switzerland
| | - Peter Paal
- Department of Anaesthesiology and Intensive Care Medicine, St. John of God Hospital, Paracelsus Medical University, Salzburg, Austria
| | - Katharina Hüfner
- Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, University Clinic for Psychiatry II (Psychosomatic Medicine), Innsbruck Medical University, Innsbruck, Austria
| | - Giancelso Agazzi
- International Commission for Mountain Emergency Medicine (ICAR MedCom), Zürich, Switzerland; Italian Society of Mountain Medicine, Padua, Italy; Italian Alpine Club Medical Commission, Milan, Italy
| | - Frank Butler
- US Department of Defense Joint Trauma System, San Antonio, TX; Departments of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD
| | - Les Gordon
- Department of Anaesthesia, University Hospitals of Morecambe Bay Trust, Lancaster, United Kingdom
| | - Tomasz Darocha
- Department of Anesthesiology and Intensive Care, Medical University of Silesia, Katowice, Poland
| | - Ken Zafren
- International Commission for Mountain Emergency Medicine (ICAR MedCom), Zürich, Switzerland; Department of Emergency Medicine, Alaska Native Medical Center, Anchorage, AK; Department of Emergency Medicine, Stanford University Medical Center, Stanford, CA
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Frudinger A, Gauruder-Burmester A, Graf W, Lehmann JP, Gunnarsson U, Mihov M, Ihnát P, Kosorok P, Orhalmi J, Slauf P, Emmanuel A, Hristov V, Jungwirthova A, Lehur PA, Müller A, Amort M, Marksteiner R, Thurner M. Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study. Clin Gastroenterol Hepatol 2023; 21:476-486.e8. [PMID: 35961517 DOI: 10.1016/j.cgh.2022.07.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/08/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Fecal incontinence (FI) improvement following injection of autologous skeletal muscle-derived cells has been previously suggested. This study aimed to test the efficacy and safety of said cells through a multicenter, placebo-controlled study, to determine an appropriate cell dose, and to delineate the target patient population that can most benefit from cell therapy. METHODS Patients experiencing FI for at least 6 months were randomized to receive a cell-free medium or low or high dose of cells. All patients received pelvic floor electrical stimulation before and after treatment. Incontinence episode frequency (IEF), FI quality of life, FI burden assessed on a visual analog scale, Wexner score, and parameters reflecting anorectal physiological function were all assessed for up to 12 months. RESULTS Cell therapy improved IEF, FI quality of life, and FI burden, reaching a preset level of statistical significance in IEF change compared with the control treatment. Post hoc exploratory analyses indicated that patients with limited FI duration and high IEF at baseline are most responsive to cells. Effects prevailed or increased in the high cell count group from 6 to 12 months but plateaued or diminished in the low cell count and control groups. Most physiological parameters remained unaltered. No unexpected adverse events were observed. CONCLUSIONS Injection of a high dose of autologous skeletal muscle-derived cells followed by electrical stimulation significantly improved FI, particularly in patients with limited FI duration and high IEF at baseline, and could become a valuable tool for treatment of FI, subject to confirmatory phase 3 trial(s). (ClinicalTrialRegister.eu; EudraCT Number: 2010-021463-32).
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Affiliation(s)
- Andrea Frudinger
- Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria.
| | | | - Wilhelm Graf
- Department of Surgery, Akademiska Sjukhuset, Uppsala, Sweden
| | | | - Ulf Gunnarsson
- Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden
| | - Minko Mihov
- Medical Center Unimed EOOD, Sevlievo, Bulgaria
| | - Peter Ihnát
- Department of Surgical Studies, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Pavle Kosorok
- Department of Proctology, Iatros Medical Centre, Ljubljana, Slovenia
| | - Julius Orhalmi
- Department of Surgery, University Hospital Hradec Kralove, Faculty of Medicine in Hradec Kralove, Charles University, Prague, Czech Republic
| | - Petr Slauf
- Surgical Clinic 1, Faculty of Medicine, University Hospital Bulovka, Charles University, Prague, Czech Republic
| | - Anton Emmanuel
- Gastrointestinal Physiology Unit, University College Hospital, London, United Kingdom
| | | | - Anna Jungwirthova
- Department of Gastroenterology, St. Anna Clinic, Prague, Czech Republic
| | - Paul-Antoine Lehur
- Clinique de Chirurgie Digestive et Endocrinienne, Institut des Maladies de l'Appareil Digestif, University Hospital of Nantes, Nantes, France
| | - Andreas Müller
- GastroZentrum Hirslanden, Klinik Hirslanden, Zürich, Switzerland
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20
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Wang F, Zhou CX, Zheng Z, Li DJ, Li W, Zhou Y. Metformin reduces myogenic contracture and myofibrosis induced by rat knee joint immobilization via AMPK-mediated inhibition of TGF-β1/Smad signaling pathway. Connect Tissue Res 2023; 64:26-39. [PMID: 35723580 DOI: 10.1080/03008207.2022.2088365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-β) 1/Smad signaling pathway. MATERIALS AND METHODS An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-β1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-β1/Smad signaling pathway. RESULTS We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-β1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-β1 and TGF-β1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-β1/Smad signaling pathway by metformin. CONCLUSION Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-β1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.
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Affiliation(s)
- Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China.,Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Chen Xu Zhou
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Zhi Zheng
- Department of Ultrasound Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Du Juan Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Wen Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
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21
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Suwankanit K, Shimizu M. Rat Model of Quadriceps Contracture by Joint Immobilization. BIOLOGY 2022; 11:biology11121781. [PMID: 36552289 PMCID: PMC9775761 DOI: 10.3390/biology11121781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022]
Abstract
Muscle contracture is an abnormal pathologic process resulting in fibrosis and muscle atrophy, which can lead to limitation of joint motion. To establish a diagnostic method to detect muscle contracture and a method to control its progression, we investigated an appropriate method to create an animal model of quadriceps contracture using rats. Eighteen Wistar rats were divided into three groups, and bilateral hindlimbs were immobilized with either a cast (Group I), a Velcro hook-and-loop fastener (Group V), or steel wire (Group S) with the knee and ankle joints in extension position for two weeks. Five rats in a control group (Group C) were not immobilized. After two weeks, the progression of quadriceps contracture was assessed by measuring the range of joint motion and pathohistological changes. Muscle atrophy and fibrosis were observed in all immobilization groups. The knee joint range of motion, quadriceps muscle weight, and muscle fiber size decreased only in Group S compared to the other immobilization groups. Stress on rats due to immobilization was less in Group S. These results indicate that Group S is the superior quadriceps contracture model. This model aids research investigating diagnostic and therapeutic methods for muscle contracture in humans and animals.
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Affiliation(s)
- Kanokwan Suwankanit
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-0054, Japan
- Department of Clinical Sciences and Public Health, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand
| | - Miki Shimizu
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Tokyo 183-0054, Japan
- Correspondence: ; Tel.: +81-42-367-5605
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22
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Martinez-Lozano E, Beeram I, Yeritsyan D, Grinstaff MW, Snyder BD, Nazarian A, Rodriguez EK. Management of arthrofibrosis in neuromuscular disorders: a review. BMC Musculoskelet Disord 2022; 23:725. [PMID: 35906570 PMCID: PMC9336011 DOI: 10.1186/s12891-022-05677-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 07/20/2022] [Indexed: 11/20/2022] Open
Abstract
Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.
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Affiliation(s)
- Edith Martinez-Lozano
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA
| | - Indeevar Beeram
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA
| | - Diana Yeritsyan
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA
| | - Mark W Grinstaff
- Departments of Biomedical Engineering, Chemistry, and Medicine, Boston University, 330 Brookline Avenue, Stoneman 10, Boston, MA, 02215, USA
| | - Brian D Snyder
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.,Department of Orthopaedic Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02215, USA
| | - Ara Nazarian
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.,Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, 0025, Armenia
| | - Edward K Rodriguez
- Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.
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23
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Wang F, Li W, Zhou Y, Huang PP, Zhang QB. Radial extracorporeal shock wave reduces myogenic contracture and muscle atrophy via inhibiting NF-κB/HIF-1α signaling pathway in rabbit. Connect Tissue Res 2022; 63:298-307. [PMID: 34014138 DOI: 10.1080/03008207.2021.1920934] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE We investigate the underlying biological effects and mechanisms of rESWT on myogenic contracture and muscle atrophy in a rabbit model of extending knee joint contracture. MATERIALS AND METHODS In group control, the knee joint was not fixed. In group I-4w, the knee joint was only fixed for 4 weeks. In groups SR-1 w, SR-2 w, and SR-4 w, the knee joint was fixed for 4 weeks before the rabbits underwent 1, 2, and 4 weeks of self-recovery, respectively. In groups rESWT-1 w, rESWT 2 w, and rESWT-4 w, the knee joint was fixed for 4 weeks before the rabbits underwent 1, 2, and 4 weeks of rESWT, respectively. The myogenic contracture was measured, the cross-sectional area and key protein levels for NF-κB/HIF-1α signaling pathway and myogenic regulatory factors were evaluated. RESULTS During the recovery period, biological findings showed that the levels of myogenic contracture and muscle atrophy were milder in group rESWT by compared with group SR after 2 weeks. Molecular biological analysis showed that MyoD protein levels in the group rESWT was significantly higher than those in the group SR, and importantly, phospho-NF-κB p65 and HIF-1α protein levels in the group rESWT were significantly lower than those in the group SR at the same time point. CONCLUSIONS This is the first study demonstrated that rESWT has the potential to reduce myogenic contracture and muscle atrophy after long-term immobilization in animal model. It is a possible mechanism that changing the low oxygen environment in skeletal muscle through rESWT may inhibit activation of NF-κB/HIF-1α signaling pathway.
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Affiliation(s)
- Feng Wang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Wen Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Peng Peng Huang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Quan Bing Zhang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
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24
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Stępień A, Sobińska M, Rekowski W, Krawczyk MJ. Pandemic decrease of in-person physiotherapy as a factor in parent perceived decline in function in children with neuromuscular disorders. J Pediatr Rehabil Med 2022; 15:677-689. [PMID: 36530101 DOI: 10.3233/prm-210002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Restrictions related to the COVID-19 pandemic can negatively affect patients who require physiotherapy. This study aimed to analyze the consequences of limited physiotherapy on the functional state of children with neuromuscular diseases (NMD). In addition, the caregivers' well-being and caregiver opinions on physiotherapy were analyzed. METHODS A questionnaire was shared with parents of children with NMD immediately after the COVID-19 lockdown. The survey included questions regarding the physical and mental condition of children and parents before the pandemic and during lockdown as well as their views on physiotherapy and telephysiotherapy. Statistical analysis was performed using the Wilcoxon Matched-Pairs Signed Ranks test, Spearman's Rank Correlation test, McNemar test, and Chi-square test. RESULTS Parents of 235 children participated in the study. Results indicated that children devoted more time to physiotherapy before the pandemic than during the lockdown period, which was true for those living in cities and the countryside. The functional state of 50.2% of the children deteriorated during the lockdown, in the opinion of their parents. Significant correlations were found between limited physiotherapy time and the deterioration of children's functional condition, ability to maintain a standing position, and increased anxiety. The majority of parents reported increased levels of fear and anxiety (72.8%), fatigue (67.7%), and pain (53.2%). In-person physiotherapy was rated significantly higher than telephysiotherapy by parents. CONCLUSIONS Limited access to physiotherapy and shorter therapy times may lead to functional deterioration in children with NMD, but this assumption needs to be objectively confirmed. According to the parents' opinions, telephysiotherapy is less beneficial than direct physiotherapy but may support therapy conducted directly by a physiotherapist. Results based on subjective parental opinions may be helpful in planning future projects.
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Affiliation(s)
- Agnieszka Stępień
- Józef Piłsudski University of Physical Education in Warsaw, Warsaw, Poland
| | | | - Witold Rekowski
- Józef Piłsudski University of Physical Education in Warsaw, Warsaw, Poland
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25
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Xu QY, Zhang QB, Zhou Y, Liu AY, Wang F. Preventive effect and possible mechanisms of ultrashort wave diathermy on myogenic contracture in a rabbit model. Sci Prog 2021; 104:368504211054992. [PMID: 34825614 PMCID: PMC10450593 DOI: 10.1177/00368504211054992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The purpose of this study was to determine the preventive effect of ultrashort wave diathermy on immobilization-induced myogenic contracture and to explore its underlying mechanisms. Forty-two rabbits were randomly assigned into control (Group C), immobilization (Group I, which was further divided into one week, Group I-1; two weeks, Group I-2; and four weeks, Group I-4, subgroups by the length of immobilization) and ultrashort wave prevention (Group U, which was further divided into one week, Group U-1; two weeks, Group U-2; and four weeks, Group U-4, by time of treatment) groups. Intervention effects were assessed by evaluating rectus femoris cross-sectional area (CSA), knee range of motion, and the protein levels for myogenic differentiation (MyoD) and muscle atrophy F-box (MAFbx-1) in the rectus femoris. Compared with those of Group C, in Groups I and U, total contracture, myogenic contracture, MyoD and MAFbx-1 levels were significantly elevated, and CSA was significantly smaller (p < 0.05). Compared with those of Group I at each time point, MyoD levels were significantly elevated, MAFbx-1 levels were significantly lower, CSA was significantly larger, and myogenic contracture was significantly alleviated in Group U (p < 0.05). In the early stages of contracture, ultrashort wave diathermy reduces muscle atrophy and delays the process of myogenic contracture during joint immobilization; the mechanism of this may be explained as increased expression of MyoD triggered by suppression of the MAFbx-1-mediated ubiquitin-proteasome pathway.
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Affiliation(s)
- Qi-Yu Xu
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
- Department of Rehabilitation Medicine, Anhui No.2 Provincial People’s Hospital, Hefei, Anhui, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - A-Ying Liu
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
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26
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Rebolledo DL, Lipson KE, Brandan E. Driving fibrosis in neuromuscular diseases: Role and regulation of Connective tissue growth factor (CCN2/CTGF). Matrix Biol Plus 2021; 11:100059. [PMID: 34435178 PMCID: PMC8377001 DOI: 10.1016/j.mbplus.2021.100059] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 02/07/2023] Open
Abstract
Connective tissue growth factor or cellular communication network 2 (CCN2/CTGF) is a matricellular protein member of the CCN family involved in several crucial biological processes. In skeletal muscle, CCN2/CTGF abundance is elevated in human muscle biopsies and/or animal models for diverse neuromuscular pathologies, including muscular dystrophies, neurodegenerative disorders, muscle denervation, and muscle overuse. In this context, CCN2/CTGF is deeply involved in extracellular matrix (ECM) modulation, acting as a strong pro-fibrotic factor that promotes excessive ECM accumulation. Reducing CCN2/CTGF levels or biological activity in pathological conditions can decrease fibrosis, improve muscle architecture and function. In this work, we summarize information about the role of CCN2/CTGF in fibrosis associated with neuromuscular pathologies and the mechanisms and signaling pathways that regulate their expression in skeletal muscle.
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Affiliation(s)
- Daniela L Rebolledo
- Centro de Envejecimiento y Regeneración, CARE Chile UC, Chile.,Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Punta Arenas, Chile
| | | | - Enrique Brandan
- Centro de Envejecimiento y Regeneración, CARE Chile UC, Chile.,Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.,Fundación Ciencia y Vida, Santiago, Chile
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27
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Cruz-Montecinos C, Pérez-Alenda S, Cerda M, Maas H. Modular reorganization of gait in chronic but not in artificial knee joint constraint. J Neurophysiol 2021; 126:516-531. [PMID: 34133242 DOI: 10.1152/jn.00418.2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
It is currently unknown if modular reorganization does occur if not the central nervous system, but the musculoskeletal system is affected. The aims of this study were to investigate 1) the effects of an artificial knee joint constraint on the modular organization of gait in healthy subjects; and 2) the differences in modular organization between healthy subjects with an artificial knee joint constraint and people with a similar but chronic knee joint constraint. Eleven healthy subjects and eight people with a chronic knee joint constraint walked overground at 1 m/s. The healthy subjects also walked with a constraint limiting knee joint movement to 20°. The total variance accounted (tVAF) for one to four synergies and modular organization were assessed using surface electromyography from 11 leg muscles. The distribution of number of synergies were not significantly different between groups. The tVAF and the motor modules were not significantly affected by the artificial knee constraint. A higher tVAF for one and two synergies, as well as merging of motor modules were observed in the chronic knee constraint group. We conclude that in the short-term a knee constraint does not affect the modular organization of gait, but in the long-term a knee constraint results in modular reorganization. These results indicate that merging of motor modules may also occur when changes in the mechanics of the musculoskeletal system is the primary cause of the motor impairment.NEW & NOTEWORTHY It is currently unknown if modular reorganization does occur if not the central nervous system, but the musculoskeletal system is affected. This study showed that in the short-term a knee constraint does not affect the modular organization of gait, but in the long-term a knee constraint results in modular reorganization. These results indicate that modular reorganization may also occur when changes in the mechanics of the musculoskeletal system is the primary cause of the motor impairment.
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Affiliation(s)
- Carlos Cruz-Montecinos
- Physiotherapy in Motion Multispeciality Research Group (PTinMOTION), Department of Physiotherapy, University of Valencia, Valencia, Spain.,Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands.,Laboratory of Clinical Biomechanics, Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Sofía Pérez-Alenda
- Physiotherapy in Motion Multispeciality Research Group (PTinMOTION), Department of Physiotherapy, University of Valencia, Valencia, Spain
| | - Mauricio Cerda
- Integrative Biology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.,Center for Medical Informatics and Telemedicine, Faculty of Medicine, Universidad de Chile, Santiago, Chile.,Biomedical Neuroscience Institute, Santiago, Chile
| | - Huub Maas
- Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, The Netherlands
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28
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Cheng YY, Chen CM, Huang WC, Chiang SL, Hsieh PC, Lin KL, Chen YJ, Fu TC, Huang SC, Chen SY, Chen CH, Chen SM, Chen HS, Chou LW, Chou CL, Li MH, Tsai SW, Wang LY, Wang YL, Chou W. Rehabilitation programs for patients with COronaVIrus Disease 2019: consensus statements of Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation. J Formos Med Assoc 2021; 120:83-92. [PMID: 32863084 PMCID: PMC7430281 DOI: 10.1016/j.jfma.2020.08.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 08/09/2020] [Accepted: 08/10/2020] [Indexed: 01/08/2023] Open
Abstract
The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.
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Affiliation(s)
- Yuan-Yang Cheng
- Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, No.1650 Taiwan Boulevard Sect. 4, Taichung, Taiwan,School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan
| | - Chin-Ming Chen
- Department of Intensive Care Medicine, Chi-Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, Taiwan,Center for Quality Management, Chi-Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, Taiwan,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Wei-Chun Huang
- School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan,Department of Critical Care Medicine and Cardiology Center, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan,Department of Physical Therapy, Fooyin University, No. 151 Jinxue Rd., Daliao Dist., Kaohsiung, Taiwan,Graduate Institute of Clinical Medicine, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Rd., Sanmin Dist., Kaohsiung, Taiwan
| | - Shang-Lin Chiang
- Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, No.325, Sec.2, Chenggong Rd., Neihu District, Taipei, Taiwan,School of Medicine, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, Taiwan
| | - Pei-Chun Hsieh
- Department of Physical Medicine and Rehabilitation, National Cheng Kung University Hospital, No. 138, Sheng Li Rd., Tainan, Taiwan,Institute of Clinical Medicine, National Cheng Kung University, No. 1, University Rd., Tainan, Taiwan
| | - Ko-Long Lin
- Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan
| | - Yi-Jen Chen
- Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, School of Medicine, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Rd., Sanmin Dist., Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, Kaohsiung Municipal Siaogang Hospital, No. 482, Shanming Rd, Siaogang Dist., Kaohsiung, Taiwan,Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, No. 100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, Taiwan
| | - Tieh-Cheng Fu
- Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, No. 222, Maijin Rd., Anle Dist., Keelung, Taiwan,Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, No. 222, Maijin Rd., Anle Dist., Keelung, Taiwan,School of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, Taiwan
| | - Shu-Chun Huang
- School of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, Taiwan,Department of Physical Medicine and Rehabilitation, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital, No. 6, Sec. 2, Jincheng Rd., Tucheng Dist., New Taipei City, 236, Taiwan,Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, No. 5, Fuxing St., Guishan Dist., Taoyuan, Taiwan,Healthy Aging Research Center, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, Taiwan
| | - Ssu-Yuan Chen
- Division of Physical Medicine and Rehabilitation, Fu Jen Catholic University Hospital, School of Medicine, College of Medicine, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan District, New Taipei City, Taiwan,Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 1, Changde St., Zhongzheng Dist., Taipei, Taiwan
| | - Chia-Hsin Chen
- Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, Taiwan,Department of Physical Medicine and Rehabilitation, School of Medicine, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Rd., Sanmin Dist., Kaohsiung, Taiwan,Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, No. 100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, Taiwan
| | - Shyh-Ming Chen
- School of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, Taiwan,Section of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan
| | - Hsin-Shui Chen
- Department of Physical Medicine & Rehabilitation, National Taiwan University Hospital, Yunlin Branch, No.579, Sec. 2, Yunlin Rd., Douliu City, Yunlin, Taiwan,PHD Program of College of Medicine, China Medical University, No. 2, Yuh-Der Rd., Taichung, Taiwan
| | - Li-Wei Chou
- Department of Physical Medicine and Rehabilitation, China Medical University Hospital, No. 91, Hsueh-Shih Rd., Taichung, Taiwan,Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, No. 91, Hsueh-Shih Rd., Taichung, Taiwan,Department of Rehabilitation, Asia University Hospital, No. 500, Lioufeng Rd., Wufeng, Taichung, Taiwan
| | - Chen-Liang Chou
- School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan,Department of Physical Medicine & Rehabilitation, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, Taiwan
| | - Min-Hui Li
- Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung, Taiwan
| | - Sen-Wei Tsai
- Department of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 88, Sec. 1, Fengxing Rd., Tanzi Dist., Taichung, Taiwan,School of Medicine, Tzu Chi University, No. 701, Zhongyang Rd., Sec. 3, Hualien, Taiwan
| | - Lin-Yi Wang
- School of Medicine, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan, Taiwan,Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan
| | - Yu-Lin Wang
- Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, Taiwan,Center of General Education, Southern Taiwan University of Science and Technology, No. 1, Nan-Tai Street, Yongkang Dist., Tainan, Taiwan
| | - Willy Chou
- Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan, Taiwan; Center of General Education, Southern Taiwan University of Science and Technology, No. 1, Nan-Tai Street, Yongkang Dist., Tainan, Taiwan.
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Wong SK, Ima-Nirwana S, Chin KY. Effects of astaxanthin on the protection of muscle health (Review). Exp Ther Med 2020; 20:2941-2952. [PMID: 32855659 PMCID: PMC7444411 DOI: 10.3892/etm.2020.9075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 06/17/2020] [Indexed: 02/07/2023] Open
Abstract
Sarcopenia refers to the involuntary and generalized deterioration of skeletal muscle mass and strength, which may lead to falls, frailty, physical disability, loss of independence, morbidity and mortality. The majority of molecular and cellular changes involved in the degeneration of muscle tissues are mediated by oxidative stress. Therefore, astaxanthin may act as a potential adjunct therapy for sarcopenia owing to its antioxidant activity. The present review examines the effects of astaxanthin on the promotion of skeletal muscle performance and prevention of muscle atrophy and the potential mechanisms underlying these effects. The available evidence till date was retrieved from PubMed and Medline electronic databases. The present review reported the beneficial effects of astaxanthin in preventing muscle degeneration in various animal models of sarcopenia. In humans, the effects of astaxanthin in combination with other antioxidants on muscle health are mixed, wherein positive and negligible effects were reported. Mechanistic studies revealed that astaxanthin promotes muscle health by reducing oxidative stress, myoblast apoptosis and proteolytic pathways while promoting mitochondria regeneration and formation of blood vessels. Thus, astaxanthin is a potential therapeutic agent for sarcopenia but its effects in humans require further validation.
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Affiliation(s)
- Sok Kuan Wong
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Soelaiman Ima-Nirwana
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Ya'acob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
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Wang F, Zhang QB, Zhou Y, Liu AY, Huang PP, Liu Y. Effect of ultrashort wave treatment on joint dysfunction and muscle atrophy in a rabbit model of extending knee joint contracture: Enhanced expression of myogenic differentiation. Knee 2020; 27:795-802. [PMID: 32201041 DOI: 10.1016/j.knee.2020.02.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 12/01/2019] [Accepted: 02/05/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To investigate the effects of ultrashort wave treatment on joint dysfunction and muscle atrophy in a rabbit model of extending knee joint contracture. METHODS Forty rabbits were randomly divided into eight groups. In group C, the left knee joint was not fixed. In group I-8, the left knee joint was only fixed for eight weeks. In groups R-1, R-2, and R-4, the left knee joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of self-recovery, respectively. In groups T-1, T-2, and T-4, the left knee joint was fixed for eight weeks before the rabbits underwent one, two, and four weeks of ultrashort wave treatment, respectively. The degree of total contracture and myogenic contracture were measured, the cross-sectional area (CSA) and protein levels for myogenic differentiation (MyoD) of the rectus femoris were evaluated. RESULTS There was a tendency toward a reduced degree of total and myogenic contracture, and also a tendency toward an increased CSA of the rectus femoris and increased protein levels for MyoD after both self-recovery and ultrashort wave treatment. The ultrashort wave was more effective than self-recovery in reducing the total and myogenic contracture, and increasing the CSA and MyoD protein levels of the rectus femoris. CONCLUSIONS Ultrashort wave treatment may ameliorate joint dysfunction and muscle atrophy by upregulating the expression of MyoD protein in a rabbit model of extending knee joint contracture.
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Affiliation(s)
- Feng Wang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Quan Bing Zhang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China.
| | - A Ying Liu
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Peng Peng Huang
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
| | - Yi Liu
- Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China
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31
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Li X, Leng Y, Li X, Wang Y, Luo P, Zhang C, Wang Z, Yue X, Shen C, Chen L, Liu Z, Shi C, Xie L. The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery. Aging (Albany NY) 2020; 12:8837-8857. [PMID: 32452828 PMCID: PMC7288943 DOI: 10.18632/aging.102997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 02/04/2020] [Indexed: 12/18/2022]
Abstract
Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.
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Affiliation(s)
- Xueru Li
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
| | - Yu Leng
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
| | - Xiangji Li
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
| | - Yawei Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Peng Luo
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Chi Zhang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Ziwen Wang
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Xiaofeng Yue
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
| | - Chongxing Shen
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
| | - Long Chen
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Zujuan Liu
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Chunmeng Shi
- Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
| | - Lin Xie
- Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
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Preventive Effects of Schisandrin A, A Bioactive Component of Schisandra chinensis, on Dexamethasone-Induced Muscle Atrophy. Nutrients 2020; 12:nu12051255. [PMID: 32354126 PMCID: PMC7282012 DOI: 10.3390/nu12051255] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/24/2020] [Accepted: 04/25/2020] [Indexed: 12/11/2022] Open
Abstract
Muscle wasting is caused by various factors, such as aging, cancer, diabetes, and chronic kidney disease, and significantly decreases the quality of life. However, therapeutic interventions for muscle atrophy have not yet been well-developed. In this study, we investigated the effects of schisandrin A (SNA), a component extracted from the fruits of Schisandra chinensis, on dexamethasone (DEX)-induced muscle atrophy in mice and studied the underlying mechanisms. DEX+SNA-treated mice had significantly increased grip strength, muscle weight, and muscle fiber size compared with DEX+vehicle-treated mice. In addition, SNA treatment significantly reduced the expression of muscle degradation factors such as myostatin, MAFbx (atrogin1), and muscle RING-finger protein-1 (MuRF1) and enhanced the expression of myosin heavy chain (MyHC) compared to the vehicle. In vitro studies using differentiated C2C12 myotubes also showed that SNA treatment decreased the expression of muscle degradation factors induced by dexamethasone and increased protein synthesis and expression of MyHCs by regulation of Akt/FoxO and Akt/70S6K pathways, respectively. These results suggest that SNA reduces protein degradation and increases protein synthesis in the muscle, contributing to the amelioration of dexamethasone-induced muscle atrophy and may be a potential candidate for the prevention and treatment of muscle atrophy.
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Nguyen TTN, Choi H, Jun HS. Preventive Effects of Dulaglutide on Disuse Muscle Atrophy Through Inhibition of Inflammation and Apoptosis by Induction of Hsp72 Expression. Front Pharmacol 2020; 11:90. [PMID: 32153405 PMCID: PMC7046759 DOI: 10.3389/fphar.2020.00090] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 01/27/2020] [Indexed: 12/23/2022] Open
Abstract
Pathological conditions such as joint immobilization, long-time bed rest, or inactivity may result in disuse-induced muscle wasting and dysfunction. To investigate the effect of dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist, on disuse muscle atrophy, disuse condition was induced by spiral wire immobilization in C57BL/6 mice and the mice were treated with dulaglutide. Dulaglutide treatment effectively improved muscle function and increased muscle mass compared with vehicle treatment. Dulaglutide inhibited the decrease of muscle fiber size and the expression of atrophic factors such as myostatin, atrogin-1/MAFbx, and muscle RING-finger protein-1 in immobilized mice. In addition, dulaglutide inhibited nuclear factor kappa B activation, leading to a decrease in the mRNA levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in muscle of immobilized mice. Dulaglutide suppressed the expression of apoptotic markers such as caspase-3, cleaved poly-ADP ribose polymerase, and Bax under immobilization condition and increased the expression of heat shock protein 72 (Hsp72), which is related to the amelioration of inflammation and apoptosis during disuse time. Further study showed that dulaglutide could induce Hsp72 expression via the regulation of 5′-AMP-activated protein kinase signaling. Our data suggest that dulaglutide could exert beneficial effects against disuse-induced muscle atrophy.
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Affiliation(s)
- Tram Thi Ngoc Nguyen
- College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, South Korea
| | - Hojung Choi
- College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, South Korea.,Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea
| | - Hee-Sook Jun
- College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, South Korea.,Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea.,Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea
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