RESUMEN

Microglial polarization modulation has been considered the potential therapeutic strategy for relieving cognitive impairment in sepsis survivors. Rosmarinic acid (RA), a water-soluble polyphenolic natural compound, processes a strong protective effect on various types of neurological disorders including Parkinson's disease, depression, and anxiety. However, its role and potential molecular mechanisms in sepsis-associated cognitive impairment remain unclear. To investigate the preventive and therapeutic effect of RA on sepsis-associated cognitive impairment and elucidate the potential mechanism of RA on regulating microglial polarization, we established a CLP-induced cognitive impairment model in mice and a lipopolysaccharide-induced microglia polarization cell model in BV-2. RACK1 siRNA was designed to identify the potential molecular mechanism of RACK1 on microglial polarization. The preventive and therapeutic effect of RA on cognitive impairment followed by PET-CT and behavioral tests including open-field test and tail suspension test. RACK1/HIF-1α pathway and microglial morphology in the hippocampus or BV-2 cells were measured. The results showed that RA significantly ameliorated the CLP-induced depressive and anxiety-like behaviors and promoted whole-brain glucose uptake in mice. Moreover, RA markedly improved CLP-induced hippocampal neuron loss and microglial activation by inhibiting microglial M1 polarization. Furthermore, experiments showed RACK1 was involved in the regulation of LPS-induced microglial M1 polarization via HIF-1α, and RA suppressed lipopolysaccharide or sepsis-associated microglial M1 polarization via RACK1/HIF-1α pathway (rescued the decrease of RACK1 and increase of HIF-1α). Taken together, RA could be a potential preventive and therapeutic medication in improving cognitive impairment through RACK1/HIF-1α pathway-regulated microglial polarization.

Asunto(s)

Disfunción Cognitiva , Ácido Rosmarínico , Sepsis , Animales , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Microglía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptores de Cinasa C Activada/efectos de los fármacos , Receptores de Cinasa C Activada/metabolismo , Ácido Rosmarínico/farmacología , Ácido Rosmarínico/uso terapéutico , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Transducción de Señal , Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo

RESUMEN

Mining activities frequently result in severe contamination of river water. This study aimed to better understand the spatial distribution characteristics of Tl and other metals (e.g., Al, Cd, Co, Mn, Ni, Zn, Pb, V, As, Mo, and Sb), and to assess their risks to human health. Surface water samples were collected from the upper Beijiang River (South China) via grab sampling and the diffusive gradients in thin-films (DGT) technique. The concentrations of Tl measured by grab sampling and δ-MnO2-DGT ranged from 0.045 µg L-1 to 0.231 µg L-1 and from 0.056 µg L-1 to 0.131 µg L-1, respectively. Most of the metals monitored were below the threshold levels allowed by the drinking water standard in China, except for As, Sb, and Mn at specific sampling sites. The concentrations of other metals measured by grab sampling were higher than those measured using the DGT technique because of the differences in speciation during these measurements. The hazard quotient (5.43 × 10-4-8.0 × 10-1 for grab sampling and 2.23 × 10-4-2.8 × 10-1 for DGT technique) for the monitored trace metals demonstrated minimal health risk to human beings. The pollution status of these toxic metals in the study area was generally acceptable. As was found to be potentially the most harmful metal in the studied area, with hazard quotients at some sampling sites calculated by grab sampling of >1. It has previously been suggested that As is the most important non-carcinogenic contaminant. The combination of grab sampling and the DGT technique provides a comprehensive understanding of trace metals, especially Tl, in terms of potential bioavailability and ecological assessment.

Asunto(s)

Ríos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Humanos , Compuestos de Manganeso , Óxidos , Talio , Contaminantes Químicos del Agua/análisis

RESUMEN

Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF-ß1. RACK1 is the downstream target gene of TGF-ß1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS-2B cells were cultured and exposed to recombinant soluble human TGF-ß1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA-challenged mice, as well as TGF-ß1-induced apoptosis and EMT of BEAS-2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF-ß1 up-regulated EMT related protein levels (N-cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF-ß1-induced N-cadherin and Snail up-regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF-ß1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF-ß1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

Asunto(s)

Apoptosis , Transición Epitelial-Mesenquimal , Proteínas de Neoplasias/metabolismo , Receptores de Cinasa C Activada/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Pulmón , Ratones Endogámicos BALB C , Modelos Biológicos , Ovalbúmina , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología

RESUMEN

The development of DNA barcoding method has given rise to a promising way of studying genetic taxonomy. Our previous study showed that pyrosequencing profile of 18S rDNA V7 hypervariable region can be used for identifying water sources without resolving the exact components of diatom colonies in water samples. In this continued study, we aimed to improve the established analysis method and to provide scientific evidence for forensic practices. A drowning animal model was set up by injecting mimic drowning fluid into the respiratory tract of the rabbit. In order to minimize the interference of animal DNA, the hypervariable region of chloroplast ribulose-1,5-bisphosphate carboxylase large unit gene (rbcL) was used as the pyrosequencing target region for the consistency analysis of plankton populations in tissues and water samples. After decoding the pyrosequencing profile of the targeted rbcL gene with the AdvISER-M-PYRO algorithm, the plankton colony that was inhaled into drowning animal lung tissue could be successfully traced back to the source of drowning fluid. Our data suggest that this method could be a reliable tool assisting forensic drowning site inference.

Asunto(s)

Código de Barras del ADN Taxonómico , Diatomeas/clasificación , Ahogamiento/patología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ribulosa-Bifosfato Carboxilasa/genética , Animales , Genética Forense , Patologia Forense , Modelos Animales , Reacción en Cadena de la Polimerasa , Conejos , Sensibilidad y Especificidad

RESUMEN

OBJECTIVE: To analyze the correlation of K-ras gene mutations with the protein expressions of transforming growth factor-ß activating kinase 1 (TAK1) protein and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) protein in colorectal cancer. METHODS: K-ras gene mutations were detected by DNA sequencing analysis, and the expressions of TAK1 protein and MAP4K2 protein were detected by immunohistochemical method in 76 cases of colorectal cancer tissues. RESULTS: In 76 cases of colorectal cancer tissues, the mutation rate of K-ras gene was 32.89% (25 cases), and K-ras gene mutations were correlated with the degrees of cell differentiation ( P<0.05). The positive rates of TAK1 protein and MAP4K2 protein were 48.68% and 46.05%, respectively. The protein expressions of TAK1 and MAP4K2 were positively correlated with the degrees of cell differentiation and lymph node metastases, respectively ( P<0.05). There was no correlation between K-ras gene mutation and either TAK1 protein or MAP4K2 protein expression ( P>0.05). In 25 cases of colorectal cancer with K-ras mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein ( P<0.05). CONCLUSION: K-ras gene mutation, TAK1 and MAP4K2 protein expressions were related to the degree of differentiation of colorectal cancer, but not to the depth of invasion. In colorectal cancer with K-ras gene mutation, the expression of TAK1 protein was positively correlated with the expression of MAP4K2 protein.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras)/genética , Genes ras , Quinasas del Centro Germinal , Humanos , Metástasis Linfática , Quinasas Quinasa Quinasa PAM , Mutación , Proteínas Serina-Treonina Quinasas

RESUMEN

KRAS mutations are one of the most prevalent genetic alterations in colorectal cancer (CRC). Although directly targeting KRAS still is a challenge in anti-cancer therapies, alternatively inhibiting KRAS related signaling pathways has been approached effectively. Here we firstly reported that MAP kinase, transforming growth factor-ß-activated kinase 1 (TAK1), commonly expressed in CRC cell lines and significantly associated with KRAS mutation status. Inhibition of TAK1 by the small molecular inhibitor NG25 could inhibit CRC cells proliferation in vitro and in vivo, especially in KRAS-mutant cells. NG25 induced caspase-dependent apoptosis in KRAS-mutant cells and in orthotopic CRC mouse models by regulating the B-cell lymphoma-2 (Bcl-2) family and the inhibitor of apoptosis protein (IAP) family. Besides inhibiting molecules downstream of MAPK, including ERK, JNK and p38 phosphorylation, NG25 could block NF-κB activation in KRAS-mutant cells. As a target gene of NF-κB, down-regulated XIAP expression may be not only involved in apoptosis induced by NG25, but also reducing the formation of TAK1-XIAP complex that can activate TAK1 downstream signaling pathways, which forms a positive feedback loop to further induce apoptosis in KRAS-mutant CRC cells. Together, these findings indicated that TAK1 is an important kinase for survival of CRCs harboring KRAS mutations, and that NG25 may be a potential therapeutic strategy for KRAS-mutant CRC.

Asunto(s)

Adenocarcinoma/patología , Antineoplásicos/farmacología , Benzamidas/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Piperazinas/farmacología , Piridinas/farmacología , Pirroles/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Animales , Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Mutación , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genética , Piridinas/uso terapéutico , Pirroles/uso terapéutico

RESUMEN

Over the past 35 years, DNA has been used to produce various nanometer-scale constructs, nanomechanical devices, and walkers. Construction of complex DNA nanostructures relies on the creation of rigid DNA motifs. Paranemic crossover (PX) DNA is one such motif that has played many roles in DNA nanotechnology. Specifically, PX cohesion has been used to connect topologically closed molecules, to assemble a three-dimensional object, and to create two-dimensional DNA crystals. Additionally, a sequence-dependent nanodevice based on conformational change between PX and its topoisomer, JX2, has been used in robust nanoscale assembly lines, as a key component in a DNA transducer, and to dictate polymer assembly. Furthermore, the PX motif has recently found a new role directly in basic biology, by possibly serving as the molecular structure for double-stranded DNA homology recognition, a prominent feature of molecular biology and essential for many crucial biological processes. This review discusses the many attributes and usages of PX-DNA-its design, characteristics, applications, and potential biological relevance-and aims to accelerate the understanding of PX-DNA motif in its many roles and manifestations.

Asunto(s)

ADN/química , Nanotecnología/métodos , Modelos Moleculares , Nanotecnología/instrumentación , Conformación de Ácido Nucleico

RESUMEN

Colorectal cancer (CRC) is the third most common type of cancer, and its incidence and mortality are markedly increasing worldwide. Oncogenic mutations of KRAS occur in up to 40% of CRC cases and pose a great challenge in the treatment of the disease. Quercetin is a dietary flavonoid that exerts anti-oxidant, anti-inflammatory, and anti-cancer properties. The current study investigated the anti-proliferative effect of quercetin on CRC cells harboring mutant or wild-type KRAS. The effect of quercetin on cell viability was investigated by MTT and colony formation assays, and apoptosis was detected using flow cytometry by labeling cells with Annexin V-FITC. The expression of the relevant proteins was examined by Western blotting. The data revealed that KRAS-mutant cells were more sensitive to quercetin-induced apoptosis than wild-type cells. Caspase activation was involved in quercetin-induced apoptosis. In addition, quercetin selectively activated the c-Jun N-terminal kinase (JNK) pathway in KRAS-mutant cells, while inhibition of phospho-JNK by SP600125 blocked quercetin-induced apoptosis. The results of the present study suggest that treatment with quercetin, a common flavonoid in plants, is potentially a useful strategy for the treatment of CRCs carrying KRAS mutations.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas p21(ras)/genética , Quercetina/farmacología , Antracenos/farmacología , Caspasas/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Mutación , Proteínas Proto-Oncogénicas c-akt/metabolismo

RESUMEN

BACKGROUND: Previous studies have reported that polymorphisms in the interleukin-1 gene may be involved in tumorigenesis and tumor progression. AIM: The purpose of the present study was to evaluate whether an insertion/deletion polymorphism, rs3783553, located in the miR-122 target gene interleukin-1α, was associated with the risk of colorectal cancer. METHODS: Genomic DNA was extracted from peripheral venous blood of 382 patients with colorectal cancer and 433 controls, and the polymorphism was genotyped using a polymerase chain reaction assay. RESULTS: Significantly decreased colorectal cancer risk was observed to be associated with the interleukin-1α rs3783553 insertion/insertion genotype ( P=0.0001; OR=0.41; 95% CI 0.26, 0.65) and the insertion allele ( P<0.001; OR=0.68; 95% CI 0.55, 0.83). Stratification analysis based on clinical and pathological features also revealed that the "TTCA" insertion allele of rs3783553 contributes to slow the progression of colorectal cancer. CONCLUSION: These results suggest that the rs3783553 polymorphism could be a useful genetic marker to predict the size/extent of colorectal cancer.

RESUMEN

Azithromycin is a potent agent that prevents airway remodeling. In this study, we hypothesized that azithromycin (35 mg/kg orally) alleviated airway remodeling through suppression of epithelial-to-mesenchymal transition (EMT) via downregulation of transforming growth factor-beta 1 (TGF-ß1)/receptor for activated C-kinase1 (RACK1)/snail in mice. An ovalbumin (OVA)-induced Balb/c mice airway allergic inflammatory model was used. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. E-cadherin and N-cadherin (molecular markers of EMT) were analyzed by immunofluorescence, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting; α-smooth muscle actin (α-SMA) was evaluated using immunohistochemistry (IHC), qRT-PCR, and western blotting; and expression of TGF-ß1/RACK1/Snail in lungs was measured by qRT-PCR and western blotting. Our data showed that azithromycin significantly reduced inflammation score, peribronchial smooth muscle layer thickness, goblet cell metaplasia, and deposition of collage fibers (P < 0.05), and effectively suppressed airway EMT (upregulated E-cadherin level, and downregulated N-cadherin and α-SMA levels) compared with the OVA group (P < 0.05). Moreover, the increasing mRNA and protein expressions of TGF-ß1 and RACK1 and mRNA level of Snail in lung tissue were all significantly decreased in azithromycin-treated mice (P < 0.05). Taken together, our results suggest that azithromycin has the greatest effects on reducing airway remodeling by inhibiting TGF-ß1/RACK1/Snail signal and improving the EMT in airway epithelium.

Asunto(s)

Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Azitromicina/uso terapéutico , Mucosa Respiratoria/efectos de los fármacos , Alérgenos/inmunología , Animales , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Receptores de Cinasa C Activada/metabolismo , Mucosa Respiratoria/patología , Factores de Transcripción de la Familia Snail/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo

RESUMEN

OBJECTIVES: Tanshinone IIA (Tan IIA) may exert significant protective effects against the neurotoxicity induced by ß-amyloid protein (Aß). This study was designed to investigate the possible neuroprotective mechanism of Tan IIA on Aß25-35 -induced spatial memory impairment in mice. METHODS: After 3 weeks of preventive treatment (Tan IIA or oil), all male Kunming mice were subjected to Aß25-35 (10 µl, intracerebroventricularly (i.c.v.)) to establish the spatial memory impairment model. The Morris water maze (MWM), haematoxylin and eosin staining, real-time PCR and Western blot were performed to determine the ability of spatial memory, neuronal damage and expression of extracellular signal-regulated kinase (ERK), receptors for activated C kinase1 (RACK1) and autophagy-related genes. Additionally, ShRACK1 was used to decrease the level of RACK1 in the hippocampus to test Beclin1 in hippocampus by real-time PCR and Western blot. KEY FINDINGS: Tanshinone IIA (Tan IIA, 80 mg/kg) administration notably protected mice from Aß25-35 -induced spatial memory impairment and neurotoxicity, increased pERK/ERK and the expression of RACK1, and reduced the elevated levels of BECLIN1 and LC3-II/I in the hippocampus. In addition, ShRACK1 i.c.v markedly upregulated BECLIN1 level, but not altered Beclin1 mRNA expression in the hippocampus. CONCLUSIONS: Tanshinone IIA may exert neuroprotective effects via upregulating RACK1 and inhibiting autophagy in the hippocampus of mice.

Asunto(s)

Abietanos/farmacología , Abietanos/uso terapéutico , Péptidos beta-Amiloides/toxicidad , Autofagia/efectos de los fármacos , Hipocampo/metabolismo , Trastornos de la Memoria/prevención & control , Neuropéptidos/metabolismo , Fragmentos de Péptidos/toxicidad , Animales , Beclina-1/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Fármacos Neuroprotectores/farmacología , ARN Interferente Pequeño/farmacología , Receptores de Cinasa C Activada , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known for its ability to preferentially induce apoptosis in malignant cells without causing damage to most normal cells. However, inherent and acquired resistance of tumor to TRAIL-induced apoptosis limits its therapeutic applicability. Here we show that the orally available tyrosine kinase inhibitor, BAY61-3606, enhances the sensitivity of human colon cancer cells, especially those harboring active mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene, to TRAIL-induced apoptosis in vitro and in vivo. The sensitization was achieved by up-regulating death receptor 4 (DR4) and the tumor suppressor p53. BAY61-3606-induced the up-regulation of DR4 is p53-dependent. Knockout of p53 decreased BAY61-3606-induced DR4 expression and inhibited the effect of BAY61-3606 on TRAIL-induced apoptosis. In addition, BAY61-3606 suppressed activity of NF-κB and regulated its gene products, which might also contribute to TRAIL-induced apoptosis. In conclusion, our results showed that BAY61-3606 sensitizes colon cancer cells to TRAIL-induced apoptosis via up-regulating DR4 expression in p53-dependent manner and inhibiting NF-κB activity, suggesting that the combination of TRAIL and BAY61-3606 may be a promising therapeutic approach in the treatment of colon cancer.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , FN-kappa B/metabolismo , Niacinamida/análogos & derivados , Pirimidinas/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Sinergismo Farmacológico , Células HCT116 , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Mutación , Niacinamida/farmacología , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transfección , Carga Tumoral/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

OBJECTIVES: Inhibition of Notch signalling is a potential therapeutic strategy for pulmonary fibrosis. This study was designed to investigate the antifibrosis effects and possible mechanism of astragalus injection (AI) on bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in male SD rats. All rats received daily intraperitoneally administration of dexamethasone (DEX, 3 mg/kg), astragalus injection (AI, 8 g/kg) or saline 1 day after bleomycin instillation daily for 28 days. Histological changes in the lung were evaluated by haematoxylin and eosin and Masson's trichrome staining. The expression of α-smooth muscle protein (α-SMA) was assayed by immunohistochemical (IHC). The mRNA and protein level of Jagged1, Notch1 and transforming growth factor-ß1 (TGF-ß1) was analysed by qPCR and Western blot. KEY FINDINGS: BLM-induced severe alveolitis and pulmonary fibrosis; together with significant elevation of α-SMA, TGF-ß1, Jagged1 and Notch1. Astragalus injection (AI, 8 g/kg) administration notably attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of α-SMA, TGF-ß1, Jagged1 and Notch1 in lungs. CONCLUSIONS: Astragalus injection (AI, 8 g/kg) may exert protective effects on bleomycin-induced pulmonary fibrosis via downregulating Jagged1/Notch1 in lung.

Asunto(s)

Planta del Astrágalo/química , Regulación hacia Abajo/efectos de los fármacos , Proteína Jagged-1/metabolismo , Pulmón/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Fibrosis Pulmonar/tratamiento farmacológico , Receptor Notch1/metabolismo , Actinas/metabolismo , Animales , Bleomicina/farmacología , Modelos Animales de Enfermedad , Pulmón/metabolismo , Masculino , Fibrosis Pulmonar/inducido químicamente , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo

RESUMEN

OBJECTIVE: To study the expressions and clinical significance of vasculogenic mimicry (VM) and the related protein Mig-7 and MMP-2 in gastric carcinoma. METHODS: We observed the expressions of CD34, Mig-7 and MMP-2 in 110 patients with gastric carcinoma using immunohistochemistry, VM was determined by CD34/PAS double staining, and analyzed their correlations with the clinical and pathological characteristics of the patients. RESULTS: In the 110 patients with gastric carcinoma, 35(31.82%) were found positive for VM expression, and it was correlated with the pathological degree and lymph node metastasis (P<0.05), that was, the positive rate of VM in the poorly-differentiated tissues (34%) was higher than that in the well-differentiated tissues (10%), and it was also higher in the lymph node metastasis than that in the non-lymph node metastasis. The expression of Mig-7 was found in 104 out of the 110 cases of gastric carcinoma, with a positive rate of 94.54%. The high expression of Mig-7 was related to lymph node metastasis (P<0.05). The expression rates of Mig-7 and MMP-2 were higher in the VM-positive group than in the VM-negative group (P<0.05). The average survival time and median survival time of the VM-positive group were shorter than those of the VM-negative group (P<0.05). CONCLUSION: The presence of VM in gastric carcinoma tissues is proved. The high expressions of Mig-7 and MMP-2 in gastric carcinoma tissues may have a synergistic promoting effect on VM formation. VM is closely associated with the invasion, metastasis and poor prognosis of gastric carcinoma.

Asunto(s)

Metaloproteinasa 2 de la Matriz/metabolismo , Imitación Molecular , Proteínas de Neoplasias/metabolismo , Neovascularización Patológica , Neoplasias Gástricas/irrigación sanguínea , Neoplasias Gástricas/patología , Humanos , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/metabolismo

RESUMEN

OBJECTIVE: To investigate the mechanism of vasodilatory effects of C-type natriuretic peptide (CNP). METHODS: Tension changes in aortic rings of rabbits were recorded with the presence of CNP or C-type natriuretic peptide receptor (NPR-C) agonist (cANF4-23) after pretreatment with epinephrine (NE) or 60 mmol/L KCl. The vasodilatory effects of four types of potassium channel blocker and NPR-C antagonist (cANF4-28) were also tested. RESULTS: A maximal vasorelaxant effects of (33.5 +/- 5.9) % and (38.4 +/- 10.6)% were recorded in the presence of 1 micromol/L CNP and cANF4-23, respectively, cANF4-28 attenuated the action of CNP [(19.8 +/- 8.3)%]. The vasorelaxant effects of CNP and cANF4-23 decreased significantly after pretreatment with 60 mmol/L KCl (P < 0.01). Glibenclamide and BaCl2 also attenuated the relaxant activities of CNP (P < 0.05). But only BaClZ decreased the vasodilatory action of cANF4-23 (P < 0.05). CONCLUSION: The relaxant activity of CNP is mediated through three paths: NPR-B/KATP, NPR-C/KIR and NPR-C/calcium channels.

Asunto(s)

Aorta Torácica/fisiología , Péptido Natriurético Tipo-C/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Canales de Calcio/efectos de los fármacos , Femenino , Técnicas In Vitro , Masculino , Músculo Liso Vascular/fisiología , Canales de Potasio de Rectificación Interna/efectos de los fármacos , Conejos

RESUMEN

We have used DNA double crossover (DX) molecules to produce a translation system that generates unique molecular products. The particular species of DX molecule used contains an even number of half-turns between crossover points, so there is a continuous strand on both sides of the molecule. One of these strands acts as the input strand containing the message, and a second strand acts as the product of translation. The crossover strands carry the "code" that connects the two sides of the molecule. This system is more robust, more extendable, and simpler than previous DNA-based translation systems that have been reported. It is designed to be useful in a variety of applications that utilize the concept of translating from one code to another.

Asunto(s)

Computadores Moleculares , ADN/química , ADN/genética , Nanotecnología/métodos , Biosíntesis de Proteínas , Fenómenos Biomecánicos

RESUMEN

It was reported that pancreatic arteries constricted during the early phase of bile salt-induced acute pancreatitis (AP), leading to pancreatic microcirculatory disturbance. We conducted this experiment to verify whether the above-mentioned finding was true. AP was induced with intraductal injection of taurodeoxyholate. Small pancreatic artery pressure in dogs was recorded. Functional capillaries were counted and calibrated by multiplying wet weight of pancreas. Pancreatic perfusion was measured with Laser Doppler flowmeter. Pancreatic arterioles of rats dilated during the initial 20 min of AP, and pancreatic arterial pressure declined during the early phase of AP in dogs (from 104.5 +/- 4.8 mmHg to 54.6 +/- 5.6 mmHg). The hematocrit of blood from inferior vena cava was significantly lower than that of portal vein at 5 min after pancreatitis induction. The "true" pancreatic functional capillary density increased. The early pancreatic microcirculatory disturbance coincided with a marked increase of portal vein pressure (PVP) as high as 9.18 +/- 0.78 mmHg. Reduction of PVP to baseline level was followed by a marked increase of pancreatic perfusion (by 1.4-fold). Arterial dilatation, but not constriction, occurred during the early phase of bile salt-induced AP. The pancreatic microcirculatory disturbance was due to a marked rise in PVP that greatly reduced the pressure difference in the pancreatic blood vessels and increased plasma extravasation which led. to local hemoconcentration.

Asunto(s)

Ácidos y Sales Biliares/efectos adversos , Hipertensión Portal/complicaciones , Páncreas/irrigación sanguínea , Pancreatitis/etiología , Presión Portal , Animales , Masculino , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Pancreatitis/fisiopatología , Vena Porta/fisiopatología , Ratas , Ratas Sprague-Dawley

RESUMEN

OBJECTIVE: To investigate the changes of excitability of rats' gastrocnemius after rats were died from mechanic asphyxia, so as to make an objective evidence for estimating of the early postmortem interval. METHODS: After rats were sacrificed by mechanic asphyxia, the reaction of rats' gastrocnemius to variable electric stimulation at different period after death were recorded by electricphysiological method. RESULTS: Changes in the properties of excitable tissue to electric stimulate in rats' gastrocnemius after mechanic asphyxia seems to be well correlated with the early postmortem interval and appeared a linear relation in certain period. CONCLUSION: The regular changes of excitability in muscle might be a useful means for estimating of early postmortem interval.

Asunto(s)

Potenciales de Acción/fisiología , Asfixia , Electromiografía/métodos , Músculo Esquelético/fisiología , Cambios Post Mortem , Animales , Modelos Animales de Enfermedad , Estimulación Eléctrica , Femenino , Masculino , Ratas , Ratas Wistar , Análisis de Regresión , Factores de Tiempo

RESUMEN

We present a designed cyclic DNA motif that consists of six DNA double helices that are connected to each other at two crossover sites. DNA double helices with 10.5 nucleotide pairs per turn facilitate the programming of DNA double crossover molecules to form hexagonally symmetric arrangements when the crossover points are separated by seven or fourteen nucleotide pairs. We demonstrate by atomic force microscopy well-formed arrays of hexagonal six-helix bundle motifs both in 1D and in 2D.

Asunto(s)

Intercambio Genético , ADN/química , Secuencia de Bases , ADN/genética , Microscopía de Fuerza Atómica , Modelos Moleculares , Datos de Secuencia Molecular , Conformación de Ácido Nucleico

RESUMEN

In recent years, the chemistry of DNA has expanded from biological systems to nanotechnology. The generalization of the biological processes of reciprocal exchange leads to stable branched motifs that can be used for the construction of DNA-based geometrical and topological objects, arrays and nanomechanical devices. The information in DNA is the basis of life, but it can also be used to control the physical states of a variety of systems, leading ultimately to nanorobotics; these devices include shape-changing, walking and translating machines. We expect ultimately to be able to use the dynamic information-based architectural properties of nucleic acids to be the basis for advanced materials with applications from nanoelectronics to biomedical devices on the nanometer scale.