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1.
Dalton Trans ; 49(3): 583-587, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31834333

RESUMO

Polyoxometalates (POMs) are intriguing catalysts for various reactions. However, the function of their counter-cations is overlooked. Here, we show that flexible counter-cations of methyltrioctylammonium can trigger polyoxovanadates to transform from octahedrally coordinated H2V10O284- to tetrahedrally coordinated V10O262-. This structural transformation enhances the performance tunability of POM chemistry and improves catalyst design.

2.
Mol Neurobiol ; 57(1): 278-289, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31325023

RESUMO

Cerebral amyloid angiopathy (CAA) refers to pathological changes occurring in cerebral blood vessels caused by deposition of beta amyloid (Aß) protein. However, the mechanisms involved in the origin of Aß for the formation of CAA and its link to parenchymal amyloid depositions remained to be unraveled. Here, we found CAA and parenchymal plaques distributed separately instead of mingling with each other in the spinal cord of TgCRND8 mice. Parenchymal plaques predominantly located in the dorsal horn whereas CAA distributed in the ventral horn. We further found that the ratio of Aß40/Aß42 was significantly higher in the ventral than that in the dorsal by ELISA assay, suggesting that origin of Aß forming parenchymal plaques may be different from that of CAA in the spinal cord. This hypothesis was further demonstrated by the surgical methods which indicated eliminating parenchymal plaques did not alter CAA in the affected spinal cord. We also examined the ratio of Aß40/Aß42 in the cerebral spinal fluid (CSF) in order to identify the origin of the CAA formation, and found the Aß40/Aß42 ratio was similar to that of CAA formation in the ventral horn. We further demonstrated that CSF tracer distributed along ventral horn vessels, in exactly the same pattern as Aß deposition in CAA in ventral part of spinal cord. These findings verified the concept that CSF influx may act as a constant source for delivering Aß, and contribute to the growth of paraarterial deposits in CAA. Taken together, the results of the present study highlight the important role of the Aß40/Aß42 ratio in determining vascular versus parenchymal amyloid deposition. Unlike parenchymal plaques, Aß of CAA comes from CSF; thus, manipulation of CSF Aß could represent a novel strategy to treat CAA.

3.
PLoS One ; 14(12): e0225708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815964

RESUMO

Culturing slowly growing tree seedlings is a potential approach for managing the conflict between the increasing demand for ornamental stock and the decreasing area of farmlands due to urbanization. In this study, Buddhist pine (Podocarpus macrophyllus [Thunb.] D. Don) seedlings were raised in multishelves with light-emitting diode lighting in the spectrum of 17:75:8 (red:green:blue) at 190-320 µmol m-2 s-1 with controlled temperature and relative humidity at 19.5°C and 60%, respectively. Seedlings were fed by exponential fertilization (EF) (nitrogen [N]-phosphorus [P]2O5-K2O, 10-7-9) at eight rates of 0 (control), 20 (E20), 40 (E40), 60 (E60), 80 (E80), 100 (E100), 120 (E120), and 140 (E140) mg N seedling-1 for four months through 16 fertilizer applications. The nutritional responses of Buddhist pine seedlings can be identified and classified into various stages in response to increasing doses, up to and over 120 N seedling-1. Morphological traits, i.e., the green color index and leaf area (LA) obtained by digital analysis and the fine root growth, all remained constant in response to doses that induced steady nutrient loading. LA had a positive relationship with most of the nutritional parameters. A dose range between 60 and 120 mg N seedling-1 was recommended for the culture of Buddhist pine seedlings. At this range of fertilizer doses, measuring the leaf area through digital scanning can easily and rapidly indicate the inherent nutrient status of the seedlings.

4.
Free Radic Biol Med ; 143: 454-470, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472247

RESUMO

Brachial plexus avulsion (BPA) occurs when the spinal nerve roots are pulled away from the surface of the spinal cord and disconnects neuronal cell body from its distal downstream axon, which induces massive motoneuron death, motor axon degeneration and de-innervation of targeted muscles, thereby resulting in permanent paralysis of motor functions in the upper limb. Avulsion injury triggers oxidative stress and intense local neuroinflammation at the lesioned site, leading to the death of most motoneurons. Berberine (BBR), a natural isoquinoline alkaloid derived from medicinal herbs of Berberis and Coptis species, has been reported to possess neuro-protective, anti-inflammatory and anti-oxidative effects in various animal models of central nervous system (CNS)-related disorders. In this study, we aimed to investigate the effect of BBR on motoneuron survival and axonal regeneration following spinal root avulsion plus re-implantation in rats. Our results indicated BBR significantly accelerated motor function recovery in the forelimb as revealed by the increased Terzis grooming test score, facilitated motor axon regeneration as evidenced by the elevated number of Fluoro-Gold-labeled and P75-positive regenerative motoneurons. The survival of motoneurons was notably promoted by BBR administration presented with boosted ChAT-immunopositive and neutral red-stained neurons. BBR treatment efficiently alleviated muscle atrophy, attenuated functional motor endplates loss in biceps and prevented the reduction of motor axons in the musculocutaneous nerve. Additionally, BBR treatment markedly mitigated the avulsion-induced neuroinflammation via inhibiting microglial and astroglial reactivity, up-regulated the expression of antioxidative indicator Cu/Zn SOD, and down-regulated the levels of nNOS, 3-NT, lipid peroxidation and NF-κB, as well as promoted SIRT1, PI3K and Akt activation. Collectively, BBR might be a promising therapy to assist re-implantation surgery for the treatment of BPA.

5.
Biomark Med ; 13(7): 567-575, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31140826

RESUMO

Aim: We aimed to investigate IL-33 polymorphisms with risk of colorectal cancer (CRC). Materials & methods: IL-33 rs7025417 and rs1332290 were genotyped using a quantitative allelic Taqman assay. The expression of IL-33 mRNA was determined by real-time PCR and promoter activity was assayed using the Dual-Luciferase Reporter Assay. Results: The IL-33 rs7025417 CC genotype and C allele may decrease CRC risk. The IL-33 rs1332290 AC carriers had an increased risk of developing clinical Stage III-IV CRC. Lower levels of IL-33 mRNA were present in individuals with the rs7025417 CC genotype. Moreover, the rs7025417 C allele suppressed promoter activity of IL-33. Conclusion: These data suggest that the rs7025417 CC genotype may downregulate IL-33 mRNA and subsequently reduce the risk of CRC.

6.
Neuroscience ; 409: 152-161, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31034974

RESUMO

Axonopathy manifested by axon swellings might constitute one of the earliest pathological features of Alzheimer's disease. It has been proposed that axonopathy might be associated with the origin of Aß plaques. However, how axonopathy leads to Aß plaque pathogenesis remains elusive. Our previous studies have shown that Aß neuropathology (mainly diffuse plaques) selectively occurred in the regions of corticospinal tract (CST) pathway and its innervated region in the spinal cord of TgCRND8 mice. In this study, we investigated the occurrence and progression of axonopathy and the possible implication in Aß plaque pathogenesis in the spinal cord of TgCRND8 mice. By anterograde labeling of CST system with a neuroanatomical tracer, we found that dilated corticospinal axons started to appear at 7 months, then exhibited an age-dependent increase. These abnormal structures appear before any plaque deposits are visible in the spinal cord of the mice. Importantly, they colocalized with Aß plaques in either the white matter or gray matter of the spinal cord at later stages, suggesting that these axonal swellings might represent the initial stages of Aß plaque formation, and could play a role in Aß plaque pathogenesis. Furthermore, using ultrastructural analysis we demonstrated that intracellular contents in the axonal dystrophies such as various dense vesicles leaked out into the extracellular matrix under a condition of axon swelling rupture in CST pathways of spinal cord. This provided precise structural evidence that how the Aß leaks out from the axonal dystrophies into extracellular matrix and how an axonal swelling might serve as a nidus of amyloid plaque formation.


Assuntos
Doença de Alzheimer/patologia , Axônios/patologia , Placa Amiloide/patologia , Medula Espinal/patologia , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Substância Cinzenta/patologia , Camundongos , Camundongos Transgênicos , Tratos Piramidais/patologia , Substância Branca/patologia
7.
AJR Am J Roentgenol ; : 1-8, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995094

RESUMO

OBJECTIVE. The purpose of this study is to perform a systematic review and meta-analysis to estimate the clinical value of MRI in assessing the stability of osteochondritis dissecans (OCD) lesions. MATERIALS AND METHODS. A systematic review of the literature published from January 1995 to July 2018 was performed by two independent reviewers using predefined search terms. The reference standard was established as arthroscopy or open surgery. True- and false-positive results as well as true- and false-negative results were counted. The quality of the selected studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooling of diagnostic accuracy, subgroup analysis, and identification of publication bias were included. RESULTS. Sixteen studies were included in the general data pooling. The pooled sensitivity and specificity were 0.92 (95% CI, 0.87-0.95; I2 = 0.55) and 0.85 (95% CI, 0.64-0.95; I2 = 0.88), respectively. The pooled sensitivity and specificity for juvenile OCD lesions were 0.93 (95% CI, 0.82-0.97) and 0.68 (95% CI, 0.41-0.86), respectively. Subgroup analysis showed that the staging system of Dipaola and colleagues and the criteria of De Smet and colleagues had a significant independent association with sensitivity. There was no evidence of publication bias (p = 0.57). CONCLUSION. The current meta-analysis suggested that MRI has a high diagnostic value for assessing the stability of OCD lesions. However, the MRI criteria applied for adult OCD lesions do not perform well in predicting stability of juvenile OCD lesions. Although some new juvenile OCD-specific MRI criteria yielding a satisfactory outcome have been proposed, further investigations are warranted.

8.
Clin Res Hepatol Gastroenterol ; 43(6): 707-714, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31029643

RESUMO

Acetaminophen (APAP) overdose/abuse is the leading cause of acute liver failure in many countries. Fibroblast growth factor 1 (FGF 1) is a metabolic regulator with several physiological functions. Previous studies suggested that FGF1 promotes differentiation and maturation of liver-derived stem cells. In this study, we investigated the protective effects of FGF1 against APAP-induced hepatotoxicity in mice. APAP markedly increased circulating levels of ALT and AST, while FGF1 significantly inhibited increases in the serum levels of ALT and AST, as compared to littermates. In addition, histopathological evaluation of the livers revealed that FGF1 prevented APAP-induced centrilobular necrosis. Livers exhibited severe inflammation, apoptosis, oxidative stress and endoplasmic reticulum stress in response to APAP toxicity, whereas these changes were reversed by a single injection of FGF1. In conclusion, our findings suggest that FGF1 protects mice from APAP-induced hepatotoxicity through suppression of inflammation, apoptosis, and oxidative and endoplasmic reticulum stress. Therefore, FGF1 may represent a promising therapeutic agent for APAP-induced acute liver injury.

9.
J Ethnopharmacol ; 234: 44-56, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30610932

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum Linne (C. indicum), a healthy food and folk medicine in China for thousands of years, has been reported to exert heat-clearing and detoxifying effects and extensively applied to treat various symptoms such as inflammation diseases, hepatitis and headache. AIM OF THIS STUDY: The purpose of the present study was to investigate the protective effect of the supercritical carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE) on D-galactose-induced brain and liver damage during aging process and to illuminate the underlying mechanisms. MATERIALS AND METHODS: Mice were orally administrated with CISCFE (100, 150 and 300 mg/kg) after injection with D-galactose. 24 h after the last administration, the blood samples, whole brain and liver tissues were collected for biochemical analysis, histological examination and western blot analysis. The body weight, spleen and thymus indexes, alanine transaminase (ALT), aspartate transaminase (AST), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) in brain and liver, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and necrosis factor-α (TNF-α) were detected. Besides, the expressions of Bax, Bcl-2 and cleaved caspase-3 were determined by western blot assay. RESULTS: The results indicated that CISCFE effectively increased the suppressed body weight, attenuated the decline of thymus and spleen indexes, and reduced the elevated levels of ALT and AST induced by D-gal. Furthermore, CISCFE might notably alleviate D-gal-induced abnormal alterations in structure and function of brain and liver dose-dependently via renewing normal antioxidant enzymes activities (SOD, CAT, GSH-Px), reducing MDA accumulation, decreasing inflammatory cytokines productions (IL-1ß, IL-6, TNF-α), as well as attenuating the increase of Bax/Bcl-2 ratio and cleaved caspase-3 activation in the liver and brain. CONCLUSIONS: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and liver diseases.


Assuntos
Chrysanthemum/química , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Envelhecimento/patologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Dióxido de Carbono/química , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Flores , Galactose/toxicidade , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Superóxido Dismutase/metabolismo
10.
Nat Commun ; 9(1): 4017, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30275470

RESUMO

Steels belong to one of the best established materials, however, the mechanisms of various phase transformations down to the nano length scale are still not fully clear. In this work, high-resolution transmission electron microscopy is combined with atomistic simulations to study the nanoscale carbide precipitation in a Fe-Cr-C alloy. We identify a cooperative growth mechanism that connects host lattice reconstruction and interstitial segregation at the growing interface front, which leads to a preferential growth of cementite (Fe3C) nanoprecipitates along a particular direction. This insight significantly improves our understanding of the mechanisms of nanoscale precipitation in interstitial alloys, and paves the way for engineering nanostructures to enhance the mechanical performance of alloys.

11.
Biochem Biophys Res Commun ; 503(2): 1130-1133, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29953859

RESUMO

Liposarcoma is the most common soft tissue malignancy. We investigated the relationship between the expression of fibroblast growth factor -21 protein and recurrence in the liposarcoma tissues from 40 patients. The patients were divided into two groups (low/no- and high-expressing) for further survival analysis according to fibroblast growth factor -21 expression in their tumor tissue. Immunohistochemical staining showed that fibroblast growth factor -21 protein was located in the cytoplasm. The fibroblast growth factor -21 protein was significantly less expressed in liposarcoma than in normal tissue (p < 0.05). Fibroblast growth factor -21 protein expression was related to gender, but not age, cell differentiation or tumor size. The patients in the low/no fibroblast growth factor 21 expression group were more likely to relapse and die in a shorter period of time. The patients in the high-expression group had a better prognosis and less recurrence. fibroblast growth factor -21 has the potential to act both as a biomarker for liposarcoma prognosis as well as a marker for the response to therapy.


Assuntos
Fatores de Crescimento de Fibroblastos/análise , Lipossarcoma/diagnóstico , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Prognóstico , Análise de Sobrevida
12.
J Phys Chem Lett ; 9(11): 2903-2908, 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29763326

RESUMO

Hybrid perovskites such as MAPbI3 (MA = CH3NH3) exhibit a unique spin texture. The spin texture (as calculated within the Rashba model) has been suggested to be responsible for a suppression of radiative recombination due to a mismatch of spins at the band edges. Here we compute the spin texture from first principles and demonstrate that it does not suppress recombination. The exact spin texture is dominated by the inversion asymmetry of the local electrostatic potential, which is determined by the structural distortion induced by the MA molecule. In addition, the rotation of the MA molecule at room temperature leads to a dynamic spin texture in MAPbI3. These insights call for a reconsideration of the scenario that radiative recombination is suppressed and provide an in-depth understanding of the origin of the spin texture in hybrid perovskites, which is crucial for designing spintronic devices.

13.
Int J Mol Med ; 41(5): 2901-2908, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29436592

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Livin are important in the development of gastric cancer (GC). PTEN and Livin are involved in the regulation of tumor cell proliferation, migration and apoptosis. The modulation of PTEN or Livin has been investigated extensively in various cancer models. However, no studies have been performed to evaluate the combined effect of concurrently modulating these two genes on the development of GC. In the present study, the BGC823 human gastric carcinoma cell line was transfected with a dual gene modified vector (pCL-neo-PTEN-siLivin) in parallel with single gene modified vectors (pCL­neo­PTEN or pRNAT­U6.1­siLivin), and an empty control vector. Dual gene modulation (pCL­neo­PTEN­siLivin) had a more marked effect on the inhibition of cell proliferation, induction of apoptosis, and reduction of cell penetration in Matrigel, compared with either single gene alone or empty vector transfection. In a xenograft nude mouse model, the inoculation of pCL­neo­PTEN­siLivin­transfected BGC823 cells led to a markedly reduced tumor burden, compared with that in all other inoculation groups. In conclusion, the overexpression of PTEN concomitant with Livin gene silencing was confirmed as a feasible and effective in vitro and in vivo gene modulation method, which may represent a potential therapeutic strategy for the treatment of GC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos/uso terapêutico , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Animais , Apoptose , Linhagem Celular Tumoral , Inativação Gênica , Terapia Genética/métodos , Vetores Genéticos/genética , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Regulação para Cima
14.
Int J Biol Sci ; 13(12): 1520-1531, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230100

RESUMO

After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear. Here, we show that NBP prevented BSCB disruption after SCI via inhibition of ER stress. Following a moderate contusion injury of the T9 level of spinal cord, NBP was administered by oral gavage and further treated once a day. NBP significantly attenuated BSCB permeability and breakdown of adherens junction (AJ) and tight junction (TJ) proteins, then improved locomotion recovery following SCI. The protective role of NBP on BSCB disruption is associated with the restrain of ER stress caused by SCI. Furthermore, NBP considerably constrained the expression of ER stress-associated proteins and degradation of TJ and AJ in human brain microvascular endothelial cells (HBMECs) treated with TG. In conclusion, our results indicate that ER stress is associated with the disruption of BSCB integrity after injury, NBP attenuates BSCB disruption via inhibiting ER stress and improve functional recovery following SCI.


Assuntos
Benzofuranos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/efeitos dos fármacos , Junções Aderentes/efeitos dos fármacos , Animais , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Locomoção/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Junções Íntimas/efeitos dos fármacos
15.
BMC Gastroenterol ; 17(1): 148, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29216847

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract. The current study aimed to examine the association between visceral hypersensitivity in IBS and cortical activation using functional magnetic resonance imaging (fMRI), and to elucidate the role of psychological factors in the pathogenesis of IBS. METHODS: The present study included 31 patients with IBS and 20 healthy controls. Cerebral function was assessed using fMRI. During imaging, a Sengstaken-Blakemore tube was placed within the rectum approximately 10 cm from the anus, following which gas was rapidly injected into the airbag using a 150-ml syringe. Images were obtained at 40 ml, 80 ml, and 120 ml of expansion. Psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Anxiety and depression scores were higher among patients with IBSthan among controls (both P < 0.05), although scores in both groups were below the level of clinical diagnosis. Brain activation in regions of interest (parietal areas, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) increased along with increases in rectal balloon dilation, except in women with IBS and patients with disease duration less than 5 years. Furthermore, region of interest (ROI) activation (such as the parietal region, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) differed significantly between the 40-ml and 120-ml conditions, and between the 80-ml and 120-ml conditions (P < 0.05), among patients with IBS with anxiety or depression scores less than 9 points. CONCLUSIONS: Overall, our findings indicate that changes in brain activation due to changes in rectal balloon distension can be objectively and accurately measured using fMRI. Although our results indicated that visceral hypersensitivity during IBS is associated with changes in cortical activation, further studies utilizing larger sample sizes are required to more fully elucidate the association between psychological factors and visceral hypersensitivity in IBS.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Síndrome do Intestino Irritável/diagnóstico por imagem , Síndrome do Intestino Irritável/fisiopatologia , Imagem por Ressonância Magnética , Adolescente , Adulto , Idoso , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Feminino , Humanos , Síndrome do Intestino Irritável/psicologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
J Cell Mol Med ; 21(11): 3010-3022, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28842949

RESUMO

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling.


Assuntos
Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Linhagem Celular , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Microglia/citologia , Microglia/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/imunologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/patologia , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
17.
Exp Ther Med ; 14(2): 1184-1192, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28810577

RESUMO

The incidence of inflammatory bowel disease (IBD), characterized by chronic, relapsing intestinal inflammation, has continually increased in recent years. A previous study by our group identified five potential metabolic markers possibly associated with the pathology of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD in rats. The present study aimed to examine the potential therapeutic effects of the essential oil of Pogostemon cablin (also known as patchouli; PO) on TNBS-induced rats and investigate the concomitant metabolic changes by targeting the previously identified potential markers. Pogostemon cablin is widely used to treat gastrointestinal diseases, including IBD, in China. The results of the present study showed that PO (270 mg/kg, rectal instillation) significantly alleviated colonic damage and reduced disease activity indicators and colonic myeloperoxidase in TNBS-induced rats. In addition, a targeted metabolic profiling study identified that four metabolites were elevated in the urine of the animals in the TNBS group, which were significantly inhibited by treatment with PO: Two tryptophan metabolites [4-(2-aminophenyl)-2,4-dioxobutanoic acid and 4,6-cihydroxyquinoline] and two gut microbial metabolites (phenylacetylglycine and p-cresol glucuronide). Taken together, these findings suggested that PO ameliorated the symptoms of TNBS-induced IBD and reversed the metabolic changes potentially associated with TNBS-induced IBD in rats.

18.
Mol Med Rep ; 16(5): 5908-5914, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28849207

RESUMO

A strategy to suppress the expression of the DNA repair enzyme O6­methylguanine­DNA methyltransferase (MGMT) by inhibition of Wnt/ß­catenin signaling may be useful as a novel treatment for pituitary adenoma. Previous studies have reported that Tanshinone IIA (TSA), a major quinone compound isolated from Salvia miltiorrhiza, had antitumor effects. However, whether TSA has antitumor effects against pituitary adenoma and whether the mechanisms are associated with the Wnt/ß­catenin/MGMT pathway remains to be clarified. In the present study, TSA treatment caused apoptosis in AtT­20 cells in a concentration­dependent manner, as demonstrated by cell viability reduction, phophatidylserine externalization detected by Annexin V staining and mitochondrial membrane potential disruption detected by JC­1 staining, which were associated with activation of caspase­3 and DNA fragmentation detected by TUNEL in AtT­20 cells. T­cell factor (TCF)­lymphoid­enhancing factor (LEF) reporter activity was determined by dual luciferase reporter assay and the interaction between ß­catenin and TCF­4 were detected using a co­immunoprecipitation kit. The results indicated TSA treatment increased ß­catenin phosphorylation, inhibited ß­catenin nuclear translocation, reduced ß­catenin/TCF­4 complex formation and TCF­LEF luciferase reporter activity, and subsequently reduced the expression of cyclin D1 and MGMT. Notably, overexpression of MGMT in ß­catenin knock down AtT­20 cells abrogated the TSA­mediated effects in AtT­20 cells. In conclusion, TSA induced apoptosis via inhibition of Wnt/ß­catenin­dependent MGMT expression, which may provide novel insights into the understanding of the mechanism of the antitumor effects of Salvia miltiorrhiza.


Assuntos
/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Corticotrofos/efeitos dos fármacos , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Regulação Neoplásica da Expressão Gênica , Salvia miltiorrhiza/química , Proteínas Supressoras de Tumor/genética , beta Catenina/genética , /isolamento & purificação , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Corticotrofos/metabolismo , Corticotrofos/patologia , Fragmentação do DNA , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/metabolismo , Relação Dose-Resposta a Droga , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Camundongos , Extratos Vegetais/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição 4/genética , Fator de Transcrição 4/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , beta Catenina/metabolismo
19.
Phys Rev Lett ; 118(23): 236101, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28644663

RESUMO

Employing ab initio calculations we demonstrate that the complex structural modulations experimentally observed in ultrathin Fe films on Cu(001) originate from Fe bulk phases that arise under extreme deformations. Specifically, we show that the structural modulations correspond to the motifs observed when transforming fcc Fe to bcc Fe in the Pitsch orientation relationship [(001)_{fcc}||(11[over ¯]0)_{bcc}]. The observed structural equivalence between surface and unstable bulk structures naturally explains the experimentally reported magnetic and structural transitions when going from low (two to four MLs) to intermediate (four to ten MLs) film coverages.

20.
Am J Transl Res ; 9(3): 1075-1087, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386335

RESUMO

Endoplasmic reticulum (ER) stress-induced apoptosis occurs in the spinal cord following traumatic spinal cord injury (SCI). Dl-3-n-butylphthalide (NBP) exerts an neuroprotective effects against both ischemic brain injury and neurodegenerative diseases; however, the relationship between ER stress-induced apoptosis and the therapeutic effect of NBP in SCI remains unclear. In this study, moderate spinal cord injuries were induced in Sprague-Dawley (SD) rats with a vascular clip. NBP was administered by oral (80 mg/kg/d) gavage 2 h before injury and then once daily for 28 d thereafter. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotion rating scale, the inclined plane test, and the footprint analysis. Neuronal cell death was examined by TUNEL staining at 7 days post-injury. ER stress and apoptosis-related proteins were quantified by immunofluorescence staining and western blotting both in vivo and in vitro. Our results showed that NBP significantly decreased spinal cord lesion cavity area and improved locomotor recovery in SD rats after SCI. NBP also decreased neuronal apoptosis and inhibited activation of the caspase 3 cascade. Upregulation of ER stress-related proteins, such as GRP78, ATF-6, ATF-4, PDI, XBP-1, and CHOP, was reversed by NBP treatment in SD rats with SCI. Similarly, NBP effectively ameliorated ER stress and apoptosis-related protein expression induced by incubation with thapsigargin (TG) in PC12 cells. Our findings demonstrate that NBP treatment alleviates secondary SCI by inhibiting ER stress-induced apoptosis, thereby promoting neurological and locomoter functional recovery.

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