RESUMO
Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.
Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Cobre/farmacologia , Cobre/metabolismo , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológicoRESUMO
Cancer is the most severe health problem facing most people today. Photodynamic therapy (PDT) for tumors has attracted attention because of its non-invasive nature, negligible adverse reactions, and high spatiotemporal selectivity. Developing biocompatible photosensitizers that can target, guide, and efficiently kill cancer cells is desirable in PDT. Here, two amphiphilic organic compounds, PS-I and PSS-II, were synthesized based on the D-π-A structure with a positive charge. The two AIEgens exhibited near-infrared emission, large Stokes shift, high 1O2 and O2-â generation efficiency, good biocompatibility, and photostability. They were co-incubated with cancer cells and eventually accumulated to lysosomes by cell imaging experiments. In vitro and in vivo experiments demonstrated that PS-I and PSS-II could effectively kill cancer cells and sufficiently inhibit tumor growth under light irradiation. PS-I had a higher fluorescence quantum yield in the aggregated state, which made it better for bio-imaging in imaging-guided photodynamic therapy. In contrast, PSS-II with a longer conjugated structure had more ROS generation to kill tumor cells under illumination, and the tumor growth inhibition of mice reached 71.95% during the treatment. No observable injury or undesirable outcomes were detected in the vital organs of the mice within the treatment group, suggesting that PSS-II/PS-I had a promising future in efficient imaging-guided PDT for cancer.
Assuntos
Raios Infravermelhos , Lisossomos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Humanos , Animais , Camundongos , Estrutura Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Desenho de Fármacos , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/diagnóstico por imagem , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , FemininoRESUMO
PURPOSE: The aim of the study was to evaluate the feasibility of a bioabsorbable cage consisting of magnesium and magnesium phosphate cement (MPC) in a porcine lumbar interbody fusion model. METHODS: Twelve male Ba-Ma mini pigs underwent lumbar discectomy and fusion with an Mg-MPC cage or a PEEK cage at the L3/L4 and L4/L5 level. Computed tomography (CT) scans were made to evaluate the distractive property by comparing average disc space height (DSH) before and at 6, 12, and 24 weeks after the operation. After the lumbar spines were harvested at 6 or 24 weeks after the operation, micro-CT examination was conducted to analyze the fusion rate, and stiffness of motion segments was investigated through mechanical tests. A histological study was performed to evaluate the tissue type, inflammation, and osteolysis in the intervertebral space. RESULTS: CT scans showed no significant difference between the two groups in average DSH at each time point. Micro-CT scans revealed an equal fusion rate in both groups (0% at 6 weeks, 83.3% at 24 weeks). Both groups showed time-dependent increases in stability, the Mg-MPC cages achieved an inferior stiffness at 6 weeks and a comparable stiffness at 24 weeks. Histologic evaluation showed the presence of newly formed bone in both groups. However, empty spaces were observed at the interface or around the Mg-MPC cages. CONCLUSION: Compared with the PEEK cages, the Mg-MPC cages achieved comparable distraction, fusion rate, and spinal stability at 24 weeks after the operation. However, due to inferior stiffness at the early stage and fast degradation, further modification of material composition and design are necessary.
RESUMO
In this study, we identified HIF 1α as a potential target for reversing taxol resistance in lung cancer by combining bioinformatics analysis with pharmacological analysis. Furthermore, pomalidomide derivative LY103 was also be synthesized by introducing an isatin analogue into the amino terminal ofpomalidomide, and it has a broad antitumor spectrum and showed excellent activity against A549/Taxol cells (IC50 = 6.33 ± 0.51 µM). The results of molecular docking showed that not only LY103 was inclined to bind to HIF 1α stably, it could also form multiple hydrogen bonds with VAL376, ASP256, ILE454, and GLU455 of HIF 1α even was reduced to LY103-NH2 by nitroreductase, which was further stabilized the complex formed by them, thereby inhibiting the activity of HIF 1α. LY103 was able to significantly induce DNA damage and inhibit angiogenesis. Concurrently, LY103 activated the immune response, reduced the expression of cytokines TNF-α, IL-6, and IL-1ß, thus might be inhibit the proliferation and metastasis of tumor cells. Pharmacological analysis proved that LY103 led to cell apoptosis through the mitochondrial pathway, and its combination with taxol significantly promoted this process. In general, the consumption of glutathione, the crosstalk of energy metabolism, and the improvement of the tumor microenvironment caused by LY103 eventually led to the decrease of ABCC1 protein expression and the drug resistance was reversed. The rational design of LY103 provided a basis for the application of nitro compounds in the treatment of hypoxic tumors and the reversal of taxol resistance.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Metabolismo Energético , Neoplasias Pulmonares/patologia , Simulação de Acoplamento Molecular , Paclitaxel/farmacologia , Microambiente TumoralRESUMO
Organelle-targeted photodynamic therapy has been increasingly investigated in recent decades, but little attention has been paid to the damage caused to other non-primary target organelles during the course of action, even though these non-primary target organelles may play a substantial role in inhibiting the growth of cancer cells. In this contribution, we report an AIE-type strong endoplasmic reticulum-targeted luminogen (MTOQS) with a distorted structure, which is efficient in producing ROS both in cellular and non-cellular environment, causing an effective reduction of high levels of GSH and MDA in cancer cells through the efficient accumulation of intracellular ROS, and the levels of ATP, l-lactic acid, anti-apoptotic factor Bcl-2 and apoptotic protein caspase-3 were determined. Through the identification of these markers, it was evidenced that MTOQS-induced dual organelle oxidative stress could diminish the degree of oxidative phosphorylation and glycolysis in cancer cells and trigger an alteration in the culture environment of cancer cells, while causing damage to the endoplasmic reticulum and mitochondria through multiorganelle oxidative stress, turning on the pathway of apoptosis and consequently driving cancer cells to apoptosis.
Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Retículo Endoplasmático/metabolismo , Mitocôndrias , Apoptose , Neoplasias/metabolismoRESUMO
BACKGROUND: Adjacent segment degeneration (ASD) is a common complication of lumbar interbody fusion; the paraspinal muscles significantly maintain spinal biomechanical stability. This study aims to investigate the biomechanical effects of proximal multifidus injury on adjacent segments during posterior lumbar interbody fusion (PLIF). METHODS: Data from a lumbosacral vertebral computed tomography scan of a healthy adult male volunteer were used to establish a normal lumbosacral vertebral finite element model and load the muscle force of the multifidus. A normal model, an L4/5 PLIF model (PFM) based on a preserved proximal multifidus, a total laminectomy PLIF model (TLPFM), and a hemi-laminectomy PLIF model based on a severed proximal multifidus were established, respectively. The range of motion (ROM) and maximum von Mises stress of the upper and lower adjacent segments were analyzed along with the total work of the multifidus muscle force. RESULTS: This model verified that the ROMs of all segments with four degrees of freedom were similar to those obtained in previous research data, which validated the model. PLIF resulted in an increased ROM and maximum von Mises stress in the upper and lower adjacent segments. The ROM and maximum von Mises stress in the TLPFM were most evident in the upper adjacent segment, except for lateral bending. The ROM of the lower adjacent segment increased most significantly in the PFM in flexion and extension and increased most significantly in the TLPFM in lateral bending and axial rotation, whereas the maximum von Mises stress of the lower adjacent segment increased the most in the TLPFM, except in flexion. The muscle force and work of the multifidus were the greatest in the TLPFM. CONCLUSIONS: PLIF increased the ROM and maximum von Mises stress in adjacent cranial segments. The preservation of the proximal multifidus muscle contributes to the maintenance of the physiological mechanical behavior of adjacent segments, thus preventing the occurrence and development of ASD.
Assuntos
Fusão Vertebral , Adulto , Humanos , Masculino , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Músculos Paraespinais/diagnóstico por imagem , Análise de Elementos Finitos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/fisiologia , Fenômenos Biomecânicos/fisiologia , Amplitude de Movimento ArticularRESUMO
Bradysia odoriphaga and Bradysia difformis are destructive root maggots that cause severe losses to vegetables, flowers and edible fungi. Due to the long-term dependence on single pesticides, Bradysia resistance to insecticides has increased, and field control efficacy has decreased obviously. To screen alternative insecticides, and compare the insecticide susceptibility of these two species, we tested the toxicity of eight insecticides to B. odoriphaga and B. difformis, and measured the sublethal effects of Dinotefuran and Lufenuron on life-history parameters and detoxification enzyme activities. Bioassay results indicated that Dinotefuran and Lufenuron had relatively higher toxicity to B. odoriphaga and B. difformis compared to other neonicotinoid and insect growth regulator insecticides, respectively. Significant adverse impacts caused by sublethal concentrations (LC20) of Dinotefuran and Lufenuron on the life-history parameters of F0 and F1 generations of B. odoriphaga and B. difformis were observed. These included reduced survival, prolonged larval development and reduced adult longevity and fecundity. B. odoriphaga had greater resistance and adaptation to insecticides than B. difformis, and an LC20 concentration of Dinotefuran stimulated the reproduction of B. odoriphaga F1 generation and increased the life table parameters. Detoxifying enzymes (CarE and GSTs) and P450 activities fluctuated after a sublethal concentration (Dinotefuran and Lufenuron) treatment, and at the peak value of enzyme activities, the enhancement of detoxifying enzymes of B. odoriphaga was significantly higher than that of B. difformis. These results indicated that Dinotefuran and Lufenuron should be considered as alternatives to other insecticides for control of root maggots. B. odoriphaga exhibited stronger adaptation to insecticides than B. difformis. These data provide guidance for control of root maggots, and the basic information presented here can help reveal the differences in adaptive mechanisms between B. odoriphaga and B. difformis.
Assuntos
Dípteros , Inseticidas , Animais , Inseticidas/toxicidade , Neonicotinoides/toxicidade , LarvaRESUMO
Bradysia odoriphaga Yang and Zhang (Diptera: Sciaridae), the Chinese chive root maggot, is a destructive pest of Allium vegetables and flowers that causes severe losses in northern China. Novel biological control technologies are needed for controlling this pest. We identified a new entomopathogenic fungus isolated from infected B. odoriphaga larvae and evaluated the susceptibility of the biological stages of B. odoriphaga and the effects of temperature on fungus growth and pathogenicity. Based on morphological characteristics and molecular phylogeny, the fungus was identified as Mucor hiemalis BO-1 (Mucorales: Mucorales). This fungus had the strongest virulence to B. odoriphaga larvae followed by eggs and pupae, while B. odoriphaga adults were not susceptible. A temperature range of 18-28°C was optimum for the growth and sporulation of M. hiemalis BO-1 and virulence to B. odoriphaga larvae. At 3 and 5 d after inoculation with 105 spores/ml at 23°C, the survival rates were 24.8% and 4.8% (2nd instar larvae), respectively, and 49.6% and 12.8% (4th instar larvae), respectively. The potted plant trials confirmed that M. hiemalis BO-1 exerted excellent control efficiency against B. odoriphaga larvae, and the control exceeded 80% within 5 d when the spore concentration applied exceeded 107 spores/ml. In conclusion, these findings supported the hypotheses that this fungus could serve as an effective control agent against B. odoriphaga larvae and is worth being further tested to determine its full potential as a biocontrol agent.
Assuntos
Dípteros , Inseticidas , Mucorales , Animais , Inseticidas/farmacologia , Larva , Mucor , Óvulo , VirulênciaRESUMO
STUDY DESIGN: Analyze the position of the aorta in patients with Pott's thoracolumbar angular kyphosis by computed tomography. OBJECTIVE: To investigate the anatomic position of the aorta relative to spine in patients with Pott's thoracolumbar angular kyphosis. SUMMARY OF BACKGROUND DATA: The complication of aorta injury is rare in the procedure of spinal osteotomy for the correction of Pott's thoracolumbar angular kyphotic deformity. However, there would be a disastrous consequence once it happened. Therefore, knowing about the position of aorta relative to the spine is of great importance. From the authors' knowledge, there are no reports about the research on the position of the aorta relative to the spine in patients with Pott's thoracolumbar angular kyphosis. METHODS: Thirty patients with Pott's thoracolumbar angular kyphosis and thirty patients without spine deformity were recruited and divided into two groups. The CT images of both groups from T10 to L1 were obtained to evaluate the left pedicle-aorta angle and distance. In the patients with Pott's thoracolumbar angular kyphosis, the affected vertebral bodies were fused, so we measured the left pedicle-aorta angle and distance of the fused vertebral bodies. For the normal group, we measured the left pedicle-aorta angle and distance from T10 to L1 and got the average data, then compared with the Pott's group with independent sample t test. The Pearson correlation analysis was used to evaluate the association between the change of the aortic position and Konstam's angle and LL. RESULTS: The left pedicle-aorta angles (-8.95 + 2.89°) in Pott's group are smaller and the distances (6.36 + 0.77 cm) are larger than those in normal group (P < 0.05). In patients with Pott's thoracolumbar angular kyphosis, with increased Konstam's angle, the left pedicle-aorta angles becomes smaller (r = -0.495, P < 0.05) and the left pedicle-aorta distances becomes larger (r = 0.486, P < 0.05). However, there is no remarkable correlation between lumbar lordosis and the left pedicle-aorta angles or distances. CONCLUSION: In patients with Pott's thoracolumbar angular kyphosis, the aorta of the fused vertebrate shifts anteromedially to the vertebral body, and the aorta is relatively farther away from the vertebral body compared with the normal subjects. Therefore, the surgeon should be aware of the change of the position of the aorta to avoid the disastrous complication vessel injury.
Assuntos
Aorta Torácica/anatomia & histologia , Complicações Intraoperatórias/prevenção & controle , Cifose/diagnóstico por imagem , Vértebras Lombares/anatomia & histologia , Vértebras Torácicas/anatomia & histologia , Tuberculose da Coluna Vertebral/complicações , Adulto , Aorta Torácica/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Cifose/etiologia , Cifose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Tuberculose da Coluna Vertebral/diagnóstico por imagemRESUMO
BACKGROUND/AIMS: Neuroinflammation mediated by activated microglia may play a pivotal role in a variety of central nervous system (CNS) pathologic conditions, including ethanol-induced neurotoxicity. The purpose of this study was to investigate the function of Tß4 in ethanol-induced microglia activation. METHODS: Quantitative real-time PCR was conducted to assess the expression of Tß4 and miR-339-5p. Western blot analysis was used to measure the expression of Tß4, phosphorylated p38, ERK, JNK, Akt, and NF-x03BA;B p65. The concentration of TNF-α and IL-1ß was determined using ELISA. NO concentration was measured using a nitric oxide colorimetric BioAssay Kit. Double immunofluorescence was performed to determine Tß4 expression, in order to assess microglial activation in neonatal mouse FASD model. RESULTS: Increased Tß4 expression was observed in ethanol treated microglia. Knockdown of Tß4 enhanced ethanol-induced inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and nitric oxide (NO) in BV-2 cells was performed. Exogenous Tß4 treatment significantly inhibited expression and secretion of these inflammatory mediators. Tß4 treatment attenuated p38, ERK MAPKs, and nuclear factor-kappa B (NF-x03BA;B) pathway activation, and enhanced miR-339-5p expression induced by ethanol exposure in microglia. A neonatal mouse fetal alcohol spectrum disorders (FASD) model showed that Tß4 expression in the microglia of the hippocampus was markedly enhanced, while Tß4 treatment effectively blocked the ethanol-induced increase in inflammatory mediators, to the level expressed in vehicle-treated control animals. CONCLUSION: This study is the first to demonstrate the function of Tß4 in ethanol-induced microglia activation, thus contributing to a more robust understanding of the role of Tß4 treatment in CNS disease.
Assuntos
Etanol/efeitos adversos , Inflamação/induzido quimicamente , Inflamação/imunologia , Microglia/efeitos dos fármacos , Microglia/imunologia , Timosina/imunologia , Animais , Linhagem Celular , Feminino , Inflamação/genética , Interleucina-1beta/imunologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais , Timosina/genética , Fator de Necrose Tumoral alfa/imunologia , Regulação para CimaRESUMO
The ROCK signaling pathway is involved in numerous fundamental cellular functions such as cell migration, apoptosis, inflammatory responses, and neurite outgrowth. Previous studies demonstrate that Fasudil exhibited therapeutic potential of experimental autoimmune encephalomyelitis (EAE) possibly through immune-modulation and anti-inflammation. In this study, we observed the effect of Fasudil on synaptic protection of EAE mice. Fasudil ameliorated the clinical severity of EAE and inhibited Rho kinase (ROCK), especially ROCK II, in brain and spinal cord of EAE mice. Protein extracts from spinal cord of Fasudil-treated EAE mice promoted the formation of neurite outgrowth when co-cultured with primary neurons, indicating that peripheral administration of Fasudil can enter the central nervous system (CNS) and exhibited its biological effect on the formation of neurite outgrowth. Synapse-related molecule synaptophysin was enhanced, and CRMP-2, AMPA receptor, and GSK-3ß were declined in spinal cord of Fasudil-treated mice. Neurotrophic factor BDNF and GDNF as well as immunomodulatory cytokine IL-10 in spinal cord were elevated in Fasudil-treated mice, while inflammatory cytokine IL-17, IL-1ß, IL-6, and TNF-α were obviously inhibited, accompanied by the decrease of inflammatory M1 iNOS and the increase of anti-inflammatory M2 Arg-1, providing a microenvironment that contributes to synaptic protection. Our results indicate that Fasudil treatment protected against synaptic damage and promoted synaptic formation, which may be related with increased neurotrophic factors as well as decreased inflammatory microenvironment in the CNS of EAE mice.
Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Fármacos Neuroprotetores/farmacologia , Sinapses/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Western Blotting , Células Cultivadas , Citocinas , Modelos Animais de Doenças , Feminino , Quinase 3 da Glicogênio Sintase , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento NeuralRESUMO
Carbon monoxide (CO) poisoning is one of the most common diseases induced by CO injury. More than a half of the survivors still likely to have cognitive dysfunction, which is delayed encephalopathy after acute CO poisoning. There is no other effective treatment for delayed encephalopathy after acute CO poisoning except hyperbaric oxygen. Hydrogen sulfide is a novel signal molecule for the central nervous system regulation and plays a role of neural protection in many diseases. H2S has the inhibitory effects on oxidative stress and apoptosis to protect against oxidative damage of nerve. A CO-poisoning rat model was established to detect the effect of H2S on delayed encephalopathy after acute CO poisoning. Spatial learning and memory was tested by Morris water maze. Nissl staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay were used to examine apoptosis induced by CO poisoning in the brain. Then, the protein levels of proinflammatory cytokines and the indicators of oxidative damage were measured. We found that H2S significantly improved cognitive function, reduced apoptosis and the inflammatory response, and decreased the oxidative damage induced by CO poisoning in rats. These results suggest that H2S may be a novel specific and effective treatment of delayed encephalopathy of CO poisoning.
Assuntos
Encefalopatias/tratamento farmacológico , Encefalopatias/etiologia , Intoxicação por Monóxido de Carbono/complicações , Sulfeto de Hidrogênio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cognição/efeitos dos fármacos , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Memória/efeitos dos fármacos , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacosRESUMO
Activated microglia, especially polarized M1 cells, produce pro-inflammatory cytokines and free radicals, thereby contributing directly to neuroinflammation and various brain disorders. Given that excessive or chronic neuroinflammation within the central nervous system (CNS) exacerbates neuronal damage, molecules that modulate neuroinflammation are candidates as neuroprotective agents. In this study, we provide evidence that Safflor yellow (SY), the main active component in the traditional Chinese medicine safflower, modulates inflammatory responses by acting directly on BV2 microglia. LPS stimulated BV2 cells to upregulate expression of TLR4-Myd88 and MAPK-NF-κB signaling pathways and to release IL-1ß, IL-6, TNF-α, and COX-2. However, SY treatment inhibited expression of TLR4-Myd88 and p-38/p-JNK-NF-κB, downregulated expression of iNOS, CD16/32, and IL-12, and upregulated CD206 and IL-10. In conclusion, our results demonstrate that SY exerts an anti-inflammatory effect on BV2 microglia, possibly through TLR-4/p-38/p-JNK/NF-κB signaling pathways and the conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype.
Assuntos
Anti-Inflamatórios/farmacologia , Chalcona/análogos & derivados , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Polaridade Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalcona/farmacologia , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Microglia/fisiologia , Fator 88 de Diferenciação Mieloide/fisiologia , NF-kappa B/fisiologia , Receptor 4 Toll-Like/fisiologiaRESUMO
PURPOSE: Liposarcoma, one of the most common soft tissue sarcomas originates from primitive mesenchymal cells. But spinal involvement of either primary or metastatic liposarcoma is rare. Here we present our experience of seven consecutive patients with spinal liposarcoma. METHOD: We retrospectively reviewed our patients who have spinal liposarcoma from January 2009 to December 2013. All patients were surgically treated at least once at our spine tumor center and be confirmed as liposarcoma after surgery. All patients' information and follow-up data were collected afterwards. RESULTS: A total of six male and one female patients have been included. Five of them had mobile spinal involvement while the others had sacral involvement. Six piecemeal and one en-bloc resections were successfully performed. Patients' Frankel scores were upgraded with one level or at least preserved postoperatively. The average time of follow-up was 24.6 ± 13.9 months. Three patients died 13, 15 and 24 months after surgical treatment, respectively while the other four patients were still alive and one of them alive with disease at the end of follow-up. CONCLUSION: The outcome and prognosis of spinal liposarcoma is poor, and surgical resections should be considered when diagnosis is confirmed. For those whose tumors were too large to resect and/or with multiple metastases, effective treatment options are currently limited. Therefore, multidisciplinary treatment should be adopted, intraoperative chemotherapy, systemic chemotherapy and radiotherapy for instance.
Assuntos
Lipossarcoma/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sacro , Sarcoma/cirurgia , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
AIM: Fasudil, a selective Rho kinase (ROCK) inhibitor, has been shown to alleviate the severity of experimental autoimmune encephalomyelitis (EAE) via attenuating demyelination and neuroinflammation. The aim of this study was to investigate the effects of fasudil on interactions between macrophages/microglia and T cells in a mice EAE model. METHODS: Mouse BV-2 microglia were treated with IFN-γ and fasudil. Cell viability was detected with MTT assay. BV-2 microglia polarization was analyzed using flow cytometry. Cytokines and other proteins were detected with ELISA and Western blotting, respectively. Mice were immunized with MOG35-55 to induce EAE, and then treated with fasudil (40 mg/kg, ip) every other day from d 3 to d 27 pi. Encephalomyelitic T cells were prepared from the spleen of mice immunized with MOG35-55 on d 9 pi. RESULTS: Treatment of mouse BV-2 microglia with fasudil (15 µg/mL) induced significant phenotype polarization and functional plasticity, shifting M1 to M2 polarization. When co-cultured with the encephalomyelitic T cells, fasudil-treated BV-2 microglia significantly inhibited the proliferation of antigen-reactive T cells, and down-regulated IL-17-expressing CD4(+) T cells and IL-17 production. Furthermore, fasudil-treated BV-2 microglia significantly up-regulated CD4(+)CD25(high) and CD4(+)IL-10(+) regulatory T cells (Tregs) and IL-10 production, suggesting that the encephalomyelitic T cells had converted to Tregs. In EAE mice, fasudil administration significantly decreased both CD11b(+)iNOS(+) and CD11b(+)TNF-α(+) M1 microglia, and increased CD11b(+)IL-10(+) M2 microglia. CONCLUSION: Fasudil polarizes BV-2 microglia into M2 cells, which convert the encephalomyelitic T cells into Tregs in the mice EAE model.
Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Anti-Inflamatórios/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Microglia/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/imunologia , Feminino , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Microglia/enzimologia , Microglia/imunologia , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Peptídeos , Fenótipo , Linfócitos T Reguladores/imunologia , Quinases Associadas a rho/metabolismoRESUMO
In most biophysiological processes, sulfur dioxide (SO2) is an important intracellular signaling molecule that plays an important role. The change of SO2 in cells are closely related to various diseases such as neurological disorders and lung cancer, so it is necessary to develop fluorescent probes with the ability to accurately detect SO2 during physiological processes. In this work, we designed and synthesized a multifunctional fluorescent probe TIS. TIS has excellent properties such as near-infrared emission, large stokes shift, excellent SO2 detection capabilities, low detection limit, high specificity and visualization of color change before and after reaction. Simultaneously, TIS has low cytotoxicity, good biocompatibility, clear cell imaging capability and mitochondrial targeting ability. In addition, the ability of TIS to be applied to different material surfaces for latent fingerprint fluorescence imaging was also explored. TIS provides an excellent method for the accurate detection of SO2 derivatives and shows great potential applications in near-infrared cellular imaging and latent fingerprint fluorescence imaging.
Assuntos
Corantes Fluorescentes , Dióxido de Enxofre , Humanos , Corantes Fluorescentes/metabolismo , Dióxido de Enxofre/metabolismo , Células HeLa , Mitocôndrias/metabolismo , Imagem ÓpticaRESUMO
Periplaneta americana residue is a byproduct of using Periplaneta americana in pharmaceutical research and development for extracting active ingredients. Three hundred Three-yellow chickens were selected for the experiment and randomly divided into 6 groups (5 replications per group, 10 chickens per replicate): the control group (group A) was fed a basal ration, and the experimental groups (groups B, C, D, E, and F) were fed experimental diets in which P. americana residue replaced puffed soybean meal at proportions of 20, 40, 60, 80, and 100%, respectively, for a period of 42 d. The aim was to assess the impact of different levels of P. americana residue on the growth, survival, intestinal morphology, digestive enzyme activity, intestinal flora, and intestinal transcriptional responses of Three-yellow chickens. The results indicated that the increase in P. americana residue levels had a linear and quadratic impact on the average daily gain (ADG) and feed conversion ratio (FCR), respectively. The ADG was notably greater in the 40% group than in the 100% group, while the FCR was significantly lower in the 20% and 40% groups than in the 100% group (P < 0.05). Protease, lipase, and amylase activities exhibited a quadratic increase with increasing concentrations of P. americana residue (P < 0.05). Protease and lipase activities were notably greater in the 20% and 40% groups than in the 0% group (control group), amylase activity was significantly greater in the 40% group than in the 0% group (control group) (P < 0.05). Duodenal crypt depth (CD) decreased quadratically with increasing P. americana residue (P < 0.05). The duodenal villus height/crypt depth ratio (V/C) was significantly lower in the 100% group than in the 60% group (P < 0.05). The intestinal villus height (VH) increased quadratically with increasing levels of P. americana residue. The VH in the 60% group was significantly greater than that in the 0% (control group), 20, 80, and 100% groups (P < 0.05). The Chao and Ace indices demonstrated linear and quadratic increases with increasing levels of P. americana residue, while the Pd index showed a quadratic increase with increasing levels of P. americana residue (P < 0.05). The relative abundance profile of Lactobacillus exhibited a linear and quadratic decrease with increasing levels of P. americana residue, with the 100% group showing a significantly lower abundance than the 0% (control group) and 40% groups (P < 0.05). The transcriptome results showed that P. americana residue could enhance the digestive system by promoting vitamin, fat, carbohydrate digestion and absorption, cholesterol metabolism, etc. In conclusion, P. americana residue can replace puffed soybean meal without negatively affecting the growth performance of three-yellow chickens. The low and medium groups had positive effects on the growth performance, digestive enzyme activity, intestinal morphology, intestinal flora, and substance digestion and absorption of three-yellow chickens. The recommended replacement of P. americana residue for puffed soybean meal in the diets of three-yellow chickens ranged from 20% to 60%.
Assuntos
Ração Animal , Galinhas , Dieta , Glycine max , Periplaneta , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/fisiologia , Dieta/veterinária , Ração Animal/análise , Glycine max/química , Distribuição Aleatória , Fenômenos Fisiológicos da Nutrição Animal , Masculino , Microbioma Gastrointestinal/fisiologia , Relação Dose-Resposta a Droga , Intestinos/anatomia & histologiaRESUMO
OBJECTIVE: This study aimed at reporting the results of a transthoracic approach in the treatment of patients with calcified giant herniated thoracic discs (HTDs). METHODS: Fifteen consecutive patients, 11 males and 4 females with a mean age of 46 years (range 33-61), with calcified giant HTDs underwent transthoracic decompression and segmental instrumentation with interbody fusion from November 2004 to September 2010. Clinical data retrospectively examined and compared were levels and types of disc herniation, operative time, blood loss, pre- and postoperative Frankel grades and Japanese Orthopedic Association (JOA) score, and complications. RESULTS: Of the 15 patients, 2 had HTDs at two levels and affected discs were primarily at the T11/12 level (60%). Presenting symptoms included myelopathy, axial back pain, urinary symptoms, and radiculopathy. Disc herniations were classified as central (40%) or paracentral (60%). All discs were successfully removed without dural tears or cerebral spinal fluid leakage. The mean operation time was 179 ± 27 min (range 140-210 min), and the mean estimated blood loss was 840 ± 470 ml (range 300-2,000 ml). Frankel grades improved in 9 patients postoperatively and 12 patients at the last follow-up. The mean JOA score improved from 4.9 to 7.7. All patients reported improvement in symptoms. The average duration of follow-up was 45 ± 24 months (range 7-77 months). CONCLUSIONS: Transthoracic decompression combined with reconstruction, fusion, and fixation is an effective method for the treatment of these lesions and is associated with a low rate of complications, morbidity, and neurological impairment.
Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Calcinose , Descompressão Cirúrgica , Discotomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral , Resultado do TratamentoRESUMO
â¢This is a diagnostic study for a classification for posterior spinal osteotomy procedures via the intervertebral space.â¢Proposed âa novel classification âwith âexcellent reliability âand âvalidity, differ from the SRS-Schwab osteotomy classification.â¢Give a novel definition of "trans-intervertebral osteotomy" (TIO) for posterior spinal osteotomy procedures.â¢Thoroughly discussed about the histories of posterior spinal osteotomy procedures via the intervertebral space.â¢Systematically introduced the TIO technique with fine original schematics.
RESUMO
OBJECTIVE: To analyze the biomechanical effects of proximal iatrogenic muscle-ligaments complex (MLC) damage on adjacent segments following posterior lumbar interbody fusion (PLIF) by finite element (FE) analysis. METHODS: The multifidus muscle force was loaded in the validated intact lumbosacral finite element model. Based on whether undergoing PLIF or the proximal MLC damage, three models were established. Range of motion (ROM) and the maximum von Mises (VM) stress of adjacent segments were analyzed, as well as the average muscle force and work capacity in four loading directions. RESULTS: PLIF results in significant changes in ROM and stress. ROM changed significantly in the upper adjacent segment, the PLIF model changed the most in extension, and the largest change in the lower adjacent segment occurred after MLC damage. The VM stress of the upper adjacent segment occurred in extension of the PLIF model, and that of the lower adjacent segment occurred in rotation after MLC damage. In flexion, ROM, and stress of the damaged MLC fusion model were significantly increased compared with the normal and PLIF models, there was a stepwise amplification. The average muscle force comparison of three models was 5.8530, 12.3185, and 13.4670 N, respectively. The total work capacity comparison was close to that of muscle force. CONCLUSION: PLIF results in increased ROM and the VM stress of adjacent segments, the proximal MLC damage will aggravate this change. This may increase the risk of ASD and chronic low back pain. Preserving the proximal MLC reduces the biomechanical effects on adjacent segments.