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1.
Int J Neurosci ; 129(2): 179-188, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29962282

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology and transplantation medicine. This study aims to investigate effects of rapamycin on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris water maze test was applied to evaluate the learning and memory abilities. The fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol, triglyceride and serum insulin level were measured. RT-qPCR and Western blot analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry was used to detect the Aß deposition and immunoblotting to test the total tau, p-tau and Aß precursor APP expressions. RESULTS: After treated with rapamycin, T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA expression and p-AMPK and decreased Aß deposition, mTOR mRNA expression and p-mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby improving AD lesion in hippocampus of T2DM rats.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Diabetes Mellitus Tipo 2/metabolismo , Hipocampo/metabolismo , Sirolimo/administração & dosagem , Serina-Treonina Quinases TOR/metabolismo , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Diabetes Mellitus Tipo 2/complicações , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fosforilação , Ratos Sprague-Dawley , Transdução de Sinais , Proteínas tau/metabolismo
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 13-19, 2019 Jan.
Artigo em Zh | MEDLINE | ID: mdl-31037899

RESUMO

OBJECTIVE: To explore the role mechanism of hsa-miR-302a-3p overexpression in the inhibition of proliferation of gastric cancer cell SGC-7901 by targeted-regulating vascular endothelial growth factor A (VEGFA). METHODS: The cell transfection was used to transfect hsa-miR-302a-3p mimic into miR mimic group and transfect pc-VEGFA into VEGFA group, and the two genes were co-transfected into miR+VEGFA group. The transfection efficiency was detected by RT-PCR and Western blot. The bioinformatics targeting prediction and fluorescein assay were used to verify the targeting relationship between the two genes. Cell proliferation was detected by CCK-8 test, and Transwell assay was used to detect the invasion ability of each group, and scratch assay was used to detect the migration ability of each group. The morphology changes of epithelial-mesenchymal transition (EMT) in cells were observed under microscope. Western blot was used to detect the protein expression levels of survival-related proteins Ki67 and Caspase-3, EMT-related proteins E-cadherin, Vimentin, N-cadherin and Snail and VEGFA downstream target genes p-P38, p-MAPKAPK and p-Hsp27. RESULTS: VEGFA was the predicted target site of miR-302a-3p. Compared with control group, the number of cells, the invasion and migration rates were also reduced ( P<0.05) in miR mimic group, and the number of cells was increased ( P<0.05) as well as the invasion and migration rates in VEGFA group. Compared with VEGFA group, the number of cells, the invasion and migration rates were also decreased ( P<0.05) in miR+VEGFA group. The protein expression level of E-cadherin was up-regulated ( P<0.05) while the protein expression levels of Vimentin, N-cadherin and Snail were down-regulated ( P<0.05), and the protein expression levels of p-P38, p-MAPKAPK and p-Hsp27 were also down-regulated ( P<0.05). CONCLUSION: hsa-miR-302a-3p overexpression can inhibit the proliferation and promote apoptosis of gastric cancer cell SGC-7901 by targeting negative regulation of VEGFA expression.


Assuntos
Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs , Fator A de Crescimento do Endotélio Vascular
3.
Biol Pharm Bull ; 41(7): 1024-1033, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962399

RESUMO

Acarbose and voglibose are the most widely used diabetes drugs as glycosidase inhibitors. In this study, the use of these two inhibitors significantly increased the content of starch in large intestine, and altered the concentration of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota. However, there are some differences in the intestinal microbiome of the two groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in caecum in voglibose group were significantly higher than those in acarbose group and two kinds of glycosidase inhibitors were close in the production of butyrate in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data indicated that different productions of acetate and propionate between acarbose group and voglibose group may be related to 2-oxoisovalerate dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested that voglibose had less effect on epithelial cells than acarbose after direct stimulation. According to the recent researches of SCFAs produced by intestinal microbiota, our comparative study shown higher concentration of these beneficial fatty acids in the lumen of voglibose-treated mice, which implied a lower level of inflammation.


Assuntos
Ácidos Graxos Voláteis/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , Mucosa Intestinal/metabolismo , Acarbose/farmacologia , Animais , Bacteroidaceae/efeitos dos fármacos , Bacteroidaceae/metabolismo , Células CACO-2 , Desulfovibrionaceae/efeitos dos fármacos , Desulfovibrionaceae/metabolismo , Células Epiteliais/efeitos dos fármacos , Humanos , Inositol/análogos & derivados , Inositol/farmacologia , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Amido/análise
4.
Med Sci Monit ; 24: 5943-5950, 2018 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-30145601

RESUMO

BACKGROUND Our study aimed to explore the levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in healthy participants, type 2 diabetes mellitus (T2DM) patients, and diabetic peripheral neuropathy (DPN) patients in order to find their effects on DPN. MATERIAL AND METHODS The clinical data of 110 healthy participants (age: 57.3±8.2 year, height: 165.4±5.5 cm, weight: 64.1±7.5 kg), 83 T2DM patients (age: 56.5±7.9 year, height: 164.8±6.2 cm, and weight: 63.6±6.6 kg), and 65 DPN patients (age: 58.2±7.3 year, height: 166.7±6.7 cm, weight: 63.1±5.8 kg) were observed. ELISA was applied to detect serum NGF and BDNF levels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic value of serum NGF and BDNF levels in DPN. Logistic regression analysis was performed to analyze risk factors for DPN. RESULTS Serum NGF and BDNF levels decreased most in DPN patients. Subsequently, we determined that serum NGF and BDNF levels were correlated with: the course of disease for patients, fasting C-peptide (FCP), 2-hour postprandial C-peptide level (2-h PCP), glycosylated hemoglobin level (HbAlc), and 24-hour urinary microalbumin excretion (24-h UME). ROC curve analysis identified high sensitivity, specificity, and accuracy of NGF and BDNF levels on DPN. Serum levels of NGF and BDNF, course of disease, 2-h PCP level, and postprandial blood glucose level were determined to be risk factors for DPN. CONCLUSIONS Our study highlights that serum levels of NGF and BDNF might be associated with the occurrence and development of DPN.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/metabolismo , China , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/sangue , Fator de Crescimento Neural/metabolismo , Curva ROC , Fatores de Risco
5.
Immunol Cell Biol ; 95(2): 189-197, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27616751

RESUMO

Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.


Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/imunologia , Memória Imunológica , Antígenos Comuns de Leucócito/metabolismo , Transplante de Pele , Baço/citologia , Linfócitos T/imunologia , Doadores de Tecidos , Animais , Apoptose , Proliferação de Células , Feminino , Sobrevivência de Enxerto/imunologia , Inflamação/patologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Depleção Linfocítica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Análise de Sobrevida , Linfócitos T Reguladores/imunologia
6.
Soft Matter ; 13(6): 1291-1298, 2017 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-28106900

RESUMO

Ultrashort single-chain fatty acids self-assemble to form vesicles under certain proton-driven conditions. The protonation provides a larger charge area around the hydrophilic carbonyl headgroups, and proton shift as the key driving parameter was studied. The ultrashort fatty acids (C4-C8) formed stable unilamellar vesicles predominantly through out the whole range of tested pH levels (6.5-9.5). A proton-driven self-assembly process and effects on the phase transition were characterized by dynamic light scattering, transmission electron microscopy and cryo-transmission electron microscopy. In particular, we studied in greater detail the molecular packing characteristics of FA vesicles for geometric reasons and the protonation effect changes the molecular surface charge and further carboxylic acid headgroup motion. This study enhances the understanding of the physicochemical specificity of these membrane vesicles, and may facilitate the alteration of membrane function caused by FAs.

7.
Exp Cell Res ; 324(2): 146-56, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24726912

RESUMO

The cytokine interferon-α (IFNα) belongs to the group of type I interferons already used in cancer therapy. This drug possesses radio- and chemo-sensitizing, and shows anti-angiogenic properties. Cancer stem cells (CSC) are a unique population of tumor cells that initiate secondary tumors, and are responsible for metastasis formation. Patients with pancreatic ductal adenocarcinoma (PDAC) have an especially poor prognosis, with 5-year survival rates of only ~1% and median survival of 4-6 months. PDAC is characterized by the presence of CSC. In this work we demonstrate for the first time that IFNα up-regulates the expression of the CSC markers CD24, CD44 and CD133 in in vitro and in vivo models of PDAC. We showed the IFNα effects on the migration and invasion of PDAC cells, which is associated with the level of the CSC marker expression. In vivo, this drug inhibits tumor growth but promotes metastasis formation in the early stage of tumor growth. We propose that IFNα may enhance the enrichment of CSC in PDAC tumors. Additionally we also suggest that in combination therapy of solid tumors with IFNα, this drug should be given to patients prior to chemotherapy to achieve the CSC activation.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Interferon-alfa/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/genética , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon-alfa/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Chin Med Sci J ; 29(1): 15-22, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24698673

RESUMO

OBJECTIVE: To investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD). METHODS: Patients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score. RESULTS: Eighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%. CONCLUSIONS: Autologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.


Assuntos
Doença Hepática Terminal/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Artéria Hepática , Veia Porta , Adulto , Idoso , Intervalo Livre de Doença , Doença Hepática Terminal/patologia , Feminino , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
9.
NPJ Sci Food ; 8(1): 2, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182603

RESUMO

Sweet taste receptors found in oral and extra oral tissues play important roles in the regulation of many physiological functions. Studies have shown that urine volume increases during the lifetime exposure to artificial sweeteners. However, the detailed molecular mechanism and the general effects of different artificial sweeteners exposure on urine volume remain unclear. In this study, we investigated the relationship between urinary excretion and the sweet taste receptor expression in mice after three artificial sweeteners exposure in a higher or lower concentration via animal behavioral studies, western blotting, and real-time quantitative PCR experiment in rodent model. Our results showed that high dose of acesulfame potassium and saccharin can significantly enhance the urine output and there was a positive correlation between K+ and urination volume. The acesulfame potassium administration assay of T1R3 knockout mice showed that artificial sweeteners may affect the urine output directly through the sweet taste signaling pathway. The expression of T1R3 encoding gene can be up-regulated specifically in bladder but not in kidney or other organs we tested. Through our study, the sweet taste receptors, distributing in many tissues as bladder, were indicated to function in the enhanced urine output. Different effects of long-term exposure to the three artificial sweeteners were shown and acesulfame potassium increased urine output even at a very low concentration.

10.
Chem Senses ; 38(5): 447-55, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23537561

RESUMO

Exposure to artificial sweetener acesulfame-K (AK) at early development stages may influence the adult sweet preference and the periphery gustatory system. We observed that the intraoral AK stimulation to mice from postnatal day 4 (P4) to weaning decreased the preference thresholds for AK and sucrose solutions in adulthood, with the preference pattern unchanged. The preference scores were increased in the exposure group significantly when compared with the control group at a range of concentrations for AK or sucrose solution. Meanwhile, more α-Gustducin-labeled fungiform taste buds and cells in a single taste bud were induced from week 7 by the early intraoral AK stimulation. However, the growth in the number of α-Gustducin-positive taste bud or positive cell number per taste bud occurred only in the anterior region, the rostral 1-mm part, but not in the intermediate region, the caudal 4-mm part, of the anterior two-third of the tongue containing fungiform papillae. This work extends our previous observations and provides new information about the developmental and regional expression pattern of α-Gustducin in mouse fungiform taste bud under early AK-stimulated conditions.


Assuntos
Preferências Alimentares/efeitos dos fármacos , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia , Papilas Gustativas/efeitos dos fármacos , Tiazinas/administração & dosagem , Tiazinas/farmacologia , Transducina/biossíntese , Administração Oral , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR , Papilas Gustativas/metabolismo
11.
Chem Senses ; 36(9): 763-70, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21653241

RESUMO

This study investigates whether mother's exposure to the artificial sweetener acesulfame-K (AK) during pregnancy or lactation affected her adult offspring's sweet preference. It was found that mother's dietary exposure to AK in pregnancy or lactation decreased the preference thresholds for AK and sucrose solutions in the adult offspring, whereas the preference pattern and the most preferred concentration for AK or sucrose solution were unchanged. Furthermore, the preference scores in the exposure groups were increased significantly when compared with the control group at a range of concentrations for AK or sucrose solution. The existence of AK and its dynamic changes within 24 h in amniotic fluid during pregnancy or in mother's milk during lactation after a single oral infusion of AK solution were revealed by the methods of reversed-phase high-performance liquid chromatography and mass spectrometry. Our data suggest that AK can be ingested by the prenatal or postnatal mice through their mother's amniotic fluid or breast milk, producing a long-dated function on the adult's sweet preference.


Assuntos
Dieta , Preferências Alimentares/efeitos dos fármacos , Lactação , Efeitos Tardios da Exposição Pré-Natal , Paladar/fisiologia , Tiazinas/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Exposição Materna , Troca Materno-Fetal , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Sacarose , Paladar/efeitos dos fármacos
12.
Food Chem ; 128(1): 134-44, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25214340

RESUMO

The thermodynamics of the mimetic interaction of lactisole and sweeteners with fullerenols as a synthetic sweet receptor model was elucidated by Isothermal Titration Calorimetry (ITC) technique. The presence of lactisole resulted in great differences in thermodynamics of the sweeteners binding with fullerenols in which lactisole led to much more entropy contribution to the free energy compared with the interaction of sweeteners with fullerenols. Two interaction equilibrium states were found in ITC titration profiles and competitive binding of lactisole and sweeteners with fullerenols was disclosed. Our results indicated that the larger value of the ratio of two equilibrium constant K1/K2, the more effectively lactisole inhibited the sweetness of the sweetener. The combined results of sensory evaluation and ITC thermodynamics revealed that introducing a synthetic receptor model to interact with the sweeteners and inhibitors helps to understand the inhibition mechanism and the thermodynamic basis for the initiation of sweetness inhibition.

13.
J Neural Transm (Vienna) ; 117(11): 1261-4, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20838827

RESUMO

The gustatory system is susceptible to anatomical modification by postnatal taste stimulations. This study investigated the effects of early intraoral infusion of acesulfame-K solution on the development of fungiform taste buds in mice. It was found that the acesulfame-K infusion increased the number, promoted the maturation, and enlarged the size of taste bud during the postnatal stages, compared with the age-matched controls. This provides fundamental and new information about the development of taste bud under normal and early acesulfame-K-stimulated conditions.


Assuntos
Papilas Gustativas/efeitos dos fármacos , Papilas Gustativas/crescimento & desenvolvimento , Tiazinas/administração & dosagem , Administração Oral , Animais , Camundongos
14.
Ann Palliat Med ; 9(4): 2271-2278, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32576011

RESUMO

Hepatic alveolar echinococcosis (HAE) is a cosmopolitan zoonosis distribute widely in the northern hemisphere with high estimated 10-year mortality. Radical resection combined with oral albendazole administration are the major methods for HAE treatment, whereas most patients delayed diagnosis and treatment because which was considered as benign disease. For the cases with end-stage HAE could not be treated through conventional hepatectomy, allograft liver transplantation (LT) was regarded as a life-saving technique previously. However, graft shortage, high recurrence rate and long-term immunosuppressive therapy limited its utilization. Since the ex-vivo liver resection and autotransplantation (ERAT) procedure was first used in treating for end-stage HAE in 2011, there are more than 120 HAE cases patients were reported treating in this method up to now. Comparing with LT, ERAT needs neither an organ donor nor long term immunosuppressive therapy, and provide preferable overall survival rates. Based on the conventional ERAT procedure, some modification such as auxiliary partial autologous LT were introduced in the high selected end-stage HAE patients presently. However, the standard procedures for ERAT including surgical details and perioperative management have not been established because of limited reported cases. Also, the present ERAT experience for end-stage HAE treatment are all summarizes by the Chinese surgeon groups. For summarizing the knowledge and experience details, we reviewed present opinions about ERAT for end-stage HAE patients, and presented the future perspectives about this topic in this manuscript. We aimed at discussing the feasibility, indications, preparation, technical details, and postoperative outcomes of ERAT for HAE patients.


Assuntos
Equinococose Hepática , Transplante de Fígado , Equinococose Hepática/cirurgia , Hepatectomia , Humanos , Transplante Autólogo
15.
Chem Senses ; 34(1): 93-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18854510

RESUMO

The aim of this study was to investigate the relationship of fungiform papillae density with taste detection thresholds for sucrose of young male adults. One hundred and eighty two subjects aged 18-23 years (mean age: 21.9 +/- 1.2 years) were included. The densities of fungiform papillae were recorded with the aid of the digital camera, and the taste detection thresholds for sucrose were detected using a modified forced-choice triangle test. The mean density of papillae within all 170 statistic participants was 92.43 +/- 2.64/cm(2), for the 6-mm-diameter stained section of the tongue tip. The average detection threshold was 10.83 +/- 0.24 mmol/l, and the highest and lowest detection thresholds were 19.88 +/- 1.31 and 5.85 +/- 0.43 mmol/l, respectively. Also, an inverse correlation between the fungiform papillae density and the detection threshold was observed.


Assuntos
Limiar Diferencial/efeitos dos fármacos , Sacarose/farmacologia , Papilas Gustativas/anatomia & histologia , Papilas Gustativas/citologia , Adolescente , Humanos , Masculino , Estimulação Química , Adulto Jovem
16.
BMC Mol Cell Biol ; 20(1): 9, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31039730

RESUMO

BACKGROUND: The purpose of this study was to determine the aberrant expression of the long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) in 5-fluorouracil-resistant colonic neoplasm cells and to elucidate its effects on the 5-fluorouracil sensitivity of human colonic neoplasm cells. The aberrant expression of lncRNAs in normal tissues and colonic neoplasm tissues was detected by microarray assay. qRT-PCR analysis was performed to assess CCAT1 expression levels in colonic neoplasm cell lines and corresponding normal tissues. After constructing the 5-FU-resistant cell lines and validating the resistance by measuring the IC50 value, the CCAT1 expression levels in parental and artificially resistant cell lines were determined by qRT-PCR. Transfection was used to modulate the expression of CCAT1. Cell proliferation and apoptosis were then detected by CCK-8 and flow cytometry, respectively. RESULTS: CCAT1 in colon cancer tissues was higher than that in noncancer tissues, and the levels of CCAT1 in HCT 116, SW1417, HT-29, and KM12 cell lines were higher than those in the human normal colon epithelial NCM460 cell line. Moreover, the expression levels of CCAT1 were high in HCT 116/5-FU and HT-29/5-FU cell lines, whose apoptosis rates induced by 5-FU were lower than those in corresponding parental cells. The results of qRT-PCR and CCK-8 assay showed that enhancement of lncRNA CCAT1 expression levels in HCT 116 and HT-29 cell lines increased their IC50 of 5-FU and decreased their apoptosis rates. Meanwhile, siRNA-CCAT1 effectively inhibited the expression of CCAT1 and enhanced the 5-FU-sensitivity of HCT 116/5-FU and HT-29/5-FU, in which apoptosis rates were increased at the same time. CONCLUSIONS: Downregulation of CCAT1 effectively reversed the resistance of HCT 116/5-FU and HT-29/5-FU cells to 5-FU chemotherapeutic, opening a new avenue in colon cancer therapy.


Assuntos
Neoplasias do Colo/patologia , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , RNA Longo não Codificante/genética , Animais , Apoptose , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Longo não Codificante/antagonistas & inibidores , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Transplante Heterólogo , Carga Tumoral
17.
Colloids Surf B Biointerfaces ; 179: 488-494, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005744

RESUMO

Vesicles possess unique biofilm structures and offer biomimetic advantages for drug and gene delivery. Herein, we report the spontaneous vesicle formation from ultrashort alkyl-phosphonic acids in the presence of amino acids. The aggregation characteristics and self-assembly structures of vesicles in aqueous solution were investigated by using dynamic light scattering, zeta potential, and cryo-transmission electron microscopy. We combined low-field nuclear magnetic resonance and Fourier transform infrared spectroscopy to study the H-proton-induced multilamellar vesicle formation. When we increased the molar fraction of serine, stable and closed spherical vesicles were formed at relatively low critical micelle concentrations. This transition of the self-assembled structure indicates that vesicle formation occurs when the chain length and the magnitude of the surface charge cause a fluctuation in the volume of the vesicle. Density functional theory reveals the critical role of the mixed alkyl-phosphonic acid/amino acid-enhanced electrostatic attraction between the head groups and hydrogen bonds associated with the aggregated states.


Assuntos
Ácidos Fosforosos/química , Serina/química , Água/química , Difusão Dinâmica da Luz , Espectroscopia de Ressonância Magnética , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
18.
Colloids Surf B Biointerfaces ; 173: 69-76, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30267956

RESUMO

The properties of vesicles formed from the self-assembly of amphiphilic molecules can mimic the functionality of the natural lipid membranes. In this study, the self-assembly process of the amphiphilic structures formed by the interaction between ultra-small fatty acids [FAs, Cn (n = 4-8)] and amino acids (AAs) to generate vesicles under aqueous conditions were investigated in detail, along with the corresponding dynamic vesiculation mechanisms. Our results showed that the molar ratio of FAs/AAs and the chain length of FAs largely affected the structural characteristics and dispersion of vesicles. The detailed information about the entire size distributions and morphology of obtained vesicles were explored by the cryogenic transmission electron microscopy (Cryo-EM). Fourier transform infrared (FT-IR) spectra and quantum calculations suggested that the intermolecular hydrogen bond and electrostatic interactions between ultra-small molecules (FAs and AAs) during the aggregation processes were responsible for the formation of vesicles, where the hydrogen-bonding effect was dominant. Our findings shed new light on the effective and simple preparation of biological vesicles via ultra-small molecules self-assembly in aqueous solutions, which may have potential applications in vesicle physiology and drug delivery systems, and also get a mature understanding of the fundamental intermolecular interactions in life process.


Assuntos
Aminoácidos/química , Ácidos Graxos/química , Tensoativos/química , Água/química , Alanina/química , Ácido Butírico/química , Caproatos/química , Caprilatos/química , Glicina/química , Ácidos Heptanoicos/química , Ligação de Hidrogênio , Isoleucina/química , Leucina/química , Microesferas , Tamanho da Partícula , Ácidos Pentanoicos/química , Eletricidade Estática
19.
Chem Senses ; 33(4): 357-62, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18296428

RESUMO

The regional differences between distribution patterns and alpha-gustducin expression patterns of the fungiform (FF) taste buds were investigated in the adult mouse, using hematoxylin-eosin staining and immunofluorescence histochemistry on the most anterior region of the tongue (the first millimeter) through the intermediate region of the tongue (the last 1-4 mm). Paraffin sections were prepared from the tip to posterior regions (anterior and intermediate region containing the FF taste buds) of the adult mouse tongue. Results indicate that there were significant regional differences in size and density of taste buds, the cell counts of the single taste bud, and the alpha-gustducin-immunoreactive taste buds between the 2 regions. The taste bud had a characteristic onion-like appearance, and the alpha-gustducin-immunoreactive cell was spindle shaped with elongated processes extending from the base to the pore of the taste buds. These results provide a detailed insight to better understand regional descriptions of mouse taste bud density and size and alpha-gustducin expression with the mouse model.


Assuntos
Proteínas Heterotriméricas de Ligação ao GTP/biossíntese , Língua , Animais , Contagem de Células , Imunofluorescência , Masculino , Camundongos , Papilas Gustativas/citologia , Papilas Gustativas/metabolismo , Língua/anatomia & histologia , Língua/citologia , Língua/metabolismo
20.
Arch Oral Biol ; 53(6): 583-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18294610

RESUMO

The aim of this study was to investigate the age-related developmental changes of taste bud distribution within the subpopulations at different postnatal ages in the mouse oral cavity. Developmental changes of taste bud distribution on the soft palate, fungiform, foliate and circumvallate papillae in the mouse oral cavity were examined histologically at different postnatal ages. After paraffin embedding, complete serial sections at 10mum thickness were made and stained by routine hematoxylin-eosin staining methods. Digitised images for each section were examined carefully. The existence of a taste pore was used to identify mature taste buds. A two-way analysis of variance (group versus age) was used to analyse differences in taste bud number and characteristics for each of the developmental changes. An independent measures t-test was used to compare two means. No taste buds with pores were observed at birth within circumvallate and foliate papillae. However, 61% of the circumvallate and 58% of the foliate taste buds contained taste pores at 2 weeks after birth. In contrast, at birth, 55% of the taste buds on the soft palate and only 22% of the taste buds within fungiform papillae contained taste pores. Then, the number of mature taste buds (taste buds with pores) increased rapidly 1 week after birth, resulting in 90% of soft palate taste buds and 32% of fungiform taste buds containing taste pores. These results suggests that the earlier maturation of soft palate taste buds compared with the other populations in the oral cavity raises evidence of their significant role in the taste mechanism, especially in the early life of the mouse.


Assuntos
Boca/crescimento & desenvolvimento , Papilas Gustativas/crescimento & desenvolvimento , Fatores Etários , Animais , Animais Recém-Nascidos , Feminino , Masculino , Camundongos , Palato Mole/crescimento & desenvolvimento
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