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1.
EFORT Open Rev ; 9(4): 297-308, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579787

RESUMO

Reverse total shoulder arthroplasty (rTSA) has been demonstrated to be an effective intervention for various shoulder disorders. The number of rTSA-related studies performed has increased annually over the past three decades. The Journal of Shoulder and Elbow Surgery had the highest number of publications and citations in the rTSA-related research domain and is therefore considered to be the most influential journal in this field. The USA published the most publications and established a high degree of cooperation with many countries worldwide. The University of Florida, the Hospital for Special Surgery, and Rush University, Mayo Clinic were representative and active institutions in this field. It is anticipated that advancements in prosthesis design, specifically with regards to lateralized design concepts, expanding indications for rTSA, a trend toward younger patient populations, and the management of postoperative complications will emerge as research hotspots in the following years. The most valuable publications, influential journals, major researchers, and leading countries were analyzed. The findings of our study will help researchers gain insights into current research hotspots and frontiers and shape their research focus in the field of rTSA.

2.
Int J Surg ; 110(4): 2389-2395, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38668665

RESUMO

BACKGROUND: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. RESULTS: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=-2.94, 95% CI: -5.52, -0.37, P=0.03, I²=60%], Visual Analog Scale (VAS) (MD=-2.0, 95% CI: -2.5, -1.5, P<0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P<0.00001, I²=0%), and Lequesne index (MD=-2.85, 95% CI: -3.64, -2.07, P<0.00001, I²=48%). CONCLUSION: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Medição da Dor , Resultado do Tratamento
3.
Orthop Surg ; 16(5): 1207-1214, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38488245

RESUMO

OBJECTIVE: Given the intricate challenges and potential complications associated with periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH). Our study aimed to compare the clinical and imaging benefits and drawbacks of two surgical approaches, the modified Stoppa combined iliac spine approach and the modified Smith-Peterson approach, for treating PAO and to provide guidance for selecting clinical approaches. METHODS: A retrospective analysis of 56 patients with 62 DDHs was conducted from June 2018 to January 2022. The experimental group underwent surgery via the modified Stoppa combined iliac spine approach, while the control group underwent surgery via the modified Smith-Peterson approach for periacetabular osteotomy and internal fixation. Basic statistical parameters, including age, sex, BMI, and preoperative imaging data, were analyzed. Differences in surgical time, intraoperative blood loss, and postoperative imaging data were compared, as were differences in preoperative and postoperative imaging data between the two groups. RESULTS: There were 28 hips in the experimental group and 34 in the control group. Moreover, there was no significant difference in the basic parameters between the experimental and control groups. Before and after the operation, for the LCE angle, ACE angle, and Tonnis angle, there was no significant difference in acetabular coverage (p > 0.05). However, there were significant differences between the two groups in terms of the above four indicators before and after the operation (p < 0.05). After the operation, the experimental group exhibited significant increases in both lateral and anterior acetabular coverage of the femoral head. However, the experimental group had longer operation times and greater bleeding volumes than did the control group. Despite this, the experimental group demonstrated significant advantages in protecting the lateral femoral cutaneous nerve compared to the control group. CONCLUSION: The modified Stoppa combined iliac spine approach can be considered a practical approach for PAO and is more suitable for patients with DDH who plan to be treated by one operation than the classic modified Smith-Peterson approach for PAO.


Assuntos
Acetábulo , Displasia do Desenvolvimento do Quadril , Osteotomia , Humanos , Estudos Retrospectivos , Feminino , Osteotomia/métodos , Masculino , Displasia do Desenvolvimento do Quadril/cirurgia , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Adulto , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto Jovem , Adolescente
4.
Mol Brain ; 17(1): 8, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350944

RESUMO

Inositol pyrophosphates are key signaling molecules that regulate diverse neurobiological processes. We previously reported that the inositol pyrophosphate 5-InsP7, generated by inositol hexakisphosphate kinase 1 (IP6K1), governs the degradation of Na+/K+-ATPase (NKA) via an autoinhibitory domain of PI3K p85α. NKA is required for maintaining electrochemical gradients for proper neuronal firing. Here we characterized the electrophysiology of IP6K1 knockout (KO) neurons to further expand upon the functions of IP6K1-regulated control of NKA stability. We found that IP6K1 KO neurons have a lower frequency of action potentials and a specific deepening of the afterhyperpolarization phase. Our results demonstrate that deleting IP6K1 suppresses neuronal excitability, which is consistent with hyperpolarization due to an enrichment of NKA. Given that impaired NKA function contributes to the pathophysiology of various neurological diseases, including hyperexcitability in epilepsy, our findings may have therapeutic implications.


Assuntos
Inositol , ATPase Trocadora de Sódio-Potássio , Transdução de Sinais , Transporte Proteico , Neurônios/fisiologia
5.
Clin Nucl Med ; 49(5): 468-469, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377388

RESUMO

ABSTRACT: 18 F-FDG PET/CT was performed in a 1-year-old girl who had a heterogeneous mass in the right abdominal cavity revealed by abdominal ultrasound. A heterogeneous mass with internal necrosis, cystic changes, and hemorrhage in the right kidney, accompanied by a slight increase of FDG uptake, was observed in FDG PET/CT. Malignant renal tumor was considered, and Wilms tumor was preferentially suspected. However, the mass was demonstrated as clear cell sarcoma of the kidney by histopathological examination.


Assuntos
Neoplasias Renais , Sarcoma de Células Claras , Feminino , Humanos , Lactente , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Sarcoma de Células Claras/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia
6.
J Cell Biochem ; 125(3): e30526, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38229533

RESUMO

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases with no effective cure. GGGGCC repeat expansion in C9orf72 is the most common genetic cause of both ALS and FTD. A key pathological feature of C9orf72 related ALS/FTD is the presence of abnormal dipeptide repeat proteins translated from GGGGCC repeat expansion, including poly Glycine-Arginine (GR). In this study, we observed that (GR)50 conferred significant mitochondria damage and cytotoxicity. Metformin, the most widely used clinical drug, successfully relieved (GR)50 induced mitochondrial damage and inhibited (GR)50 related cytotoxicity. Further research revealed metformin effectively restored mitochondrial function by upregulating AKT phosphorylation in (GR)50 expressed cells. Taken together, our results indicated restoring mitochondrial function with metformin may be a rational therapeutic strategy to reduce poly(GR) toxicity in C9orf72 ALS/FTD patients.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Humanos , Demência Frontotemporal/tratamento farmacológico , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Fosforilação , Dipeptídeos
7.
BMJ Open ; 13(12): e065254, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114287

RESUMO

INTRODUCTION: Anterior cruciate ligament (ACL) rupture is one of the most common knee injuries in sports, and the gold standard for treating ACL rupture is tendon graft reconstruction. Internal brace technology is being used nowadays for ligament repair; however, more relevant in vivo clinical evidence is required for using internal brace technology in ACL reconstruction (ACLR). We conducted a randomised controlled trial to investigate the clinical efficacy of internal brace technology in ACLR. METHODS AND ANALYSIS: This randomised, parallel-controlled trial included patients with ACL rupture who underwent inpatient surgery at the Department of Orthopaedics, Xiangya Hospital, Central South University. Random number table method was used to assign the participants to either the test or the control group. The test group underwent ACLR using the internal brace technique, whereas the control group underwent standard ACLR. Uniform postoperative rehabilitation protocol was used for both the groups. Patient-reported outcomes included preoperative baseline and postoperative recovery at 1, 3, 6, 12 and 24 months. The primary outcome was International Knee Documentation Committee function from baseline (ACL rupture) to 6 months postoperatively. Secondary outcomes included (1) other patient outcome reporting metrics, Lysholm knee score, Knee Injury and Osteoarthritis Outcome Score and Visual Analog Scale; (2) the use of Kneelax3 knee stabiliser to assess knee stability; (3) occurrence of adverse events, such as graft refraction or symptomatic instability, postoperative infection and contralateral injury and (4) magnetic resonance images at 12 and 24 months after ACLR. ETHICS AND DISSEMINATION: This trial was approved by the Medical Ethics Committee of the Xiangya Hospital of Central South University on 26 October 2021. Data will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200057526.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Traumatismos do Joelho , Humanos , Articulação do Joelho/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Resultado do Tratamento , Traumatismos do Joelho/cirurgia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Medicina (Kaunas) ; 59(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37763783

RESUMO

Background and Objectives: Patient-reported outcome measures (PROMs), also known as self-report measures, are critical tools for evaluating health outcomes by gathering information directly from patients without external interpretation. There has been a growing trend in the number of publications focusing on PROMs in orthopedic-related research. This study aims to identify the most valuable publications, influential journals, leading researchers, and core countries in this field using bibliometric analysis, providing researchers with an understanding of the current state and future trends of PROMs in orthopedic research. Materials and Methods: All PROMs in orthopedic-related publications from 1991 to 2022 were obtained from the WoSCC database. R software (version 4.2.2), VOSviewer (version 1.6.17), and Microsoft Excel (version 2303) were used for the bibliometric and visual analysis. Results: A total of 2273 publication records were found from 1991 to 2022. The results indicated that the United States (US) has made significant contributions to orthopedic-related PROMs. The majority of active research institutions are located in the US. J ORTHOP RES has published the most articles. J BONE JOINT SURG AM has the highest total citations. Conclusions: Our study provides a valuable reference for further exploration of the application of PROMs in orthopedics. PROMs have emerged as an increasingly popular area of research within the field of orthopedics, both in clinical practice and academic research. We conducted a bibliometric analysis in terms of journals, authors, countries, and institutions in this field. Additionally, we analyzed the potentialities and advantages of using PROMs in orthopedic research. There is an increasing trend towards using network-based or short message service (SMS)-based electronic patient-reported outcome measures (ePROMs) in orthopedic medical practices. It is anticipated that the role of PROMs in psychological and mental health research and telemedicine will continue to grow in importance.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Humanos , Bibliometria , Bases de Dados Factuais , Medidas de Resultados Relatados pelo Paciente
9.
Mol Cell Endocrinol ; 574: 111988, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37302518

RESUMO

Haematopoietically Expressed Homeobox (HHEX) gene is highly expressed in the thyroid gland and plays critical roles in the development and differentiation of the thyroid gland. While it has been indicated to be downregulated in thyroid cancer, its function and the underlying mechanism remain unclear. Herein, we observed low expression and aberrant cytoplasmic localization of HHEX in thyroid cancer cell lines. Knockdown of HHEX significantly enhanced cell proliferation, migration and invasion, while overexpression of HHEX showed the opposite effects in vitro and in vivo. These data provide evidence that HHEX is a tumor suppressor in thyroid cancer. Additionally, our results showed that HHEX overexpression upregulated the expression of sodium iodine symporter (NIS) mRNA and also enhanced NIS promoter activity, suggesting a favorable effect of HHEX in promoting thyroid cancer differentiation. Mechanistically, HHEX exerted a regulatory effect on the expression of transducin-like enhancer of split 3 (TLE3) protein, which inhibited the Wnt/ß-catenin signaling pathway. Nuclear localized HHEX bound to and upregulated TLE3 expression by preventing TLE3 protein from being distributed to the cytoplasm and being ubiquitinated. In conclusion, our study suggested that restoring HHEX expression has the potential to be a new strategy in the treatment of advanced thyroid cancer.


Assuntos
Genes Homeobox , Neoplasias da Glândula Tireoide , Humanos , Proteínas de Ligação a DNA/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Diferenciação Celular , Via de Sinalização Wnt , Linhagem Celular Tumoral , Proliferação de Células/genética , beta Catenina/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/genética , Proteínas Correpressoras/metabolismo
10.
Front Surg ; 10: 1003022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761023

RESUMO

Purpose: To determine the effect of local infiltration anesthesia (LIA) at the donor site combined with a femoral nerve block (FNB) on short-term postoperative pain, functional outcomes, and rehabilitation after arthroscopic hamstring tendon autograft anterior cruciate ligament reconstruction (ACLR). Methods: This study was a single center, randomized controlled trial. Seventy-three subjects with ACL rupture were enrolled. Participants were randomly allocated to two groups, 47 in the experimental group (Group A) and 26 in the control group (Group B). All operations were performed under FNB. In Group A, 10 ml of 1% ropivacaine was injected precisely at the hamstring donor site. Patients in Group B were treated with the same amount of saline. Preoperatively and postoperatively, pain scores based on the numerical rating scale (NRS) and consumption of opioids were recorded. In addition, knee functions were assessed by the International Knee Documentation Committee Subjective Knee Form (IKDC), the Lysholm score, and the Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively and postoperatively at 1 and 3 months. In addition, we applied the KNEELAX3 arthrometer to evaluate the stability of the knee preoperatively and postoperatively so that subjective and objective knee conditions were obtained to help us assess knee recovery in a comprehensive manner. Results: The hamstring donor-site block reduced pain within the first 12 postoperative hours. There were no significant differences between two groups in pain intensity preoperatively and equal to or greater than 24 hours postoperatively. Furthermore, there were no differences between the groups concerning knee functions preoperatively or in the short-term follow-up at 1 and 3 months. Conclusion: LIA at the donor site can effectively improve the early postoperative pain of patients after ACLR and reduce the use of opioids without affecting the functional outcomes of the surgery.

11.
Orthop Surg ; 15(2): 591-605, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36453119

RESUMO

OBJECTIVE: With the rising prevalence of chronic kidney disease (CKD) and the increasing demand for joint arthroplasty, the management of CKD patients in the perioperative period of joint arthroplasty has become an issue worthy of attention for orthopedic surgeons. This study aimed to explore comprehensive perioperative period management strategies for CKD patients. METHODS: From March 2017 to August 2022, 62 patients who underwent joint arthroplasty in our hospital were included in a retrospective study, including 31 CKD patients (mean age 69.8 ± 13.4 years old) and 31 non-CKD patients (mean age 69.4 ± 14.2 years old). The outcome indicators were analyzed, including serum urea, serum creatinine, blood uric acid, hematocrit, and hemoglobin. RESULTS: All patients included in the retrospective study had an average preoperative preparation time of 4.3 ± 2.6 days and an average hospitalization time of 11.0 ± 7.3 days. There were no significant differences in the changes in the serum urea values between the preoperative and postoperative measurements in the CKD patients or in the serum creatinine values and blood uric acid values (P > 0.05). The hemoglobin value in postoperative measurements was lower than in preoperative measurements in the CKD patients (P < 0.05). The hematocrit value in postoperative measurements was lower than in preoperative measurements in the CKD patients (P < 0.001). CONCLUSION: Patients with CKD have distinct characteristics compared to non-CKD patients, and they generally have a higher risk for postoperative complications and adverse events. Recognition of risk factors, suitable timing of surgery, the undertaking of protective strategies, and proper management of complications are vital for managing CKD patients in the perioperative period of joint arthroplasty.


Assuntos
Artroplastia de Quadril , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos , Creatinina , Ácido Úrico , Insuficiência Renal Crônica/complicações , Fatores de Risco , Hemoglobinas , Período Perioperatório , Ureia
12.
Front Surg ; 9: 927638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189396

RESUMO

Purpose: Rotator cuff diseases, as a common cause of shoulder pain and disability, have seriously affected the patients' daily life. Rotator cuff repair techniques have been a hot topic in the arthroscopic therapy field. Our study was to use bibliometrics analysis to clarify the current status and research trends in the field of arthroscopic therapy of rotator cuff diseases. Methods: The publications relating to arthroscopic therapy of rotator cuff diseases published from 2001 to 2021 were obtained from the Web of Science Core Collection (WoSCC) database. The R software and VOSviewer software were used for the cross-sectional bibliometric and scientometric analysis. Results: A total of 4,567 publications about arthroscopic therapy of rotator cuff diseases published between 2002 and 2021 retrieved from the WoSCC database were analyzed in our study. The results showed that the United States made the largest contribution to this field. The most relevant institutions were Seoul National University, Rush University, and Hospital for Special Surgery. Stephen S Burkhart was the most relevant researcher in this field with the largest number of publications, as well as the highest H-index and G-index. The journal ARTHROSCOPY contributed the largest number of publications in the past 2 decades. Considering the H-index and G-index, ARTHROSCOPY was also the journal with the largest impact in this field. Conclusions: Arthroscopic Therapy of Rotator Cuff Diseases Related research presented a rising trend in the past 2 decades. The United States can be regarded as the leader because of its huge contributions to this field. The journal ARTHROSCOPY published the largest number of publications in this field. It can be predicted that research about advanced arthroscopic techniques and postoperative pain management of patients with rotator cuff diseases will be the next research hotspots in the following years.

13.
Small ; 18(13): e2104112, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34816589

RESUMO

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.


Assuntos
Ativação de Macrófagos , NF-kappa B , Macrófagos , Poliésteres
14.
Front Cell Dev Biol ; 9: 735374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650980

RESUMO

Sarcopenia is an age-related disease in which muscle mass, strength and function may decline with age or can be secondary to cachexia or malnutrition and can lead to weakness, falls and even death. With the increase in life expectancy, sarcopenia has become a major threat to the health of the elderly. Currently, our understanding of bone-muscle interactions is not limited to their mechanical coupling. Bone and muscle have been identified as secretory endocrine organs, and their interaction may affect the function of each. Both muscle-derived factors and osteokines can play a role in regulating muscle and bone metabolism via autocrine, paracrine and endocrine mechanisms. Herein, we comprehensively summarize the latest research progress on the effects of the osteokines FGF-23, IGF-1, RANKL and osteocalcin on muscle to explore whether these cytokines can be utilized to treat and prevent sarcopenia.

15.
J Orthop Surg Res ; 16(1): 330, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020667

RESUMO

BACKGROUND: To investigate the effect of complete rupture of the posterior cruciate ligament (PCL) on the biomechanics and histology of the medial collateral ligament (MCL). MATERIALS AND METHODS: Seventy-two male rabbits were randomly divided into two groups: the ruptured group was treated with complete PCL amputation, while the intact group was only subjected to PCL exposure without amputation. Eighteen rabbits were randomly sacrificed at 8, 16, 24, and 40 weeks after the operation, and their specimens were processed for mechanical tensile testing, nano-indentation experiments, hematoxylin-eosin (HE) staining, and picrosirius-polarization staining. RESULTS: There was no significant difference in the length and maximum displacement of the MCL between the ruptured group and the intact group at each time point. The maximum load of the ruptured group was significantly smaller than that of the intact group at 40 W. The elastic modulus and micro-hardness of the ruptured group increased significantly at 24 W and decreased significantly at 40 W. At 16 W and 24 W after PCL rupture, the number of type I collagen fibers and type III collagen fibers in the MCL of the ruptured group was significantly increased compared with that of the intact group. While the type I collagen fibers of the ruptured group were significantly decreased compared with the intact group at 40 W, there was no significant difference in type III collagen fibers between the ruptured group and the intact group. CONCLUSION: PCL rupture has no significant effect on the mechanical and histological properties of MCL in a short period of time under physiological loading, but the histological and mechanical properties of MCL decrease with time.


Assuntos
Ligamento Colateral Médio do Joelho/patologia , Ligamento Colateral Médio do Joelho/fisiopatologia , Ligamento Cruzado Posterior/lesões , Ruptura/patologia , Animais , Fenômenos Biomecânicos , Colágeno/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Coelhos , Fatores de Tempo
16.
Front Cell Dev Biol ; 9: 793088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35083219

RESUMO

Aging promotes most degenerative pathologies in mammals, which are characterized by progressive decline of function at molecular, cellular, tissue, and organismal levels and account for a host of health care expenditures in both developing and developed nations. Sarcopenia is a prominent age-related disorder in musculoskeletal system. Defined as gradual and generalized chronic skeletal muscle disorder, sarcopenia involves accelerated loss of muscle mass, strength and function, which is associated with increased adverse functional outcomes and evolutionally refers to muscle wasting accompanied by other geriatric syndromes. More efforts have been made to clarify mechanisms underlying sarcopenia and new findings suggest that it may be feasible to delay age-related sarcopenia by modulating fundamental mechanisms such as cellular senescence. Cellular senescence refers to the essentially irreversible growth arrest mainly regulated by p53/p21CIP1 and p16INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP) while cellular senescence may have beneficial functions in counteracting cancer progression, tissue regeneration and wound healing. By now diverse studies in mice and humans have established that targeting cellular senescence is a powerful strategy to alleviating sarcopenia. However, the mechanisms through which senescent cells contribute to sarcopenia progression need to be further researched. We review the possible mechanisms involved in muscle stem cells (MuSCs) dysfunction and the SASP resulting from cellular senescence, their associations with sarcopenia, current emerging therapeutic opportunities based on targeting cellular senescence relevant to sarcopenia, and potential paths to developing clinical interventions genetically or pharmacologically.

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