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Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP-/-) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP-/- mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-κB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-κB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP-/- mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination.
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Enfermedades Transmisibles , Osteomielitis , Ratones , Animales , FN-kappa B , Lipopolisacáridos/farmacología , Staphylococcus aureus , Ubiquitinación , Proteasas Ubiquitina-Específicas/genética , Proteína Serina-Treonina Quinasa 2 de Interacción con ReceptorRESUMEN
Astragalus membranaceus (AM) is a traditional Chinese herbal medicine extensively utilized in vascular cognitive impairment (VCI) treatment. However, due to the complex components of AM, its exact molecular mechanism remains unclear. Therefore, this study investigated the target and molecular mechanism of AM to treat VCI based on network pharmacology and molecular docking. Firstly, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, STITCH, and SwissTargetPrediction were utilized to gather the primary active ingredients of AM. The potential therapeutic targets of VCI were collected through GeneCards, OMIM, and DisGeNET databases. Secondly, the protein-protein interaction network was built using the STRING database. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genome pathways was carried out in the R language. Finally, The network topology calculation of Cytoscape software was combined with module analysis to predict the binding properties of its active ingredients and targets. Twenty effective compounds and 733 targets were screened from AM, among which 158 targets were seen as possible targets of AM to treat VCI. MAPK3 and MMP9 were the critical targets of AM intervention in VCI. The crucial pathways include PI3K/Akt, MAPK, Rap1, and Ras signaling pathways. Besides, calycosin and quercetin might be the potential active compounds of AM for VCI treatment. AM intervenes in VCI through a multi-ingredient, multi-target, and multi-pathway coordination mechanism. These findings provide a foundation for a deeper understanding of the molecular mechanisms by which AM is effective in treating VCI.
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Disfunción Cognitiva , Medicamentos Herbarios Chinos , Humanos , Simulación del Acoplamiento Molecular , Astragalus propinquus , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Disfunción Cognitiva/tratamiento farmacológico , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
The magnetic morphotropic phase boundary (MPB) was first discovered in Laves-phase magnetoelastic system Tb-Dy-Co alloys (PRL 104, 197201 (2010)). However, the composition-dependent and temperature-dependent magnetostrictive behavior for this system, which is crucial to both practical application and the understanding of transitions across the MPB, is still lacking. In this work, the composition-dependence and temperature-dependence of magnetostriction for Tb1-xDyxCo1.95 (x = 0.3~0.8) are presented. In a ferrimagnetic state (as selected 100 K in the present work), the near-MPB compositions x = 0.6 and 0.7, exhibit the largest saturation magnetization MS and the lowest coercive field HC; by contrast, the off-MPB composition x = 0.5, exhibits the largest magnetostriction, the lowest MS, and the largest HC. Besides, a sign change of magnetostriction is observed, which occurs with the magnetic transition across the MPB. Our results suggest the combining effect from the lattice strain induced from structure phase transition, and the influence of the MPB on magnetocrystalline anisotropy. This work may stimulate the research interests on the transition behavior around the MPB and its relationship with physical properties, and also provide guidance in designing high-performance magnetostrictive materials for practical applications.
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A three-dimensional crosslinked CFs@CNT/CoSx nanocomposite was successfully synthesized by in situ growing carbon nanotubes on carbon nanofibers and a facile sulfurization process. The carbon nanotubes synthesized by sintering melamine under the catalysis of cobalt can increase the specific surface areas and provide abundant sodium ion diffusion channels for the composite. Meanwhile, the formed cobalt sulfide nanoparticles will increase the active sites on the surface of CFs@CNT/CoSx. Due to the rational design of the composite structure, such an anode can deliver a specific capacity of 423.7 mA h g-1 after 100 cycles at 100 mA g-1 and exhibit superior rate performance of retaining 324.1 mA h g-1 at 2 A g-1 for sodium storage.
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Merlin is known as a tumor suppressor, while its role in osteomyelitis remains unclear. This study aimed to investigate the role of Merlin in Staphylococcus aureus-induced osteomyelitis and its underlying mechanisms. S. aureus-induced osteomyelitis mouse model was established in Merlinfl/fl Lyz2cre/+ and Merlinfl/fl Lyz2+/+ mice. Bone marrow-derived macrophages (BMDMs) were isolated and stimulated by lipopolysaccharide (LPS). Bioassays, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays, were conducted to determine the levels of target genes or proteins. Immunoprecipitation was applied to determine the interactions between proteins. DCAF1fl/fl mice were further crossed with Lyz2-Cre mice to establish myeloid cell conditional knockout mice (DCAF1fl/fl Lyz2cre/+ ). It was found that the level of Merlin was elevated in patients with osteomyelitis and S. aureus-infected BMDMs. Merlin deficiency in macrophages suppressed the production of inflammatory cytokines and ameliorated the symptoms of osteomyelitis induced by S. aureus. Merlin deficiency in macrophages also suppressed the production of proinflammatory cytokines in BMDMs induced by LPS. The inhibitory effects of Merlin deficiency on the inflammatory response were associated with DDB1-Cul4-associated factor 1 (DCAF1). In summary, Merlin deficiency ameliorates S. aureus-induced osteomyelitis through the regulation of DCAF1.
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Osteomielitis , Infecciones Estafilocócicas , Animales , Citocinas , Humanos , Lipopolisacáridos/farmacología , Ratones , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Staphylococcus aureus/metabolismoRESUMEN
Propofol is a commonly used anesthetic drug in clinic. In recent years, a series of non-anesthetic effects of propofol have been discovered. Studies have shown that propofol has many effects on the intestine. Epidermal growth factor (EGF) is one of the most important growth factors that could regulate intestinal growth and development. In the current study, we studied the effect of protocol on the biological activity of EGF on intestinal tissue and cell models. Through flow cytometry, indirect immunofluorescence and Western-blot and other technologies, it was found that propofol reduced the activity of EGF on intestinal cells, which inhibited EGF-induced intestinal cell proliferation and changed the cell behavior of EGF. To further explore the potential mechanism by which propofol down-regulated epidermal growth factor receptor (EGFR)-induced signaling, we carried out a series of related experiments, and found that propofol may inhibit the proliferation of intestinal cells by inhibiting the EGFR-mediated intracellular signaling pathway. The current research will lay the theoretical and experimental basis for further study of the effect of propofol on the intestine.
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Anestésicos Intravenosos/farmacología , Factor de Crecimiento Epidérmico/metabolismo , Intestinos/citología , Propofol/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the efficacy of total hip arthroplasty (THA) assisted by the MAKO robotic arm via posterolateral approach. METHODS: The clinical data of 70 patients treated with THA via posterolateral approach between March 2017 and March 2019 who met the selection criteria were retrospectively analyzed. According to different treatment methods, the patients were divided into two groups, 35 were treated with MAKO robotic arm assisted THA (MAKO group) and 35 with traditional THA (THA group). There was no significant difference in gender, age, body mass index, disease duration, etiology, perioperative time, preoperative activity of daily living (ADL) scale index, American Society of Anesthesiologists (ASA) classification, walking ability, comorbidities, hemoglobin, and other general data between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stay, postoperative acetabular abduction and anteversion angles, postoperative length difference of bilateral lower limbs, and proportions of intraoperative blood transfusion, immediate postoperative loading, wound drainage time more than 2 days, and complications were recorded and compared between the two groups. According to the X-ray films at 6 months after operation, the reduction quality was judged. The forgotten joint score, Harris score, and proportions of independent walking and ADL index increased were used to evaluate the function recovery of patients. RESULTS: Patients in both groups were followed up 6-18 months, with an average of 8 months. There was no significant difference ( P>0.05) between the two groups in operation time, intraoperative blood loss, hospital stay, acetabular abduction and anteversion angles, and length difference of both lower limbs at 6 months after operation. There was no significant difference in the proportions of intraoperative blood transfusion, immediate postoperative loading, and wound drainage time more than 2 days between the two group ( P>0.05). X-ray reexamination at 6 months after operation showed that there was no significant difference in the reduction quality between the two groups ( Z=4.191, P=0.123). Postoperative complications occurred in 7 patients (20.0%) in the MAKO group and 10 patients (28.6%) in the THA group, showing no significant difference in the incidence of complications between the two groups ( χ 2=2.121, P=0.224). Two patients (5.7%) in the MAKO group and 4 patients (11.4%) in the THA group underwent revision within 6 months, showing no significant difference in the revision rate between the two groups ( χ 2=0.729, P=0.673). At 3 and 6 months after operation, the proportions of independent walking and ADL index increased showed no significant difference between the two groups ( P>0.05). Harris scores in both groups improved significantly when compared with preoperative scores ( P<0.05); there was no significant difference in the forgotten joint scores and Harris scores between the two groups ( P>0.05). CONCLUSION: Compared with traditional THA, MAKO robotic arm assisted THA has longer operation time and more intraoperative blood loss, but it has the advantages of accurate positioning and simple operation, and there is no significant difference in short-term postoperative function recovery.
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Artroplastia de Reemplazo de Cadera , Procedimientos Quirúrgicos Robotizados , Humanos , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Diabetes mellitus is characterized by hyperglycemia which displays insufficiency or resistance to insulin. One of the complications of diabetes is the increased risk of fracture and the impairment of bone repair and regulation. There have been evidences from previous studies that mesenchymal stem cells (MSCs) from bone marrow promote cartilage and callous formation. In addition, IL-10, an anti-inflammatory cytokine, has been observed to relieve inflammation-related complications in diabetes. METHODS: In this study, the role of IL-10-overexpressing bone marrow-derived MSCs (BM-MSCs) was examined in the diabetic mice model with femur fracture. MSCs were isolated from the BALB/c mice and IL-10 over expression was conducted with lentivirus transduction. The streptozotocin (STZ)-induced diabetes model with femoral fracture was established. BM-MSCs with IL-10 over expression were transplanted into the fracture area. The expressions of inflammatory factors IL-6, TNF-α and INF-γ were examined by qPCR and immunoblot; the biomechanical strength of the fracture site of the mice was examined and evaluated. RESULTS: Data showed that IL-10 overexpressed BM-MSCs transplantation decreased inflammatory response, promoted bone formation, and increased the strength of the fracture site in STZ-induced diabetic mice with femoral fracture. CONCLUSION: IL-10 overexpressed BM-MSCs transplantation accelerated fracture repair in STZ-induced diabetic mice, which in turn provides potential clinical application prospects.
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Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetic patients, and osteoporosis is one of the complications during T2DM process. ATP6V1H (V-type proton ATPase subunit H) displays crucial roles in inhibiting bone loss, but its role in osteogenic differentiation remains unknown. Therefore in this study, we aimed to explore the biological role of ATP6V1H in osteogenic differentiation. OM (osteogenic medium) and HG (high glucose and free fatty acids) were used to induce the MC3T3-E1 cells into osteogenic differentiation in a T2DM simulating environment. CCK8 assay was used to detect cell viability. Alizarin Red staining was used to detect the influence of ATP6V1H on osteogenic differentiation. ATP6V1H expression increased in OM-MC3T3-E1 cells, while decreased in OM+HG-MC3T3-E1 cells. ATP6V1H promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. Overexpression of ATP6V1H inhibited Akt/GSK3ß signaling pathway, while knockdown of ATP6V1H promoted Akt/GSK3ß signaling pathway. ATP6V1H overexpression promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. The role of ATP6V1H in osteogenic differentiation in a T2DM simulating environment involved in Akt/GSK3ß signaling pathway. These data demonstrated that ATP6V1H could serve as a potential target for osteogenic differentiation in a T2DM simulating environment.
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Regulación de la Expresión Génica , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Osteogénesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Células 3T3 , Animales , Diferenciación Celular , Supervivencia Celular , Ratones , Osteoblastos/citología , Transducción de SeñalRESUMEN
BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. METHODS: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. RESULTS: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. CONCLUSIONS: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
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Necrosis de la Cabeza Femoral/epidemiología , Adulto , Distribución por Edad , Anciano , Pueblo Asiatico , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto JovenAsunto(s)
Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Hematoma/etiología , Seroma/etiología , Adulto , Implantación de Mama/métodos , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Hematoma/fisiopatología , Hematoma/cirugía , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/cirugía , Reoperación/métodos , Estudios Retrospectivos , Seroma/fisiopatología , Seroma/cirugía , Geles de Silicona/efectos adversos , Resultado del TratamientoRESUMEN
An actinomycete, designated strain GIMN4.003(T), was isolated from seawater collected in Sanya, China. It produced white aerial mycelium and yellow substrate mycelium on Gause's synthetic agar medium no. 1. The substrate mycelium colour was not sensitive to pH. Scanning electron microscopy observations revealed that GIMN4.003(T) produced straight to flexuous spore chains of rough to warty spores. ll-Diaminopimelic acid was present in the cell-wall hydrolysate. Based on chemotaxonomy and morphological features, strain GIMN4.003(T) was identified as a member of the genus Streptomyces. Melanin was not produced. No antimicrobial activity was detected against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Penicillium citrinum or Candida albicans. Analysis of the 16S rRNA gene sequence revealed that the highest sequence similarity was to Streptomyces radiopugnans R97(T) (99.0%). However, DNA relatedness between GIMN4.003(T) and S. radiopugnans DSM 41901(T) was low (41.24±1.47%). Furthermore, the morphological, physiological and biochemical characteristics of strain GIMN4.003(T) were different from those of S. radiopugnans DSM 41901(T) and the type strains of other closely related Streptomyces species. On the basis of its physiological and molecular properties, it is evident that strain GIMN4.003(T) (=CCTCCM 208215(T) =NRRL B-24801(T)) represents the type strain of a novel species within the genus Streptomyces, for which the name Streptomyces fenghuangensis sp. nov. is proposed.
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Agua de Mar/microbiología , Streptomyces/clasificación , Streptomyces/aislamiento & purificación , ADN Ribosómico/genética , Ácidos Grasos/metabolismo , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Streptomyces/genética , Streptomyces/metabolismoRESUMEN
A component from Emilia sonchifolia (L.) DC, γ-humulene, was investigated. Significantly decreased cell viability of human colorectal cancer HT29 cells in a dose-dependent manner with IC50 53.67±2.99 µM for 24-h treatment was found. γ-Humulene induced apoptotic cell death and apoptosis was confirmed by morphological assessment. The staining with propidium iodide (PI) and flow cytometric analysis also showed that γ-humulene significantly promoted the sub-G1 phase (an apoptotic population) in HT29 cells. Colorimetric assays indicated that pretreatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced activities of caspase-8 and caspase-3 in examined HT29 cells. γ-Humulene stimulated the death receptor 5 (DR5), DR4, Fas-associated protein with death domain (FADD), the cleavage of caspase-8 and cleavage caspase-3, but reduced the protein levels of cellular Fas-associated death-domain-like IL-1ß-converting enzyme inhibitory protein (c-FLIP) by Western blot analysis. Consequently, γ-humulene-triggered cell death was significantly attenuated by DR5 siRNA and the caspase-8 inhibitor. Based on our results, we suggest that γ-humulene induced apoptotic cell death in HT29 cells through a DR5-mediated caspase-8 and -3-dependent signaling pathway. Therefore, this agent might be useful for developing new therapeutic regimens for treatment of colorectal cancer in the future.
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Adenocarcinoma/patología , Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/patología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/fisiología , Receptores del Factor de Necrosis Tumoral/metabolismo , Sesquiterpenos/farmacología , Adenocarcinoma/metabolismo , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Células HT29 , Humanos , Modelos Biológicos , Sesquiterpenos Monocíclicos , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Receptores del Factor de Necrosis Tumoral/fisiología , Transducción de Señal/fisiologíaRESUMEN
Late hematoma or seroma and galactocele caused by augmentation mammaplasty have been reported in patients with silicon breast prostheses but are extremely rare in patients injected with polyacrylamide gel (PAAG). In a retrospective survey, the incidence, clinical manifestations, and management of late hematoma, seroma, and galactocele in 28 of 2,610 patients who underwent breast augmentation with PAAG injection were investigated, and 5 typical cases are presented. The diagnostic and managing methods for this complication have been assessed. The incidence of late hematoma or seroma was 0.65% and that of galactocele was 0.35% among patients with PAAG-injected breast augmentations. The clinical onsets of such late PAAG complications were of two types: rapid enlargement in 17 patients and progressive expansion in another 11 patients. Aspiration, ultrasound, and magnetic resonance imaging (MRI) are useful and sensitive tools for diagnosis. Foreign body reaction, PAAG-related tissue necrosis and fibrosis, and granuloma were shown, and the bacterial cultures in all 12 cases were negative. Needle aspiration with pressure dressing has been advocated as a reliable method for small diseases, and surgical exploration with irrigation-vacuum drainage and evacuation with capsulectomy have been considered more effective for recurrent, large, and long-term cases. In conclusion, these late complications rarely present after large-volume injections of PAAG for breast augmentation. The PAAG-related pathologic inflammatory tissue changes are suggested as the pathogenesis for the complication. Trauma and breastfeeding are considered to be stimulating factors.
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Resinas Acrílicas/administración & dosificación , Resinas Acrílicas/efectos adversos , Quiste Mamario/inducido químicamente , Hematoma/inducido químicamente , Mamoplastia/efectos adversos , Mamoplastia/métodos , Seroma/inducido químicamente , Adulto , Femenino , Humanos , Inyecciones , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Capsaicin was reported to inhibit cancer cell growth. The aim of this study was to evaluate the antitumor potential of capsaicin by studying antitumor activity in vitro as well as in vivo. The in vitro studies are to examine the effects of capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The results showed that capsaicin induced cytotoxic effects in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential (ΔΨ(m)) in colo 205 cells. Data from Western blotting analysis indicated that the levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In vivo studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed that capsaicin effectively inhibited tumor growth. The potent in vitro and in vivo antitumor activities of capsaicin suggest that capsaicin might be developed for the treatment of human colon cancer.
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Antineoplásicos Fitogénicos/administración & dosificación , Capsaicina/administración & dosificación , Neoplasias del Colon/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Caspasas/genética , Caspasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/fisiopatología , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Curcumin, a naturally occurring yellow pigment isolated from turmeric, is a well known antioxidant with broad spectrum of anti-tumor activities against many human cancer cells. In this study, curcumin-induced cytotoxic effect of mouse-rat hybrid retina ganglion cells (N18) were investigated. For determining cell viability, the trypan blue exclusion and flow cytometric analysis were used. The curcumin-caused cell cycle arrest in N18 cells was examined by flow cytometry. Curcumin affect on the production of reactive oxygen species and Ca2+ and on the decrease of the level of mitochondria membrane potential (DeltaPsim) were also examined by flow cytometry. Curcumin-induced apoptosis was determined by DAPI staining and Western blotting was used for examining the apoptotic signaling proteins. Cell cycle analysis showed that G2/M phase arrest and sub-G1 occurs in N18 cells following 48 h exposure to curcumin. Curcumin also caused a marked increase in apoptosis, as characterized by DNA fragmentation (sub-G1 phase formation) and DAPI staining, and dysfunction of mitochondria, which was associated with the activation of caspase-8, -9 and -3. Curcumin also promoted the levels of Fas and FADD, Bax, cytochrome c release, but decreased the levels of Bcl-2 causing changes of DeltaPsim. Curcumin also induced endoplasmic reticulum stress in N18 cells which was based on the changes of GADD153 and GRP78 and caused Ca2+ release. Curcumin induced apoptosis through the intrinsic pathway and caspase-3-dependent and -independent pathways in N18 cells.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Curcumina/farmacología , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Receptor fas/metabolismo , Animales , Calcio/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Chaperón BiP del Retículo Endoplásmico , Células Híbridas , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Células Ganglionares de la Retina/enzimología , Células Ganglionares de la Retina/patología , Factores de TiempoRESUMEN
Curcumin is reported to be a potent inhibitor of the initiation and promotion of many cancer cells. We investigated to examine whether or not curcumin induce DNA damage in mouse-rat hybrid retina ganglion cell line N18 cells. The Comet assay showed that incubation of N18 cells with 10, 25 and 30 microM of curcumin led to a longer DNA migration smear (Comet tail). The DNA gel electrophoresis showed that 20 microM of curcumin for 24 and 48 h treatment induced DNA damage and fragments in N18 cells. The real time PCR analysis showed that 20 microM of curcumin for 48 h treatment decreased ATM, ATR, BRCA1, 14-3-3sigma, DNA-PK and MGMT mRNA, and ATM and MGMT mRNA expression were inhibited in a time-dependent manner. Our results indicate that curcumin caused DNA damage and inhibited DNA repair genes which may be the factors for curcumin-inhibited cell growth.
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Antiinflamatorios no Esteroideos/farmacología , Curcumina/farmacología , Reparación del ADN/genética , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Línea Celular , Ensayo Cometa , Daño del ADN , Fibroblastos , Expresión Génica/efectos de los fármacos , Humanos , Ratones , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Polyacrylamide hydrogel (PAAG) as an implanted material for augmentation mammaplasty has been used for years in China. Many kinds of complications associated with PAAG use have been reported in the clinical literature. This report presents two cases of breast cancer occurring after injection of PAAG in augmented breasts. The delayed diagnosis and more aggressive disease due to PAAG injection should be cause for concern. It is very important to detect breast cancer early when it is covered by the induration of the injected gel and inflammation reaction after PAAG injection. PAAG injection for augmentation mammaplasty may affect the outcome of breast cancer diagnosis and prognosis.
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Resinas Acrílicas/administración & dosificación , Resinas Acrílicas/efectos adversos , Neoplasias de la Mama/inducido químicamente , Geles/administración & dosificación , Geles/efectos adversos , Mamoplastia/métodos , Adulto , Femenino , Humanos , InyeccionesRESUMEN
After the comprehensive consideration of the effects of temperature and light on the development physiology of processing tomato, the intrinsic development factor (IDF) was introduced, and, through the analysis of the dynamic relationships between the development stages of different type processing tomato and related environmental factors, the simulation model for the development stages of processing tomato was constructed, based on the concept of physiological development time (PDTv). Different years' experimental data about ecological zones, varieties, and planting modes were used to validate the model. The simulated results about the number of days from sowing to seedling emergence, flowering, fruit-setting, maturing, and ending accorded well with the observed ones, the root mean squared error (RMSE) being 1.09, 2.03, 2.05, 2.77 and 2.53 days, respectively, and the prediction accuracy of this model was significantly higher than that of the growth degree day (GDD)-based model, with the corresponding RMSE being 1.90, 6.63, 6.33, 9.36 and 6.84 days, respectively.
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Ecosistema , Modelos Biológicos , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/fisiología , China , Simulación por Computador , Plantones/crecimiento & desarrollo , Plantones/fisiología , Factores de TiempoRESUMEN
Degenerate primers were designed based on all possible sequences of the N-terminal and C-terminal regions of Delonix regia trypsin inhibitor (DrTI). Five hundred sixty-one bp of polymerase chain reaction (PCR) product was amplified using the above degenerate primers and genomic DNA and cDNA of Delonix regia as a template. The amplified PCR products were cloned and sequenced. DNA sequence analysis of cDNA and genomic clones of DrTI have the same nucleotide sequence in the coding region, and manifested a genomic clone without intervening sequences in the coding region. The amino acid sequence deduced from the DrTI genomic and cDNA clones agreed with that identified via amino acid sequencing analysis, except that two amino acid residues, Ser and Lys, existed between residues Lys141 and Ser142. DrTI open reading frame was then amplified and cloned in-frame with GST in pGEX4T-1 and overexpressed in Escherichia coli to yield a glutathione S-transferase (GST)-fusion protein with a calculated molecular mass of about 45 kDa. The recombinant DrTI (reDrTI) was derived by treating the GST-DrTI fusion protein with thrombin. Both the reDrTI and GST-DrTI fusion protein exhibited a strong identical inhibitory effect on trypsin activity.