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1.
Ann Hematol ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916741

RESUMEN

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.

2.
Fitoterapia ; 172: 105713, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37949304

RESUMEN

The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids.


Asunto(s)
Alcaloides , Morfinanos , Estructura Molecular , Morfinanos/química , Morfinanos/metabolismo , Morfinanos/farmacología , Alcaloides/farmacología , Derivados de la Morfina
3.
World J Clin Cases ; 11(31): 7656-7662, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-38078131

RESUMEN

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with Sneddon's syndrome (SS) and cerebral venous sinus thrombosis (CVST). Particular emphasis is placed on the comprehensive elucidation of SS's clinical manifestations, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A 26-year-old woman presented with recurrent episodes of paroxysmal unilateral limb weakness accompanied by skin mottling, seizures, and cognitive impairment. Digital subtraction angiography revealed CVST. Despite negative antiphospholipid antibody results, skin biopsy indicated chronic inflammatory cell infiltration. The patient was treated using anticoagulation, antiepileptic therapy, and supportive care, which resulted in symptom improvement. The coexistence of SS and CVST is rare and the underlying pathophysiology remains uncertain. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of SS with CVST and reviewed the relevant literature to improve the clinical understanding of this rare condition.

4.
Nat Prod Res ; : 1-7, 2023 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-37661314

RESUMEN

2,7,2'-Trihydroxy-3,4,4'7'-tetramethoxy-1,1'-biphenanthrene (1), a previously undescribed biphenanthrene, and five known phenanthrenes, i.e. 2,5-dihydroxy-4-methoxy-9,10-dihydroxyphenanthrene (2), 2,4-dihydroxy -7-methoxy-9,10-dihydroxyphenanthrene (3), 7-hydroxy-2-methoxy-phenanthrene-1,4-dione (4), 7-hydroxy-2-methoxy-9,10-dihydro-phenanthrene-1,4-dione (5), and 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene (6) were isolated from the whole plant (stems, leaves, roots and fruits) of Liparis nervosa (Thunb.) Lindl., which is a medicinal plant of the genus Liparis in the Orchidaceae family. The structures of isolates were identified using spectroscopic methods, including NMR and mass spectrometry. Additionally, the cytotoxic potency of all the isolates against human lung cancer A549 cell line was evaluated by an MTT assay. All the isolated compounds showed cytotoxic activities with IC50 values in the range of 10.20 ± 0.81 to 42.41 ± 2.34 µM. The obtained data highlight the importance of L. nervosa as a source of natural lead compounds for cancer therapy.

5.
Pediatr Infect Dis J ; 41(8): e332-e335, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35421043

RESUMEN

Brucellosis is a zoonotic disease. Severe refractory thrombocytopenia caused by brucellosis is very rare and easily misdiagnosed. We reported a 5-year-old girl who developed severe refractory thrombocytopenia secondary to brucellosis. The first-line treatment including corticosteroids and intravenous immunoglobulin did not elevate her platelets, but eltrombopag worked well and her platelet count recovered rapidly.


Asunto(s)
Brucelosis , Trombocitopenia , Benzoatos/uso terapéutico , Brucelosis/complicaciones , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Preescolar , Femenino , Humanos , Hidrazinas/uso terapéutico , Pirazoles , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológico
6.
Kidney Med ; 3(6): 1003-1013.e1, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34939009

RESUMEN

RATIONALE & OBJECTIVE: Immunoglobulin A nephropathy (IgAN) is a common glomerular disease, with mesangial cell proliferation as a major feature. There is no disease-specific treatment. Platelet-derived growth factor (PDGF) contributes to the pathogenesis of IgAN. To better understand its pathogenic mechanisms, we assessed PDGF-mediated AXL phosphorylation in human mesangial cells and kidney tissue biopsy specimens. STUDY DESIGN: Immunostaining using human kidney biopsy specimens and in vitro studies using primary human mesangial cells. SETTING & PARTICIPANTS: Phosphorylation of AXL was assessed in cultured mesangial cells and 10 kidney-biopsy specimens from 5 patients with IgAN, 3 with minimal change disease, 1 with membranous nephropathy, and 1 with mesangioproliferative glomerulonephritis (GN). PREDICTOR: Glomerular staining for phospho-AXL in kidney biopsy specimens of patients with mesangioproliferative diseases. OUTCOMES: Phosphorylated AXL detected in biopsy tissues of patients with IgAN and mesangioproliferative GN and in cultured mesangial cells stimulated with PDGF. ANALYTIC APPROACH: t test, Mann-Whitney test, and analysis of variance were used to assess the significance of mesangial cell proliferative changes. RESULTS: Immunohistochemical staining revealed enhanced phosphorylation of glomerular AXL in IgAN and mesangioproliferative GN, but not in minimal change disease and membranous nephropathy. Confocal-microscopy immunofluorescence analysis indicated that mesangial cells rather than endothelial cells or podocytes expressed phospho-AXL. Kinomic profiling of primary mesangial cells treated with PDGF revealed activation of several protein-tyrosine kinases, including AXL. Immunoprecipitation experiments indicated association of AXL and PDGF receptor proteins. An AXL-specific inhibitor (bemcentinib) partially blocked PDGF-induced cellular proliferation and reduced phosphorylation of AXL and PDGF receptor and the downstream signals (AKT1 and ERK1/2). LIMITATIONS: Small number of kidney biopsy specimens to correlate the activation of AXL with disease severity. CONCLUSIONS: PDGF-mediated signaling in mesangial cells involves transactivation of AXL. Finding appropriate inhibitors to block PDGF-mediated transactivation of AXL may provide new therapeutic options for mesangioproliferative kidney diseases such as IgAN.

8.
Front Pediatr ; 8: 159, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32351918

RESUMEN

Background: Thalassemia is an autosomal genetic disorder, found throughout the world. It is still not treatable and create socio economic problems. In this study, we investigated the prevalence and spectrum features of thalassemia in Yunnan Province, the southwestern area of China. During 2014-2018, a total of 3,539 suspected thalassemia children were detected with α- and ß-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Kunming Children's Hospital. Results: Of these patients, 1,130 were diagnosed thalassemia gene carriers with a carrying rate of 31.92%. Among them, α-thalassemia was 43.63%, ß-thalassemia was 53.98%, cases with both α- and ß- thalassemia was 2.39%. In α-thalassemia patients, the most common mutations was -SEA/αα (52.13%), followed by -α3.7/αα (27.79%), hemoglobin H disease (18.46%), and -α4.2/αα (1.62%). Fifteen gene mutations and 30 genotypes were identified in ß-thalassemia patients, with the five most common mutations CD17 (A>T) (29.51%), CD41-42 (-TTCT) (27.87%), IVS-II-654 (C>T) (14.92%), CD26 (G>A) (6.89%), and CD26/CD27 (2.62%) accounting for 81.81% of the ß-globin gene mutations. Furthermore, we founded two rare mutations CD34 (TGG → TAG) and Int in Chinese populations. Conclusions: Our results suggested that the prevalence and gene mutation spectrum of thalassemia display obviously heterogeneity among children in Yunnan Province. The findings provide the valuable information for premarital and pre-pregnancy screening, prenatal diagnostic services, and designing appropriate prevention programs to control thalassemia for future in this area.

9.
J Agric Food Chem ; 67(26): 7274-7280, 2019 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-31244200

RESUMEN

Bioactivity-guided separation led to the isolation of six novel phenanthrenes, spiranthesphenanthrenes A-F (1-6), together with 19 known compounds, including seven phenanthrenes (7-13), one bibenzyl compound (14), five flavonoids (15-16 and 20-22), and six simple phenolic compounds (17-19 and 23-25), from the petroleum ether (PE) and ethyl acetate (EtOAc) extracts of Spiranthes sinensis (Pers.) Ames, an edible medicinal plant named "panlongshen" in Chinese that is popularly used in medicinal foods and herbal teas. The structures of the obtained compounds were identified on the basis of extensive NMR spectroscopy and HR-ESI-MS analyses. The cytotoxicities of the phenanthrenes (1-13), the bibenzyl compound (14) , and the flavonoids (15-16 and 20-22) toward SGC-7901, HepG2, and B16-F10 cell lines were examined in vitro. Compounds 1 and 7 exhibited moderate cytotoxic activities toward all of the selected cancer cell lines, and their IC50 values ranged from 19.0 ± 7.3 to 30.2 ± 5.6 µM. Spiranthesphenanthrene A (1) exhibited higher cytotoxic activity than the positive control cisplatin toward the B16-F10 cell line (IC50 = 19.0 ± 7.3 µM). A wound healing assay revealed the inhibition of the migration of B16-F10 cancer cells in a time- and dose-dependent pattern by treatment with 2.5, 5, and 10 µM solutions of compound 1 for 24 and 48 h, respectively. Western blots revealed that compound 1 obviously increased the level of the E-cadherin protein (an epithelial marker) and decreased the levels of the vimentin and N-cadherin proteins (mesenchymal markers). Furthermore, the level of the transcription factor Snail was also obviously decreased by compound 1 in a dose-dependent manner. Taken together, compound 1 inhibits the migration of B16-F10 cancer cells, which may be closely related to the inhibition of the epithelial-mesenchymal transition. Compound 1 represents a promising drug candidate for the prevention of tumor metastasis.


Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Orchidaceae/química , Fenantrenos/química , Fenantrenos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Fenantrenos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación
10.
BMC Pediatr ; 19(1): 62, 2019 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-30777044

RESUMEN

BACKGROUND: Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. CASE PRESENTATION: The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2-3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 µmol/L, IBIL24 µmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. CONCLUSIONS: Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation.


Asunto(s)
Ancirinas/genética , Mutación , Esferocitosis Hereditaria/genética , Transfusión Sanguínea , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Esferocitosis Hereditaria/terapia
11.
J Asian Nat Prod Res ; 21(5): 462-475, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30010416

RESUMEN

Poria cocos (P. cocos) polysaccharides (PCPs) are used to improve immunity and possess antitumor activities. We compared three cultivars of P. cocos (5.78, XJ 28 and JHYH) PCP contents. Then we determined that malZ, galA, SORD, gnl and bglX are key enzymes within the PCP biosynthetic pathway by using HiSeq2500 transcriptome and qRT-PCR validation. Our results provide more detailed information about the PCP biosynthesis pathway at the molecular level in P. cocos and establish the functions for the molecular breeding to produce polysaccharides in general for therapeutic use in Chinese medicinal plants.


Asunto(s)
Polisacáridos Fúngicos/metabolismo , Transcriptoma , Wolfiporia/metabolismo , Polisacáridos Fúngicos/genética , Regulación Fúngica de la Expresión Génica , Wolfiporia/genética
12.
Oncotarget ; 8(51): 89095-89107, 2017 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-29179502

RESUMEN

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

13.
Exp Ther Med ; 14(2): 1789-1794, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28810651

RESUMEN

Kanglaite (KLT) was shown to alleviate the development of multidrug resistance (MDR) clinically. The purpose of this study is to examine the mechanism of KLT for chemotherapy resistance in gastric cancer cells involving the regulation of MDR-related proteins. The cisplatin-resistant BGC823/DPP and SGC7901/DDP cells were treated with 1, 2.5 and 5 µl/ml of KLT for 24, 36 and 48 h. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to detect the cell viability and cell apoptosis, respectively. The expression of MDR1 and multidrug resistance associated protein 1 (MRP1) were examined by quantitative PCR and western blotting in BGC823/DPP cells and SGC7901/DDP cells treated with KLT. The effect of KLT on the expression of PVT1 was investigated. PVT1-overexpression vector was constructed and transfected into BGC823/DPP cells and SGC7901/DDP cells which were treated with KLT. KLT inhibited the cell viability and promoted the cell apoptosis of BGC823/DPP cells and SGC7901/DDP cells in a concentration-dependent manner. KLT suppressed the expression of MDR1 and MRP1 and the level of PVT1. PVT1 overexpression reversed the increased percentage of apoptotic cells induced by KLT. Finally, we found that PVT1 overexpression also abrogated the effect of KLT on the mRNA level and protein level of MDR1 and MRP1 in BGC823/DPP and SGC7901/DDP cells. KLT inhibited the expression of MDR1 and MRP1 via suppressing the expression of PVT1, which suggested the potential mechanism of KLT involving in MDR in gastric cancer.

14.
Fitoterapia ; 115: 15-18, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27642042

RESUMEN

Three new biphenanthrenes, Liparisphenanthrenes A-C (1-3), along with three known ones were obtained from the ethanolic extract of Liparis nervosa (Orchidaceae) by bioactivity-guided fractionation. Their structures were elucidated on the basis of extensive spectroscopic analysis. All the compounds obtained were tested in vitro for cytotoxic activities against stomach (HGC-27) and colon (HT-29) cancer cell lines. 1, 4 and 5 showed potent cytotoxicities to HGC-27 cell line with IC50 values of 8.21-9.95µmol/L, and 1 and 5 also exhibited potent cytotoxic activities to HT-29 cell line with IC50 values of 8.53-9.27µmol/L.


Asunto(s)
Antineoplásicos Fitogénicos/química , Orchidaceae/química , Fenantrenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Células HT29 , Humanos , Estructura Molecular , Fenantrenos/aislamiento & purificación , Plantas Medicinales/química
15.
J Xray Sci Technol ; 24(4): 521-30, 2016 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-27061797

RESUMEN

PURPOSE: This study aimed to investigate the feasibility of efficiently using a rigid image registration (RIR) algorithm or a deformable image registration (DIR) algorithm to match medical images and evaluate the impact of setup errors on intensity modulated radiation therapy of lung cancer patients. METHODS: Ten lung cancer patients were chosen randomly each day and were subjected to image-guided radiotherapy. The clinical registration between cone-beam computed tomography (CBCT) images and treatment planning system CT images was performed by applying both RIR and DIR; the clinical registration was evaluated on the basis of the contour index, including dice similarity coefficient, sensitivity, and positive predictive value; the optimal scheme of image registration was selected to ensure that the actual irradiation isocenter was consistent with the treatment planning isocenter. In each patient, the translational errors in the right-left (x), superior-inferior (y), and anterior-posterior (z) directions and the rotational errors in the u, υ, and w directions formed by the x, y, and z directions were calculated and analyzed daily in the whole course of treatment; margins were calculated according to this equation: M = 2.5∑+ 0.7δ. RESULTS: The tumors and the surrounding soft tissues of the patients are shown more clearly in the CBCT images than in the CT images. DIR can be applied more efficiently than RIR to determine the morphological and positional changes in the organs shown in the images with the same or different modalities in the different period. The setup errors in translation in the x, y and z axes were 0.05±0.16, 0.09±0.32 and -0.02±0.13 cm, respectively; by contrast, the setup errors in rotation in u, υ and w directions were (0.41±0.64)°, (-0.08±0.57)° and (-0.03±0.62)°, respectively. The setup errors in the x, y and z axes of the patients indicated that the margins expansions were 0.82, 1.15 and 0.72 cm, respectively. CONCLUSION: CBCT with DIR can measure and correct the setup errors online; as a result, setup errors in lung cancer treatments can be significantly reduced and the accuracy of radiotherapy can be enhanced.


Asunto(s)
Tomografía Computarizada de Haz Cónico/métodos , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Algoritmos , Humanos
16.
J Zhejiang Univ Sci B ; 16(10): 824-31, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26465130

RESUMEN

Insect resistance and glyphosate tolerance have been two of the most important traits in the genetic improvement of various crops. In this study, two Bacillus thuringiensis (Bt) insecticidal genes, Cry1Ac and Cry1Ig, and a modified glyphosate-tolerant 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene (G10) were combined into a single transferred DNA (T-DNA) fragment and introduced into rice by Agrobacterium-mediated transformation. A transgenic line with single-copy T-DNA insertion named GAI-14 was found to be highly resistant to striped stem borer and rice leaf roller, and tolerant to glyphosate. Analysis of T-DNA border sequence suggested that the transgenes were inserted at the chromosome 3 and appeared to have not interrupted any known or putative genes. A field trial observed no significant difference in the basic agronomic traits between GAI-14 and the recipient rice.


Asunto(s)
3-Fosfoshikimato 1-Carboxiviniltransferasa/metabolismo , Proteínas Bacterianas/metabolismo , Endotoxinas/metabolismo , Glicina/análogos & derivados , Proteínas Hemolisinas/metabolismo , Insectos/fisiología , Oryza/fisiología , Transfección/métodos , 3-Fosfoshikimato 1-Carboxiviniltransferasa/genética , Animales , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , ADN Bacteriano/genética , Tolerancia a Medicamentos , Endotoxinas/genética , Mejoramiento Genético/métodos , Glicina/administración & dosificación , Proteínas Hemolisinas/genética , Insecticidas/metabolismo , Oryza/efectos de los fármacos , Oryza/parasitología , Control Biológico de Vectores/métodos , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/parasitología , Plantas Modificadas Genéticamente/fisiología , Glifosato
17.
Biochem Biophys Res Commun ; 462(3): 227-32, 2015 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-25956062

RESUMEN

BACKGROUND: The development of multidrug resistance (MDR) is a crucial problem of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Plasmacytoma variant translocation 1 (PVT-1), a long non-coding RNA (lncRNA), was previously found to be increased in gastric cancer patients and regulated the chemotherapy sensitivity in pancreatic cancer cells. However, the role of PVT1 in multidrug resistant Gastric cancer remains largely unexplored. METHODS: In this study, the mRNA levels of PVT1 in gastric cancer tissues of cisplatin-resistant patients and two kinds of cisplatin-resistant cells BGC823/DDP and SGC7901/DDP were detected by qRT-PCR. The influence of PVT1 knockdown or overexpression on anticancer drug resistance was assessed by measuring the cytotoxicity of cisplatin and the rate of apoptosis detected by CCK-8 assay and flow cytometry, respectively. Further, we investigated the expression levels of MDR1, MRP, mTOR and HIF-1α by qRT-PCR and western blotting. RESULTS: PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. In addition, BGC823/DDP and SGC7901/DDP cells transfected with PVT-1 siRNA and treated with cisplatin exhibited significant lower survival rate and high percentage of apoptotic tumor cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1α. CONCLUSIONS: Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.


Asunto(s)
ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Anciano , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Cisplatino/farmacología , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/genética , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , ARN Largo no Codificante/antagonistas & inhibidores , ARN Interferente Pequeño/genética , Neoplasias Gástricas/metabolismo
18.
Ren Fail ; 36(6): 974-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24678913

RESUMEN

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR = 0.76, 95% CI: 0.43-1.34, p = 0.34; CC genotype: OR = 1.18, 95% CI: 0.63-2.22, p = 0.60). Interestingly, AA genotype was associated with the T2DN risk (OR = 0.68, 95% CI: 0.49-0.96, p = 0.03). In the sensitivity analysis according to the Hardy-Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (≥ 100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple
19.
Ren Fail ; 36(2): 321-6, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24060183

RESUMEN

This meta-analysis was conducted to evaluate the association of transforming growth factor-ß1 (TGF-ß1) G915C, G800A, C509T gene polymorphism with the risk of diabetic nephropathy (DN). The association literatures were identified from PubMed, Cochrane Library, and CBM-disc (China Biological Medicine Database) on March 1, 2013, and eligible reports were recruited and synthesized. Seven reports were recruited into this meta-analysis for the association of TGF-ß1 G800A, C509T, G915C gene polymorphism with DN risk. GG genotype, CC genotype, and C allele of TGF-ß1 G915C were not associated with the DN risk (GG: OR = 0.84, 95% CI: 0.62-1.14, p = 0.27; CC: OR = 1.05, 95% CI: 0.50-2.22, p = 0.90; C allele: OR = 1.16, 95% CI: 0.88-1.51, p = 0.29). Furthermore, TGF-ß1 G800A, C509T gene polymorphism was not associated with the DN risk. In conclusion, TGF-ß1 G915C, G800A, and C509T gene polymorphism are not associated with the DN risk. However, more studies should be performed to confirm this relationship in the future.


Asunto(s)
Nefropatías Diabéticas/genética , Polimorfismo de Nucleótido Simple , Factor de Crecimiento Transformador beta1/genética , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo
20.
BMB Rep ; 46(1): 31-6, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23351381

RESUMEN

Heat shock proteins play an important role in plant stress tolerance and are mainly regulated by heat shock transcription factors (Hsfs). In this study, we generated transgenic rice over-expressing OsHsfA7 and carried out morphological observation and stress tolerance assays. Transgenic plants exhibited less, shorter lateral roots and root hair. Under salt treatment, over-expressing OsHsfA7 rice showed alleviative appearance of damage symptoms and higher survival rate, leaf electrical conductivity and malondialdehyde content of transgenic plants were lower than those of wild type plants. Meanwhile, transgenic rice seedlings restored normal growth but wild type plants could not be rescued after drought and re-watering treatment. These findings indicate that over-expression of OsHsfA7 gene can increase tolerance to salt and drought stresses in rice seedlings.


Asunto(s)
Sequías , Oryza/efectos de los fármacos , Proteínas de Plantas/metabolismo , Cloruro de Sodio/farmacología , Biología Computacional , Regulación de la Expresión Génica de las Plantas , Oryza/genética , Oryza/metabolismo , Filogenia , Proteínas de Plantas/clasificación , Proteínas de Plantas/genética , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/metabolismo
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