RESUMO
To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1â¶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-â /LC3B-â ¡, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-â ¡/LC3B-â , SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sirtuína 1/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Autofagia , FígadoRESUMO
Spinal cord injury (SCI) results in a loss of normal motor and sensory function, leading to severe disability and reduced quality of life. The aim of this work was to investigate the effect of receptor for advanced glycation end products (RAGE) deficiency on the function recovery in a mouse model of SCI. Mice received a mid-thoracic spinal contusion injury. Upregulation of RAGE protein expression in spinal cord tissue was evident at 12 h after SCI and continued at 2 and 5 days. Furthermore, we showed that locomotor recovery was improved and lesion pathology was reduced after SCI in RAGE-deficient mice. RAGE deficiency in mice attenuated apoptosis after SCI through inhibiting p53/Bax/caspase-3 pathway. RAGE deficiency in mice inhibited inflammation after SCI, marked by reduced myeloperoxidase activity, NFκB nuclear translocation, and TNF-α, IL-1ß, and IL-6 mRNA and protein levels. RAGE deficiency in mice exposed to SCI suppressed the upregulation of inducible nitric oxide synthase (iNOS) and gp91-phox and attenuated oxidative and nitrosative stresses, marked by reduced formation of malondialdehyde, reactive oxygen species, peroxynitrite (OONO(-)), and 3-nitrotyrosine. RAGE deficiency in mice exposed to SCI attenuated glial scar at the injury site, marked by decreased expression of glial fibrillary acidic protein. These data indicate that the RAGE plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.
Assuntos
Regulação da Expressão Gênica/genética , Inflamação/genética , Estresse Oxidativo/genética , Receptores Imunológicos/biossíntese , Traumatismos da Medula Espinal/genética , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/patologia , Interleucina-6/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologiaRESUMO
OBJECTIVES: To retrospectively investigate the outcome of transpedicular intracorporeal grafting and posterolateral grafting in treatment of thoracolumbar burst fractures. METHODS: Forty-six patients treated with transpedicular intracorporeal grafting from January 1999 to December 2009 and followed up for 19-119 months (average 67 ± 13 months) were reviewed retrospectively, and were compared with 18 patients who had underwent posterolateral fusion during the same period through radiographic analysis. Radiographic measurements included Cobb angle, vertebral wedge angle (VWA), ratio between anterior and posterior vertebral height (APHR), upper inter-vertebral angle, lower inter-vertebral angle on X-ray, CT and MRI. RESULTS: In transpedicular intracorporeal grafting group, the VWA was corrected from 27.2° ± 6.5° to 7.0° ± 3.0° and the APHR from (53.3 ± 11.8)% to (92.3 ± 2.4)%. In posterolateral fusion group, the VWA was corrected from 23.9° ± 4.4° to 8.8° ± 2.1° and the APHR from (60.7 ± 10.0)% to (88.5 ± 3.3)%. Transpedicular intracorporeal grafting group showed better postoperative correction results than posterolateral fusion group (P < 0.05), and had less loss of correction of Cobb angle, VWA and APHR at final follow-up (P < 0.05). CONCLUSIONS: The transpedicular intracorporeal grafting can improve injured vertebral body morphology recovery better than posterolateral bone grafting, but can not prevent the late loss of correction after implant removal.
Assuntos
Transplante Ósseo/métodos , Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To investigate the spatial structure of pedicle rib units in normal thoracic human spines and to compare the dimensions of the pedicle rib unit with corresponding dimensions. METHODS: Thoracic spine specimens in four fresh adult cadaveric were used. Computerized tomographic (CT) images (including two-dimensional, three-dimensional reconstruction) of the thoracic spines were obtained. Measurement parameters include:the width, the height, the chord length and the sagittal angles of the pedicle rib unit compared with pedicle, especially for the pedicle-rib overlapping height. RESULTS: The pedicle rib unit was not a simple two-dimensional structure but a three-dimensional structure. The shortest height of pedicle rib unit was (12.6 ± 0.8) mm (T(1)), while the longest was (16.9 ± 1.1) mm (T(11)). The shortest height of pedicle-rib overlap was (7.2 ± 0.3) mm (T(1)), while the longest was (11.8 ± 1.0) mm (T(10)). The height of pedicle rib unit and the height of pedicle were significantly larger than that of the pedicle-rib overlap (P < 0.05), while there was no significantly difference between the height of pedicle rib unit and the height of pedicle (P > 0.05). CONCLUSIONS: The pedicle rib unit is a complicated spatial structure, and the longitudinal height of pedicle-rib overlap should be taken as the real height of the unit.
Assuntos
Costelas/anatomia & histologia , Vértebras Torácicas/anatomia & histologia , Adulto , Parafusos Ósseos , Humanos , Masculino , Radiografia , Costelas/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgiaRESUMO
OBJECTIVE: To study the influence of different age and short or long segments of pedicle screw fixation to the clinical efficacy of early single thoracolumbar fracture. METHODS: From June 2005 to June 2008, 27 patients of early single thoracolumbar fracture were treated using short or long segments pedicle screw instrumentation, fracture vertebral (AO classification: type A1 or A2) was between T11 or L2. All patients were divided into A or B group according to age. A group: 12 cases mean age (32.6+/-10.7) years old (range, 16-55 years old). B group: 15 cases mean age (66.8+/-9.2) years old (range, 56-78 years old). All patients were treated with bony autograft by transpedicular of fracture vertebral and internal fixation by pedicle instrumentation. Pedicle screws were inserted in the pedicles of above and lower adjacent vertebral body of fracture vertebral, and others were inserted in the pedicles of above and lower two vertebral bodies of injured vertebral. Recorded operation time, blood loss and occurrence of complications. All patients took X radiograph plane examination (anterior-posterior position and lateral position) before operation and during 1 week of post operation and more than 1 year of follow up. Measured percentage of anterior compression vertebral high and kyphosis angle of the fracture vertebral by the same one group doctors. RESULTS: Mean follow up time was (29.6+/-9.1) months (range, 10 - 34 months). The patients using short segments pedicle screw fixation in A and B group, mean operation time were (102+/-16) min and (118+/-24) min (P=0.072), mean volume of loss blood were (315+/-87) ml and (331+/-87) ml (P=0.064) respectively. The patients using long segments pedicle screw fixation in A and B group, Mean operation time were (138+/-22) min and (159+/-31) min (P=0.052), Mean volume of loss blood were (446+/-102) ml and (482+/-148) ml (P=0.055) respectively. There was no statistic different significantly between A and B group. The patients using short segments fixation, preoperative, during one week of post operation, one year of follow up, in A group the percentage of anterior compression vertebral high were 41.3+/-14.0, 5.4+/-1.0, 13.6+/-1.1, and 38.5+/-11.2, 8.3+/-2.1, 21.4+/-5.2 in B group. The patients using long segments fixation, at some time of preoperative, during one week of post operation and one year of follow up the percentage of anterior compression vertebral high were 40.8+/-11.5, 4.6+/-1.2, 8.3+/-1.0 in group A, and 44.3+/-10.2, 9.7+/-2.1, 11.2+/-3.0 in group B. In group A and B the kyphosis angle of fracture segment was 17.5 degrees+/-1.0 degrees and 16.3 degrees+/-3.1 degrees before operation, 4.2 degrees+/-1.0 degrees and 6.0 degrees+/-1.1 degrees in one week of postoperation and 11.5 degrees+/-1.0 degrees, 13.4 degrees+/-3.0 degrees in one year later postoperation. All the compression vertebral high was recovered and kyphosis was corrected significantly during one week and one year after operation (P<0.05), but there was some loss of kyphosis correction rate in follow up. CONCLUSION: There is better clinical efficacy of short segments pedicle instrumentation for treating early thoracolumbar fracture in the young group, but long segments fixation of pedicle instrumentation is more suitable for the older group.
Assuntos
Fixação Interna de Fraturas/métodos , Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To explore the detailed innervation of the lumbar spine of humans. METHODS: Six adult cadavers fixed in a solution containing 10% formalin were investigated under a stereomicroscope. The lumbar spine, together with the abdominal aorta, inferior vena cava and psoas muscle, was extracted. The dissection was focused on various patterns of rami communicantes (RC), including superficial oblique rami (SOR) and deep transverse rami (DTR), and their relationship to the psoas major muscle, the minute nerve supply of the anterior and posterior longitudinal ligaments, vertebral bodies and the intervertebral discs. RESULTS: Two types of RC were observed: SOR and DTR. SOR ran obliquely between the superficial heads of the psoas major muscle, connecting the sympathetic trunk and T12-L2 spinal nerves non-segmentally. DTR, running along the lumbar arteries and veins, were distributed segmentally, close to the vertebral bodies. On the anterior aspect of the lumbar spine, the anterior longitudinal ligaments received branches from the sympathetic trunk and splanchnic nerves non-segmentally. On the lateral side of the lumbar spine, the vertebral bodies and the intervertebral discs received branches from the DTR and ventral rami segmentally, branches from the sympathetic trunk, and, in the upper lumbar region, SOR non-segmentally. Within the vertebral canal, the posterior aspect of the intervertebral discs and the posterior longitudinal ligaments received the sinu-vertebral nerves originating from DTR. CONCLUSION: Exist two different types of innervation in the lumbar vertebrae: one originating directly from the spinal nerve segmentally, and one reaching the vertebral body and intervertebral disc via the sympathetic nerves non-segmentally. Therefore, sympathetic nerves are involved in the innervation of the spinal column and intervertebral disc and are likely involved in discogenic low back pain.
Assuntos
Vértebras Lombares/inervação , Sistema Nervoso Simpático/anatomia & histologia , Adulto , Cadáver , HumanosRESUMO
OBJECTIVE: To discuss the prevention and management of the neurological complications during treatment for severe scoliosis. METHODS: Seventy-one patients with the coronal Cobb angle more than 80 degrees underwent operation. The average coronal Cobb angle was 96.6 degrees (80 degrees - 135 degrees ), and 31 patients combined with kyphotic deformity with average sagittal Cobb angle 83.0 degrees (52 degrees - 145 degrees ). Fourteen patients were treated with posterior pedicle screw fixation alone, 21 combined with posterior wedge resection, 34 with staged operation, and 2 with combined anterior and posterior approach. Intraoperative somatosensory evoked potentials (SEP) monitoring and wake up test were used in 61 cases, and wake up test was used alone in 10 cases. RESULTS: The average coronal curve correction was 59.2% (average 39.6 degrees ) and sagittal curve correction was 61.6% (average 31.9 degrees ). Thirty-nine patients were followed up with average 51 months (5 - 81 months). Among them, 33 patients achieved solid spinal fusion and the rate of correction loss was 2.1%. Two patients underwent reoperation because of the breakages of the internal fixation. Among 8 patients with neurological dysfunction pre-operatively, 3 patients obtained complete recovery, 1 patient incomplete recovery, and the rest had not recovered because of post-poliomyelitis syndrome. Four of 5 patients developed neurological dysfunction post-operatively obtained complete recovery and 1 partial recovery. CONCLUSIONS: Halo-pelvic distraction and apical vertebra osteotomy are useful for increasing the correction rate and decreasing the neurological dysfunction. Intraoperative SEP monitoring combined with wake up test can call attention to early nerve injury. Early using of glucocorticoids and dehydration therapy promptly post-operatively is benefit to prevent neurological complications.
Assuntos
Doenças do Sistema Nervoso/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Monitorização Intraoperatória , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Osteotomia/métodos , Complicações Pós-Operatórias/terapia , Escoliose/patologia , Escoliose/cirurgia , Tração/métodosRESUMO
Tow new arylalkenyl α,ß-unsaturated δ-lactones named cryptoconcatones K (1) and L (2) were obtained from the leaves and twigs of Cryptocarya concinna. Their structures were established on the basis of spectroscopic data (MS, 1D and 2D NMR). Compounds 1 and 2 showed cytotoxic activities with IC50 values of 4.5 and 3.9 µM against Huh7 cancer cell line, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cryptocarya/química , Lactonas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Lactonas/química , Lactonas/farmacologia , Espectroscopia de Ressonância Magnética , Folhas de Planta/químicaRESUMO
BACKGROUND: Transpedicular screws may cause damage to the cartilage in the neural arch of the vertebra, and give continuous pressure to the skeleton besides the vertebral body. The aim of this study is to examine the morphological change of the vertebral body at fixation sites and development of the vertebral body after fixation. METHODS: A piglet model was used to study the influence of transpedicular screw fixation on spine development. Transpedicular screw fixation was adjusted to meet specific requirements of surgery on piglet. The screws and plates were placed at L1-L3 vertebral plates via routine surgical approach. Scoliosis and kyphosis Cobb angles were measured. RESULTS: Anatomical characteristics of 6-week-old piglets fit the transpedicular screw system, and can meet the requirements of related studies. Transpedicular screw fixation system has no significant influence on the development of canalis vertebralis. Fixation did not cause developmental stenosis of canalis vertebralis and damage to spinal cord or nerve root. However, transpedicular screw fixation significantly impacted the development of the spine: it shortened the spine by curtailing the length of the vertebral body and intervertebral space. Our results also suggested that slow growth of epiphyseal plate may contribute to the shortening of the vertebral body. CONCLUSION: Transpedicular screw fixation system is beneficial for fixation of the developing spine. It may not cause scoliosis but could lead to change of cervical curvature.
Assuntos
Parafusos Ósseos , Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/cirurgia , Animais , Parafusos Ósseos/efeitos adversos , Modelos Animais de Doenças , Feminino , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/crescimento & desenvolvimento , Vértebras Lombares/patologia , Masculino , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/instrumentação , Procedimentos Ortopédicos/métodos , Escoliose/diagnóstico por imagem , Escoliose/etiologia , Sus scrofa , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To introduce a new kind of grade system for thoracic pedicle screws placement by performing postoperative computerized tomography (CT) scanning and discussion the clinical purpose. METHODS: Four hundred and fifty thoracic pedicle screws were implanted in 64 patients with the assistance of fluoroscopy. Postoperative CT scanning was conducted to determine a grade for each screw: Part A, screw entirely contained within pedicle; Part B(1), violate lateral or upper pedicle but screw tip entirely contained within the vertebral body (VB); Part B(2), violate medial or inferior of pedicle; Part B(3), tip penetrated anterior or lateral VB; Part C, violate pedicle or VB and endangers spinal cord, nerve roots, or great vessels. Based on anatomical morphometry, thoracic vertebral were subdivided into upper (T(1 - 2)), middle (T(3 - 6)), and lower (T(7 - 12)) regions. The mean follow-up period was 25.8 months. RESULTS: The postoperative CT scanning-documented grade were determined: Part A, 367 screws (81.6%); Part B, 78 (17.3%), B(1) 40 (8.1%); Part B(2), 23 (5.1%); Part B(3), 15 (3.4%); Part C, 5 (1.1%). There were not significant difference between upper and lower thoracic that the placement of pedicle screws in part B or C. In part C, 5 pedicle screws were all in the middle thoracic. CONCLUSION: Postoperative CT scanning should be considered as a routine examination for evaluating thoracic pedicle screw placement.
Assuntos
Parafusos Ósseos , Fusão Vertebral/instrumentação , Vértebras Torácicas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Parafusos Ósseos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Polyphyllin I (PPI), a bioactive phytochemical isolated from the rhizoma of Paris polyphyllin, exerts preclinical anticancer efficacy in various cancer models. However, the effects of PPI on regulatory human hepatocellular carcinoma (HCC) cell proliferation and its underlying mechanisms remain unknown. PURPOSE: This study investigated the antiproliferation effect of PPI on HCC cells and its underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Cell death, apoptosis and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by Western blot analysis. RESULTS: PPI induced apoptosis through the caspase-dependent pathway and activated autophagy through the PI3K/AKT/mTOR pathway. Blockade of autophagy by pharmacological inhibitors or RNA interference enhanced the cytotoxicity and antiproliferation effects of PPI. Moreover, chloroquine (CQ) enhanced the antiproliferation effect of PPI on HCC cells via the caspase-dependent apoptosis pathway by inhibiting protective autophagy. Therefore, the combination therapy of CQ and PPI exhibited synergistic effects on HCC cells compared with CQ or PPI alone. CONCLUSION: The current findings strongly indicate that PPI can induce protective autophagy in HCC cells, thereby providing a novel target in potentiating the anticancer effects of PPI and other chemotherapeutic drugs in liver cancer treatment. Moreover, the combination therapy of CQ and PPI is an effective and promising candidate to be further developed as therapeutic agents in the treatment of liver cancer.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Diosgenina/análogos & derivados , Neoplasias Hepáticas/patologia , Caspases/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Diosgenina/farmacologia , Sinergismo Farmacológico , Humanos , Estrutura Molecular , Saponinas/farmacologia , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate the accuracy and safety of pedicle screw insertion with the aid of novel patient-specific drill-guide templates in scoliosis cases. METHODS: Ten patients with scoliosis were selected to participate in the research (the observation group) from December 2013 to December 2014. The data was obtained from CT scanning, and put into the computer to perform reconstruction of spine, simulation of pedicle screw insertion, and design of patient-specific drill-guide templates with software. The templates were made with rapid prototyping technique. After sterilization, the templates were used to aid the pedicle screw insertion intraoperatively. The blood loss, operation duration, change of creatinine level pre- and post-operation, and complications related to pedicle screw insertion were recorded. The location of pedicle screws were graded so as to evaluate the accuracy. A comparative study was then performed with the data of ten scoliosis cases operated with free-hand method during the same period (control group). There were 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the observation group, including 3 males and 7 females. Their average age was 11.9 years old (ranged, 4 to 18 years old), and the average Cobb angle of main curve was 54.9° (ranged, 42.1° to 78.4°). There were also 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the control group,including 2 males and 8 females. Their average age was 12.6 years old (ranged, 6 to 17 years old), and the average Cobb angle of main curve was 56.6° (ranged, 38.2° to 93.4°). RESULTS: A total of 167 pedicle screws were inserted intraoperatively, with 138 screws (82.6%) in grade I, 26 screws (15.0%) in grade II, 4 screws in grade III (2.4%), but no screws in grade IV according to the CT image. There were 29 (17.4%) screws perforated, and 163 (97.6%) screws could be accepted. In the control group, a total of 165 pedicle screws were inserted intraoperatively, with 98 screws (59.4%) in grade I, 39 screws (23.6%) in grade II, 21 screws in grade III (12.7%), and 7 screws in grade IV (4.2%). There were 67 (40.6%) screws perforated, and 137 (83.0%) screws could be accepted. The grade distribution of screw position, ratio of perforated and accepted screws were significantly different between the two groups respectively (Z=-5.013, P=0.000; χ2=9.347, P=0.002; χ2=20.242, P=0.000). The correction rate of Cobb angle were (74.1±10.0)% vs (69.7±17.6)%; blood loss were (455±447) ml vs (415±389) ml; operation duration were (163.5±53.7) min vs (164.0±48.7) min; and the changes of creatinine level pre- and post-operatively were (-5.3±3.2) µmol/L vs (-3.4±3.1) µmol/L; all above data had no significant differences respectively (t=0.696, P=0.496; t=0.214, P=0.833; t=0.022, P=0.983; t=1.375, P=0.192). There were no complications related to pedicle screw insertion in each group. CONCLUSION: The novel patient-specific drill guide template can be used to assist the insertion of pedicle screws in scoliosis cases with much higher accuracy than that of freehand method and fair safety.
Assuntos
Parafusos Pediculares , Escoliose/cirurgia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
In this study, the anti-cancer effect of Icariside II (IS), a natural plant flavonoid, against hepatoblastoma cells and the underlying mechanisms were investigated. The in vitro and in vivo studies show that IS decreased the viability of human hepatoblastoma HepG2 cells in a concentration- and time-dependent manner and inhibited tumor growth in mice transplanted with H22 liver carcinomas. IS impaired mitochondria and lysosomes as evidenced by signs of induced mitochondrial and lysosomal membrane permeabilization, resulting in caspase activation and apoptosis. SQSTM1 up-regulation and autophagic flux measurements demonstrated that IS exposure also impaired autophagosome degradation which resulted in autophagosome accumulation, which plays a pro-survival role as the genetic knockdown of LC3B further sensitized the IS-treated cells. Electron microscopy images showed that autophagosome engulfs IS-impaired mitochondria and lysosomes, thus blocking cytotoxicity induced by further leakage of the hydrolases from lysosomes and pro-apoptosis members from mitochondria. In conclusion, these data suggest that IS plays multiple roles as a promising chemotherapeutic agent that induces cell apoptosis involving both mitochondrial and lysosomal damage.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Hepatoblastoma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Hepatoblastoma/patologia , Humanos , Neoplasias Hepáticas/patologia , Lisossomos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy-induced osteoporosis. EXPERIMENTAL APPROACH: Ovariectomized rats were fed with HW (1.3 ± 0.2 mg·L⻹) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone. KEY RESULTS: HW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL-6 and TNF-α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats. CONCLUSIONS AND IMPLICATIONS: HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.
Assuntos
Antioxidantes/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/prevenção & controle , Osso e Ossos/química , Hidrogênio/uso terapêutico , Estresse Oxidativo , Animais , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Fenômenos Químicos , Feminino , Regulação da Expressão Gênica , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Fenômenos Mecânicos , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Ovariectomia/efeitos adversos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND AND PURPOSE: Sublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of the present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal cord-injured rats. EXPERIMENTAL APPROACH: Complete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400 mg·kg(-1) body mass per day(-1) , intragastrically) was initiated 12 h after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI. KEY RESULTS: Treatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral total sulfhydryl content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the up-regulation of mRNA levels of PPARγ, adipose-specific fatty-acid-binding protein and lipoprotein lipase, and restored mRNA levels of Wnt1, low-density lipoprotein-related protein 5, Axin2, ctnnb1, insulin-like growth factor 1 (IGF-1) and receptor for IGF-1 in femurs and tibiae. CONCLUSIONS AND IMPLICATIONS: Treatment with RES attenuated sublesional bone loss in spinal-cord-injured rats, associated with abating oxidative stress, attenuating inflammation, depressing PPARγ signalling, and restoring Wnt/ß-catenin and IGF-1 signalling.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Fêmur/efeitos dos fármacos , Osteoporose/prevenção & controle , Traumatismos da Medula Espinal/tratamento farmacológico , Estilbenos/farmacologia , Tíbia/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Masculino , Malondialdeído/metabolismo , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Radiografia , Ratos , Ratos Sprague-Dawley , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Compostos de Sulfidrila/metabolismo , Tíbia/diagnóstico por imagem , Tíbia/metabolismoRESUMO
OBJECTIVE: To investigate retrospectively the clinical effects and recurrence rate of 143 cases who underwent one level discectomy and followed up more than 10 years. To evaluate the outcome of patients in groups of different operating age and extents of disc herniation, and analyse whether difference exists in each group. METHODS: There were 143 patients (operation time from January 1996 to December 2000) including 80 males and 63 females, aged from 18 to 66 years old with an average of 37.85 years. The followed-up time was 10 to 15 years with an average of 12.7 years. Patients were divided into 3 groups depends on operating age: < 30 years old, 30 to 50 years old and > 50 years old; 87 patients who's pre-operative CT scan could be collected among 143 cases were divided into 3 groups depends on extents of disc herniation: I degree, II degrees, and III degrees. The final followed-up was obtained in 2011, to evaluate each group and the holistic clincal outcome with JOA scores and ODI scores, and observe whether there were difference between every groups; to judge the effects by patient himself with modified Macnab Criteria. RESULTS: (1) JOA scores pre-operation and final followed-up was 5.11 +/- 2.02 and 12.51 +/- 2.35 respectively; ODI scores pre-operation and final followed-up was 33.98 +/- 7.42 and 13.39 +/- 6.79 respectively. There were significant differences between pre-operative and final followed-up in JOA and ODI (P < 0.01). The excellent-good rate was 83.2% (119/143 ) according to modified Macnab Classification with recurrence rate of 6.3% at final follow-up. (2) Obvious difference was found in JOA scores in group who's age at operation less than 30 years old compared with other 2 groups at followed-up time, and no significant difference was found in JOA scores between other two groups ; no significant difference was found in ODI scores among the three groups. (3) Significant difference was found in JOA and ODI scores in group with III degrees lumbar disc herniation group compared with other 2 groups, and no statistical difference was found in clincal scores between other 2 groups. CONCLUSION: (1) Long-term followed-up of 143 cases prove mono-level lumbar discectomy is an option for disc herniation with good curative effect and lower recurrent rate, the technique should be the prior selection in dealing with patients with lumbar disc herniation. (2) 51% patients (19/37) in group under 30 years old endure persistent low back pain. (3) The long-term clinical effects in patients with severe disc protrution who underwent lumbar discectomy is worse than those patients with mild lumbar disc herniation.
Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Disco Intervertebral/cirurgia , Laminectomia/métodos , Vértebras Lombares/cirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To measure the diameter of T4 pedicle-rib compomers in normal human spines and discuss the importance of related dates. METHODS: T4 computerized tomography (CT) images,including two-dimensional,three-dimensional reconstruction, of 12 random adult patients were harvested. There were 7 males and 5 females with a mean age of 23 years (ranged, 19 to 28 years). The patients were divided into groups by self control,which means the diameter of pedicle compared with that of pedicle-rib unit in the same side of each T4. The facility was GE light speed 16. Measurement of the body specimens from T3 to T5 . The parameter included the width of pedicle-rib unit compared with pedicle,the longitudinal diameter of pedicle-rib unit compared with pedicle, especially for the pedicle-rib overlap. RESULTS: The relationship of T4 pedicle and rib were not on the same level but overlapping. The width of pedicle-rib unit was significantly larger than that of pedicle (P<0.05). The longitudinal diameters of pedicle-rib unit or pedicle were significantly larger than those of pedicle-rib overlap (P<0.05); while there was no significantly difference between the pedicle-rib unit and pedicle (P>0.05). CONCLUSION: The overlapping relationship of T4 pedicle and rib is partly but not whole, which means the longitudinal diameter of T4 pedicle-rib overlap should not be considered as the same of unit or pedicle.