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1.
PLoS One ; 19(9): e0309014, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39241034

RESUMEN

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.


Asunto(s)
Adenocarcinoma , Apoptosis , Proliferación Celular , Fluorouracilo , Glucógeno Sintasa Quinasa 3 beta , Ratones Desnudos , Norisoprenoides , Transducción de Señal , Neoplasias Gástricas , Animales , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Fluorouracilo/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Norisoprenoides/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Sinergismo Farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Glucógeno Sintasa Quinasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/metabolismo
2.
Mol Carcinog ; 63(10): 2013-2025, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38980215

RESUMEN

γ-Tocotrienol (γ-T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ-T3 has effects on anti-inflammation, anti-oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ-T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ-T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ-T3 (0-90 µmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Autophagy was increased in MKN45 cells treated with γ-T3 (0-45 µmol/L), especially at a dose of 30 µmol/L for 24 h. These effects were reversed by 3-methyladenine pretreatment. Furthermore, γ-T3 (30 µmol/L) also significantly downregulated the expression of pGSK-3ß (ser9) and ß-catenin protein in MKN45 cells, and γ-T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK-3ß inhibitor-CHIR-99021 reversed the negative regulation of GSK-3ß/ß-Catenin signaling and autophagy. Our findings indicated that γ-T3 enhances autophagy in gastric cancer cells mediated by GSK-3ß/ß-Catenin signaling, which provides new insights into the role of γ-T3 enhancing autophagy in gastric cancer.


Asunto(s)
Autofagia , Proliferación Celular , Cromanos , Glucógeno Sintasa Quinasa 3 beta , Neoplasias Gástricas , Vitamina E , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Autofagia/efectos de los fármacos , Humanos , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones , beta Catenina/metabolismo , Vitamina E/análogos & derivados , Vitamina E/farmacología , Proliferación Celular/efectos de los fármacos , Cromanos/farmacología , Línea Celular Tumoral , Ratones Endogámicos BALB C , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos , Transducción de Señal/efectos de los fármacos
3.
Curr Protoc ; 2(1): e339, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35044725

RESUMEN

Viruses that spread transsynaptically provide a powerful means to study interconnected circuits in the brain. Here we describe the use of adeno-associated virus, serotype 1 (AAV1), as a tool to achieve robust, anterograde transsynaptic spread in a variety of unidirectional pathways. A protocol for performing intracranial AAV1 injections in mice is presented, along with additional guidance for planning experiments, sourcing materials, and optimizing the approach to achieve the most successful outcomes. By following the methods presented here, researchers will be able to reveal postsynaptically connected neurons downstream of a given AAV1 injection site and access these input-defined cells for subsequent mapping, recording, and manipulation to characterize their anatomical and functional properties. © 2022 Wiley Periodicals LLC. Basic Protocol: Stereotaxic injection of AAV1 for anterograde transsynaptic spread.


Asunto(s)
Dependovirus , Neuronas , Animales , Encéfalo , Dependovirus/genética , Ratones , Vías Nerviosas , Serogrupo
4.
Ocul Immunol Inflamm ; 30(7-8): 1559-1563, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34125650

RESUMEN

PURPOSE: To clarify the cut off value of blood CMV load to indicate CMV retinitis and its relationships with ocular features. METHODS: Patients were divided into non-CMV and CMV retinitis groups. A logistic regression model was applied to estimate the association of each variable with CMV retinitis. Spearman correlation was used to estimate the correlation between the blood and aqueous CMV load. RESULTS: Blood CMV load higher than 4log10 (OR, 6.897; CI: 2.813-16.910; P < .001) was the major predictor of CMV retinitis. Blood CMV load wasn't different between the initial and early stage (P = .066). No correlation was observed between the blood and aqueous CMV load (P = .083, r = 0.228). CONCLUSIONS: Blood CMV load higher than 4log10 is an important predictor for CMV retinitis in HIV/AIDS patients, but it couldn't indicate the ocular features. Ophthalmologic screening is still necessary.Abbreviations: CMV: Cytomegalovirus; CMVR: Cytomegalovirus retinitis; HIV: Human Immunodeficiency Virus; AIDS: Acquired Immune Deficiency Syndrome; ART: Antiretroviral therapy; EOD: End-organ diseases; PCR: Polymerase Chain Reaction; OR: Odds Ratio; CI: 95% Confidence Interval; IQR: Interquartile range.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Retinitis por Citomegalovirus , Humanos , Retinitis por Citomegalovirus/diagnóstico , VIH , Citomegalovirus/genética , Estudios Transversales
5.
Quant Imaging Med Surg ; 11(6): 2634-2641, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34079729

RESUMEN

BACKGROUND: The aim of the present study was to evaluate the clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). METHODS: A total of 96 eyes from 80 patients with AIDS and CMVR who received anticytomegalovirus (anti-CMV) treatment in the ophthalmology and infection centers of Beijing YouAn Hospital, between June 2016 and August 2018 were retrospectively investigated. The patients were randomly divided into a nonlaser group (50 eyes from 43 patients), who were treated with anti-CMV therapy, and a laser group (46 eyes from 37 patients), who were treated with a fundus laser method to close the retinopathy area after commencing the maintenance stage of anti-CMV treatment. Both groups were followed up for 24 months. The safety of laser therapy was observed, and the efficacy of the therapy was determined by evaluating the incidence of retinal detachment. RESULTS: The percentage of retinal detachment in the nonlaser group was 24% compared with 6.5% in the laser group (P=0.018). There was no significant difference between the two groups in the number of CD4+ T cells, the load of human immunodeficiency virus, or the time between the detachment and the end of the induction period. After laser therapy, 39.13% of patients exhibited keratic precipitates (KP), 30.43% had anterior chamber flare (±), 50% had anterior chamber flare (+), and 19.57% had anterior chamber flare (++). Intraocular pressure (IOP) increased in 3 eyes within 2 weeks of laser therapy. The retinal pigment reaction was not obvious in 8 eyes. CONCLUSIONS: The use of laser therapy in the main maintenance period of anti-CMV treatment can effectively reduce the incidence of retinal detachment in patients with AIDS and CMVR, and the therapy is safe and reliable.

6.
Tissue Eng Regen Med ; 18(3): 441-451, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33847914

RESUMEN

BACKGROUND: Although bone tissue engineering has already been applied clinically, its regeneration efficacy is not always sufficient. Local inflammatory cytokines are considered as the major factors that induce apoptosis of transplanted cells, thus leading to insufficient new bone formation. In this study, we focused on the effects of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) on differentiation and apoptosis of compact bone-derived cells (CBDCs). METHODS: CBDCs were obtained from mouse legs and cultured. The effects of TNF-α and/or IL-6 on the osteogenic differentiation and apoptosis of CBDCs were analyzed in vitro. To confirm the expression of local inflammatory cytokines in vivo, CBDCs were transplanted to the back of immunocompetent mice. RESULTS: IL-6 exerted inconsistent effects on the expression of the different osteogenic markers tested, while significantly upregulating Fas. By contrast, the addition of TNF-α dramatically reduced the expression of all tested osteogenic markers and increased Fas expression. The highest dose of IL-6 could partially reverse the repressive effect of TNF-α, while the addition of IL-6 further increased Fas expression in CBDCs compared to TNF-α alone. The results from in vivo experiments showed the presence of transplants with and without new bone formation. The transplants without bone formation were characterized by higher IL-6 and lower IL-10 expression than those with bone formation, while the expression of TNF-α did not show notable difference. CONCLUSION: The results of this study suggest an important role for IL-6 in modulating the efficacy of bone tissue engineering, which can affect osteogenic cells both positively and negatively.


Asunto(s)
Interleucina-6 , Osteogénesis , Animales , Diferenciación Celular , Hueso Cortical , Ratones , Factor de Necrosis Tumoral alfa
7.
Tissue Eng Part C Methods ; 27(4): 253-263, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33798009

RESUMEN

Spontaneously formed spheroids from mouse compact bone-derived mesenchymal stromal cells (CB-MSCs) possess enhanced stemness and superior plasticity. In this study, the effect of cryopreservation on viability, stemness, and osteogenic differentiation capability of spontaneous CB-MSC spheroids were investigated. CB-MSCs were isolated from mouse femur and tibia. Spheroids were cryopreserved with various concentrations of dimethyl sulfoxide (DMSO). After thawing, the number of living and dead cells was measured. The expression levels of stem cell markers and osteogenic marker genes were analyzed. The cryopreserved and noncryopreserved spheroids were transplanted in mice with a beta-tricalcium phosphate as a scaffold to evaluate the in vivo bone-forming capability. The percentage of living cells was highest when 5% DMSO was used as a cryoprotectant, confirmed by the number of dead cells. The expression of stem cell marker genes and osteogenic differentiation capability were maintained after cryopreservation with 5% DMSO. The cryopreserved spontaneous CB-MSC spheroids showed remarkable new bone formation in vivo, identical to that of the noncryopreserved spheroids even without osteogenic induction. The cryopreserved spontaneous CB-MSC spheroids retained stemness and osteogenic differentiation capability and highlight the utility of spontaneous CB-MSC spheroids as ready-to-use tissue-engineered products for bone tissue engineering.


Asunto(s)
Células Madre Mesenquimatosas , Animales , Diferenciación Celular , Células Cultivadas , Hueso Cortical , Criopreservación , Ratones , Osteogénesis , Ingeniería de Tejidos
8.
Exp Ther Med ; 21(6): 563, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33850535

RESUMEN

Obesity is currently an important health problem and is associated with an increased likelihood of various diseases. The efficacies of various natural treatments have been assessed for their utility in treating obesity. Alliin (S-allyl-L-cysteine sulfoxides) is considered the major component of garlic and has a wide range of natural antioxidant properties. However, the direct effects of alliin on obesity have not been well clarified. The present study investigated the effects and possible mechanisms of alliin on adipocyte differentiation. The 3T3-L1 cells were treated with alliin (0-40 µg/ml) during adipogenic differentiation. The effect of alliin on lipid accumulation was evaluated by Oil red O staining. Reverse transcription-quantitative PCR was performed to investigate the expression levels of adipogenic differentiation-related genes. The accumulation of lipid droplets was markedly inhibited following alliin treatment. The expression levels of multiple adipogenic transcription markers, such as CCAAT/enhancer-binding protein (C/EBP) ß, C/EBP α and peroxisome proliferation-activity receptor γ, were markedly decreased following treatment with alliin during adipogenic differentiation. Expression levels of several adipocyte-related genes were subsequently suppressed. Additionally, alliin suppressed PKB/Akt and PI3K expression. These results suggested that alliin exhibits anti-adipogenic activity by downregulating major adipogenic differentiation-related genes and Akt/PI3K expression. Alliin may have a potential therapeutic effect on metabolic disease.

9.
Arch Toxicol ; 93(10): 2993-3003, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31506784

RESUMEN

As one of the isoprenoids and widely derived from many fruits and vegetables, ß-ionone (BI) has a potent inhibitory proliferation of cancer cells in vitro and in vivo. However, its exact mechanism is still uncompleted understood and needs to be further verified. Cyclooxygenase-2 (COX-2), as a potential target of cancer chemoprevention, has been played pivotal roles in proliferation of tumor cells and carcinogenesis. Thus, the objective of present study was to determine that BI inhibited the activity of COX-2 in breast cancer and related to cancer cell models. Cell proliferation, DNA synthesis, the distribution of cell cycle, apoptosis induction and the expression of P38-MAPK protein were determined in MCF-7 cells by methylene blue, 3H-thymidine (TdR) incorporation, flow cytometry, TUNEL and Western blotting assays. Quinone reductase (QR) activity was determined in murine hepatoma Hepa1c1c7 cells by enzyme-linked immunosorbent assay (ELISA). The expression of COX-2 in a phorbol-12-myristate-13-acetate (PMA)-induced cell model and mammary tumor tissues was examined by Western blotting and immunohistochemistry. The results showed that BI significantly inhibited cell proliferation and DNA synthesis, arrested the distribution of cell cycle at the S phase or decreased proteins related to cell cycle such as cyclin D1 and CDK4, induced apoptosis and increased the expression of p-P38 in MCF-7 cells. BI at low doses (< 50 µmol/L) significantly increased QR activity, decreased the expression of COX-2 protein and prostaglandin E2 (PEG2) release in cell models. In addition, BI also significantly decreased the expression of COX-2 protein in rat mammary tumor tissues. Therefore, our findings indicate that BI possesses inhibitory proliferation of breast cancer cells through down-regulation of COX-2 activity.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/efectos de los fármacos , Norisoprenoides/farmacología , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Carcinoma Hepatocelular/enzimología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Neoplasias Hepáticas/enzimología , Células MCF-7 , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/enzimología , Neoplasias Mamarias Experimentales/patología , Ratones , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Norisoprenoides/administración & dosificación , Ratas
10.
Inorg Chem ; 58(9): 5388-5392, 2019 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-30985114

RESUMEN

The alloying of monometal nanoparticles with a transition element has recently attracted extensive interest; however, the dealloying of alloy nanoparticles has rarely been reported. Two-way alloying and dealloying in metal nanoparticles is not known so far to the best of our knowledge. In this work, for the first time, we successfully achieved two-way alloying and dealloying of cadmium in metalloid gold clusters via an antigalvanic reaction in combination with a quasi-antigalvanic reaction and demonstrated reactant-ion-dependent dealloying as well.

11.
J Cell Biochem ; 120(8): 13573-13582, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30938856

RESUMEN

BACKGROUND: Matrine might play a vital role in cardiovascular diseases progression and treatment. OBJECTIVES: We aimed to explore the protective effects and potential mechanism of matrine against diabetic cardiomyopathy (DCM) in rat model. METHOD: A rat model of DCM was induced by streptozotocin, which were then divided into two groups and treated with matrine. Inflammatory cytokines were investigated in serum and myocardial cells after matrine administration. The effects of matrine on cardiac reactive oxygen species (ROS) generation, Malondialdehyde (MDA) levels, and Glutathione peroxidase (GPx), PPARγ1 activity were detected in myocardial cells. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway in endoplasmic reticulum stress was studied to elaborated protective effects of matrine in DCM rat by Western blot analysis. Fasting blood glucose and hemodynamic parameters were analyzed after treatment with matrine. RESULTS: Matrine-inhibited expression levels of inflammatory cytokines of tumor necrosis factor alpha (TNF-α) and interleukin 6. Matrine administration decreased ROS generation, MDA, and transforming growth factor beta levels, and Peroxisome proliferator-activated receptor beta (PPARß) and Peroxisome proliferator-activated receptorγ 1 (PPARγ1) activity. Matrine administration also significantly inhibited PERK expression. Endogenic expression of PERK canceled matrine-induced apoptosis of myocardial cells. Notably, treatment with matrine significantly decreased nonfasting blood glucose levels and improved hemodynamic parameters of DCM rat. CONCLUSIONS: Matrine may be a promising agent for the treatment of DCM.


Asunto(s)
Alcaloides/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Quinolizinas/farmacología , Factor de Crecimiento Transformador beta/genética , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/patología , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/genética , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Malondialdehído/metabolismo , Miocardio/metabolismo , Miocardio/patología , PPAR gamma/genética , Proteínas Quinasas/genética , ARN/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , eIF-2 Quinasa/genética , Matrinas
12.
Food Chem Toxicol ; 128: 212-222, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30991129

RESUMEN

Perchlorate, as an oxidizer, has many applications such as explosives and pyrotechnics, especially in rocket propellants and missile motors. Because it was found in water including wells and drinking water in the US, its effect on human health was being noted. However, the reproductive toxic effect on perchlorate is still unclear. In present study, the effects of repeated exposure to perchlorate on reproductive toxicity were evaluated in Wistar rats. The rats were treated orally with perchlorate at doses of 0.05, 1.00 or 10.00 mg/kg body weight (b.w.) daily for 8 weeks. The levels of T3 and T4 hormones in the rat serum were detected by radioimmunoassay kit. The indexes of reproduction, percentage of organ in body weight (%) and frequency of abnormal sperm cells were also analyzed in this study. DNA damage in testicular cells was evaluated by Comet assay. The levels of MDA, GSH and SOD were examined in testicle tissues of rats by ELISA. The expression of c-fos and fas protein was examined in testicle tissues by immunohistochemistry. The results showed that perchlorate did not affect the body weight of rats. Perchlorate also significantly decreased indexes of live birth and weaning in the groups of 1.00 and 10.00 mg/kg, and viability index only in the 10.00 mg/kg group (P < 0.05). Perchlorate also significantly decreased the serum level of T3 in male rats of 1.00 and 10.00 mg/kg groups, increased the rate of sperm abnormality (10.00 mg/kg), potentially caused DNA damage in testicular cells and altered the status of oxidative stress in male rats. In addition, because of the increase in the expression of fas and c-fos protein in testicle tissues, perchlorate could induce apoptosis in spermatogenesis. Thus, these findings indicate that perchlorate could cause DNA damage in testicular tissues and reduce testicular spermatogenic ability, resulting in reproductive toxicity.


Asunto(s)
Percloratos/toxicidad , Compuestos de Amonio Cuaternario/toxicidad , Reproducción/efectos de los fármacos , Animales , Ensayo Cometa , Daño del ADN , Femenino , Masculino , Estrés Oxidativo/efectos de los fármacos , Percloratos/administración & dosificación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Compuestos de Amonio Cuaternario/administración & dosificación , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/metabolismo , Tiroxina/sangre , Triyodotironina/sangre , Receptor fas/metabolismo
13.
J Comp Neurol ; 526(15): 2428-2443, 2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30252130

RESUMEN

Progress in determining the precise organization and function of the claustrum (CLA) has been hindered by the difficulty in reliably targeting these neurons. To overcome this, we used a projection-based targeting strategy to selectively label CLA principal neurons. Combined with adeno-associated virus (AAV) and monosynaptic rabies tracing techniques, we systematically examined the pre-synaptic input and axonal output of this structure. We found that CLA neurons projecting to retrosplenial cortex (RSP) collateralize extensively to innervate a variety of higher-order cortical regions. No subcortical labeling was found, with the exception of sparse terminals in the basolateral amygdala (BLA). This pattern of output was similar to cingulate- and visual cortex-projecting CLA neurons, suggesting a common targeting scheme among these projection-defined populations. Rabies virus tracing directly demonstrated widespread synaptic inputs to RSP-projecting CLA neurons from both cortical and subcortical areas. The strongest inputs arose from classically defined limbic regions, including medial prefrontal cortex, anterior cingulate, BLA, ventral hippocampus, and neuromodulatory systems such as the dorsal raphe and cholinergic basal forebrain. These results suggest that the CLA may integrate information related to the emotional salience of stimuli and may globally modulate cortical state by broadcasting its output uniformly across a variety of higher cognitive centers.


Asunto(s)
Claustro/fisiología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Animales , Axones/fisiología , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Claustro/anatomía & histología , Claustro/citología , Emociones/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/anatomía & histología , Red Nerviosa/citología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/citología , Terminales Presinápticos/fisiología , Sinapsis/fisiología
14.
Sci Rep ; 8(1): 8021, 2018 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-29789580

RESUMEN

CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN-γ+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-γ, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-ß1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Trasplante de Córnea/métodos , Péptidos/inmunología , Péptidos/metabolismo , Precursores de Proteínas/inmunología , Precursores de Proteínas/metabolismo , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Córnea/efectos de los fármacos , Córnea/inmunología , Trasplante de Córnea/efectos adversos , Regulación hacia Abajo , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Inmunología del Trasplante/efectos de los fármacos , Trasplante Homólogo
15.
Brain Struct Funct ; 223(6): 2841-2858, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29663135

RESUMEN

Tractography is a powerful technique capable of non-invasively reconstructing the structural connections in the brain using diffusion MRI images, but the validation of tractograms is challenging due to lack of ground truth. Owing to recent developments in mapping the mouse brain connectome, high-resolution tracer injection-based axonal projection maps have been created and quickly adopted for the validation of tractography. Previous studies using tracer injections mainly focused on investigating the match in projections and optimal tractography protocols. Being a complicated technique, however, tractography relies on multiple stages of operations and parameters. These factors introduce large variabilities in tractograms, hindering the optimization of protocols and making the interpretation of results difficult. Based on this observation, in contrast to previous studies, in this work we focused on quantifying and ranking the amount of performance variation introduced by these factors. For this purpose, we performed over a million tractography experiments and studied the variability across different subjects, injections, anatomical constraints and tractography parameters. By using N-way ANOVA analysis, we show that all tractography parameters are significant and importantly performance variations with respect to the differences in subjects are comparable to the variations due to tractography parameters, which strongly underlines the importance of fully documenting the tractography protocols in scientific experiments. We also quantitatively show that inclusion of anatomical constraints is the most significant factor for improving tractography performance. Although this critical factor helps reduce false positives, our analysis indicates that anatomy-informed tractography still fails to capture a large portion of axonal projections.


Asunto(s)
Mapeo Encefálico , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Vías Nerviosas/diagnóstico por imagen , Algoritmos , Análisis de Varianza , Animales , Conectoma , Dependovirus/genética , Dependovirus/metabolismo , Difusión , Femenino , Imagenología Tridimensional , Ratones , Ratones Endogámicos C57BL , Curva ROC
16.
Cancer Biol Ther ; 19(2): 105-112, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29219668

RESUMEN

Advances in multiplex immunohistochemistry (IHC) techniques and digital pathology platforms allow quantification of multiple proteins at same tissue section and produce continuous data. TGF-ß signaling plays crucial and complex roles in colorectal cancer (CRC). We here aimed to investigate clinical pathological relevant of proteins involved in TGF-ß signaling at CRC tissues. Multiplex fluorescent IHC was used to quantitative analysis. The levels of eight proteins (TGF-ß1, TGFBRI, TGFBRII, SMAD4, SMAD2/3, p-SMAD2/3, SMAD1/5/9, and p-SMAD1/5/9) were determined in TMA sections. Quantitative analysis was carried out by a scoring system by InForm software. It revealed that TGF-ß signaling was hyper active. The levels of TGF-ß1, TGFBRI, TGFBRII, SMAD4, SMAD1/5/9 and p-SMAD2/3 were significantly increased in cancer tissues when compared their levels in normal tissues. Furthermore, the levels of eight proteins in stroma were significantly lower than the levels that in cancer tissues. Clinical pathological relevant analysis exhibited that TGF-ß signaling inclined to suppress the progression of tumor. SMAD1/5/9, TGFBRII, SMAD2/3 were confirmed as significant predictors for overall survival. In conclusion, we established a method based on multispectral imaging to extensively explore the clinical relevant of TGF-ß signaling proteins. These results provided an opportunity to consider the novel application for proteins involving TGF-ß signaling that used as diagnostic or prognostic biomarkers to conduct tumor therapy.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Transducción de Señal , Análisis de Matrices Tisulares/métodos , Factor de Crecimiento Transformador beta/análisis , Anciano , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Femenino , Fluoroinmunoensayo/métodos , Humanos , Inmunohistoquímica/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fosforilación , Pronóstico
17.
Artículo en Inglés | MEDLINE | ID: mdl-27916916

RESUMEN

The toxicity and carcinogenicity of aniline in humans and animals have been well documented. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear. In our research, primary cultured hepatocytes were exposed to aniline (0, 1.25, 2.50, 5.0 and 10.0 µg/mL) for 24 h in the presence or absence of N-acetyl-l-cysteine (NAC). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), mitochondrial membrane potential, DNA damage, cell viability, and apoptosis were detected. Levels of ROS and MDA were significantly increased and levels of GSH and CAT, activity of SOD, and mitochondrial membrane potential in hepatocytes were significantly decreased by aniline compared with the negative control group. The tail moment and DNA content of the tail in exposed groups were significantly higher than those in the negative control group. Cell viability was reduced and apoptotic death was induced by aniline in a concentration-dependent manner. The phenomena of ROS generation, oxidative damage, loss of mitochondrial membrane potential, DNA damage and apoptosis could be prevented if ROS inhibitor NAC was added. ROS generation is involved in the loss of mitochondrial membrane potential and DNA injury, which may play a role in aniline-induced apoptosis in hepatocytes. Our study provides insight into the mechanism of aniline-induced toxicity and apoptosis of hepatocytes.


Asunto(s)
Compuestos de Anilina/toxicidad , Apoptosis/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Hepatocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína , Animales , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glutatión/metabolismo , Hepatocitos/metabolismo , Humanos , Masculino , Malondialdehído/metabolismo , Potencial de la Membrana Mitocondrial , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo
18.
J Comp Neurol ; 524(18): 3827-3848, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27197019

RESUMEN

Pituitary adenylate cyclase-activating polypeptide (PACAP, gene name Adcyap1) regulates a wide variety of neurological and physiological functions, including metabolism and cognition, and plays roles in of multiple forms of stress. Because of its preferential expression in nerve fibers, it has often been difficult to trace and identify the endogenous sources of the peptide in specific populations of neurons. Here, we introduce a transgenic mouse line that harbors in its genome a bacterial artificial chromosome containing an enhanced green fluorescent protein (EGFP) expression cassette inserted upstream of the PACAP ATG translation initiation codon. Analysis of expression in brain sections of these mice using a GFP antibody reveals EGFP expression in distinct neuronal perikarya and dendritic arbors in several major brain regions previously reported to express PACAP from using a variety of approaches, including radioimmunoassay, in situ hybridization, and immunohistochemistry with and without colchicine. EGFP expression in neuronal perikarya was modulated in a manner similar to PACAP gene expression in motor neurons after peripheral axotomy in the ipsilateral facial motor nucleus in the brainstem, providing an example in which the transgene undergoes proper regulation in vivo. These mice and the high-resolution map obtained are expected to be useful in understanding the anatomical patterns of PACAP expression and its plasticity in the mouse. J. Comp. Neurol. 524:3827-3848, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Proteínas Fluorescentes Verdes/metabolismo , Ratones Transgénicos , Modelos Animales , Neuronas/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Animales , Axotomía , Encéfalo/citología , Encéfalo/metabolismo , Traumatismos del Nervio Facial/metabolismo , Traumatismos del Nervio Facial/patología , Perfilación de la Expresión Génica , Proteínas Fluorescentes Verdes/genética , Inmunohistoquímica , Masculino , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Médula Espinal/citología , Médula Espinal/metabolismo
19.
Shanghai Kou Qiang Yi Xue ; 25(1): 72-6, 2016 Feb.
Artículo en Chino | MEDLINE | ID: mdl-27063313

RESUMEN

PURPOSE: Changes of root shape of impacted upper central incisor before and after orthodontic traction were observed with dental cone-beam CT(CBCT), the timing for traction of impacted upper central incisor was investigated. METHODS: Ten impacted maxillary central incisors were diagnosed via panoramic radiograph. CBCT images were taken preoperatively for accurate localization. Following combined treatment of dental surgery and orthodontic traction, ten impacted maxillary central incisors were guided out and aligned well. Final treatment results and the root development status were evaluated via CBCT. RESULTS: Ten impacted maxillary central incisors were tracted to normal position. CBCT images before and after treatment showed that the root of impacted incisors with completed root apex had no change in shape, while the root of impacted incisors with uncompleted root apex developed continually with obviously improved shape and length. CONCLUSIONS: Optimistic results can be achieved if the traction of impacted upper central incisor is carried out before root development completed.


Asunto(s)
Incisivo , Diente Impactado/terapia , Tracción , Tomografía Computarizada de Haz Cónico , Humanos , Maxilar , Radiografía Panorámica , Raíz del Diente
20.
Nanoscale ; 5(22): 11019-27, 2013 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-24068181

RESUMEN

We report a general approach for the synthesis of large-scale gallium nitride (GaN) nanostructures by the graphene oxide (GO) assisted chemical vapor deposition (CVD) method. A modulation effect of GaN nanostructures on cell adhesion has been observed. The morphology of the GaN surface can be controlled by GO concentrations. This approach, which is based on the predictable choice of the ratio of GO to catalysts, can be readily extended to the synthesis of other materials with controllable nanostructures. Cell studies show that GaN nanostructures reduced cell adhesion significantly compared to GaN flat surfaces. The cell-repelling property is related to the nanostructure and surface wettability. These observations of the modulation effect on cell behaviors suggest new opportunities for novel GaN nanomaterial-based biomedical devices. We believe that potential applications will emerge in the biomedical and biotechnological fields.


Asunto(s)
Galio/química , Grafito/química , Nanoestructuras/química , Animales , Plaquetas/citología , Adhesión Celular/efectos de los fármacos , Línea Celular , Humanos , Células MCF-7 , Ratones , Microscopía Confocal , Células 3T3 NIH , Nanoestructuras/toxicidad , Óxidos/química , Propiedades de Superficie
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