RESUMO
PURPOSE: This study aimed to find a standard of the vertebra kinematics during functional weight-bearing activities in degenerative lumbar scoliosis (DLS) patients. METHODS: Fifty-four patients were involved into this study with forty-two in DLS group and twelve in the control group. The three-dimensional (3D) vertebral models from L1 to S1 of each participant were reconstructed by computed tomography (CT). Dual-orthogonal fluoroscopic imaging, along with FluoMotion and Rhinoceros software, was used to record segmental vertebral kinematics during functional weight-bearing activities. The primary and coupled motions of each vertebra were analyzed in patients with DLS. RESULTS: During flexion-extension of the trunk, anteroposterior (AP) translation and craniocaudal (CC) translation at L5-S1 were higher than those at L2-3 (9.3 ± 5.1 mm vs. 6.4 ± 3.5 mm; P < 0.05). The coupled mediolateral (ML) translation at L5-S1 in patients with DLS was approximately three times greater than that in the control group. During left-right bending of the trunk, the coupled ML rotation at L5-S1 was higher in patients with DLS than that in the control group (17.7 ± 10.3° vs. 8.4 ± 4.4°; P < 0.05). The AP and CC translations at L5-S1 were higher than those at L1-2, L2-3, and L3-4. During left-right torsion of the trunk, the AP translation at L5-S1 was higher as compared to other levels. CONCLUSIONS: The greatest coupled translation was observed at L5-S1 in patients with DLS. Coupled AP and ML translations at L5-S1 were higher than those in healthy participants. These data improved the understanding of DLS motion characteristics.
Assuntos
Vértebras Lombares , Escoliose , Humanos , Vértebras Lombares/diagnóstico por imagem , Escoliose/diagnóstico por imagem , Fenômenos Biomecânicos , Amplitude de Movimento Articular , RotaçãoRESUMO
Intervertebral disc degeneration (IDD) is the most important pathological basis of degenerative spinal diseases, for which effective interventions are still lacking. Oxidative stress is considered to be one of the leading pathological mechanisms contributing to IDD. However, the exact role of DJ-1 as an essential member of the antioxidant defense system in IDD is still unclear. Therefore, the aim of this study was to investigate the role played by DJ-1 in IDD and to reveal its potential molecular mechanisms. Western blot and immunohistochemical staining assays were performed to detect the expression of DJ-1 in degenerative nucleus pulposus cells (NPCs). After overexpression of DJ-1 in NPCs by lentiviral transfection, DCFH-DA and MitoSOX fluorescent probes were used to evaluate the levels of reactive oxygen species (ROS); while western blot, TUNEL staining, and Caspase-3 activity were used to assess apoptosis. Immunofluorescence staining was used to demonstrate the relationship between DJ-1 and p62. After inhibition of lysosomal degradation function with chloroquine, p62 degradation and apoptosis in DJ-1 overexpressing NPCs were further examined. In vivo, we assessed the therapeutic effect of upregulated DJ-1 on IDD by X-ray, MRI and Safranin O-Fast green staining. The protein expression of DJ-1 was significantly decreased in degenerated NPCs, accompanied by increased apoptosis. However, overexpression of DJ-1 significantly inhibited the elevated ROS levels and apoptosis in NPCs under oxidative stress. Mechanistically, our results showed that upregulation of DJ-1 promoted p62 degradation via the autophagic lysosomal pathway and that the protective effect of DJ-1 on NPCs under oxidative stress was partially mediated by promoting lysosomal pathway degradation of p62. Moreover, intradiscal injection of adeno-associated virus for overexpression of DJ-1 mitigated the progression of IDD in rats. This study reveals that DJ-1 maintains the homeostasis of NPCs by promoting the degradation of p62 through the autophagic lysosomal pathway, suggesting that DJ-1 is a promising new target for IDD intervention.
Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Ratos , Apoptose , Autofagia , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Espécies Reativas de Oxigênio , Terapia de Alvo MolecularRESUMO
Aging is an inevitable biological process, and longevity may be related to bone health. Maintaining strong bone health can extend one's lifespan, but the exact mechanism is unclear. Bone and extraosseous organs, including the heart and brain, have complex and precise communication mechanisms. In addition to its load bearing capacity, the skeletal system secretes cytokines, which play a role in bone regulation of extraosseous organs. FGF23, OCN, and LCN2 are three representative bone-derived cytokines involved in energy metabolism, endocrine homeostasis and systemic chronic inflammation levels. Today, advanced research methods provide new understandings of bone as a crucial endocrine organ. For example, gene editing technology enables bone-specific conditional gene knockout models, which allows the study of bone-derived cytokines to be more precise. We systematically evaluated the various effects of bone-derived cytokines on extraosseous organs and their possible antiaging mechanism. Targeting aging with the current knowledge of the healthy skeletal system is a potential therapeutic strategy. Therefore, we present a comprehensive review that summarizes the current knowledge and provides insights for futures studies.
Assuntos
Osso e Ossos , Sistema Endócrino , Humanos , Sistema Endócrino/metabolismo , Osso e Ossos/metabolismo , Envelhecimento , Longevidade , Citocinas/metabolismoRESUMO
STUDY DESIGN: Systematic review. BACKGROUND CONTEXT: Thoracic ossification of the ligamentum flavum (TOLF) has become the principal cause of thoracic spinal stenosis. Dural ossification (DO) was a common clinical feature accompanying with TOLF. However, on account of the rarity, we know little about the DO in TOLF so far. PURPOSE: This study was conducted to elucidate the prevalence, diagnostic measures, and impact on the clinical outcomes of DO in TOLF by integrating the existing evidence. METHODS: PubMed, Embase, and Cochrane Database were comprehensively searched for studies relevant to the prevalence, diagnostic measures, or impact on the clinical outcomes of DO in TOLF. All retrieved studies meeting the inclusion and criterion were included into this systematic review. RESULTS: The prevalence of DO in TOLF treated surgically was 27% (281/1046), ranging from 11 to 67%. Eight diagnostic measures have been put forward to predict the DO in TOLF using the CT or MRI modalities, including "tram track sign", "comma sign", "bridge sign", "banner cloud sign", "T2 ring sign", TOLF-DO grading system, CSAOR grading system, and CCAR grading system. DO did not affect the neurological recovery of TOLF patients treated with the laminectomy. The rate of dural tear or CSF leakage in TOLF patients with DO was approximately 83% (149/180). CONCLUSION: The prevalence of DO in TOLF treated surgically was 27%. Eight diagnostic measures have been put forward to predict the DO in TOLF. DO did not affect the neurological recovery of TOLF treated with laminectomy but was associated with high risk of complications.
Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Humanos , Osteogênese , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/epidemiologia , Ossificação Heterotópica/cirurgia , Ligamento Amarelo/diagnóstico por imagem , Ligamento Amarelo/cirurgia , Prevalência , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Estudos RetrospectivosRESUMO
Here, we report a novel amino-modified mesoporous-structured aluminum-based metal-organic framework adsorbent, MIL-68(Al)/MCM-41-NH2, for dye sewage treatment. The introduction of molecular sieves overcomes the inherent defects of microporous MOFs in contaminant transfer and provides more active sites to enhance adsorption efficiency. Compared with using organic amino ligands directly, this strategy is ten times cheaper. The composite was well characterized and analyzed in terms of morphology, structure and chemical composition. Batch experiments were carried out to study the influences of essential factors on the process, such as pH and temperature. In addition, their interactions and the optimum conditions were examined using response surface methodology (RSM). The adsorption kinetics, isotherms and thermodynamics were systematically elucidated. In detail, the adsorption process conforms to pseudo-second-order kinetics and follows the Sips and Freundlich isothermal models. Moreover, the maximum adsorption capacity Qs of methyl orange (MO) was 477 mg g-1. It could be concluded that the process was spontaneous, exothermic, and entropy-reducing. Several binary dye systems have been designed for selective adsorption research. Our material has an affinity for anionic pigments. The adsorption mechanisms were discussed in depth. The electrostatic interaction might be the dominant effect. Meanwhile, hydrogen bonding, π-π stacking, and pore filling might be important driving forces. The excellent thermal stability and recyclability of the adsorbent are readily noticed. After five reuse cycles, the composite still possesses a removal efficiency of 90% for MO. Overall, the efficient and low-cost composite can be regarded as a promising adsorbent for the selective adsorption of anionic dyes from wastewater.
Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Adsorção , Alumínio/química , Compostos Azo , Corantes , Concentração de Íons de Hidrogênio , Cinética , Esgotos , Dióxido de Silício , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Heterotopic ossification (HO) is a common disease characterized by pain, dysfunction and calcification. The mechanisms underlying HO have not been completely elucidated. Palovarotene, a retinoic acid receptor γ agonist, significantly inhibits the formation of HO in vivo. However, its specific mechanism of action remains unclear. Therefore, we aimed to evaluate the signalling pathways related to the formation of HO as well as the mechanism of palovarotene action. We constructed in vitro and in vivo models of HO. Osteogenic differentiation of bone mesenchymal stem cells (BMSCs) was observed by alizarin red and alkaline phosphatase staining assays in vitro. X-ray and haematoxylin-eosin staining were performed in vivo. Western blots and reverse transcription-polymerase chain reaction were performed to determine the levels of osteogenic- and inflammation-related genes. Immunofluorescence and immunocytochemistry were used to assess the levels of p65, the core molecule of the nuclear factor κ-B (NF-κB) signalling pathway. We demonstrated that, in vitro, under inflammatory stimulation, pathological calcium deposition increased in BMSCs. The levels of osteogenesis- and inflammation-related genes were also upregulated, along with an enhanced expression of p65. Immunofluorescence assays revealed that p65 entered the nucleus, thereby stimulating the downstream effectors of the NF-κB pathway. The above trends were reversed after palovarotene treatment. In conclusion, the NF-κB signalling pathway played an important role in HO, and palovarotene could alleviate HO by blocking the NF-κB cascade. Our results may provide a theoretical basis for palovarotene in the treatment of HO. Further studies on the side effects of palovarotene are warranted in the future.
Assuntos
Ossificação Heterotópica , Pirazóis , Transdução de Sinais , Estilbenos , Animais , Diferenciação Celular , Humanos , Inflamação , Células-Tronco Mesenquimais , NF-kappa B , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/prevenção & controle , Osteogênese , Pirazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologiaRESUMO
Background: Inflammation has been considered to play an important role in the pathogenesis of the thoracic ossification of the ligamentum flavum (OLF). However, the inflammation-related risk factors of thoracic OLF have not been fully investigated to date. Methods: A total of 95 patients (48 in the OLF group and 47 in the control group) were included in this retrospective study to explore the independent risk factors of thoracic OLF. The following demographic and clinical variables were compared between the two groups: gender, age, body mass index (BMI), coexistence of hypertension or diabetes, and inflammation-related variables. Multivariate logistic regression analysis was utilized to determine the independent risk factors. Results: High systemic immune-inflammation index (SII) (≥621) (odds ratio [OR] = 12.16, 95% confidence interval [CI] = 2.95-50.17, p < 0.01) and BMI (≥25 kg/m2) (OR = 9.17, 95%CI = 3.22-26.08, p < 0.01) were independent risk factors of thoracic OLF. SII (R = 0.38, p < 0.01) and BMI (R = 0.46, p < 0.01) were positively associated with OLF score. Conclusion: High SII and BMI were the independent risk factors of thoracic OLF. Multicenter prospective studies with a large population should be conducted in the future to verify our findings.
Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Índice de Massa Corporal , Humanos , Inflamação/patologia , Ligamento Amarelo/patologia , Ossificação Heterotópica/patologia , Osteogênese , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Vértebras Torácicas/patologiaRESUMO
PURPOSE: To investigate the risk factors for thoracic ossification of the ligamentum flavum (TOLF), especially the relationship between BMI and TOLF. METHODS: A total of 856 individuals consisting of 326 controls without ossification of spinal ligaments and 530 TOLF inpatients who underwent thoracic spine decompression surgery at our hospital between January 2013 and September 2020 were included. All subjects were classified into 4 grades: Grade 0) control; Grade 1) single-segment TOLF; Grade 2) multi-segment TOLF; and Grade 3) TOLF combined thoracic ossification of the posterior longitudinal ligament (T-OPLL). Logistic regression analysis was performed to identify the risk factors for TOLF. The TOLF index was calculated to assess the severity of TOLF, and its relationship with BMI was investigated by correlation analysis. RESULTS: Overall, TOLF patients are most numerous in the 50-59 age group. Age and gender were considered as independent risk factors for Grades 1 and 2. BMI was identified as an independent risk factor for TOLF. Furthermore, BMI was significantly higher in Grade 1 (26.1 VS 24.5 kg/m2, P = 0.0001), Grade 2 (28.2 VS 24.5 kg/m2, P < 0.0001), and Grade 3 (29.1 VS 24.5 kg/m2, P < 0.0001) than Grade 0. Notably, in TOLF patients without combined T-OPLL, BMI was positively correlated with TOLF index, while BMI was negatively correlated with age in younger individuals. CONCLUSION: BMI is a crucial risk factor for TOLF. It highlights the necessity of close follow-up of asymptomatic TOLF patients with high BMI to detect and treat their TOLF progression promptly.
Assuntos
Ligamento Amarelo , Ossificação do Ligamento Longitudinal Posterior , Ossificação Heterotópica , Humanos , Índice de Massa Corporal , População do Leste Asiático , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Ligamento Amarelo/cirurgia , Ligamentos Longitudinais , Ossificação Heterotópica/epidemiologia , Ossificação Heterotópica/cirurgia , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação do Ligamento Longitudinal Posterior/epidemiologiaRESUMO
OBJECTIVE: To elucidate the role of LRRK2 in intervertebral disc degeneration (IDD) as well as its mitophagy regulation mechanism. METHODS: The expression of LRRK2 in human degenerative nucleus pulposus tissues as well as in oxidative stress-induced rat nucleus pulposus cells (NPCs) was detected by western blot. LRRK2 was knocked down in NPCs by lentivirus (LV)-shLRRK2 transfection; apoptosis and mitophagy were assessed by western blot, TUNEL assay, immunofluorescence staining and mitophagy detection assay in LRRK2-deficient NPCs under oxidative stress. After knockdown of Parkin in NPCs with siRNA transfection, apoptosis and mitophagy were further assessed. In puncture-induced rat IDD model, X-ray, MRI, hematoxylin-eosin (HE) and Safranin O-Fast green (SO) staining were performed to evaluate the therapeutic effects of LV-shLRRK2 on IDD. RESULTS: We found that the expression of LRRK2 was increased in degenerative NPCs both in vivo and in vitro. LRRK2 deficiency significantly suppressed oxidative stress-induced mitochondria-dependent apoptosis in NPCs; meanwhile, mitophagy was promoted. However, these effects were abolished by the mitophagy inhibitor, suggesting the effect of LRRK2 on apoptosis in NPCs is mitophagy-dependent. Furthermore, Parkin knockdown study showed that LRRK2 deficiency activated mitophagy by recruiting Parkin. In vivo study demonstrated that LRRK2 inhibition ameliorated IDD in rats. CONCLUSIONS: The results revealed that LRRK2 is involved in the pathogenesis of IDD, while knockdown of LRRK2 inhibits oxidative stress-induced apoptosis through mitophagy. Thus, inhibition of LRRK2 may be a promising therapeutic strategy for IDD.
Assuntos
Apoptose/genética , Degeneração do Disco Intervertebral/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mitofagia/genética , Núcleo Pulposo/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Humanos , Degeneração do Disco Intervertebral/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Estresse Oxidativo/genética , RatosRESUMO
Inflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS-IV), in vitro and in vivo. Our results showed that AS-IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS-IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS-IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS-IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS-IV may become a novel therapeutic medicine for SCI.
Assuntos
Inflamação/prevenção & controle , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Microglia/citologia , Neurônios/citologia , Recuperação de Função Fisiológica , Saponinas/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Triterpenos/farmacologia , Animais , Apoptose , Autofagia , Polaridade Celular , Células Cultivadas , Modelos Animais de Doenças , Feminino , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
Diabetes mellitus may lead to intervertebral disc degeneration (IVDD). Matrix metalloproteinase-13 (MMP-13) is one of the major catabolic factors in extracellular matrix (ECM) metabolism of nucleus pulposus cells (NPCs) and contributes to diabetic IVDD. Bromodomain-containing protein 4 (BRD4) is a member of the bromodomain and extraterminal protein family and is implicated in chronic inflammation. Here, we report that the expression of BRD4 and MMP-13 was elevated in diabetic nucleus pulposus tissues as well as in advanced glycation end products (AGEs)-treated NPCs; also, the regulatory effect of BRD4 on MMP-13 was studied. We found that MMP-13 was regulated by MAPK and NF-κB signaling as well as autophagy in AGEs-treated NPCs. Next, we explored the role of BRD4 in regulation of MAPK, NF-κB signaling, and autophagy. The results showed that BRD4 is the upstream regulator of all of these 3 factors, and inhibition of BRD4 may suppress MAPK and NF-κB signaling while activating autophagy in AGEs-treated NPCs. Finally, we demonstrated that BRD4 inhibition may suppress MMP-13 expression in diabetic NPCs in vitro as well as in vivo; meanwhile, it may preserve ECM in diabetic rats. Our study demonstrates that inhibition of BRD4 may suppress MAPK and NF-κB signaling and activate autophagy to suppress MMP-13 expression in diabetic IVDD, and diabetic IVDD may be compromised by BRD4 inhibitors.-Wang, J., Hu, J., Chen, X., Huang, C., Lin, J., Shao, Z., Gu, M., Wu, Y., Tian, N., Gao, W., Zhou, Y., Wang, X., Zhang, X. BRD4 inhibition regulates MAPK, NF-κB signals, and autophagy to suppress MMP-13 expression in diabetic intervertebral disc degeneration.
Assuntos
Autofagia/fisiologia , Proteínas de Ciclo Celular/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Adulto , Animais , Diabetes Mellitus/metabolismo , Feminino , Humanos , Disco Intervertebral/metabolismo , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To determine the incidence of and risk factors for residual back pain in osteoporotic vertebral compression fracture (OVCF) patients after percutaneous kyphoplasty (PKP) treatment, we performed a retrospective analysis of prospective data. METHODS: Patients who underwent bilateral PKP and met this study's inclusion criteria were retrospectively reviewed. Back pain intensity was assessed using a visual analogue scale (VAS) after surgery. Residual back pain was defined as the presence of postoperative moderate-severe pain (average VAS score ≥ 4), and the variables included patient characteristics, baseline symptoms, radiological parameters and surgical factors. Univariate and multivariate logistic regression analyses were performed to identify risk factors. RESULTS: A total of 809 patients were included, and residual back pain was identified in 63 (7.8%) patients. Of these patients, 52 patients had complete data for further analysis. Multivariate logistic regression analysis showed that risk factors for back pain included the presence of an intravertebral vacuum cleft (OR 2.93, P = 0.032), posterior fascia oedema (OR 4.11, P = 0.014), facet joint violations (OR 12.19, P < 0.001) and a separated cement distribution (OR 2.23, P = 0.043). CONCLUSION: The incidence of postoperative residual back pain was 7.8% among 809 OVCF patients following PKP. The presence of an intravertebral vacuum cleft, posterior fascia oedema, facet joint violations and a separated cement distribution were identified as independent risk factors for residual back pain.
Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Dor nas Costas/epidemiologia , Dor nas Costas/etiologia , Cimentos Ósseos , Fraturas por Compressão/epidemiologia , Fraturas por Compressão/cirurgia , Humanos , Cifoplastia/efeitos adversos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: No study so far has paid attention to strabismus-related spinal imbalance. This study aimed to determine the epidemiology of thoracic scoliosis in children and adolescents with strabismus and investigate the association of two diseases. METHODS AND DESIGN: A cross-sectional study. Study group consists of 1935 consecutive candidates for strabismus surgery (4-18 years); Control group consists of the age- and sex-matched patients with respiratory diseases. All subjects underwent a screening program based on chest plain radiographs using the Cobb method. Their demographic information, clinical variables and results of Cobb angle were recorded and analyzed. RESULTS: A significantly higher prevalence of thoracic scoliosis (289/1935, 14.94% versus 58/1935, 3.00%) was found in study group compared with control group. Among strabismic patients, the coronal thoracic scoliosis curve mainly distributed in right and in main thoracic (198/289) and in the curves 10°-19° (224/289); Age range 7-9 years (103/1935), female (179/1935) and concomitant exotropia patients (159/851) were more likely to have thoracic scoliosis. According to the logistic regression, thoracic scoliosis had no significant association with age, BMI, duration of illness and onset age (p > 0.05). However, gender, BCVA, type of strabismus and degree of strabismus showed a significant relationship with the prevalence of thoracic scoliosis (p < 0.05). CONCLUSIONS: With a pooled prevalence of 14.94%, strabismus patients showed a great higher risk of developing thoracic scoliosis. Screening for scoliosis in strabismus patients can be helpful to discover a high prevalence of potential coronal scoliosis. More attention should be paid to ophthalmological problems in patients with scoliosis. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Escoliose , Fusão Vertebral , Estrabismo , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/cirurgia , Estrabismo/epidemiologia , Estrabismo/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do TratamentoRESUMO
Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose-dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3-methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX-527 suppressed melatonin-induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1-autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1-autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.
Assuntos
Calcinose/tratamento farmacológico , Condrócitos/efeitos dos fármacos , Melatonina/farmacologia , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Calcinose/metabolismo , Calcinose/patologia , Carbazóis/farmacologia , Células Cultivadas , Condrócitos/patologia , Modelos Animais de Doenças , Feminino , Degeneração do Disco Intervertebral/induzido quimicamente , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Sirtuína 1/antagonistas & inibidores , terc-Butil Hidroperóxido/toxicidadeRESUMO
To address the obstacles facing cancer chemotherapeutics, including toxicity, side effects, water insolubility, and lack of tumor selectivity, a novel stimuli-responsive drug-delivery system was developed based on paclitaxel-loaded poly(ethylene glycol)-disulfide-paclitaxel conjugate nanoparticles (PEG-SS-PTX/PTX NPs). The formulation emphasizes several benefits, including polymer-drug conjugates/prodrugs, self-assembled NPs, high drug content, redox responsiveness, and programmed drug release. The PTX-loaded, self-assembled NPs, with a uniform size of 103 nm, characterized by DLS, TEM, XRD, DSC, and (1)H NMR, exhibited excellent drug-loading capacity (15.7%) and entrapment efficiency (93.3%). PEG-SS-PTX/PTX NPs were relatively stable under normal conditions but disassembled quickly under reductive conditions, as indicated by their triggered-aggregation phenomena and drug-release profile in the presence of dithiothreitol (DTT), a reducing agent. Additionally, by taking advantage of the difference in the drug-release rates between physically loaded and chemically conjugated drugs, a programmed drug-release phenomenon was observed, which was attributed to a higher concentration and longer action time of the drugs. The influence of PEG-SS-PTX/PTX NPs on in vitro cytotoxicity, cell cycle progression, and cellular apoptosis was determined in the MCF-7 cell line, and the NPs demonstrated a superior anti-proliferative activity associated with PTX-induced cell cycle arrest in G2/M phase and apoptosis compared to their nonresponsive counterparts. Moreover, the redox-responsive NPs were more efficacious than both free PTX and the non-redox-responsive formulation at equivalent doses of PTX in a breast cancer xenograft mouse model. This redox-responsive PTX drug delivery system is promising and can be explored for use in effective intracellular drug delivery.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/química , Paclitaxel/uso terapêutico , Polietilenoglicóis/química , Polímeros/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , CamundongosRESUMO
Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.
Assuntos
Antioxidantes , Cobre , Antioxidantes/farmacologia , Pele , Peptídeos/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
Backgrounds: The ossification of the ligamentum flavum (OLF) is one of the major causes of thoracic myelopathy. Previous studies indicated there might be a potential link between metabolic disorder and pathogenesis of OLF. The aim of this study was to determine the potential role of metabolic disorder in the pathogenesis of OLF using the strict bioinformatic workflow for metabolism-related genes and experimental validation. Methods: A series of bioinformatic approaches based on metabolism-related genes were conducted to compare the metabolism score between OLF tissues and normal ligamentum flavum (LF) tissues using the single sample gene set enrichment analysis. The OLF-related and metabolism-related differentially expressed genes (OMDEGs) were screened out, and the biological functions of OMDEGs were explored, including the Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and protein-protein interaction. The competing endogenous RNA (ceRNA) network based on pairs of miRNA-hub OMDEGs was constructed. The correlation analysis was conducted to explore the potential relationship between metabolic disorder and immunity abnormality in OLF. In the end, the cell experiments were performed to validate the roles of GBE1 and TNF-α in the osteogenic differentiation of LF cells. Results: There was a significant difference of metabolism score between OLF tissues and normal LF tissues. Forty-nine OMDEGs were screened out and their biological functions were determined. The ceRNA network containing three hub OMDEGs and five differentially expressed miRNAs (DEmiRNAs) was built. The correlation analysis between hub OMDEGs and OLF-related infiltrating immune cells indicated that metabolic disorder might contribute to the OLF via altering the local immune status of LF tissues. The cell experiments determined the important roles of GBE1 expression and TNF-α in the osteogenic differentiation of LF cells. Conclusions: This research, for the first time, preliminarily illustrated the vital role of metabolic disorder in the pathogenesis of OLF using strict bioinformatic algorithms and experimental validation for metabolism-related genes, which could provide new insights for investigating disease mechanism and screening effective therapeutic targets of OLF in the future.
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Heterojunction structure and ion doping techniques are viable tactics in facilitating the generation and separation of photogenerated electrons and holes in photocatalysis. In the current study, a novel Bi ion-doped MIL-68(In,Bi)-NH2@BiOBr (MIBN@BOB) type-II heterojunction was first synthesized in a one-step solvothermal reaction. Doping of Bi ions not only broadened the light-sensing range but also provided reliable anchor sites for the in situ growth of BiOBr. Meanwhile, the heterostructure supplied new channels for photogenerated carriers, accelerating the transfer and inhibiting the recombination of photogenerated electron-hole. The obtained MIBN@BOB exhibited enhanced photocatalytic performance (91.1%) than MIL-68(In)-NH2 (40.8%) and BiOBr (57.5%) in ciprofloxacin (CIP) degradation under visible light, with excellent reusability. Photocatalysts were characterized in detail, and a series of photoelectrochemical tests were utilized to analyze the photoelectric properties. MIBN@BOB were deduced to conform the electron conduction mechanism of conventional type-II heterojunctions. More importantly, based on the above experiments and density functional theory (DFT) calculation, BiOBr-Bi in MIBN@BOB can serve as the major active sites of CIP enrichment, and â¢O2- and 1O2 generated at the BiOBr interface can react with the adsorbed CIP directly. Lastly, the possible degradation products and pathways of CIP were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). This study provides a reference for the construction of ion-doping-modified metal-organic framework (MOF)-based heterojunction photocatalysts and their application in antibiotic removal.
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Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.
Assuntos
Degeneração do Disco Intervertebral , Mitofagia , Proteína Desglicase DJ-1 , Animais , Ratos , Apoptose , Hexoquinase/genética , Hexoquinase/farmacologia , Hexoquinase/uso terapêutico , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Mitofagia/genética , Mitofagia/fisiologia , Proteínas Proto-Oncogênicas c-akt , Ubiquitina-Proteína Ligases/genética , Proteína Desglicase DJ-1/metabolismoRESUMO
Magnetic phosphorous biochar ï¼MPBCï¼ was prepared from Camellia oleifera shells using phosphoric acid activation and iron co-deposition. The materials were characterized and analyzed through scanning electron microscopy ï¼SEMï¼ï¼ X-ray diffractometry ï¼XRDï¼ï¼ specific surface area and pore size analysis ï¼BETï¼ï¼ Fourier infrared spectroscopy ï¼FT-IRï¼ï¼ and X-ray photoelectron spectroscopy ï¼XPSï¼. MPBC had a high surface area ï¼1 139.28 m2·g-1ï¼ and abundant surface functional groupsï¼ and it could achieve fast solid-liquid separation under the action of an external magnetic field. The adsorption behavior and influencing factors of sulfamethoxazole ï¼SMXï¼ in water were investigated. The adsorbent showed excellent adsorption properties for SMX under acidic and neutral conditionsï¼ and alkaline conditions and the presence of CO32- had obvious inhibition on adsorption. The adsorption process conformed to the quasi-second-order kinetics and Langmuir model. The adsorption rate was fastï¼ and the maximum adsorption capacity reached 356.49 mg·g-1. The adsorption process was a spontaneous exothermic reactionï¼ and low temperature was beneficial to the adsorption. The adsorption mechanism was mainly the chemisorption of pyrophosphate surface functional groups ï¼C-O-P bondï¼ between the SMX molecule and MPBC and also included hydrogen bondingï¼ π-π electron donor-acceptor ï¼π-πEDAï¼ interactionï¼ and a pore filling effect. The development of MPBC adsorbent provides an effective way for resource utilization of waste Camellia oleifera shells and treatment of sulfamethoxazole wastewater.