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1.
Plant Physiol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980916

RESUMEN

Plant pollen tubes and root hairs typical polarized tip growth. It is well established that calcium ions (Ca2+) play essential roles in maintaining cell polarity and guiding cell growth orientation. Ca2+ signals are encoded by Ca2+ channels and transporters and are decoded by a variety of Ca2+-binding proteins often called Ca2+ sensors, in which calcineurin B-like protein (CBL) proteins function by interacting with and activating a group of kinases, activate CBL-interacting protein kinases (CIPKs). Some CBL-CIPK complexes, such as CBL2/3-CIPK12/19, act as crucial regulators of pollen tube growth. Whether these calcium decoding components regulate the growth of root hairs, another type of plant cell featuring Ca2+-regulated polarized growth, remains unknown. In this study, we identified CIPK13 and CIPK18 as genes specifically expressed in Arabidopsis (Arabidopsis thaliana) root hairs. The cipk13 cipk18 double mutants showed reduced root hair length and lower growth rates. The calcium oscillations at the root hair tip were attenuated in the cipk13 cipk18 mutants as compared to the wild-type plants. Through yeast two-hybrid screens, CBL2 and CBL3 were identified as interacting with CIPK13 and CIPK18. cbl2 cbl3 displayed a shortened root hair phenotype similar to cipk13 cipk18. This genetic analysis, together with biochemical assays showing activation of CIPK13/18 by CBL2/3, supported the conclusion that CBL2/3 and CIPK13/18 may work as Ca2+-decoding modules in controlling root hair growth. Thus, the findings that CIPK12/19 and CIPK13/18 function in pollen tube and root hair growth, respectively, illustrate a molecular mechanism in which the same CBLs recruit distinct CIPKs in regulating polarized tip growth in different types of plant cells.

2.
Scand J Psychol ; 64(6): 802-809, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37345676

RESUMEN

Social avoidance and distress are the primary aspects of social anxiety. Nonautistic people with high levels of autistic traits are more likely to exhibit social avoidance and distress. However, research has yet to reveal how autistic traits induce social avoidance and distress. To fill this gap, the present study recruited 708 participants to complete the 25-item Autism Spectrum Quotient, Social Avoidance and Distress Scale, Chinese Perceived Stress Scale, and Interpersonal Alienation Subscale. The results indicated that autistic traits significantly predicted social avoidance and distress in nonautistic people. In addition, autistic traits induced social avoidance and distress through perceived stress and interpersonal alienation, respectively. Importantly, perceived stress and interpersonal alienation (including the subdimensions of interpersonal alienation: sense of loneliness, sense of social isolation, and alienation between family members) partially mediated the relationships between autistic traits and social avoidance and distress. Overall, autistic traits predict social avoidance and distress via perceived stress and interpersonal alienation. This finding extends the hypothetical model of clinical anxiety in autism spectrum disorders. Furthermore, reducing perceived stress and interpersonal alienation in nonautistic people with high levels of autistic traits may be a valid intervention method to prevent and eliminate their social avoidance and distress.


Asunto(s)
Trastorno Autístico , Pruebas Psicológicas , Humanos , Conducta Social , Autoinforme , Estrés Psicológico
3.
J Sci Food Agric ; 102(6): 2553-2562, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34687471

RESUMEN

BACKGROUND: ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP) is a physiological indicator in response to drying soil. However, how abscisic acid (ABA) modulates ß-ODAP accumulation and its related agronomic characteristics in drought stressed grass pea (Lathyrus sativus L.) continue to be unclear. The present study aimed to evaluate the effects of ABA addition on drought tolerance, agronomic characteristics and ß-ODAP content in grass pea under drought stress. RESULTS: Exogenous ABA significantly promoted ABA levels by 19.3% and 18.3% under moderate and severe drought stress, respectively, compared to CK (without ABA, used as control check treatment). ABA addition activated earlier trigger of non-hydraulic root-sourced signal at 69.1% field capacity (FC) (65.5% FC in CK) and accordingly prolonged its operation period to 45.6% FC (49.0% FC in CK). This phenomenon was mechanically associated with the physiological mediation of ABA, where its addition significantly promoted the activities of leaf superoxide dismutase, catalase and peroxidase enzymes and the biosynthesis of leaf proline, simultaneously lowering the accumulation of malondialdehyde and hydrogen peroxide under moderate and severe stresses. Interestingly, ABA application significantly increased seed ß-ODAP content by 21.7% and 21.3% under moderate and severe drought stress, but did not change leaf ß-ODAP content. Furthermore, ABA application produced similar shoot biomass and grain yield as control groups. CONCLUSION: Exogenous ABA improved the drought adaptability of grass pea and promoted the synthesis of ß-ODAP in seeds but not in leaves. Our findings provide novel insights into the agronomic role of ABA in relation to ß-ODAP enrichment in grass pea subjected to drought stress. © 2021 Society of Chemical Industry.


Asunto(s)
Lathyrus , Ácido Abscísico , Aclimatación , Aminoácidos Diaminos , Sequías , Lathyrus/química , Pisum sativum , beta-Alanina/análogos & derivados
4.
Bioorg Med Chem Lett ; 43: 128051, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33887441

RESUMEN

Successes have been achieved in developing human monoamine oxidase B (hMAO-B) inhibitors as anti-Parkinson's disease (PD) drugs. However, low efficiency and unwanted side effects of the marketed hMAO-B inhibitors hamper their medical applications, therefore, novel potent selective hMAO-B inhibitors are still of great interest. Herein we report 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as hMAO-B inhibitors, which were designed by employing a fragment-based drug design strategy to link rasagiline to hydrophobic fragments. Among the synthesized 31 compounds, K8 and K24 demonstrated very encouraging hMAO-B inhibitory activities and selectivity over hMAO-A, better than rasagiline and safinamide. In vitro studies indicated that K8 and K24 are nontoxic to nervous tissue cells and they have considerable effects against ROS formation and potential neuroprotective activity. Further mice behavioral tests demonstrated these two compounds have good therapeutic effects on MPTP-induced PD model mice. All these experiment results suggest that compounds K8 and K24 can be promising candidates for further research for treatment of PD.


Asunto(s)
Diseño de Fármacos , Indenos/farmacología , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Compuestos de Sulfhidrilo/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Indenos/síntesis química , Indenos/química , Modelos Moleculares , Estructura Molecular , Inhibidores de la Monoaminooxidasa/síntesis química , Inhibidores de la Monoaminooxidasa/química , Relación Estructura-Actividad , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/química
5.
Bioorg Med Chem Lett ; 29(9): 1090-1093, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30833108

RESUMEN

Inhibition of MAO-B has been an effective strategy for the treatment of Parkinson's disease. To find more potent and selective MAO-B inhibitors with novel chemical scaffold, we designed and synthesized a series of new 2,3-dihydro-1H-inden-1-amine derivatives on basis of our previous study. Furthermore, the corresponding structure-activity relationship (SAR) of these compounds is detailedly discussed. Compounds L4 (IC50 = 0.11 µM), L8 (IC50 = 0.18 µM), L16 (IC50 = 0.27 µM) and L17 (IC50 = 0.48 µM) showed similar MAO-B inhibitory activity as Selegiline. Moreover, L4, L16 and L17 also exhibited comparable selectivity with Selegiline, indicating that L4, L16 and L17 could be promising selective MAO-B inhibitors for further study.


Asunto(s)
Antiparkinsonianos/síntesis química , Antiparkinsonianos/farmacología , Inhibidores de la Monoaminooxidasa/síntesis química , Inhibidores de la Monoaminooxidasa/farmacología , Antiparkinsonianos/química , Clorgilina/química , Clorgilina/farmacología , Diseño de Fármacos , Humanos , Estructura Molecular , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/química , Conformación Proteica , Selegilina/química , Selegilina/farmacología , Relación Estructura-Actividad
6.
Bioorg Med Chem Lett ; 29(8): 1012-1018, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30792039

RESUMEN

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50 = 3 nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.


Asunto(s)
Diseño de Fármacos , Inhibidores de la Monoaminooxidasa/síntesis química , Monoaminooxidasa/metabolismo , Sitios de Unión , Dominio Catalítico , Cristalografía por Rayos X , Humanos , Isatina/química , Isatina/metabolismo , Simulación de Dinámica Molecular , Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/metabolismo , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/metabolismo , Relación Estructura-Actividad
7.
Nutr Neurosci ; 19(10): 461-466, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24938711

RESUMEN

OBJECTIVE: An intervention study was performed to determine if supplement containing folic acid, vitamin B6, and vitamin B12 could improve cognitive function and lower homocysteine in middle-aged and elderly patients with hyperhomocysteinemia. METHODS: One hundred and four participants with hyperhomocysteinemia were recruited in Tianjin, China, aged 55-94 years old. Fifty-seven individuals with hyperhomocysteinemia were included in the intervention group (vitamin B group, which received 800 µg/day of folate, with 10 mg of vitamin B6 and 25 µg of vitamin B12) and 47 patients in the placebo group. The endpoint was the improvement in cognitive function as evaluated by Basic Cognitive Aptitude Tests (BCATs). All parameters were measured before and after the treatment period of 14 weeks. RESULTS: The BCAT total score and four sub-tests scores (digit copy, Chinese character rotation, digital working memory, and recognition of meaningless figure) of BCAT at 14 weeks significantly increased only for the vitamin B group. Serum total homocysteine (tHcy) levels significantly decreased in the intervention group, while serum concentrations of folate, vitamin B6, and vitamin B12 significantly increased in the intervention group. CONCLUSION: The results demonstrated that supplement containing folate, vitamin B6, and vitamin B12 in middle-aged and elderly patients with hyperhomocysteinemia could improve their cognitive function partly and reduce serum tHcy levels.


Asunto(s)
Envejecimiento , Disfunción Cognitiva/prevención & control , Suplementos Dietéticos , Ácido Fólico/uso terapéutico , Hiperhomocisteinemia/dietoterapia , Vitamina B 12/uso terapéutico , Vitamina B 6/uso terapéutico , Anciano , Anciano de 80 o más Años , China/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Fenómenos Fisiológicos Nutricionales del Anciano , Femenino , Ácido Fólico/sangre , Estudios de Seguimiento , Hogares para Ancianos , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/fisiopatología , Hiperhomocisteinemia/psicología , Masculino , Persona de Mediana Edad , Casas de Salud , Prevalencia , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Vitamina B 12/sangre , Vitamina B 6/sangre
8.
Front Psychol ; 14: 1095498, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37057171

RESUMEN

Learning anxiety is one of the most critical emotional disturbances, which also has a high incidence rate in adolescents. Peer interaction is critical and unique for adolescents. Although previous studies have found that achievement goal orientation has an important role in the development of learning anxiety, its mechanism has not been clarified. This study surveyed 470 adolescents (191 middle school students and 279 high school students; 211 boys) and established a structural equation model to explore the mediating role of peer interaction in the influence of achievement goal orientation on learning anxiety. Results showed that (1) there were significant gender differences in mastery-avoidance goal orientation, peer interaction, and learning anxiety, and there were grade differences in performance-approach goal and performance-avoidance goal orientations; (2) mastery-approach, mastery-avoidance, and performance-avoidance goal orientations directly predicted learning anxiety; and (3) social anxiety in peer interactions had a mediating effect on the influence of mastery-approach, mastery-avoidance, and performance-avoidance goal orientations on learning anxiety. The findings extend theoretical considerations by teasing out the process of peer interaction affecting the relationship between achievement goal orientation and learning anxiety. Additionally, the results have practical implications for the effective use of peer interaction to reduce learning anxiety.

9.
Plants (Basel) ; 12(6)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36987105

RESUMEN

The application of carbon-based nanomaterials (CBNMs) in plant science and agriculture is a very recent development. Many studies have been conducted to understand the interactions between CBNMs and plant responses, but how fullerol regulates wheat subjected to drought stress is still unclear. In this study, seeds of two wheat cultivars (CW131 and BM1) were pre-treated with different concentrations of fullerol to investigate seed germination and drought tolerance. Our results indicate that the application of fullerol at certain concentrations (25-200 mg L-1) significantly promoted seed germination in two wheat cultivars under drought stress; the most significant effective concentration was 50 mg L-1, which increased the final germination percentage by 13.7% and 9.7% compared to drought stress alone, respectively. Wheat plants exposed to drought stress induced a significant decrease in plant height and root growth, while reactive oxygen species (ROS) and malondialdehyde (MDA) contents increased significantly. Interestingly, wheat seedlings of both cultivars grown from 50 and 100 mg L-1 fullerol-treated seeds were promoted in seedling growth under water stress, which was associated with lower ROS and MDA contents, as well as higher antioxidant enzyme activities. In addition, modern cultivars (CW131) had better drought adaptation than old cultivars (BM1) did, while the effect of fullerol on wheat had no significant difference between the two cultivars. The study demonstrated the possibility of improving seed germination, seedling growth and antioxidant enzyme activities by using appropriate concentrations of fullerol under drought stress. The results are significant for understanding the application of fullerol in agriculture under stressful conditions.

10.
Cancer ; 118(2): 536-48, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-21717442

RESUMEN

BACKGROUND: Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements). METHODS: Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo. RESULTS: The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice. CONCLUSIONS: The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment.


Asunto(s)
Terapia Genética/métodos , Neoplasias/terapia , Regiones Promotoras Genéticas , Elemento de Respuesta al Suero , Telomerasa/genética , Telomerasa/efectos de la radiación , Adenoviridae/genética , Animales , Línea Celular Tumoral , ADN Recombinante , Vectores Genéticos , Humanos , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas/efectos de la radiación , Trasplante Heterólogo
11.
Biochem Biophys Res Commun ; 412(4): 763-8, 2011 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-21875574

RESUMEN

The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expression of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.


Asunto(s)
Genes Transgénicos Suicidas , Terapia Genética/métodos , Interleucina-12/biosíntesis , Neoplasias/terapia , Telomerasa/genética , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunocompetencia , Infiltración Leucémica , Luciferasas/genética , Ratones , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/patología , Elementos de Respuesta , Linfocitos T/inmunología
12.
Cell Mol Neurobiol ; 31(2): 203-11, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21061155

RESUMEN

The nuclear matrix-intermediate filament system of human neuroblastoma SK-N-SH cells before and after retinoic acid (RA) treatment was selectively extracted and the distribution of prohibitin (PHB) in the nuclear matrix, as well as its colocalization with related genes, was observed. Results of two-dimensional gel electrophoresis (2-DE), mass spectrometry (MS) identification, and protein immunoblotting all confirm that PHB was present in the components of SK-N-SH nuclear matrix proteins and was down-regulated after RA treatment. Immunofluorescence microscopy observations show that PHB was localized in the nuclear matrix and its distribution was altered due to RA treatment. Laser confocal microscopy results reveal that PHB colocalized with the expression products of c-myc, c-fos, p53, and Rb, but the colocalization region was altered after RA treatment. Our results prove that PHB is a nuclear matrix protein and is localized in nuclear matrix fibers. The distribution of PHB in SK-N-SH cells and its colocalization with related proto-oncogenes and tumor suppressor genes suggest that PHB plays pivotal roles in the differentiation of SK-N-SH cells and deserves further study.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Neuroblastoma/metabolismo , Neuroblastoma/patología , Matriz Nuclear/metabolismo , Proteínas Represoras/metabolismo , Tretinoina/farmacología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Electroforesis en Gel Bidimensional , Humanos , Immunoblotting , Filamentos Intermedios/efectos de los fármacos , Filamentos Intermedios/metabolismo , Microscopía Fluorescente , Proteínas Asociadas a Matriz Nuclear/metabolismo , Prohibitinas , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Represoras/química , Reproducibilidad de los Resultados , Proteína de Retinoblastoma/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Proteína p53 Supresora de Tumor/metabolismo
13.
J Gastroenterol Hepatol ; 26(1): 108-15, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21175803

RESUMEN

BACKGROUND AND AIM: Nuclear-matrix proteins can be proteomic markers for cancer lesions. The present study aimed to determine the roles of heterogeneous nuclear ribonucleoproteins--A2 and B1 (hnRNP-A2/B1) in human gastric carcinogenesis. METHODS: Human gastric cancer and non-cancerous tissues were collected for immunohistochemical analysis. Proteomics technique, Western blot, laser confocal microscope, and real-time quantitative reverse transcription-polymerase chain reaction were performed to determine the aberrant expression of nuclear-matrix proteins. RESULTS: hnRNP-A2/B1 existed in the nuclear matrix of gastric cancer cells, and its expression was enhanced in human gastric cancer and decreased by hexamethylene bisacetamide. The colocalization of hnRNP-A2/B1 with c-myc, c-fos, p53, and Rb was translocated from the nucleolus to the cytoplasm during the differentiation of tumor cells. CONCLUSIONS: hnRNP-A2/B1 affected tumor cell differentiation through interaction with oncogenes and tumor-suppressor genes, and it was overexpressed in human gastric cancer. We postulate that hnRNP-A2/B1 could serve as a biomarker for the diagnosis of human gastric cancer.


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Neoplasias Gástricas/metabolismo , Acetamidas/farmacología , Adenocarcinoma/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Western Blotting , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , China , Citoplasma/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Humanos , Inmunohistoquímica , Microscopía Confocal , Matriz Nuclear/metabolismo , Pronóstico , Proteómica/métodos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/metabolismo , Proteína de Retinoblastoma/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/metabolismo
14.
Nutr Neurosci ; 13(4): 175-82, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20670473

RESUMEN

Relationships between hyperhomocysteinemia (HHE) and neurodegenerative diseases have been widely studied. However, the impact of serum total homocysteine (tHcy) levels on cognitive function has not been confirmed. C677T polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have impacts on tHcy level; it is suspected to influence cognitive function, but only few investigations have assessed its effects on non-dementia adults and the results have been controversial. Moreover, there is no report about Chinese subjects. In the present study, we determined C677T/MTHFR genotype, serum tHcy concentration and cognition in 182 nondemented subjects aged 55-88 years to probe the associations between MTHFRC677T mutation, increased tHcy levels and decreased cognitive function in a northern city in China. A serum tHcy level > or = 16 micromol/l was deemed HHE. Cognitive function was assessed by the Mini Mental State Examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT). Results showed that: (i) subjects with the T allele had higher serum tHcy levels than those without, especially in lower folate status; (ii) T allele and CT/TT genotype frequencies in subjects with HHE were higher than in non-HHE subjects (P < 0.05); and (iii) serum tHcy level was inversely related to total BCAT score (P < 0.05) but MTHFR677 C to T polymorphism had no association with it. Our results confirmed that the MTHFR 677 C to T mutation, especially in lower serum folate concentration status, results in the increase of serum tHcy levels which is bad for cognitive function and indicates that higher serum folate level is of benefit in keeping lower serum tHcy level and better cognitive function. The results provide some valuable clues for individualized nutrition intervention of HHE and cognition decline in the middle-aged and the elderly.


Asunto(s)
Cognición , Hiperhomocisteinemia/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Vitaminas/sangre , Anciano , Anciano de 80 o más Años , Envejecimiento , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/prevención & control , Femenino , Ácido Fólico/sangre , Genotipo , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Vitamina B 12/sangre , Vitamina B 6/sangre
15.
Cancer Manag Res ; 12: 10735-10747, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33149680

RESUMEN

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common malignant tumor in humans. Long non-coding RNA (lncRNA) involved in cancer progression has been reported frequently. The objective of this study was to investigate the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and explore a novel mechanism in NSCLC development. MATERIALS AND METHODS: The expression of MALAT1, copper metabolism MURR1 domain-containing 8 (COMMD8) and microRNA-613 (miR-613) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of COMMD8, Cyclin D1, Ki67, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), lactate dehydrogenase A (LDHA), CD63 and CD81 were determined by Western blot. Cell proliferation, the number of colonies and cell apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation and flow cytometry assays, respectively. Glycolysis was distinguished based on glucose consumption, lactate production and LDHA activity. The role of MALAT1 in vivo was verified by animal experiments. The relationship between miR-613 and MALAT1 or COMMD8 was predicted by the bioinformatics tool starbase and verified by dual-luciferase reporter assay. The exosomes were isolated using the corresponding kit and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RESULTS: MALAT1 and COMMD8 were aberrantly upregulated in NSCLC tissues and cells. MALAT1 or COMMD8 knockdown blocked cell proliferation, colony formation and glycolysis but accelerated cell apoptosis in vitro. Besides, MALAT1 knockdown reduced tumor growth in vivo. We found that miR-613 was a target of MALAT1, and miR-613 could bind to the 3' untranslated region (3'UTR) of COMMD8. MALAT1 regulated the expression of COMMD8 by absorbing miR-613. Moreover, the extracellular MALAT1 was transmitted by wrapping into exosomes. CONCLUSION: MALAT1 promoted malignant activities of NSCLC cells through targeting miR-613/COMMD8 axis, and exosome-mediated transfer of NSCLC might be a novel approach for NSCLC treatment.

16.
Curr Med Chem ; 27(32): 5429-5443, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30947649

RESUMEN

Cyclin-dependent Kinase 8 (CDK8), a member of the CDKs family, has been widely focused owing to investigations of its critical roles in transcription and oncogenesis in recent years. Selective inhibition of CDK8 and its paralog CDK19 offers a novel therapeutic strategy for the treatment of some cancers. Up to now, though many small molecules against CDK8 have been discovered, most of them are discontinued in the preclinical trials due to the low selectivity and poor physicochemical properties. This review mainly summarizes the design strategies of selective CDK8 inhibitors having different chemical scaffolds with the aim to improve the inhibitory activity, selectivity, metabolic stability and solubility. Their corresponding Structure-activity Relationships (SAR) are also reviewed. On the basis of the discussion in this review, we hope more effective, selective and drug-like CDK8 inhibitors will be developed and demonstrate therapeutic values in the near future.


Asunto(s)
Inhibidores de Proteínas Quinasas/farmacología , Quinasa 8 Dependiente de Ciclina/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Fosforilación , Relación Estructura-Actividad
17.
Future Med Chem ; 11(14): 1757-1775, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31288579

RESUMEN

Platelet aggregation is the central event in hemostasis and thrombosis. Up to now, many agents inhibiting platelet aggregation have been approved for the treatment of thrombotic disorders. In this review, we mainly summarized the progress in the research of platelet aggregation inhibitors based on different design strategies. The advantage and challenge of corresponding targets are also discussed in this article. We hope more platelet aggregation inhibitors with efficacy and safety will be discovered in the future.


Asunto(s)
Diseño de Fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Animales , Plaquetas/efectos de los fármacos , Humanos , Estructura Molecular , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química
18.
Wei Sheng Yan Jiu ; 37(6): 677-9, 2008 Nov.
Artículo en Zh | MEDLINE | ID: mdl-19239000

RESUMEN

OBJECTIVE: To explore the serum homocysteine levels and cognitive function status of the middle-aged and elderly persons in Tianjin city in order to provide fundamental data for the nutritional intervention trial. METHODS: The subjects between the ages of 55 and 94 years were randomly recruited in the study. The cognitive function of the subjects were evaluated by the Mini Mental State Examination (MMSE), and then screened the subjects with cognitive impairment (CI). Total homocysteine (tHcy) levels in fasting serum were measured by enzyme transition method, the correlation between tHcy levels and the cognitive function were statistically analyzed. RESULTS: The mean of serum tHcy levels were (15.95 +/- 7.29) micromol/L, the prevalence of hyperhomocysteinemia (HHE) was 45.4%; and man had a higher rates than woman ( P < 0.001); the mean MMSE scores were (26.74 +/- 2.71) points, the prevalence of CI was 26.0%, and there were no significant differences between man and woman in CI prevalence. Cognitive function status was positively correlated with education and negatively correlated with age. CONCLUSION: It was remarkable that higher prevalence of HHE and CI existed in the middle-aged and elderly persons.


Asunto(s)
Trastornos del Conocimiento/sangre , Cognición/fisiología , Homocisteína/sangre , Hiperhomocisteinemia/epidemiología , Anciano , Anciano de 80 o más Años , China/epidemiología , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/etiología , Femenino , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Muestreo
19.
Sci Rep ; 7: 40677, 2017 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-28094806

RESUMEN

Neurolathyrism is a unique neurodegeneration disease caused by ß-N-oxalyl-L-α, ß- diaminopropionic (ß-ODAP) present in grass pea seed (Lathyrus stativus L.) and its pathogenetic mechanism is unclear. This issue has become a critical restriction to take full advantage of drought-tolerant grass pea as an elite germplasm resource under climate change. We found that, in a human glioma cell line, ß-ODAP treatment decreased mitochondrial membrane potential, leading to outside release and overfall of Ca2+ from mitochondria to cellular matrix. Increased Ca2+ in cellular matrix activated the pathway of ECM, and brought about the overexpression of ß1 integrin on cytomembrane surface and the phosphorylation of focal adhesion kinase (FAK). The formation of high concentration of FA units on the cell microfilaments further induced overexpression of paxillin, and then inhibited cytoskeleton polymerization. This phenomenon turned to cause serious cell microfilaments distortion and ultimately cytoskeleton collapse. We also conducted qRT-PCR verification on RNA-sequence data using 8 randomly chosen genes of pathway enrichment, and confirmed that the data was statistically reliable. For the first time, we proposed a relatively complete signal pathway to neurolathyrism. This work would help open a new window to cure neurolathyrism, and fully utilize grass pea germplasm resource under climate change.


Asunto(s)
Aminoácidos Diaminos/farmacología , Adhesiones Focales/efectos de los fármacos , Adhesiones Focales/metabolismo , Integrina beta1/metabolismo , Toxinas Biológicas/farmacología , Calcio/metabolismo , Línea Celular , Biología Computacional/métodos , Citoesqueleto/metabolismo , Matriz Extracelular , Adhesiones Focales/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Integrina beta1/genética , Latirismo/etiología , Latirismo/metabolismo , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Multimerización de Proteína , Reproducibilidad de los Resultados , Transducción de Señal/efectos de los fármacos , Transcriptoma
20.
J Agric Food Chem ; 63(27): 6133-41, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-26027639

RESUMEN

Grass pea (Lathyrus sativus L.) cultivation is limited because of the presence in seeds and tissues of the nonprotein amino acid ß-N-oxalyl-L-α,ß-diaminopropionic acid (ß-ODAP), a neurotoxin that can cause lathyrism in humans. Seven grass pea genotypes differing in seed ß-ODAP concentration were grown in pots at three levels of water availability to follow changes in the concentration and amount of ß-ODAP in leaves and pods and seeds. The concentration and amount of ß-ODAP decreased in leaves in early reproductive development and in pods as they matured, while water stress increased ß-ODAP concentration in leaves and pods at these stages. The net amount of ß-ODAP in leaves and pods at early podding was positively associated with seed ß-ODAP concentration at maturity. We conclude that variation among genotypes in seed ß-ODAP concentration results from variation in net accumulation of ß-ODAP in leaves and pods during vegetative and early reproductive development.


Asunto(s)
Aminoácidos Diaminos/metabolismo , Frutas/crecimiento & desarrollo , Lathyrus/metabolismo , Neurotoxinas/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Semillas/metabolismo , Agua/metabolismo , Aminoácidos Diaminos/análisis , Frutas/química , Frutas/genética , Frutas/metabolismo , Genotipo , Lathyrus/química , Lathyrus/genética , Lathyrus/crecimiento & desarrollo , Neurotoxinas/análisis , Hojas de la Planta/química , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Semillas/química , Semillas/genética , Semillas/crecimiento & desarrollo , Agua/análisis
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