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1.
J Nanobiotechnology ; 22(1): 445, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39069607

RESUMO

BACKGROUND: The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge. RESULTS: In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration. CONCLUSIONS: In general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.


Assuntos
Regeneração Óssea , Hidrogéis , Células-Tronco Mesenquimais , Osteogênese , Ratos Sprague-Dawley , Alicerces Teciduais , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Alicerces Teciduais/química , Ratos , Células-Tronco Mesenquimais/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Masculino , Diferenciação Celular/efeitos dos fármacos , Inflamação , Engenharia Tecidual/métodos , Espécies Reativas de Oxigênio/metabolismo , Condrogênese/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Células Cultivadas
2.
Cell Mol Biol (Noisy-le-grand) ; 69(6): 186-192, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37605572

RESUMO

Osteoporosis (OP) is a prevalent metabolic disease, with aging and menopause being the major risk factors. Studies have shown that nearly one-third of postmenopausal women suffer from osteoporosis. However, there is a scarcity of research on antioxidant systems for the prevention and treatment of postmenopausal osteoporosis (PM-OP). To address this gap, we performed differential analysis using Limma to identify differentially expressed genes (DEGs) in PM-OP samples. We employed weighted correlation network analysis (WGCNA) to identify oxidative stress (OS)-related genes (OSRGs) highly correlated with PM-OP. The intersection of key modular genes and DEGs yielded differentially expressed OSRGs (DE-OSRGs) specific to PM-OP. We conducted GO and KEGG functional enrichment analyses on these genes. Additionally, we constructed a protein-protein interaction (PPI) network and utilized support vector machine recursive feature elimination (SVM-RFE) and random forest (RF) algorithms to identify signature genes. The diagnostic value of the signature genes was evaluated and validated using ROC curves. GSEA enrichment analysis was employed to explore the potential mechanisms associated with the signature genes. Finally, we constructed a regulatory network involving TF-miRNA-mRNA interactions for the signature genes and verified the biological roles of FOXO3 and DDIT3 in PM-OP and healthy groups using quantitative real-time PCR (qRT-PCR). Our analysis revealed 20 DE-OSRGs specific to PM-OP, obtained by intersecting modular and differential genes. The PPI network identified central genes (DDIT3, MAPK8, CDK2, SIRT1, and FOXO3) with more than 3 nodes. Through integration with machine learning algorithms, we identified DDIT3 and FOXO3 as signature genes. The ROC curve analysis indicated that the AUC value was greater than 0.7, suggesting the potential diagnostic value of these signature genes. Furthermore, GSEA results revealed their involvement in pathways related to the regulation of neutrophil activation, oxidative phosphorylation, MAPK signaling, mitochondrial matrix, and phagocytosis. Lastly, we constructed a regulatory network comprising 27 nodes (22 TFs, 3 miRNAs, and 2 mRNAs) and 28 edges. Additionally, qRT-PCR confirmed the significant up-regulation of FOXO3 and DDIT3 expressions in the PM-OP group compared to the healthy control group. In summary, this study employed bioinformatics analysis to identify OS-related biomarkers (DDIT3 and FOXO3) in PM-OP, providing new biological targets for clinical treatment.


Assuntos
MicroRNAs , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Osteoporose Pós-Menopausa/genética , Estresse Oxidativo/genética , MicroRNAs/genética , Biomarcadores
3.
Am J Obstet Gynecol ; 226(1): 97.e1-97.e16, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461074

RESUMO

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.


Assuntos
Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adolescente , Adulto , Brasil , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Preservação da Fertilidade , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Traquelectomia , Neoplasias do Colo do Útero/mortalidade , Adulto Jovem
4.
J Nanobiotechnology ; 20(1): 433, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36182921

RESUMO

Developing smart hydrogels with integrated and suitable properties to treat intervertebral disc degeneration (IVDD) by minimally invasive injection is of high desire in clinical application and still an ongoing challenge. In this work, an extraordinary injectable hydrogel PBNPs@OBG (Prussian blue nanoparticles@oxidized hyaluronic acid/borax/gelatin) with promising antibacterial, antioxidation, rapid gelation, and self-healing characteristics was designed via dual-dynamic-bond cross-linking among the oxidized hyaluronic acid (OHA), borax, and gelatin. The mechanical performance of the hydrogel was studied by dynamic mechanical analysis. Meanwhile, the swelling ratio and degradation level of the hydrogel was explored. Benefiting from its remarkable mechanical properties, sufficient tissue adhesiveness, and ideal shape-adaptability, the injectable PBNPs containing hydrogel was explored for IVDD therapy. Astoundingly, the as-fabricated hydrogel was able to alleviate H2O2-induced excessive ROS against oxidative stress trauma of nucleus pulposus, which was further revealed by theoretical calculations. Rat IVDD model was next established to estimate therapeutic effect of this PBNPs@OBG hydrogel for IVDD treatment in vivo. On the whole, combination of the smart multifunctional hydrogel and nanotechnology-mediated antioxidant therapy can serve as a fire-new general type of therapeutic strategy for IVDD and other oxidative stress-related diseases.


Assuntos
Hidrogéis , Degeneração do Disco Intervertebral , Animais , Antibacterianos , Antioxidantes/farmacologia , Boratos , Gelatina/química , Ácido Hialurônico , Hidrogéis/química , Peróxido de Hidrogênio , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Ratos , Espécies Reativas de Oxigênio
5.
Eur Radiol ; 29(6): 3036-3043, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30506217

RESUMO

OBJECTIVE: To investigate the value of prospectively ECG-triggered coronary CT angiography (CCTA) for lean patients with body mass index (BMI) ≤ 23 kg/m2 using 70 kVp and high-level volume-based adaptive statistical iterative reconstruction (ASiR-V) algorithm on a 16-cm wide-detector CT system for reducing both radiation and contrast doses in comparison with the conventional 100-kVp protocol. MATERIALS AND METHODS: Thirty patients (group A) were prospectively enrolled to undergo 70-kVp CCTA on a 16-cm wide-detector CT scanner with noise index (NI) of 36 HU and at weight-dependent contrast dose rate of 16 mg I/kg/s for 9-s injection. Images were reconstructed with 80% ASiR-V. Radiation dose, contrast dose, and image quality were statistically compared with 30 patients (group B) in database with matching BMI who underwent conventional 100-kVp CCTA with NI of 25 HU, and at 25 mg I/kg/s rate for 10-s injection and reconstructed with 60% ASiR-V. RESULTS: There was no significant difference in patient demographics between the two groups (all p > 0.05). The two groups also had similar mean CT values and contrast-noise ratio (CNR) and subjective image quality (all p > 0.05). However, group A with 70 kVp reduced the effective dose by 75.3% compared with group B (0.43 ± 0.20 mSv vs. 1.74 ± 1.01 mSv, p < 0.001), and required 42.4% less contrast dose than group B (22.46 ± 2.94 ml vs. 38.99 ± 5.10 ml, p < 0.001). CONCLUSIONS: Prospectively ECG-triggered CCTA using 70 kVp and high-level ASiR-V on a 16-cm wide-detector CT system provides diagnostic images with substantial reduction in both radiation and contrast doses for patients with BMI ≤ 23 kg/m2 compared to the conventional 100-kVp protocol. KEY POINTS: • 70-kVp CCTA produces excellent images at sub-millisievert radiation. • 70-kVp CCTA reduces both radiation and contrast doses over conventional protocol. • Achieving low-dose CCTA with combined low kVp and high-level ASIR-V.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Adulto , Idoso , Algoritmos , Índice de Massa Corporal , Protocolos Clínicos , Meios de Contraste/administração & dosagem , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Cintilografia , Magreza
6.
Int J Gynecol Cancer ; 29(3): 635-638, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30765489

RESUMO

BACKGROUND: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. PRIMARY OBJECTIVE: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. STUDY HYPOTHESIS: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. STUDY DESIGN: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. INCLUSION CRITERIA: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). EXCLUSION CRITERIA: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. PRIMARY ENDPOINT: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. SAMPLE SIZE: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.


Assuntos
Traquelectomia/métodos , Neoplasias do Colo do Útero/cirurgia , Intervalo Livre de Doença , Feminino , Preservação da Fertilidade/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias do Colo do Útero/patologia
7.
Arch Gynecol Obstet ; 300(4): 967-973, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31494695

RESUMO

PURPOSE: As a serious type of deep infiltrating endometriosis (DIE), ureteral endometriosis (UE) can result in decreased kidney function. The aims of this study are to investigate risk factors and surgical treatments for UE. METHODS: The study enrolled 329 patients with deep infiltrating endometriosis, who were treated with laparoscopic surgery between January 2014 to September 2018. All patients were divided into one of two groups: UE or non-UE. Clinical information and other surgery variables of the two groups were examined. RESULT: Out of 329 patients with DIE, 68 (20.67%) cases of UE were diagnosed. Among them, 37 patients also had hydroureteronephrosis. In a multivariate analysis, the variables revised American Fertility Society (rAFS) stage IV, uterosacral ligament (USL) DIE lesion ≥ 3 cm in diameter and previous surgery for endometriosis significantly increased the risk of UE. A total of 27.03% (10/37) of patients with UE and hydroureteronephrosis showed decreased kidney function. Ureterolysis was performed in 59 patients, and an ureteroneocystostomy was performed in 9 patients. A double-J stent was placed in 37 patients with UE. Only 1 patient developed acute pyelonephritis postoperatively. During more than 2 years of follow-up, no patient experienced recurrence. CONCLUSIONS: The variables of rAFS stage IV, USL DIE lesion ≥ 3 cm in diameter and previous surgery for endometriosis significantly increased the risk of UE. Laparoscopic ureterolysis and ureteroneocystostomy are feasible and safe procedures with low complication and recurrence rates.


Assuntos
Endometriose/patologia , Ureter/patologia , Doenças Ureterais/patologia , Adulto , Endometriose/complicações , Feminino , Humanos , Testes de Função Renal , Laparoscopia/métodos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Fatores de Risco , Ureter/cirurgia , Doenças Ureterais/complicações
8.
J Comput Assist Tomogr ; 42(6): 906-911, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30119063

RESUMO

OBJECTIVE: The aim of this study was to investigate radiation dose and image quality of coronary computed tomography (CT) angiography (CCTA) for patients with high heart rate variability (HRv) using 16-cm wide-detector CT scanner. METHODS: One hundred sixty-six patients with uncontrolled heart rate underwent CCTA on a 16-cm wide-detector CT system and were divided into 2 groups based on their HRv for analysis: group A (n = 95, HRv ≤10 beats/min [bpm]) and group B (n = 71, HRv >10 bpm). Images in both groups were reconstructed with motion correction algorithm. Subjective and objective image qualities were analyzed. RESULTS: There were no significant differences in age, body mass index, and heart rate (68.1 ± 11.4 vs 67.6 ± 12.3 bpm) between the 2 groups (P > 0.05). However, group B had significantly higher HRv than group A (33.5 ± 24.4 vs 7.8 ± 1.2 bpm, P < 0.001). All images were acceptable for clinical diagnosis. Compared with group A, image quality scores in group B decreased slightly (4.1 ± 0.5 vs 4.0 ± 0.6). However, the difference was not statistically significant. The mean effective doses were both relatively low at 2.2 ± 1.1 mSv in group A and 2.6 ± 1.4 mSv in group B. CONCLUSIONS: Single-heartbeat free-breathing CCTA can be performed for patients with high HRv using 16-cm wide-detector CT scanner to achieve diagnostic image quality with low radiation dose.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Frequência Cardíaca/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Angiografia por Tomografia Computadorizada/instrumentação , Angiografia Coronária/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Razão Sinal-Ruído
9.
Chemistry ; 23(69): 17444-17448, 2017 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-29048136

RESUMO

Patterned surfaces of responsive polymers find applications in diverse fields. However, it is still a great challenge to fabricate hierarchical patterns with long-range orders. Herein controllable hierarchical surface patterns that can be fabricated by combining nanoembossing techniques with the surface instability of supramolecular hydrogels are presented. Nanoembossed nanostripe arrays of polyethylene glycol (PEG)-based polyurethane-urea supramolecular hydrogels are fabricated and exposed to water, whereby the lateral expansion of nanostripes is confined and leads to the formation of folded in-plane or out-of-plane patterns depending on the aspect ratios. The direction of folds is perpendicular to the nanostripes. Both the amplitude and the wavelength of out-of-plane folds are proportional to the thickness of nanostripes. Therefore, hierarchical structures, in which one periodicity is defined by the nanoembossing processes and the other is determined by surface buckling, can be quickly fabricated in supramolecular hydrogel thin films.

10.
Eur Spine J ; 26(1): 210-220, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26687124

RESUMO

PURPOSE: To evaluate the effect of pure muscle retraction on multifidus injury and atrophy. MATERIALS AND METHODS: Sixty-three adult New Zealand white rabbits were divided evenly into three groups: 1-h retraction (group R1), 2-h retraction (R2), and sham surgery (C). The multifidus muscle was evaluated using magnetic resonance imaging (MRI) and histology after 3 and 48 h, and 1, 3, 6, 12, and 24 weeks after surgery. RESULTS: Multifidus muscle injury and atrophy were not observed in group C, but were obvious in groups R1 and R2. Edema, necrosis, and inflammation mainly occurred in the first week postoperatively, and were more severe in R2 than in R1 (P < 0.01). Muscle fiber regeneration began at week 1, fibrotic changes mainly occurred at weeks 3 and 6, and fat degeneration became obvious at weeks 12 and 24 postoperatively. The fibrosis and fat degeneration scores of R2 were higher than those of R1 (P < 0.01). Decreased acetylcholine activity and granular degeneration of the neuromuscular junction were observed in both retraction groups, but was more severe in R2 than in R1 (P < 0.01). CONCLUSION: Muscle retraction was an important factor not only for multifidus injury, but also for long-term multifidus atrophy after posterior lumbar surgery; a longer retraction time caused more severe multifidus injury and atrophy. Muscle fibers can be regenerated postoperatively, and denervation might be the reason for muscle atrophy.


Assuntos
Vértebras Lombares/cirurgia , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/patologia , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Animais , Edema/diagnóstico por imagem , Edema/patologia , Inflamação/diagnóstico por imagem , Inflamação/patologia , Vértebras Lombares/lesões , Imageamento por Ressonância Magnética , Modelos Animais , Necrose , Coelhos
11.
Lab Invest ; 96(5): 561-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26901836

RESUMO

Intervertebral disc degeneration is a major cause of low back pain. The nucleus pulposus (NP) is an important intervertebral disc component. Recent studies have shown that carbonic anhydrase 12 (CA12) is a novel NP marker. However, the mechanism by which CA12 is regulated and its physiological function are unclear. In our study, CA12, hypoxia-inducible factor 1α (HIF-1α) and HIF-2α expression levels were examined in 81 human degenerated NP samples using real-time RT-PCR, immunohistochemistry and western blot. Rat NP cells were cultured in a hypoxic environment, and hypoxia-induced CA12 expression was examined. Rat NP cells were treated with HIF-1α siRNA or the prolyl hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) to evaluate the role of PHD/HIF-1 in regulating CA12 expression. Rat NP cells were treated with CA12 siRNA to determine the function of CA12. A rat ex vivo model was established to confirm that PHD, HIF-1, and CA12 have important roles in disc degeneration. We found that CA12 was significantly downregulated in degenerated human NP samples at the mRNA and protein levels. CA12 expression sharply increased by ~30-fold in response to hypoxia. The expression of HIF-1α, but not HIF-2α, also decreased in degenerated human NP samples and was positively correlated with CA12 expression. HIF-1α knockdown under hypoxia reduced the CA12 mRNA and protein expression levels. DMOG treatment increased HIF-1α and CA12 expression. CA12 knockdown significantly inhibited anabolic protein expression, whereas catabolic enzymes remained unchanged. The ex vivo experiments supported our in vitro studies of the role of PHD/HIF-1/CA12. In conclusion, CA12 is downregulated in degenerated NPs, and its expression may be regulated by the PHD/HIF-1 axis. Decreased CA12 expression may lead to decreased extracellular matrix synthesis, which contributes to degenerative disc disease progression.


Assuntos
Anidrases Carbônicas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/prevenção & controle , Prolil Hidroxilases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Anidrases Carbônicas/genética , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Células Cultivadas , Feminino , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Degeneração do Disco Intervertebral/genética , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima , Adulto Jovem
12.
Clin Orthop Relat Res ; 474(8): 1818-26, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27146654

RESUMO

BACKGROUND: Modic changes are the MRI signal changes of degenerative lumbar vertebral endplate and which lead to or accelerate intervertebral disc degeneration. NLRP3, caspase-1, and interleukin-1ß (IL-1ß) play a pivotal role in the pathogenesis of many inflammatory diseases, such as osteoarthritis. However, the roles of IL-1ß and its activators caspase-1 and NLRP3 are unclear in the degenerative endplate. QUESTIONS/PURPOSES: We asked: (1) What are the degenerative changes of the histologic features and chondrogenic markers' gene expressions between the cartilaginous endplates of patients with Modic changes and trauma (control)? (2) How does the NLRP3/caspase-1/IL-1ß axis in the cartilaginous endplates of patients with Modic changes compare with control (trauma) specimens? METHODS: Surgical specimens of cartilaginous endplates were divided into Modic changes (n = 56) and the trauma control (n = 16) groups. Hematoxylin and eosin and safranin O staining of cartilaginous endplate tissues were done to evaluate the extracellular matrix. Reverse transcription-polymerase chain reaction was performed on these tissues to investigate mRNA expression of type II collagen (Col II), SOX-9, matrix metalloproteinase-3, and a disintegrin like and metalloproteinase thrombospondin type I motifs-5. NLRP3, caspase-1, and IL-1ß were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: Hematoxylin and eosin and safranin O staining showed the extracellular matrix degraded in the cartilaginous endplates of patients with Modic changes but not in the control cartilaginous endplates. Chondrogenic Col II (p = 0.024) and SOX9 (p = 0.053) were downregulated in the Modic changes group compared with the control group. In contrast to the control group, the transcriptional levels of NLRP3 (p < 0.001), caspase-1 (p = 0.054), and IL-1ß (p = 0.001) were all upregulated in the Modic changes group. CONCLUSIONS: The expression of NLRP3, caspase-1, and IL-1ß was upregulated in the patients with low back pain and Modic changes on MRI compared with patients with vertebral burst fracture without degenerative changes on MRI. The data suggest the NLRP3/caspase-1/IL-1ß axis may be implicated in lumbar cartilaginous endplate degeneration. CLINICAL RELEVANCE: The NLRP3/caspase-1/IL-1ß axis is active in cartilaginous endplates of patients with Modic changes and inflammatory cascades can exacerbate the cartilaginous endplate degeneration which may act as a trigger for intervertebral disc degeneration and low back pain. If these findings can be confirmed by others, we hope that new and effective therapy could be developed directed against this target.


Assuntos
Cartilagem Articular/enzimologia , Caspase 1/análise , Interleucina-1beta/análise , Vértebras Lombares/enzimologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Doenças da Coluna Vertebral/enzimologia , Adolescente , Adulto , Idoso , Cartilagem Articular/patologia , Estudos de Casos e Controles , Caspase 1/genética , Matriz Extracelular/patologia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1beta/genética , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Doenças da Coluna Vertebral/genética , Doenças da Coluna Vertebral/patologia , Transcrição Gênica , Regulação para Cima , Adulto Jovem
13.
Phys Rev Lett ; 115(26): 267601, 2015 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-26765029

RESUMO

The correlation between hierarchical structures and polarization switching in ferroelectric poly(vinylidene fluoride-ran-trifluoroethylene) has been probed by combining transmission electron microscopy studies with piezoresponse force microscopy observations. Differences are demonstrated between homogeneous and anisotropic thin films with well-defined lamellar orientation, with the later exhibiting quadrangular domain shape and double hysteresis. We propose that the polarization switching within lamella is dominated by domain wall flow motion, while the amorphous components between lamellae impede full polarization switching. The coupling between lamellae is controlled by a creep process. These results and interpretations explain well the seemingly contradicting polarization reversal dynamics reported and offer opportunities to change domain reversal speed by making ferroelectric polymer nanostructures.

14.
Nanotechnology ; 25(19): 195503, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24762473

RESUMO

Polymer micro/nano-actuators are attracting tremendous interest due to their potential applications in micro/nano-mechanical systems and lab-on-a-chip systems. To achieve this, thin films of stimuli-responsive polymers are required to be patterned at the micro/nanometer scale, and also to possess highly ordered orientation in the responsive component. We demonstrate here that nanoscale patterning and uniaxial alignment of liquid crystalline mesogens can be simultaneously achieved by nanoimprint lithography performed in the liquid crystalline mesophase. Photoactive azobenzene mesogens were aligned parallel to the nanogratings imprinted in the films. The degree of alignment depended on the extent of nanoconfinement. The nanogratings expanded in the direction perpendicular to the film upon exposure to uniform UV irradiation, because of trans-to-cis isomerization. In addition, the reversible deformation amplitude strongly depended on the degree of alignment of the photoactive azobenzene mesogens.

15.
Macromol Rapid Commun ; 35(11): 1061-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24700744

RESUMO

Dopamine-containing monomers, N-3,4-dihydroxybenzenethyl methacrylamide (DMA) and dimethylaminoethyl methacrylate (DMAEMA), are successfully copolymerized in a well-controlled manner via ambient temperature single-electron transfer initiation and propagation through the radical addition fragmentation chain transfer (SET-RAFT) method. The controlled behaviors of the copolymerization are confirmed by the first-order kinetic plots, the linear relationships between molecular weights, and the monomer conversions while keeping relatively narrow molecular weight distribution (Mw/Mn ≤ 1.45). Moreover, biomimetic self-assembly of poly(N-3,4-dihydroxybenzenethyl methacrylamide-co-dimethylaminoethyl methacrylate) PDMA-co-PDMAEMA and inorganic particles are employed to prepare tunable honeycomb-like porous hybrid particles (HPHPs) by regulating the predesigned chemical composition. In addition, the inorganic sacrificial templates are successfully selective etched for the formation of porous organic materials.


Assuntos
Dopamina/química , Polímeros/química , Acrilamidas/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Metilmetacrilatos/química , Polimerização , Polímeros/síntese química , Porosidade
16.
Eur J Orthop Surg Traumatol ; 24(2): 127-35, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23417108

RESUMO

The approach-related morbidity resulting from iatrogenic erector spinae injury in posterior lumbar surgery has become an increasing concern for spine surgeons. Many studies have explained the injury mechanisms and reported new surgical approaches to prevent this iatrogenic injury from their own point of views, but there is still no systemic information for a thorough understanding of this iatrogenic erector spinae injury that may give spine surgeons practical advices in their individual operations. We consequently reviewed the literature on the anatomy of erector spinae, causes of injury, and relative minimally invasive approaches. We found that the local anatomic structures make the erector spinae vulnerable to injury during posterior lumbar surgery, especially the medial multifidus which is innervated only by the medial branch of the dorsal ramus, with no intersegmental nerve supply as in the other paraspinal muscles, and the injury factors mainly include dissection, retraction, denervation, and immobility. Studies suggest that the goal of prevention is to preserve the physiological structure of erector spinae and to avoid or limit the injury causes: approaches through spatium intermusculare and approaches with endoscope and tubular retractor system can prevent the erector spinae from injury by less dissection and retraction; non-fusion techniques may prevent the erector spinae from disuse atrophy by preserving the segmental motion and the adjacent erector spinae activity.


Assuntos
Doença Iatrogênica/prevenção & controle , Vértebras Lombares , Procedimentos Ortopédicos , Músculos Paraespinais , Animais , Humanos , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/cirurgia , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Músculos Paraespinais/anatomia & histologia , Músculos Paraespinais/lesões , Nervos Espinhais/anatomia & histologia , Nervos Espinhais/lesões , Resultado do Tratamento
17.
Int J Biol Macromol ; 268(Pt 2): 131854, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677683

RESUMO

Cellulose-based separators have great application prospects in the field of lithium-ion batteries (LIBs) due to their excellent wettability and thermal stability. However, most current cellulose-based separators come from high-cost nanocellulose and bacterial cellulose. Herein, regenerated cellulose (RC) separators were prepared from dissolving pulp with different degrees of polymerization (DPs) by using the NaOH/urea/thiourea dissolution system as well as a nonsolvent-induced phase separation method. The results showed that the DP of cellulose had a significant influence on the mechanical properties, pore structure, and electrochemical properties of the resultant RC separator. An appropriate increase in the DP could improve the mechanical strength, porosity, and ionic conductivity of the separator. The RC separator with a DP of 599 exhibited the best performance with a porosity of 56.1 %, an average pore size of 305 nm, an electrolyte uptake of 339 %, a tensile strength of 38.3 MPa, and an ionic conductivity of 1.88 mS·cm-1. The lithium-ion battery prepared with the optimal RC separator had a specific capacity of 156.55 mAh/g for 100 cycles at a current density of 0.5 C and a coulombic efficiency of more than 96 %, which was a clear advantage over the commercially available Celgard2400 and cellulose separators. This work makes contributions to the development of high-performance LIBs separators from cellulose.


Assuntos
Celulose , Fontes de Energia Elétrica , Lítio , Polimerização , Celulose/química , Lítio/química , Porosidade , Condutividade Elétrica , Íons/química , Resistência à Tração
18.
Bioresour Technol ; 394: 130179, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38092075

RESUMO

The current study generated co-pyrolysis biochar by pyrolyzing rice straw and pig manure at 300 °C and subsequently applying it in a field. Co-pyrolysis biochar demonstrated superior efficiency in mitigating agricultural non-point source pollution compared to biochar derived from individual sources. Furthermore, it displayed notable capabilities in retaining and releasing nutrients, resulting in increased soil levels of total nitrogen, total phosphorus, and organic matter during the maturation stage of rice. Moreover, co-pyrolysis biochar influences soil microbial communities, potentially impacting nutrient cycling. During the rice maturation stage, the soil treated with co-pyrolysis biochar exhibited significant increases in available nutrients and rice yield compared to the control (p < 0.05). These findings emphasize the potential of co-pyrolysis biochar for in-situ nutrient retention and enhanced soil nutrient utilization. To summarize, the co-pyrolysis of agricultural waste materials presents a promising approach to waste management, contributing to controlling non-point source pollution, improving soil fertility, and promoting crop production.


Assuntos
Poluição Difusa , Oryza , Animais , Suínos , Solo , Temperatura , Nitrogênio , Fósforo , Pirólise , Carvão Vegetal , Nutrientes
19.
Int J Biol Sci ; 20(2): 701-717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169523

RESUMO

Intervertebral disc degeneration (IDD) is a prevalent degenerative disorder that closely linked to aging. Numerous studies have indicated the crucial involvement of autophagy in the development of IDD. However, the non-selective nature of autophagy substrates poses great limitations on the application of autophagy-related medications. This study aims to enhance our comprehension of autophagy in the development of IDD and investigate a novel therapeutic approach from the perspective of selective autophagy receptor NBR1. Proteomics and immunoprecipitation and mass spectrometry analysis, combined with in vivo and in vitro experimental verification were performed. NBR1 is found to be reduced in IDD, and NBR1 retards cellular senescence and senescence-associated secretory phenotype (SASP) of nucleus pulposus cells (NPCs), primarily through its autophagy-dependent function. Mechanistically, NBR1 knockdown leads to the accumulation of S1 RNA-binding domain-containing protein 1 (SRBD1), which triggers cellular senescence via AKT1/p53 and RB/p16 pathways, and promotes SASP via NF-κß pathway in NPCs. Our findings reveal the function and mechanism of selective autophagy receptor NBR1 in regulating NPCs senescence and degeneration. Targeting NBR1 to facilitate the clearance of detrimental substances holds the potential to provide novel insights for IDD treatment.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Humanos , Núcleo Pulposo/metabolismo , Senescência Celular/genética , Envelhecimento , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Autofagia/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Ligação a RNA/metabolismo
20.
Front Med (Lausanne) ; 11: 1372748, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638928

RESUMO

Introduction: This meta-analysis aimed to determine the clinical efficacy of acupuncture combined with core muscle exercises on pain and functional status in patients with chronic nonspecific low back pain. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and meta-analysis criteria for systematic reviews and meta-analyses. Randomized controlled trials published till November 2023 were searched in PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature, and Wanfang databases. The search strategy was related to disease type, intervention, and control measures and was structured around the search terms "low back pain," "acupuncture therapy," and "exercise." Two reviewers applied inclusion and exclusion criteria. Sensitivity and fixed effects analyses were performed to determine the primary outcomes. Results: We included 11 randomized controlled trials (n = 727) on acupuncture combined with core muscle exercises in patients with chronic nonspecific low back pain. Compared with controls, clinical efficacy was significant, with improvements in pain scores (visual analog pain scale and numerical rating scale) and Oswestry Disability Index in the intervention group. Discussion: Acupuncture therapy combined with core muscle exercises improved pain and functional status in patients with chronic nonspecific low back pain, with favorable clinical outcomes compared with single-core muscle training. Multicenter large-sample trials are required to obtain more reliable conclusions.

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