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1.
J Intern Med ; 295(5): 620-633, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38343089

RESUMEN

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.


Asunto(s)
Anemia , Eritropoyetina , Fallo Renal Crónico , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Diálisis Renal/efectos adversos , Anemia/etiología , Anemia/complicaciones , Eritropoyetina/uso terapéutico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia
2.
J Gastroenterol Hepatol ; 39(1): 81-106, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37855067

RESUMEN

BACKGROUND AND AIM: Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS: Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS: The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS: A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.


Asunto(s)
Colonoscopía , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/epidemiología , Factores de Riesgo , Detección Precoz del Cáncer , Alucinaciones
3.
BMC Plant Biol ; 23(1): 492, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833649

RESUMEN

BACKGROUND: Orchids (Cymbidium spp.) exhibit significant variations in floral morphology, pollinator relations, and ecological habitats. Due to their exceptional economic and ornamental value, Cymbidium spp. have been commercially cultivated for centuries. SSR markers are extensively used genetic tools for biology identification and population genetics analysis. RESULT: In this study, nine polymorphic EST-SSR loci were isolated from Cymbidium goeringii using RNA-Seq technology. All nine SSR loci showed transferability in seven other congeneric species, including 51 cultivars. The novel SSR markers detected inter-species gene flow among the Cymbidium species and intra-species sub-division of C. goeringii and C. ensifolium, as revealed by neighborhood-joining and Structure clustering analyses. CONCLUSION: In this study, we developed nine microsatellites using RNA-Seq technology. These SSR markers aided in detecting potential gene flow among Cymbidium species and identified the intra-species sub-division of C. goeringii and C. ensifolium.


Asunto(s)
Genética de Población , Orchidaceae , Hibridación Genética , Hibridación de Ácido Nucleico , Orchidaceae/genética , Repeticiones de Microsatélite/genética
4.
Clin Exp Nephrol ; 27(12): 1051-1059, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37656396

RESUMEN

BACKGROUND: Poor prognosis has been associated with the absence of renal recovery after acute kidney injury (AKI). This study aimed to investigate whether urinary biomarkers at 0 and 24 h could be used independently or in conjunction with a clinical model to predict renal non-recovery in septic AKI. METHODS: A prospective observational study was conducted to measure the urinary levels of insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) at the time of AKI diagnosis (0 h) and 24 h later. Renal non-recovery within 7 days was defined as the outcome. The predictive value of urinary biomarkers for renal non-recovery in septic AKI was assessed using the area under the curve (AUC). RESULTS: A total of 198 individuals with septic AKI were included in the final analysis. Among them, 38.9% (n = 77) did not experience renal recovery within 7 days. The combination of urinary IGFBP7 and TIMP-2 at the initial time point demonstrated prognostic value for non-recovery of renal function, with an AUC of 0.782. When [TIMP-2]*[IGFBP7] was measured at 0 h, the clinical prognostic model, incorporating AKI stage 2-3 and the non-renal sequential organ failure assessment score, showed an improved AUC of 0.822 (with a sensitivity of 88.3% and specificity of 59.5%). CONCLUSIONS: The combination of urinary [TIMP-2]*[IGFBP7] at 0 h exhibited moderate predictive ability for renal non-recovery in cases of septic AKI. However, there is potential to enhance the prognostic capabilities of the [TIMP-2]*[IGFBP7]-clinical prediction model.


Asunto(s)
Lesión Renal Aguda , Inhibidor Tisular de Metaloproteinasa-2 , Humanos , Inhibidor Tisular de Metaloproteinasa-2/orina , Pronóstico , Estudios Prospectivos , Modelos Estadísticos , Biomarcadores/orina , Riñón/fisiología , Ciclo Celular
5.
Plant Physiol ; 186(1): 750-766, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-33764451

RESUMEN

Nitrate acts as a vital signal molecule in the modulation of plant growth and development. The phytohormones gibberellin (GA) is also involved in this process. However, the exact molecular mechanism of how nitrate and GA signaling pathway work together in regulating plant growth remains poorly understood. In this study, we found that a nitrate-responsive BTB/TAZ protein MdBT2 participates in regulating nitrate-induced plant growth in apple (Malus × domestica). Yeast two-hybridization, protein pull-down, and bimolecular fluorescence complementation (BiFC) assays showed that MdBT2 interacts with a DELLA protein MdRGL3a, which is required for the ubiquitination and degradation of MdRGL3a proteins via a 26S proteasome-dependent pathway. Furthermore, heterologous expression of MdBT2 partially rescued growth inhibition caused by overexpression of MdRGL3a in Arabidopsis. Taken together, our findings indicate that MdBT2 promotes nitrate-induced plant growth partially through reducing the abundance of the DELLA protein MdRGL3a.


Asunto(s)
Malus/genética , Nitratos/metabolismo , Proteínas de Plantas/genética , Malus/crecimiento & desarrollo , Malus/metabolismo , Proteínas de Plantas/metabolismo
6.
Cell Commun Signal ; 20(1): 105, 2022 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842652

RESUMEN

BACKGROUND: Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). METHODS: The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. RESULTS: In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. CONCLUSIONS: By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Video abstract.


Asunto(s)
Neoplasias de la Vesícula Biliar , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/metabolismo , Glucosa/metabolismo , Glucólisis , Ratones , Ratones Desnudos , Penfluridol/farmacología
7.
Blood Purif ; 51(2): 111-121, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33951630

RESUMEN

INTRODUCTION: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. METHODS: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. RESULTS: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 µg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786-0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. CONCLUSIONS: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice.


Asunto(s)
Terapia de Reemplazo Renal Continuo , Trasplante de Hígado , Anticoagulantes/uso terapéutico , Citratos , Ácido Cítrico/uso terapéutico , Humanos , Estudios Prospectivos , Terapia de Reemplazo Renal/efectos adversos , Estudios Retrospectivos
8.
Proc Natl Acad Sci U S A ; 116(26): 12767-12774, 2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31160461

RESUMEN

In China, pottery containers first appeared about 20000 cal. BP, and became diverse in form during the Early Neolithic (9000-7000 cal. BP), signaling the emergence of functionally specialized vessels. China is also well-known for its early development of alcohol production. However, few studies have focused on the connections between the two technologies. Based on the analysis of residues (starch, phytolith, and fungus) adhering to pottery from two Early Neolithic sites in north China, here we demonstrate that three material changes occurring in the Early Neolithic signal innovation of specialized alcoholic making known in north China: (i) the spread of cereal domestication (millet and rice), (ii) the emergence of dedicated pottery types, particularly globular jars as liquid storage vessels, and (iii) the development of cereal-based alcohol production with at least two fermentation methods: the use of cereal malts and the use of moldy grain and herbs (qu and caoqu) as starters. The latter method was arguably a unique invention initiated in China, and our findings account for the earliest known examples of this technique. The major ingredients include broomcorn millet, Triticeae grasses, Job's tears, rice, beans, snake gourd root, ginger, possible yam and lily, and other plants, some probably with medicinal properties (e.g., ginger). Alcoholic beverages made with these methods were named li, jiu, and chang in ancient texts, first recorded in the Shang oracle-bone inscriptions (ca. 3200 cal. BP); our findings have revealed a much deeper history of these diverse fermentation technologies in China.


Asunto(s)
Bebidas Alcohólicas/historia , Utensilios de Comida y Culinaria/historia , Fermentación , Bebidas Alcohólicas/microbiología , Grano Comestible/química , Manipulación de Alimentos/historia , Hongos/metabolismo , Historia Antigua , Humanos
9.
Sheng Li Xue Bao ; 74(3): 353-358, 2022 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-35770633

RESUMEN

This study was aimed to observe the distribution of Mas-related G protein-coupled receptor A (MrgA) in cerebrospinal fluid (CSF)-contacting nucleus of normal rats and its expression in neuropathic pain, and to provide morphological evidence for CSF-contacting nucleus to participate in neuropathic pain. The model of neuropathic pain with chronic constriction injury (CCI) of the sciatic nerve was made in Sprague-Dawley rats. The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured. The expressions of MrgA in the CSF-contacting nucleus were examined by double labeling with immunofluorescent staining. The results showed that on the 5th, 7th, 10th and 14th days, the values of MWT and TWL in CCI group were all lower than those in sham group (P < 0.05). MrgA was found to be distributed in CSF-contacting nucleus of normal rats; and the expression was markedly up-regulated in rats at the peak of neuropathic pain. Our data suggest that CSF-contacting nucleus may participate in neuropathic pain through the MrgA-mediated signaling pathway.


Asunto(s)
Neuralgia , Proteína Estafilocócica A , Animales , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Proteína Estafilocócica A/metabolismo , Regulación hacia Arriba
10.
Pharmacol Res ; 172: 105793, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34339836

RESUMEN

To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity. JG-1 promotes Th17 cells differentiation and inhibition of regulatory T (Treg) cells differentiation. JG-1 demonstrates robust tumor growth inhibition in multiple syngeneic models and shows a synergic effect with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibody. In tumors, JG-1 not only promotes Th17 cells differentiation and increases C-C Motif Chemokine Receptor 6 (CCR6)- Chemokine (C-C motif) ligand 20 (CCL20) expression, but also inhibits both the expression of transforming growth factor-ß1 (TGF-ß1) and the differentiation and infiltration of Treg cells. In summary, JG-1 is a lead compound showing a potent activity in vitro and robust tumor growth inhibition in vivo with synergetic effects with anti-CTLA-4.


Asunto(s)
Anticuerpos/uso terapéutico , Antineoplásicos/uso terapéutico , Antígeno CTLA-4/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/agonistas , Animales , Antineoplásicos/farmacología , Linfocitos B/efectos de los fármacos , Antígeno CTLA-4/inmunología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Ganglios Linfáticos/citología , Ratones Endogámicos C57BL , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos , Bazo/citología , Linfocitos T/efectos de los fármacos , Factor de Crecimiento Transformador beta1/genética
11.
J Environ Manage ; 286: 112163, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33618320

RESUMEN

Bioconversion of organic waste by the black soldier fly (BSF) larva yields a by-product commonly known as 'frass'. Although BSF larval frass has often been marketed as a biofertilizer, few studies have evaluated this claim. In this study, BSF larvae reared on a pure okara diet achieved an 85% waste reduction in the fresh weight of the okara. Subsequently, the frass was mixed with soil at concentrations of 10, 20, and 30% (vol/vol), and used to cultivate lettuce plants. At 10% concentration, the lettuce plants had biomasses comparable to those of the controls. Higher frass concentrations stunted the growth of the lettuce, likely because of the low C:N ratio of larval frass resulting from the rapid mineralization of nutrients. Larval frass was also found to be able to provide sufficient nutrients for lettuce growth as fertilizer application was only necessary after the first growth cycle, suggesting its suitability as a soil amendment. Analyses of the microbial community of all the growing media showed that the growth medium treatments with BSF larval frass tended to have a lower number of microbial species than the controls. Inherently higher micronutrient levels present in the frass resulted in the growth of lettuce plants. More importantly, the microbial analysis revealed that common foodborne pathogens were absent in the BSF larval frass and elemental analysis also indicated no heavy metal pollutants present. Overall, BSF larval frass was found to be a suitable soil amendment and more in-depth studies could facilitate its sensible use in agriculture.


Asunto(s)
Dípteros , Suelo , Animales , Fertilizantes , Larva , Nutrientes
12.
Br J Cancer ; 122(2): 209-220, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31819189

RESUMEN

BACKGROUND: Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear. METHODS: The mitochondrial fusion protein mitofusin-1 (MFN1) expression and its prognostic value are detected in HCC. The effects and underlying mechanisms of MFN1 on HCC metastasis and metabolic reprogramming are analysed both in vitro and in vivo. RESULTS: Mitochondrial dynamics, represented by constant fission and fusion, are found to be associated with HCC metastasis. High metastatic HCC displays excessive mitochondrial fission. Among genes involved in mitochondrial dynamics, MFN1 is identified as a leading downregulated candidate that is closely associated with HCC metastasis and poor prognosis. While promoting mitochondrial fusion, MFN1 inhibits cell proliferation, invasion and migration capacity both in vitro and in vivo. Mechanistically, disruption of mitochondrial dynamics by depletion of MFN1 triggers the epithelial-to-mesenchymal transition (EMT) of HCC. Moreover, MFN1 modulates HCC metastasis by metabolic shift from aerobic glycolysis to oxidative phosphorylation. Treatment with glycolytic inhibitor 2-Deoxy-D-glucose (2-DG) significantly suppresses the effects induced by depletion of MFN1. CONCLUSIONS: Our results reveal a critical involvement of mitochondrial dynamics in HCC metastasis via modulating glucose metabolic reprogramming. MFN1 may serve as a novel potential therapeutic target for HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Desoxiglucosa/farmacología , GTP Fosfohidrolasas/genética , Glucosa/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , GTP Fosfohidrolasas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucólisis/efectos de los fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Mitocondrias/genética , Mitocondrias/metabolismo , Dinámicas Mitocondriales/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Metástasis de la Neoplasia , Fosforilación Oxidativa/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
13.
J Surg Oncol ; 119(1): 40-46, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30480811

RESUMEN

BACKGROUND: The hepatitis B virus (HBV)-related intrahepatic cholangiocarcinoma (iCCA) was recognized as a unique subtype of iCCA, within particular features in demography, clinicopathology, and genealogy. However, how they predict prognosis, in particular, for HBV- and non-HBV-related iCCA is still unclear. METHODS: Demographic, clinicopathologic, and genetic features were retrospectively collected and reviewed to determine the specific prognostic factors, precisely predicting the overall survival (OS) in HBV-related (n = 119) and non-HBV-related ( n = 149) iCCA patients, respectively. RESULTS: In HBV-related iCCA, TP53 mutation, vascular invasion, extrahepatic metastasis, and serum levels of alpha-fetoprotein (AFP) were independent prognostic factors for OS. In non-HBV-related iCCA, RAS/ RAF mutation and lymphatic metastasis independently predicted the OS of patients. Tumor differentiation and serum levels of CA19-9 were significantly associated with OS in both HBV- and non-HBV-related iCCA patients. In a subset analysis, TP53 and RAS/RAF mutations were consistently related to poorer outcome in HBV- and non-HBV-related iCCA, respectively. CONCLUSIONS: The HBV- and non-HBV-related iCCA have different prognostic factors for the OS.


Asunto(s)
Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/metabolismo , Colangiocarcinoma/patología , Hepatectomía/mortalidad , Hepatitis B/complicaciones , Neoplasias Hepáticas/secundario , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/virología , Biomarcadores de Tumor/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/cirugía , Colangiocarcinoma/virología , Femenino , Estudios de Seguimiento , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genética , alfa-Fetoproteínas/metabolismo , Quinasas raf/genética , Proteínas ras/genética
15.
Molecules ; 24(11)2019 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-31181726

RESUMEN

A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and ßIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated. It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both ßIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent. Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of ßIII.


Asunto(s)
Compuestos Macrocíclicos/síntesis química , Compuestos Macrocíclicos/farmacología , Taxoides/síntesis química , Taxoides/farmacología , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/farmacología , Muerte Celular/efectos de los fármacos , Docetaxel/síntesis química , Docetaxel/química , Docetaxel/farmacología , Células HeLa , Humanos , Compuestos Macrocíclicos/química , Simulación del Acoplamiento Molecular , Paclitaxel/síntesis química , Paclitaxel/química , Paclitaxel/farmacología , Homología Estructural de Proteína , Taxoides/química , Tubulina (Proteína)/química
16.
Phytochem Anal ; 29(3): 284-289, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29266486

RESUMEN

INTRODUCTION: Paclitaxel (Tax) is a diterpene alkaloid isolated from Taxus species and has proved clinically effective in treating a number of malignancies. Current quantitative analytical methods for Tax such as high-performance liquid chromatography (HPLC) often involve complicated sample preparation procedures with low recovery rates. OBJECTIVE: To establish a rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) for measuring Tax in Taxus materials with convenient sample preparation and a high recovery rate. METHODS: Rabbit anti-mouse IgG was coated onto a 96-well microplate, which was then incubated with standard solutions of Tax and anti-Tax monoclonal antibody 3A3. A Eu3+ -labelled conjugate of Tax and human serum albumin was used as the tracer. The luminescent system was enhanced with a solution containing 2-naphthoyltrifluoroacetone. RESULTS: The established TRFIA showed a linear response within the Tax concentration range of 3.2 to 80 ng/mL, with a limit of detection of 1.4 ng/mL. The intra- and inter-assay coefficient of variation of the assay was 9.6% and 9.7%, respectively, with an average recovery rate from spiked samples of 108.5%. Tax contents in Taxus samples were determined using both the established TRFIA system and a previously established enzyme-linked immunosorbent (ELISA), and the results of two assays were well correlated. CONCLUSION: This TRFIA system shows a high sensitivity, precision and accuracy for detection of Tax. This assay, which is convenient and less time-consuming, allows rapid analysis of Tax and provides another option for Tax measurement for quality control of Taxus materials and products. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Antineoplásicos Fitogénicos/análisis , Técnica del Anticuerpo Fluorescente/métodos , Paclitaxel/análisis , Animales , Anticuerpos Monoclonales/inmunología , Antineoplásicos Fitogénicos/inmunología , Calibración , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Inmunoglobulina G/inmunología , Límite de Detección , Paclitaxel/inmunología , Conejos , Reproducibilidad de los Resultados , Taxus/química , Estudios de Tiempo y Movimiento
17.
Ann Plast Surg ; 78(1): 83-90, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27941495

RESUMEN

BACKGROUND: The present study was conducted to compare 2 purification methods for isolation of human adipose-derived stromal vascular fraction or stem cells (ADSCs) based on red blood cell (RBC) lysis with 155 mM ammonium chloride (NH4Cl) and hypotonic sodium chloride (NaCl) solution, and try to develop a safe, convenient, and cost-effective purification method for clinical applications. METHODS: Adipose-derived stem cells and RBC were harvested from the fatty and fluid portions of liposuction aspirates, respectively. The suitable concentration of hypotonic NaCl solution on RBC lysis for purification of ADSCs was developed by RBC osmotic fragility test and flow cytometry analysis. The effects of 155 mM NH4Cl or 0.3% NaCl solution on ADSCs proliferation and RBC lysis efficiency were examined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and lysis efficiency test, respectively. In addition, the adipogenic and osteogenic capabilities, phenotype and genetic stability of ADSCs were evaluated by oil red staining, alkaline phosphatase activity measurement, flow cytometry, and karyotype analysis, respectively. RESULTS: Sodium chloride solution in 0.3% concentration effectively removed RBCs and did not influence the survival of ADSCs in the 10-minute incubation time. The lysis efficiency did not differ significantly between 0.3% NaCl and 155 mM NH4Cl. Moreover, the adipogenic and osteogenic capabilities, surface marker expression and karyotype of the ADSCs were not affected by lysis solutions or by lysis per se. However, the proliferation capacity in the 0.3% NaCl group was superior to that in 155 mM NH4Cl group. CONCLUSIONS: Our data suggest that 0.3% NaCl solution is useful for isolating ADSCs from liposuction aspirate for clinical applications with safety, convenience, and cost-effect.


Asunto(s)
Cloruro de Amonio , Separación Celular/métodos , Hemólisis , Células Madre Mesenquimatosas , Cloruro de Sodio , Grasa Subcutánea Abdominal/citología , Adulto , Proliferación Celular , Femenino , Humanos , Soluciones Hipotónicas , Lipectomía , Masculino , Células Madre Mesenquimatosas/fisiología , Persona de Mediana Edad , Grasa Subcutánea Abdominal/cirugía
18.
Appl Opt ; 55(23): 6183-92, 2016 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-27534458

RESUMEN

The vector similarity measure (VSM), originally applied to information retrieval, has been recently introduced to analyze particle size distribution (PSD) based on forward light scattering. The VSM technique can predict the PSD with low sensitivity to the experimental errors. However, the simulations and experiments of multi-modal distributed particle systems were not satisfying. In this paper, a modified inverse algorithm is presented to improve the VSM technique. Simulated results and experimental evidence show that with this modification the VSM technique can reconstruct the PSD more efficiently.

19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(3): 874-9, 2016 Mar.
Artículo en Zh | MEDLINE | ID: mdl-27400541

RESUMEN

Optical micro-ring resonator prepared on Silicon-On-Insulator (SOI) has high sensitivity, small size and low mode volume. Its high sensitivity has been widely applied to the optical information transmission and inertial navigation devices field, while it is rarely applied in the testing of Mechanics. This paper presents a cantilever stress/strain gauge with an optical microring resonator. It is proposed the using of radius change of ring waveguide for the sensing element. When external stress is put on the structure, the radius of the SOI ring waveguide will be subjected to variation, which causes the optical resonant parameters to change. This ultimately leads to a red-shift of resonant spectrum, and shows the excellent characteristics of the structure's stress/strain sensitivity. Designed a bicyclic cascade embedded optical micro-cavity structure, which was prepared by employing MEMS lithography and ICP etching process. The characteristic of stress/strain sensitivity was calculated theoretically. Two values of 0.185 pm x kPa(-1) and 18.04 pm x microstrain(-1) were obtained experimentally, which also was verified by theoretical simulations. Comparing with the single-loop micro-cavity structure, its measuring range and stress sensitivity increased by nearly 50.3%, 10.6%, respectively. This paper provides a new method to develop micro-opto-electromechanical system (MOEMS) sensors.

20.
Zhong Yao Cai ; 39(9): 1956-9, 2016 Sep.
Artículo en Zh | MEDLINE | ID: mdl-30207649

RESUMEN

Objective: To identify the original species of fish maw sold in Guangzhou market by DNA barcoding technology. Methods: Mitochondrial cytochrome C subunit I (CO I) gene fragment of eleven fish maw samples were amplified and sequenced with the self-designed primers. UPGMA phylogenetic tree were constructed for clustering analysis. The species origin of each sample was identified with the identification engine provided in the Barcode of Life Data Systems (BOLD). Results: The self-designed primers were effective in fish maw CO I amplification and sequencing, with success rates both of 100%. BOLD identification and UPGMA clustering analysis indicated the fish maw samples were derived from five fish species of three families. Conclusion: DNA barcoding combined with BOLD identification system can accurately identify the species origin of commercial fish maw.


Asunto(s)
Código de Barras del ADN Taxonómico , Filogenia , Animales , Análisis por Conglomerados , ADN , Complejo IV de Transporte de Electrones , Peces
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