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1.
Cell Death Discov ; 10(1): 224, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724500

RESUMEN

Spinal cord injury (SCI) remains a formidable challenge, lacking effective treatments. Following SCI, neural stem cells (NSCs) migrate to SCI sites, offering a potential avenue for nerve regeneration, but the effectiveness of this intrinsic repair mechanism remains suboptimal. Salidroside has demonstrated pro-repair attributes in various pathological conditions, including arthritis and cerebral ischemia, and the ability to curtail early-stage inflammation following SCI. However, the specific role of salidroside in the late-stage repair processes of SCI remains less defined. In this investigation, we observed that continuous salidroside treatment in SCI mice improved motor function recovery. Immunofluorescence-staining corroborated salidroside's capacity to stimulate nerve regeneration and remyelination, suppress glial scar hyperplasia, reduce the activation of neurotoxic A1 astrocytes, and facilitate NSCs migration towards the injured region. Mechanistically, in vitro experiments elucidated salidroside's significant role in restraining astrocyte proliferation and A1 polarization. It was further established that A1 astrocytes hinder NSCs proliferation while inducing their differentiation into astrocytes. Salidroside effectively ameliorated this inhibition of NSCs proliferation through diminishing c-Jun N-terminal kinase (JNK) pathway phosphorylation and restored their differentiation into neurons by suppressing the signal transducer and activator of transcription 3 (STAT3) pathway. In summary, our findings suggest that salidroside holds promise as a therapeutic agent for traumatic SCI treatment.

2.
Front Bioeng Biotechnol ; 12: 1345319, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633668

RESUMEN

Introduction: The treatment of skip-level cervical degenerative disease (CDD) with no degenerative changes observed in the intervening segment (IS) is complicated. This research aims to provide a reference basis for selecting treatment approaches for noncontiguous CDD. Methods: To establish accurate finite element models (FEMs), this study included computed tomography (CT) data from 21 patients with CDD (10 males and 11 females) for modeling. The study primarily discusses four cross-segment surgical approaches: upper (C3/4) anterior cervical discectomy and fusion (ACDF) and lower (C5/6) cervical disc arthroplasty (CDA), FA model; upper CDA (C3/4) and lower ACDF (C5/6), AF model; upper ACDF (C3/4) and lower ACDF (C5/6), FF model; upper CDA (C3/4) and lower CDA (C5/6), AA model. An initial axial load of 73.6 N was applied at the motion center using the follower load technique. A moment of 1.0 Nm was applied at the center of the C2 vertebra to simulate the overall motion of the model. The statistical analysis was conducted using STATA version 14.0. Statistical significance was defined as a p value less than 0.05. Results: The AA group had significantly greater ROM in flexion and axial rotation in other segments compared to the FA group (p < 0.05). The FA group consistently exhibited higher average intervertebral disc pressure in C2/3 during all motions compared to the AF group (p < 0.001); however, the FA group displayed lower average intervertebral disc pressure in C6/7 during all motions (p < 0.05). The AA group had lower facet joint contact stresses during extension in all segments compared to the AF group (p < 0.05). The FA group exhibited significantly higher facet joint contact stresses during extension in C2/3 (p < 0.001) and C6/7 (p < 0.001) compared to the AF group. Discussion: The use of skip-level CDA is recommended for the treatment of non-contiguous CDD. The FA construct shows superior biomechanical performance compared to the AF construct.

3.
Eur Spine J ; 33(2): 386-393, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38180515

RESUMEN

PURPOSE: The aim of this study was to translate and cross-culturally adapt the Core Outcome Measures Index for (COMI) into a Simplified Chinese version (COMI-SC) and to evaluate the reliability and validity of COMI-SC in patients with neck pain. METHODS: The COMI-neck was translated into Chinese according to established methods. The COMI-neck questionnaire was then completed by 122 patients with a hospital diagnosis of neck pain. Reliability was assessed by calculating Cronbach's alpha and intraclass correlation coefficient (ICC). Construct validity was assessed by correlating the COMI-neck with the Neck Pain and Disability Scale (NPDS), the Neck Disability Index (NDI), the VAS and the Short Form (36) Health Survey (SF-36). Using confirmatory factor analysis to validate the structural, convergent and discriminant validity of the questionnaire. RESULTS: The COMI-neck total scores were well distributed, with no floor or ceiling effects. Internal consistency was excellent (Cronbach's alpha = 0.861). Moderate to substantial correlations were found between COMI-neck and NPDS (r = 0.420/0.416/0.437, P < 0.001), NDI (r = 0.890, P < 0.001), VAS (r = 0.845, P < 0.001), as well as physical function (r = - 0.989, P < 0.001), physical role (r = - 0.597, P < 0.001), bodily pain (r = - 0. 639, P < 0.001), general health (r = - 0.563, P < 0.001), vitality (r = - 0.702, P < 0.001), social functioning (r = - 0.764, P < 0.001), role emotional (r = - 0.675, P < 0.001) and mental health (r = - 0.507, P < 0.001) subscales of the SF-36. An exploratory factor analysis revealed that the 3-factor loading explained 71.558% of the total variance [Kaiser-Mayer-Olkin (KMO) = 0.780, C2 = 502.82, P < 0.001]. CMIN/DF = 1.813, Tucker-Lewis index (TLI) = 0.966 (> 0.9), Comparative Fit Index (CFI) = 0.982 (> 0.9), Normed Fit Index (NFI) = 0.961 (> 0.9), RMSEA = 0.082 (< 0.5) indicating that the model fits well. CONCLUSION: COMI-neck was shown to have acceptable reliability and validity in patients with non-specific chronic neck pain and could be recommended for patients in mainland China. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.


Asunto(s)
Comparación Transcultural , Dolor de Cuello , Humanos , Dolor de Cuello/diagnóstico , Estudios Transversales , Reproducibilidad de los Resultados , Cuello , Encuestas y Cuestionarios , Psicometría , Evaluación de la Discapacidad
4.
J Nanobiotechnology ; 22(1): 34, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38238748

RESUMEN

Severe tissue injuries pose a significant risk to human health. Conventional wound dressings fall short in achieving effective tissue regeneration, resulting in suboptimal postoperative healing outcomes. In this study, an asymmetric adhesive wound dressing (marked as SIS/PAA/LAP) was developed, originating from acrylate acid (AA) solution with laponite (LAP) nanoparticles polymerization and photo-crosslinked on the decellularized extracellular matrix small intestinal submucosa (SIS) patch. Extensive studies demonstrated that the SIS/PAA/LAP exhibited higher tissue adhesion strength (~ 33 kPa) and burst strength (~ 22 kPa) compared to conventional wound dressings like Tegaderm and tissue adhesive products. Importantly, it maintained favorable cell viability and demonstrated robust angiogenic capacity. In animal models of full-thickness skin injuries in rats and skin injuries in Bama miniature pigs, the SIS/PAA/LAP could be precisely applied to wound sites. By accelerating the formation of tissue vascularization, it displayed superior tissue repair outcomes. This asymmetrically adhesive SIS-based patch would hold promising applications in the field of wound dressings.


Asunto(s)
Adhesivos , Cicatrización de Heridas , Humanos , Ratas , Animales , Porcinos , Adhesivos/farmacología , Piel , Vendajes
6.
Biochem Genet ; 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37672187

RESUMEN

Osteosarcoma is the most common type of primary malignant bone tumor. Due to the lack of selectivity and sensitivity of chemotherapy drugs to tumor cells, coupled with the use of large doses, chemotherapy drugs often have systemic toxicity. The use of modern sequencing technology to screen tumor markers in a large number of tumor samples is a common method for screening highly specific and selective anti-tumor drugs. This study aims to identify potential biomarkers using the latest reported gene expression signatures of oncogene-induced replication stress (ORS) in aggressive cancers, and potential anti-osteosarcoma drugs were screened in different drug databases. In this study, we obtained 89 osteosarcoma-related samples in the TARGET database, all of which included survival information. According to the median expression of each of six reported ORS gene markers (NAT10/DDX27/ZNF48/C8ORF33/MOCS3/MPP6), we divided 89 osteosarcoma gene expression datasets into a high expression group and a low expression group and then performed a differentially expressed gene (DEG) analysis. The coexisting genes of 6 groups of DEGs were used as replication stress-related genes (RSGs) of osteosarcoma. Then, key RSGs were screened using LASSO regression, a Cox risk proportional regression prognostic model and a tenfold cross-validation test. GSE21257 datasets collected from the Gene Expression Omnibus (GEO) database were used to verify the prognostic model. The final key RSGs selected were used in the L1000PWD and DGIdb databases to mine potential drugs. After further validation by the prognostic model, we identified seven genes associated with ORS in osteosarcoma as key RSGs, including transcription factor 7 like 2 (TCF7L2), solute carrier family 27 member 4 (SLC27A4), proprotein convertase subtilisin/kexin type 5 (PCSK5), nucleolar protein 6 (NOL6), coiled-coil-coil-coil-coil-helix domain containing 4 (CHCHD4), eukaryotic translation initiation factor 3 subunit B (EIF3B), and synthesis of cytochrome C oxidase 1 (SCO1). Then, we screened the seven key RSGs in two drug databases and found six potential anti-osteosarcoma drugs (D GIdb database: repaglinide, tacrolimus, sirolimus, cyclosporine, and hydrochlorothiazide; L1000PWD database: the small molecule VU-0365117-1). Seven RSGs (TCF7L2, SLC27A4, PCSK5, NOL6, CHCHD4, EIF3B, and SCO1) may be associated with the ORS gene signatures in osteosarcoma. Repaglinide, tacrolimus, sirolimus, cyclosporine, hydrochlorothiazide and the small molecule VU-0365117-1 are potential therapeutic drugs for osteosarcoma.

7.
J Orthop Surg Res ; 18(1): 57, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36658557

RESUMEN

BACKGROUND: Hybrid construction (HC) may be an ideal surgical strategy than noncontinuous total disc replacement (TDR) and noncontinuous anterior cervical discectomy and fusion (ACDF) in the treatment of noncontinuous cervical spondylopathy. However, there is still no consensus on the segmental selection for ACDF or TDR in HC. The study aims to analyse the effects of different segment selection of TDR and ACDF on cervical biomechanical characteristics after HC surgery. METHODS: Twelve FEMs of C2-C7 were constructed based on CT images of 12 mild cervical spondylopathy volunteers. Two kinds of HC were introduced in our study: Fusion-arthroplasty group (Group 1), upper-level (C3/4) ACDF, and lower-level TDR (C5/6); Arthroplasty-fusion group (Group 2), upper-level (C3/4) TDR and lower-level ACDF (C5/6). The follow-load technique was simulated by applying an axial initial load of 73.6 N through the motion centre of FEM. A bending moment of 1.0 Nm was applied to the centre of C2 in all FEMs. Statistical analysis was carried out by SPSS 26.0. The significance threshold was 5% (P < 0.05). RESULTS: In the comparison of ROMs between Group 1 and Group 2, the ROM in extension (P = 0.016), and lateral bending (P = 0.038) of C4/5 were significantly higher in Group 1 group. The average intervertebral disc pressures at C2/3 in all directions were significantly higher in Group 1 than those in Group 2 (P < 0.005). The average contact forces in facet joints of C2/3 (P = 0.007) were significantly more than that in Group 2; however, the average contact forces in facet joints of C6/7 (P < 0.001) in Group 1 group were significantly less than that in Group 2. CONCLUSIONS: Arthroplasty-fusion is preferred for intervertebral disc degeneration in adjacent upper segments. Fusion-arthroplasty is preferred for patients with lower intervertebral disc degeneration or lower posterior column degeneration. TRIAL REGISTRATION: This research was registered in Chinese Clinical Trial Registry (ChiCTR1900020513).


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Fusión Vertebral , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Análisis de Elementos Finitos , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Fusión Vertebral/métodos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/cirugía , Discectomía/métodos , Fenómenos Biomecánicos , Rango del Movimiento Articular
8.
Bioact Mater ; 12: 292-302, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35087969

RESUMEN

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.

9.
Biochem Genet ; 60(3): 1025-1038, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34762200

RESUMEN

The literature has provided inconsistent findings on the relationship between interleukin IL-1 gene polymorphisms and susceptibility to ankylosing spondylitis (AS). Therefore, a systematic review and meta-analysis were conducted. Online electronic database searches were performed for relevant research published as of May 2021. Meta-analysis was performed to compare alleles and multiple genetic models (including dominant, recessive, heterozygous, and homozygous models) using random-effects models to reduce the impact of heterogeneity. A 95% confidence interval (95% CI) odds ratio (OR) was used to assess potential relationships. Nineteen studies including 6235 patients with AS and 5919 healthy controls were recruited. IL-1A-889 (rs1800587) had statistical significance in the allelic model (OR 1.38, 95% CI 1.08-1.77, P = 0.010) (I2 = 51%.1, P = 0.0001); homozygous model (OR 1.92, 95% CI 1.27-2.89, P = 0.002); heterozygous model (OR 1.49, 95% CI 1.02-2.17, P = 0.163); dominant genetic model (OR 1.53, 95% CI 1.05-2.24, P = 0.026); and recessive model (OR 1.54, 95% CI 1.04-2.28, P = 0.031). Further stratified analysis showed that the allele model (OR 1.35, 95% CI 1.08-1.69, P = 0.008), heterozygous model (OR 1.45, 95% CI 1.07-1.96, P = 0.017), and dominant model (OR 1.49, 95% CI 1.11-1.99, P = 0.007) in the English population and allele model (OR 2.21, 95% CI 1.45-3.37, P = 0.0001), homozygous model (OR 3.85, 95% CI 1.38-10.76, P = 0.010), heterozygous model (OR 3.42, 95% CI 1.85-6.32, P = 0.0001), and dominant model (OR 3.49, 95% CI 1.93-6.30, P = 0.001) in Tunis were significantly associated with susceptibility to AS. Analysis of the IL1F7 exon 2 (rs3811047) showed that the G allele frequency was higher in the normal population than in the AS population (OR 0.76, 95% CI (0.64, 0.91)). Further stratified analysis concluded that the allele model was significantly associated with AS susceptibility in Canadian (OR 0.76, 95% CI 0.61-0.94, P = 0.011) and Chinese patients (OR 0.64, 95% CI 0.41-0.98, P = 0.041). The meta-analysis showed that the IL-1 gene polymorphism IL-1A-889 (rs1800587) increases the risk of AS in English and Tunisian populations. IL1F7 exon 2 (rs3811047) is negatively correlated with susceptibility to AS in Canadian and Chinese populations, but additional studies are needed for further exploration.


Asunto(s)
Interleucina-1 , Espondilitis Anquilosante , Canadá , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Interleucina-1/genética , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante/genética
10.
Ann Palliat Med ; 10(5): 5218-5230, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33977746

RESUMEN

BACKGROUND: Rheumatoid arthritis is a long-term systemic disease that primarily affects multiple synovial joints throughout the body. Some patients with severe joint effusion even require repeated arthrocentesis or arthroscopic debridement to relieve symptoms, which causes them much suffering mentally and physically. This text-mining study was designed to find potential drugs that target key genes in this disease. METHODS: Firstly, we performed text mining by two keywords ("rheumatoid synovitis" and "joint effusion") to get a common set of genes. Secondly, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis performed on these genes, and protein-protein interaction (PPI) network was constructed. Subsequently, the significant genes clustered in the PPI network were chose to execute gene-drug interaction analysis for potential drug discovery. RESULTS: Through text mining, 68 overlapping genes were identified as an initial set of key genes. Construction of the initial gene set's PPI network showed that 25 genes clustered in a significant gene module. Ultimately, 8 out of 25 genes could be targetable by a total of 19 drugs. CONCLUSIONS: The final 8 genes (PTGS2, TNF, VEGFA, IL1B, CCL2, VWF, IL6, and ESR1) and 19 drugs may provide significant therapeutic value for rheumatoid arthritis patients with joint effusion.


Asunto(s)
Artritis Reumatoide , Descubrimiento de Drogas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Biología Computacional , Minería de Datos , Perfilación de la Expresión Génica , Humanos
11.
Rev Assoc Med Bras (1992) ; 66(6): 740-745, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32696868

RESUMEN

OBJECTIVE In this study, we aimed to investigate the role of COL6A3 on cell motility and the PI3K/AKT signaling pathway in osteosarcoma. METHODS The relative expression of COL6A3 was achieved from a GEO dataset in osteosarcoma tissue. siRNA technology was applied to decrease the COL6A3 expression in cells, and cell counting kit-8 (CCK-8) assay and colony formation analysis were used to examine the cell proliferation potential. Knockdown COL6A3 made the proliferation and colony formation abilities worse than the COL6A3 without interference. Likewise, in contrast to the si-con group, cell invasion and migration were inhibited in the si-COL6A3 group. Moreover, the western blot results suggested that the PI3K/AKT signaling pathway was manipulated by measuring the protein expression of the PI3K/AKT pathway-related markers, due to the COL6A3 inhibition. CONCLUSION COL6A3 plays a crucial role in modulating various aspects of the progression of osteosarcoma, which would provide a potentially effective treatment for osteosarcoma.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Línea Celular Tumoral , Proliferación Celular , Colágeno Tipo VI , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt
12.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 66(6): 740-745, June 2020. graf
Artículo en Inglés | Sec. Est. Saúde SP, LILACS | ID: biblio-1136283

RESUMEN

SUMMARY OBJECTIVE In this study, we aimed to investigate the role of COL6A3 on cell motility and the PI3K/AKT signaling pathway in osteosarcoma. METHODS The relative expression of COL6A3 was achieved from a GEO dataset in osteosarcoma tissue. siRNA technology was applied to decrease the COL6A3 expression in cells, and cell counting kit-8 (CCK-8) assay and colony formation analysis were used to examine the cell proliferation potential. Knockdown COL6A3 made the proliferation and colony formation abilities worse than the COL6A3 without interference. Likewise, in contrast to the si-con group, cell invasion and migration were inhibited in the si-COL6A3 group. Moreover, the western blot results suggested that the PI3K/AKT signaling pathway was manipulated by measuring the protein expression of the PI3K/AKT pathway-related markers, due to the COL6A3 inhibition. CONCLUSION COL6A3 plays a crucial role in modulating various aspects of the progression of osteosarcoma, which would provide a potentially effective treatment for osteosarcoma.


RESUMO OBJETIVO Neste estudo, investigamos a função do COL6A3 na mobilidade celular e na via PI3K/AKT em osteossarcomas. METODOLOGIA A expressão relativa do COL6A3 foi obtida a partir de dados GEO em tecidos de osteossarcoma. O RNA de interferência (siRNA) foi utilizado para reduzir a expressão do COL6A3 nas células, e o teste de contagem de células kit-8 (CCK-8) e a análise de formação de colônias foram realizados para examinar o potencial de proliferação celular. Além disso, o Transwell comprovou os efeitos do si-COL6A3 na invasão celular e migração em células de osteossarcoma. Para medir os níveis de expressão das proteínas e mRNAs, utilizamos transcriptase reversa quantitativa (qRT-PCR) e western blot. RESULTADOS O COL6A3 foi regulado nos tecidos e células do osteossarcoma quando comparado com o controle normal. A redução de COL6A3 reduziu a proliferação e a capacidades de formação de colônias em relação ao COL6A3 sem interferência. Do Mesmo modo, ao contrário do observado no grupo si-con, a invasão e migração celular foram inibidas no grupo si-COL6A3. Além disso, o resultado do western blot sugere que a via PI3K/AKT foi manipulada, medindo a expressão proteica dos marcadores relacionados à PI3K/AKT, devido à inibição do COL6A3. CONCLUSÃO O COL6A3 desempenha um papel crucial na modulação de vários aspectos da progressão do osteossarcoma, o que pode representar um possível tratamento eficaz para a doença.


Asunto(s)
Humanos , Neoplasias Óseas , Osteosarcoma , Fosfatidilinositol 3-Quinasas , Colágeno Tipo VI , Línea Celular Tumoral , Proliferación Celular , Proteínas Proto-Oncogénicas c-akt
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