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BACKGROUND: Different arthroscopic techniques exist for managing the extensor carpi radials brevis (ECRB) when treating refractory lateral epicondylitis. The purpose of this study is to compare the outcomes of a standard arthroscopic débridement with ECRB tendon release to an arthroscopic ECRB tenotomy distal to its insertion without débridement using a retrospective cohort study design. METHODS: This study included patients underwent arthroscopic treatment of lateral epicondylitis during 2 different time periods: 2016-2019 (débridement) and 2019-2021 (modified tenotomy without débridement). Patients were assessed preoperatively and at the last follow-up with Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH) score, Visual Analog Scale of pain. RESULTS: A total of 69 patients completed the follow-up (38 in the débridement group and 31 in the tenotomy group). Patients in both groups showed significant improvements were found in MEPS, DASH, and Visual Analog Scale after surgery. Patients in the tenotomy group had higher MEPSs and reported less pain with a minimum 2 year follow-up after surgery. DASH scores between groups were similar at all time periods. CONCLUSION: Arthroscopic modified tenotomy of the ECRB without débridement improves function and pain significantly for patients with refractory lateral epicondylitis, which is not inferior to arthroscopic débridement technique.
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Codo de Tenista , Tenotomía , Humanos , Tenotomía/métodos , Estudios de Cohortes , Codo de Tenista/cirugía , Codo , Estudios Retrospectivos , Artroscopía/métodos , DolorRESUMEN
Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD.
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Exosomas/metabolismo , Matriz Extracelular/efectos de los fármacos , Hidrogeles/farmacología , Degeneración del Disco Intervertebral/tratamiento farmacológico , Piroptosis , Animales , Humanos , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/cirugía , Masculino , Metaloproteinasa 13 de la Matriz/genética , Células Madre Mesenquimatosas , MicroARNs/metabolismo , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismo , Ratas , Ingeniería de TejidosRESUMEN
Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase-responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol-b-poly [2-(((4-acetyl-2-methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG-PAPO or PAPO) by activated microglia cells. A scar tissue-homing peptide (cysteine-alanine-glutamine-lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue-targeting ability. As a result, this CAQK-modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.
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Cicatriz , Micelas , Polímeros , Traumatismos de la Médula Espinal , Animales , Ratones , Microglía/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Polímeros/química , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment. It is shown that the MFG-E8-loaded copolymer system can decrease pro-inflammatory cytokine expression and neuron death. In a rat model of crush-caused SCI, the copolymer system shows significant therapeutic efficacy by ameliorating inflammation, decreasing fibrotic scar, promoting myelin regeneration and suppressing overall SCI severity.
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Antígenos de Superficie/administración & dosificación , Muerte Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Proteínas de la Leche/administración & dosificación , Vaina de Mielina/metabolismo , FN-kappa B/metabolismo , Polietilenglicoles/administración & dosificación , Poliglactina 910/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Hidrogeles/administración & dosificación , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inyecciones , Regeneración Nerviosa/efectos de los fármacos , Células PC12 , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Resultado del TratamientoRESUMEN
Objective: To assess the effectiveness of suture button fixation Latarjet procedure under total arthroscopy for anterior shoulder instability with severe bone defects. Methods: The clinical data of 15 patients with severe bone defects and anterior shoulder instability treated with suture button fixation Latarjet procedure under total arthroscopy between June 2020 and February 2023 was retrospectively analyzed, including 11 males and 4 females, with an average age of 31.1 years (range, 20-54 years). Three-dimensional CT showed that the average glenoid bone defect was 24.4% (range, 16.3%-35.2%). The average number of shoulder dislocation was 4.2 times (range, 3-8 times). The disease duration ranged from 6 to 21 months with an average of 10.6 months. The operation time and intraoperative blood loss were recorded. The pain relief was evaluated by visual analogue scale (VAS) score, and the functional recovery of shoulder joint was evaluated by Rowe score, Walch-Duplay score, and American Association for Shoulder and Elbow Surgery (ASES) score before and after operation. The range of motion (ROM) of the shoulder joint was assessed, including active flexion, lateral external rotation, abduction 90° external rotation, and internal rotation. Three-dimensional CT was performed at 6 months after operation and at last follow-up to observe the absorption of bone graft, the position of bone graft and glenoid, and the healing of bone graft. Results: The operation was successfully completed in all patients. The operation time was 85-195 minutes, with an average of 123.0 minutes. The intraoperative blood loss was 20-75 mL, with an average of 26.5 mL. All patients were followed up 13-32 months, with an average of 18.7 months. During the follow-up, there was no serious complication such as shoulder joint infection, joint stiffness, or vascular and nerve injury. One patient had partial absorption of the transplanted bone and bone nonunion at 3 months after operation, but the pain of the shoulder joint relieved at last follow-up, and no redislocation of the shoulder joint occurred; no obvious bone fracture or dislocation of the shoulder joint was found in the other patients. Bone union was achieved at 6 months during follow-up. At last follow-up, the VAS score, Rowe score, Walch-Duplay score, and ASES score significantly improved when compared with those before operation ( P<0.05), while the ROM of active flexion, lateral external rotation, abduction 90° external rotation, and internal rotation of the shoulder joint was not significantly different from those before operation ( P>0.05). Conclusion: Suture button fixation Latarjet procedure under total arthroscopy can improve shoulder joint function in patients with severe anterior shoulder instability caused by bone defects, and imaging also indicates satisfactory placement of transplanted bone blocks.
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Artroscopía , Inestabilidad de la Articulación , Articulación del Hombro , Humanos , Masculino , Femenino , Artroscopía/métodos , Adulto , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/etiología , Articulación del Hombro/cirugía , Adulto Joven , Persona de Mediana Edad , Rango del Movimiento Articular , Luxación del Hombro/cirugía , Resultado del Tratamiento , Tomografía Computarizada por Rayos XRESUMEN
The epidermal cysts are benign cysts most commonly found in the head, neck and trunk. An epidermal cyst of the knee is an unusual complication developed after total knee arthroplasty. Here, we present a case of an 83-year-old man with a palpable mass in the left knee located beneath the scar, 3 years after total knee arthroplasty. The patient underwent complete surgical excision of the mass. Histological analysis revealed an epidermoid cyst.
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Introduction: The study aimed to evaluate the efficacy of pronator quadratus (PQ) repair versus no repair following volar plate fixation of distal radius fractures. Methods: A comprehensive search was performed in PubMed, CNKI, EMBASE, Web of Science, Ovid, and Cochrane Library databases. All randomized controlled trials comparing PQ repair with no repair in distal radius fractures before January 2023 were included. Two investigators independently screened eligible articles, assessed the study quality, and extracted data from included studies. Continuous variables used standardized mean difference and 95% confidence interval as efficacy statistics. The meta-analysis was performed using the Revman 5.4 software. Results: A total of 430 patients in 7 RCT studies were included in this meta-analysis, of which 218 underwent PQ repair, while 212 patients underwent no repair. The results of the meta-analysis displayed statistically significant differences in grip strength (short-term), pronation angle (short-term), and pronation strength (short- and long-term) between the two groups. No significant difference in other outcomes was found between the two treatment arms. Discussion: The repair of PQ may further increase grip strength and pronation function in the short-term and enhance long-term pronator muscle strength compared to no repair. However, due to the small number of articles included in the study, the above conclusions need to be verified by a larger sample and multi-center clinical study.
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Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMsin vitroand NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCsin vitro. In addition, the results of MRI, x-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NPin vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animales , Conejos , Núcleo Pulposo/metabolismo , Ingeniería de Tejidos/métodos , Disco Intervertebral/metabolismo , Células Madre , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/metabolismoRESUMEN
BACKGROUND: Patellar dislocation is common in young people. Although isolated anatomic double-bundle reconstruction of the MPFL is a common and effective surgical treatment for patellofemoral instability, concerns about the risk of injury to the epiphysis remain. METHODS: A total of 21 children and adolescents (9 males, 12 females; mean age: 10.7 years; range: 8 to 13 years) with recurrent patella dislocation or symptomatic instability following a primary dislocation were enrolled in the study. In all patients, double-bundle medial patellofemoral ligament (MPFL) reconstruction and femoral sling procedure were performed under arthroscopy, using an anterior half peroneus longus tendon (AHPLT) autograft. Functional outcomes were evaluated preoperatively and during follow-ups based on Kujala and Lysholm scores. Radiological examinations including radiographs, 3D-CT, and MRI were performed pre- and post-operatively. RESULTS: Among two-year postoperative follow-up (range: 24-42 months) showed significant improvement in functional scores (p < 0.01). The Lysholm score increased from 68 (44.5) to 100 (0) and the Kujala score increased from 26 (34.5) to 100 (2) The patellar tilt angel improved significantly (p < 0.01) from 24.3° ± 10.4 preoperatively to 11.9° ± 7.0 postoperatively. MRIs performed 6- and 12-months post operation did not show any signs of dysfunction of the reconstructed MPFL or cartilage degeneration. STUDY DESIGN: Case Series; Level of evidence, 4. CONCLUSION: Arthroscopic reconstruction of the MPFL using the modified sling procedure is an effective procedure for the treatment of patellar instability in skeletally immature patients.
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Inestabilidad de la Articulación , Luxación de la Rótula , Articulación Patelofemoral , Masculino , Femenino , Adolescente , Niño , Humanos , Articulación Patelofemoral/diagnóstico por imagen , Articulación Patelofemoral/cirugía , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla/cirugía , Luxación de la Rótula/diagnóstico por imagen , Luxación de la Rótula/cirugía , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/cirugía , Ligamentos Articulares/lesiones , RótulaRESUMEN
Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.
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Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs). Next, tunable physical properties of collagen niches are fabricated based on various crosslinking degrees. Collagen niches significantly affect actomyosin cytoskeleton and then influence the maturation of iNPLCs. Using gain- and loss of function approaches, the appropriate physical states of collagen niches are found to significantly enhance the maturation of iNPLCs through actomyosin contractility. Moreover, in a rat model of degenerative disc diseases, iNPLCs with collagen niches are transplanted into the lesion to achieve significant improvements. As a result, overexpression of transcription factors in human dermal fibroblasts are efficiently converted into iNPLCs and the optimal collagen niches affect cellular cytoskeleton and then facilitate iNPLCs maturation toward human nucleus pulposus cells. These findings encourage more in-depth studies toward the interactions of niches and direct conversion, which would contribute to the development of direct conversion.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Ratas , Animales , Disco Intervertebral/patología , Actomiosina , Colágeno , Factores de TranscripciónRESUMEN
Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide-co-acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Células Madre Mesenquimatosas , Microgeles , Núcleo Pulposo , Humanos , Disco Intervertebral/metabolismo , Diferenciación Celular , Núcleo Pulposo/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Canales Iónicos/metabolismoRESUMEN
Mammalian cell membranes are decorated by the glycocalyx, which offer versatile means of generating biochemical signals. By manipulating the set of glycans displayed on cell surface, it is vital for gaining insight into the cellular behavior modulation and medical and biotechnological adhibition. Although genetic engineering is proven to be an effective approach for cell surface modification, the technique is only suitable for natural and genetically encoded molecules. To circumvent these limitations, non-genetic approaches are developed for modifying cell surfaces with unnatural but functional groups. Here, we review latest development of metabolic glycoengineering (MGE), which enriches the chemical functions of the cell surface and is becoming an intriguing new tool for regenerative medicine and tissue engineering. Particular emphasis of this review is placed on discussing current applications and perspectives of MGE.
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Ischiofemoral impingement (IFI) syndrome is considered the narrowing of the ischiofemoral space (IFS), leading to pathological changes in the quadratus femoris and sciatic nerve, causing posterior hip and sciatica-like pain. Open or arthroscopic resection of the lesser trochanter to enlarge the IFS is the main surgical procedure. However, there is a lack of research on isolated IFI, and currently known surgical procedures are at risk of weakening the flexion strength of the hip joint. In this study, four patients, who were diagnosed with isolated IFI and had undergone arthroscopic treatment with partial resection of the lesser trochanter, debridement of the quadratus femoris, and decompression of the sciatic nerve, were reviewed. To the best of our knowledge, this is the first study to describe the management of IFI using a series of surgical procedures via a posterior approach as an effective treatment option. The outcomes of this study broadened the strategies for IFI management.
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In recent years, single-cell sequencing (SCS) technologies have continued to advance with improved operating procedures and reduced cost, leading to increasing practical adoption among researchers. These emerging technologies have superior abilities to analyse cell heterogeneity at a single-cell level, which have elevated multi-omics research to a higher level. In some fields of research, application of SCS has enabled many valuable discoveries, and musculoskeletal system offers typical examples. This article reviews some major scientific issues and recent advances in musculoskeletal system. In addition, combined with SCS technologies, the research of cell or tissue heterogeneity in limb development and various musculoskeletal system clinical diseases also provides new possibilities for treatment strategies. Finally, this article discusses the challenges and future development potential of SCS and recommends the direction of future applications of SCS to musculoskeletal medicine.
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Sistema Musculoesquelético/metabolismo , RNA-Seq , Investigación , Análisis de la Célula Individual , Animales , Epigénesis Genética , Humanos , Transcriptoma/genéticaRESUMEN
The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.
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Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for repairing degenerated intervertebral discs through multiple means, including: i. Secretion of bioactive factors to regulate inflammation and, ii. The potential to differentiate into nucleus pulposus (NP)-like cells, which can integrate into host tissues. However, the differentiation ability of ADSCs to NP-like cells is limited, which emphasizes on the need for alternative approaches to regulate cell differentiations. Given that cell functions are influenced by interactions between the extracellular matrix (ECM) and cells, we hypothesize that cell surface modification promotes ADSCs adhesion and differentiation towards NP-like cells. In this study, cell surfaces of ADSCs were functionalized with unnatural sialic acid via metabolic glycoengineering. Subsequently, adhesion abilities of modified cells to three main ECM (laminin, collagen and fibronectin) were compared. The adhesion assay revealed that glycoengineered ADSCs had the highest affinity for collagen, compared to laminin and fibronectin. Moreover, cultures with collagen coated plates enhanced the differentiation of glycoengineered ADSCs to NP-like cells. Metabolic glycoengineering prolonged ADSCs viability. The glycoengineered ADSCs increased the height and elasticity of intervertebral discs, as well as the water content and ECM volumes of nucleus pulposus. In conclusion, metabolic glycoengineering of cell surfaces has a significant role in modulating cell biological functions and promoting NP tissue repair.
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Disco Intervertebral , Células Madre Mesenquimatosas , Núcleo Pulposo , Adipocitos , Diferenciación Celular/fisiología , Células CultivadasRESUMEN
According to the 2019 World Health Organization (WHO) classification, well-differentiated grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a new category of cancer of the digestive system. G3 GEP-NET research and treatment are not as robust as those of lower grade (G1/2) NETs and poorly differentiated neuroendocrine carcinomas (NECs). Previously, the management of high-grade NETs was mainly based on NEC therapies, as high-grade NETs were classified as NECs under the previous WHO classification. Despite this, G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs, due to their distinct molecular pathogenesis and course of pathological grade transition. Patients with advanced G3 GEP-NETs, who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide, have limited treatment choices. Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors. Immunotherapies, either alone or in combination with other therapies, do not have a clear function in the treatment of G3 GEP-NETs. Currently, the majority of immunotherapy studies, both prospective and retrospective, do not reliably differentiate G3 GEP-NETs from NECs. By contrast, a significant number of studies include non-GEP neuroendocrine neoplasms (NENs). Therefore, there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor. The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.
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Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Inmunoterapia , Neoplasias Intestinales/terapia , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/terapia , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Gástricas/terapia , Organización Mundial de la SaludRESUMEN
Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (m6A) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that m6A-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight m6A modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.
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Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.