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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 763-767, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38926964

RESUMEN

OBJECTIVE: To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment. METHODS: The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis. RESULTS: All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia(18.6%), and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs, 20.9%) and infections(7.0%). Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS (P =0.004). The use of daratumumab has no effect on stem cell collection, or engraftment. CONCLUSION: Daratumumab is safe and effective in RRMM.


Asunto(s)
Anticuerpos Monoclonales , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento
2.
Curr Med Sci ; 44(2): 298-308, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619682

RESUMEN

OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. METHODS: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivo tumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. RESULTS: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivo tumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. CONCLUSION: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Tubulina (Proteína) , Humanos , Proliferación Celular , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéutico
3.
World J Clin Cases ; 11(26): 6231-6239, 2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37731571

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the main cause of cancer-related death worldwide. Ectopic HCC, an extremely rare type of HCC, exhibits a wide range of clinical signs and radiographic features, making preoperative identification challenging. CASE SUMMARY: A 47-year-old man underwent routine abdominal color ultrasonography, which identified an asymptomatic tumor in the left upper abdomen. The patient had no history of hepatitis, did not drink alcohol, and had no family history of cancer. Abdominal contrast-enhanced computed tomography (CT) revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm, with blood supplied by the left inferior phrenic artery. The patient underwent laparoscopic surgery, and HCC was identified by postoperative pathology. Additionally, specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC. The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery. Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis. CONCLUSION: This asymptomatic ectopic HCC case described achieved an excellent result due to early detection, radical resection, and systematic surveillance.

4.
J Chromatogr A ; 1687: 463650, 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36462476

RESUMEN

Effective and targeted identification of chemical components of the Chinese herbal medicine Sabia parviflora remains a major challenge. Herein, we used ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to analyze the chemical composition of S.parviflora. Its chemical components were rapidly identified using the characteristic ion filtration method, which involves these steps: (1) summarize the characteristic ions based on similar skeletons and compounds with substitution patterns, and establish a database; (2) screen and classify different types of compounds in S. parviflora based on the characteristic ions; and (3) identify the compounds based on molecular weight, secondary fragments, and the database. In the present study, the characteristic ions in S. parviflora were grouped into five major classes. A total of 104 components were identified, including 12 potentially novel compounds. This rapid and accurate method provides an important basis for basic chemical research in S. parviflora.


Asunto(s)
Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Iones , Filtración
5.
J Asian Nat Prod Res ; 25(6): 547-556, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36036184

RESUMEN

Three new compounds, (8S)-2,2,7,7-tetramethyl-8-hydroxymethyl-6H-indanone-(2,3-b)-2H-pyran-9-O-ß-d-glucopyranoside (1), (7S,8S)-2,2,7-trimethyl-7-hydroxymethyl-8-hydroxy-2,7,8,9-tetrahydro-6H-naphtho-(2,3-b)-pyran-10-O-ß-d-glucopyranoside (2), 1-deoxy-1-(3,4-dihydro-7-methyl-2,3-dioxo-1(2H)-quinoxalinyl)pentitol-6-carboxylic acid (3), as well as six known compounds (4-9), were obtained. Their structures were determined by spectroscopy and comparison with NMR data of related compounds. Absolute configurations were determined by ECD spectroscopy. The hepatoprotective effects of these compounds were investigated on HepG2 and LO2 cells lines; compounds 1, 2, and 4 displayed moderate activity.


Asunto(s)
Glicósidos , Estructura Molecular , Glicósidos/química , Línea Celular , Espectroscopía de Resonancia Magnética
6.
PLoS Negl Trop Dis ; 16(5): e0010432, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35533208

RESUMEN

BACKGROUND: This study aimed to explore whether the transmission routes of severe fever with thrombocytopenia syndrome (SFTS) will be affected by tick density and meteorological factors, and to explore the factors that affect the transmission of SFTS. We used the transmission dynamics model to calculate the transmission rate coefficients of different transmission routes of SFTS, and used the generalized additive model to uncover how meteorological factors and tick density affect the spread of SFTS. METHODS: In this study, the time-varying infection rate coefficients of different transmission routes of SFTS in Jiangsu Province from 2017 to 2020 were calculated based on the previous multi-population multi-route dynamic model (MMDM) of SFTS. The changes in transmission routes were summarized by collecting questionnaires from 537 SFTS cases in 2018-2020 in Jiangsu Province. The incidence rate of SFTS and the infection rate coefficients of different transmission routes were dependent variables, and month, meteorological factors and tick density were independent variables to establish a generalized additive model (GAM). The optimal GAM was selected using the generalized cross-validation score (GCV), and the model was validated by the 2016 data of Zhejiang Province and 2020 data of Jiangsu Province. The validated GAMs were used to predict the incidence and infection rate coefficients of SFTS in Jiangsu province in 2021, and also to predict the effect of extreme weather on SFTS. RESULTS: The number and proportion of infections by different transmission routes for each year and found that tick-to-human and human-to-human infections decreased yearly, but infections through animal and environmental transmission were gradually increasing. MMDM fitted well with the three-year SFTS incidence data (P<0.05). The best intervention to reduce the incidence of SFTS is to reduce the effective exposure of the population to the surroundings. Based on correlation tests, tick density was positively correlated with air temperature, wind speed, and sunshine duration. The best GAM was a model with tick transmissibility to humans as the dependent variable, without considering lagged effects (GCV = 5.9247E-22, R2 = 96%). Reported incidence increased when sunshine duration was higher than 11 h per day and decreased when temperatures were too high (>28°C). Sunshine duration and temperature had the greatest effect on transmission from host animals to humans. The effect of extreme weather conditions on SFTS was short-term, but there was no effect on SFTS after high temperature and sunshine hours. CONCLUSIONS: Different factors affect the infection rate coefficients of different transmission routes. Sunshine duration, relative humidity, temperature and tick density are important factors affecting the occurrence of SFTS. Hurricanes reduce the incidence of SFTS in the short term, but have little effect in the long term. The most effective intervention to reduce the incidence of SFTS is to reduce population exposure to high-risk environments.


Asunto(s)
Síndrome de Trombocitopenia Febril Grave , Garrapatas , Animales , China/epidemiología , Incidencia , Conceptos Meteorológicos
7.
Sci Total Environ ; 831: 155393, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35461937

RESUMEN

BACKGROUND: Living near green spaces may benefit various health outcomes. However, no studies have investigated the greenness-bone linkage in the general population. Moreover, to which extent ambient air pollution (AAP), physical activity (PA), and body mass index (BMI) mediate this relationship remains unclear. We aimed to explore the association between greenness and bone strength and the potential mediating roles of AAP, PA, and BMI in Chinese adults. METHODS: This cross-sectional analysis enrolled 66,053 adults from the China Multi-Ethnic Cohort in 2018-2019. The normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were employed to define residential greenness. The calcaneus quantitative ultrasound index (QUI) was used to indicate bone strength. Multiple linear regression models and mediation analyses were used to estimate the residential greenness-bone strength association and potential pathways operating through AAP (represented by PM2.5 [particulate matter <2.5 µm in diameter]), PA, and BMI. Stratification analyses were performed to identify susceptible populations. RESULTS: Higher residential exposure to greenness was significantly associated with an increase in QUI, with changes (95% confidence interval) of 3.28 (3.05, 3.50), 3.57 (3.34, 3.80), 2.68 (2.46, 2.90), and 2.93 (2.71, 3.15) for every interquartile range increase in NDVI500m, NDVI1000m, EVI500m, and EVI1000m, respectively. Sex, urbanicity, annual family income, smoking, and drinking significantly modified the association of greenness-bone strength, with more remarkable associations in males, urban residents, subjects from wealthier families, smokers, and drinkers. For the NDVI500m/EVI500m-QUI relationship, the positive mediating roles of PM2.5 and PA were 6.70%/8.50 and 2.43%/2.69%, respectively, whereas those negative for BMI and PA-BMI were 0.88%/1.06% and 0.05%/0.05%, respectively. CONCLUSION: Living in a greener area may predict higher bone strength, particularly among males, urban residents, wealthier people, smokers, and drinkers. AAP, PA, BMI, and other factors may partially mediate the positive association. Our findings underscore the importance of optimizing greenness planning and management policies.


Asunto(s)
Contaminación del Aire , Adulto , Contaminación del Aire/análisis , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Humanos , Masculino , Material Particulado/análisis
8.
Parasit Vectors ; 14(1): 237, 2021 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-33957950

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is regionally distributed in Asia, with high fatality. Constructing the transmission model of SFTS could help provide clues for disease control and fill the gap in research on SFTS models. METHODS: We built an SFTS transmission dynamics model based on the susceptible-exposed-infectious-asymptomatic-recovered (SEIAR) model and the epidemiological characteristics of SFTS in Jiangsu Province. This model was used to evaluate the effect by cutting off different transmission routes and taking different interventions into account, to offer clues for disease prevention and control. RESULTS: The transmission model fits the reported data well with a minimum R2 value of 0.29 and a maximum value of 0.80, P < 0.05. Meanwhile, cutting off the environmental transmission route had the greatest effect on the prevention and control of SFTS, while isolation and shortening the course of the disease did not have much effect. CONCLUSIONS: The model we have built can be used to simulate the transmission of SFTS to help inform disease control. It is noteworthy that cutting off the environment-to-humans transmission route in the model had the greatest effect on SFTS prevention and control.


Asunto(s)
Síndrome de Trombocitopenia Febril Grave/transmisión , Animales , Vectores Arácnidos/virología , China/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Modelos Teóricos , Síndrome de Trombocitopenia Febril Grave/epidemiología , Síndrome de Trombocitopenia Febril Grave/prevención & control , Garrapatas/virología
9.
J Ethnopharmacol ; 264: 113212, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32768643

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion (CIR) injury is one of the main diseases leading to death and disability. Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Panax ginseng, has neuroprotective effects on anti-CIR injury. However, the underlying molecular mechanism of its therapeutic effects is not clear. AIM OF THE STUDY: To systematically study and explore the mechanism of Acanthopanax senticosus (Rupr. & Maxim.) Harms extract (ASE) in the treatment of CIR injury based on metabolomics and transcriptomics. MATERIALS AND METHODS: The pharmacological basis of ASE in the treatment of CIR was evaluated, and samples were used in plasma metabolomics and brain tissue transcriptomics to reveal potential biomarkers. Finally, according to online database, we analyzed biomarkers identified by the two technologies, explained reasons for the therapeutic effect of ASE, and identify therapeutic targets. RESULTS: A total of 53 differential metabolites (DMs) were identified in plasma and 3138 differentially expressed genes (DEGs) were identified in brain tissue from three groups of rats, including sham, ischemia-reperfusion (I/R), and ASE groups. Enrichment analysis showed that Nme6, Tk1, and Pold1 that are involved in the production of deoxycytidine and thymine were significantly up-regulated and Dck was significantly down-regulated by the intervention with ASE. These findings indicated that ASE participates in the pyrimidine metabolism by significantly regulating the balance between dCTP and dTTP. In addition, ASE repaired and promoted the lipid metabolism in rats, which might be due to the significant expression of Dgkz, Chat, and Gpcpd1. CONCLUSIONS: The findings of this study suggest that ASE regulates the significant changes in gene expression in metabolites pyrimidine, and lipid metabolism in CIR rats and plays an active role in the treatment of CIR injury through multiple targets and pathways.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Eleutherococcus , Metabolómica/métodos , Extractos Vegetales/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Transcriptoma/efectos de los fármacos , Animales , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Masculino , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Transcriptoma/fisiología
10.
Histol Histopathol ; 36(1): 101-112, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33215396

RESUMEN

OBJECTIVE: To examine the effect of the BRD4 inhibitor JQ1 on mice with chronic obstructive pulmonary disease (COPD) via NF-κB. METHODS: COPD models constructed by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharides (LPS) in mice were treated with JQ1 (15, 25 or 50 mg/kg). HE staining was performed to observe histopathological changes in the lung tissues. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of IL-10, IFN-γ, IL-17, IL-1ß, IL-6, TNF-α, MMP-2, MMP-9, MDA, SOD, T-AOC and HO-1, and gelatin zymography assays were used to examine MMP-2 and MMP-9 activity. A TransAMTM NF-κB p65 detection kit was used to test NF-κB p65/DNA binding activity. Western blotting was conducted to analyze NF-κB p65 in the nucleus and its acetylation. RESULTS: JQ1 dose-dependently improved the histopathological changes in the lung tissues and decreased the mean linear intercept (MLI), destructive index and inflammatory score of the mice with COPD. The mice with COPD showed increased levels of MMP-2, MMP-9, IFN-γ, IL-17, IL-1ß, IL-6 and TNF-α with decreased IL-10 level; these changes were reversed by JQ1 in a dose-dependent manner. In addition, JQ1 reduced the MDA level and increased the SOD, HO-1 and T-AOC levels in mice with COPD, with suppression of NF-κB p65 expression in the nucleus, NF-κB/p65 (Lys310) acetylation and NF-κB p65/DNA binding activity in the lung tissues. CONCLUSION: The BRD4 inhibitor JQ1 can downregulate MMP-2 and MMP-9 expression, reduce inflammatory responses, and alleviate oxidative stress in mice with COPD, and this mechanism might be related to the inhibition of NF-κB.


Asunto(s)
Azepinas/farmacología , Subunidad p50 de NF-kappa B/biosíntesis , Proteínas Nucleares/antagonistas & inhibidores , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/genética , Factores de Transcripción/antagonistas & inhibidores , Triazoles/farmacología , Animales , Citocinas/metabolismo , Regulación de la Expresión Génica , Inflamación , Leucocitos/citología , Lipopolisacáridos/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Nucleares/genética , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Pruebas de Función Respiratoria , Transducción de Señal
11.
J Clin Lab Anal ; 34(9): e23362, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32463132

RESUMEN

PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin-1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin-1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si-PAK4, LIMK1, and si-PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK-8, wound-healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co-immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin-1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice. RESULTS: The expression of PAK4/LIMK1/Cofilin-1 in both osteosarcoma tissues and cells was up-regulated. Positive PAK4, LIMK1, and Cofilin-1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p-LIMK/LIMK, and p-Cofilin-1/Cofilin-1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co-immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells. CONCLUSION: The expression of PAK4/LIMK1/Cofilin-1 pathway in osteosarcoma tissues was up-regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin-1 pathway.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/patología , Cofilina 1/metabolismo , Regulación Neoplásica de la Expresión Génica , Quinasas Lim/metabolismo , Osteosarcoma/patología , Quinasas p21 Activadas/metabolismo , Adulto , Animales , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Movimiento Celular , Proliferación Celular , Cofilina 1/genética , Femenino , Humanos , Quinasas Lim/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Osteosarcoma/genética , Osteosarcoma/metabolismo , Pronóstico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven , Quinasas p21 Activadas/genética
12.
J Asian Nat Prod Res ; 22(4): 303-315, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30843729

RESUMEN

Three new saponins (1-3), a new natural product (4) and six other known compounds (5-10) were isolated from the whole Reineckia carnea plant. Their structures were established by comparison of their NMR spectra and MS data with literature data. In addition, all the isolated compounds were evaluated in vitro for anti-inflammatory activities against LPS-stimulated nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 1-4 exhibited anti-inflammatory activities with IC50 values of 37.5 µM, 31.4 µM, 34.6 µM, and 56.1 µM, respectively. Furthermore, compounds 5-10 showed anti-inflammatory activities with IC50 values ranging from 20.3 to 42.9 µM.


Asunto(s)
Antiinflamatorios , Saponinas , Lipopolisacáridos , Macrófagos , Estructura Molecular , Óxido Nítrico , Extractos Vegetales
13.
J Phys Chem A ; 124(1): 82-89, 2020 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-31815471

RESUMEN

A new terbium (III) luminescent compound {[Tb2(PDC)2(ox)(H2O)4](H2O)2}n was synthesized by the self-assembly of Tb3+ ions with 3,5-pyridinedicarboxylate (PDC) and oxalate (ox) ligands and characterized by fluorescence spectroscopy and single-crystal X-ray diffraction. The density functional theory (DFT) and high-level correlated ab initio wave function methods with Spin-Orbit Coupling correction (CASSCF/SO and CAS-NEVPT2/SOC) were successfully applied to predict the absorption and emission spectra of this strongly correlated lanthanide system in excellent agreement with the experimental results.

14.
Sci Prog ; 103(1): 36850419891046, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31791191

RESUMEN

Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.


Asunto(s)
Neoplasias de la Mama , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclo Celular/genética , Línea Celular Tumoral , Femenino , Factores de Intercambio de Guanina Nucleótido/farmacología , Humanos , Nucleótidos/farmacología
15.
Cells ; 8(6)2019 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-31163575

RESUMEN

Two unrecognizable strains of the same bacterial species form a distinct colony boundary. During growth as colonies, Myxococcus xanthus uses multiple factors to establish cooperation between recognized strains and prevent interactions with unrecognized strains of the same species. Here, ΔMXAN_0049 is a mutant strain deficient in immunity for the paired nuclease gene, MXAN_0050, that has a function in the colony-merger incompatibility of Myxococcus xanthus DK1622. With the aim to investigate the factors involved in boundary formation, a proteome and metabolome study was employed. Visualization of the boundary between DK1622 and ΔMXAN_0049 was done scanning electron microscope (SEM), which displayed the presence of many damaged cells in the boundary. Proteome analysis of the DK1622- boundary disclosed many possible proteins, such as cold shock proteins, cell shape-determining protein MreC, along with a few pathways, such as RNA degradation, phenylalanine, tyrosine and tryptophan biosynthesis, and Type VI secretion system (T6SS), which may play major roles in the boundary formation. Metabolomics studies revealed various secondary metabolites that were significantly produced during boundary formation. Overall, the results concluded that multiple factors participated in the boundary formation in M. xanthus, leading to cellular damage that is helpful in solving the mystery of the boundary formation mechanism.


Asunto(s)
Metabolómica/métodos , Myxococcus xanthus/crecimiento & desarrollo , Myxococcus xanthus/metabolismo , Proteómica/métodos , Sistemas de Secreción Bacterianos , Recuento de Colonia Microbiana , Regulación hacia Abajo , Viabilidad Microbiana , Myxococcus xanthus/ultraestructura , Mapas de Interacción de Proteínas , Proteoma/metabolismo , Metabolismo Secundario , Regulación hacia Arriba
16.
J Cell Mol Med ; 23(8): 4991-5005, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31207106

RESUMEN

Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer therapy. Therefore, this study explores whether miR-374 targeting tyrosinase (TYR) affects melanoma and its underlying mechanism. We constructed subcutaneous melanoma models to carry out the following experiments. The cells were transfected with a series of miR-374 mimics, miR-374 inhibitors or siRNA against TYR. Dual luciferase reporter gene assay was used for the verification of the targeting relationship between miR-374 and TYR. Reverse transcription quantitative polymerase chain reaction and western blot analysis were conducted to determine the expression of miR-374, TYR, ß-catenin, B-cell leukaemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), Low-density lipoprotein receptor-related protein 6 (LRP6), Leucine-rich repeat G protein-coupled receptor 5 (LGR5) and CyclinD1. Cell proliferation, migration, invasion, cell cycle distribution and apoptosis were evaluated using cell counting kit-8 assay, scratch test, transwell assay and flow cytometry respectively. TYR was proved as a putative target of miR-374 as the evidenced by the result. It was observed that up-regulated miR-374 or down-regulated TYR increased expression of Bax and decreased expressions of TYR, ß-catenin, LRP6, Bcl-2, CyclinD1 and LGR5, along with diminished cell proliferation, migration, invasion and enhanced apoptosis. Meanwhile, cells with miR-374 inhibitors showed an opposite trend. These findings indicated that up-regulated miR-374 could inhibit the expression of TYR to suppress cell proliferation, migration, invasion and promote cell apoptosis in melanoma cells by inhibiting the Wnt signalling pathway.


Asunto(s)
Melanoma/metabolismo , MicroARNs/metabolismo , Monofenol Monooxigenasa/metabolismo , Neoplasias Cutáneas/metabolismo , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/metabolismo , Masculino , Melanoma/genética , Melanoma/patología , Ratones , Ratones Desnudos , MicroARNs/genética , Monofenol Monooxigenasa/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Interferente Pequeño , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Puntos de Control de la Fase S del Ciclo Celular/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Trasplante Heterólogo , Vía de Señalización Wnt/genética , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
17.
Microb Biotechnol ; 12(4): 763-774, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31069998

RESUMEN

Glycosylation of natural products can influence their pharmacological properties, and efficient glycosyltransferases (GTs) are critical for this purpose. The polyketide epothilones are potent anti-tumour compounds, and YjiC is the only reported GT for the glycosylation of epothilone. In this study, we phylogenetically analysed 8261 GTs deposited in CAZy database and revealed that YjiC locates in a subbranch of the Macrolide I group, forming the YjiC-subbranch with 160 GT sequences. We demonstrated that the YjiC-subbranch GTs are normally efficient in epothilone glycosylation, but some showed low glycosylation activities. Sequence alignment of YjiC-subbranch showed that the 66th and 77th amino acid residues, which were close to the catalytic cavity in molecular docking model, were conserved in five high-active GTs (Q66 and P77) but changed in two low-efficient GTs. Site-directed residues swapping at the two positions in the two low-active GTs (BssGT and BamGT) and the high-active GT BsGT-1 demonstrated that the two amino acid residues played an important role in the catalytic efficiency of epothilone glycosylation. This study highlights that the potent GTs for appointed compounds are phylogenetically grouped with conserved residues for the catalytic efficiency.


Asunto(s)
Epotilonas/metabolismo , Glicosiltransferasas/metabolismo , Moduladores de Tubulina/metabolismo , Biotransformación , Dominio Catalítico , Secuencia Conservada , Glicosilación , Glicosiltransferasas/clasificación , Glicosiltransferasas/genética , Cinética , Simulación del Acoplamiento Molecular , Filogenia , Alineación de Secuencia
18.
Sci Rep ; 8(1): 15070, 2018 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-30305664

RESUMEN

Polarization imaging detection has its unique advantage in discriminating the man-made objects from natural objects. Grating integrated super pixel for polarization imaging detection can simultaneously obtain the first three elements of the Stokes vector, which is the trend of infrared polarization imaging detection in recent years. Here, we demonstrate the first super pixel for long wavelength infrared polarization imaging detection with the extinction ratio of its four polarization directions more than 100. The measured highest polarization extinction ratio is as high as 136, which is the highest reported value of long wavelength infrared polarization imaging detection super pixel. The mechanism is attributed to the excellent mode selectivity of plasmonic microcavity according to the results of three-dimensional theoretical simulation. The experimental responses of the super pixel with four polarization directions are in good agreement with the Malus' Law. In addition, the super pixel can accurately resolve the Stokes parameters at the same time. It is expected to develop the super pixel into a new generation of practical high-polarization-discriminating long wavelength infrared focal plane array.

19.
Nanomaterials (Basel) ; 8(9)2018 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-30200542

RESUMEN

MP2 (Second order approximation of Møller⁻Plesset perturbation theory) and DFT/TD-DFT (Density functional theory/Time-dependent_density_functional_theory) investigations have been performed on metallophilic nanomaterials of host clusters [Au(NHC)2]⁺⋅⋅⋅[M(CN)2]-⋅⋅⋅[Au(NHC)2]⁺ (NHC = N-heterocyclic carbene, M = Au, Ag) with high phosphorescence. The phosphorescence quantum yield order of clusters in the experiments was evidenced by their order of µS1/ΔES1-T1 values ( µ S 1 : S0 → S1 transition dipole, ∆ E S 1 - T 1 : splitting energy between the lowest-lying singlet S1 and the triplet excited state T1 states). The systematic variation of the guest solvents (S1: CH3OH, S2: CH3CH2OH, S3: H2O) are employed not only to illuminate their effect on the metallophilic interaction and phosphorescence but also as the probes to investigate the recognized capacity of the hosts. The simulations revealed that the metallophilic interactions are mainly electrostatic and the guests can subtly modulate the geometries, especially metallophilic Au⋅⋅⋅M distances of the hosts through mutual hydrogen bond interactions. The phosphorescence spectra of hosts are predicted to be blue-shifted under polar solvent and the excitation from HOMO (highest occupied molecular orbital) to LUMO (lowest unoccupied molecular orbital) was found to be responsible for the ³MLCT (triplet metal-to-ligand charge transfer) characters in the hosts and host-guest complexes. The results of investigation can be introduced as the clues for the design of promising blue-emitting phosphorescent and functional materials.

20.
Appl Microbiol Biotechnol ; 102(13): 5599-5610, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29705958

RESUMEN

Promoter optimization is an economical and effective approach to overexpress heterologous genes and improve the biosynthesis of valuable products. In this study, we swapped the original promoter of the epothilone biosynthetic gene cluster in Myxococcus xanthus with two endogenous strong promoters P pilA and P groEL1 , respectively, which, however, decreased the epothilone production ability. The transcriptional abilities by the two promoters were found to be bloomed in the growth stage but markedly decreased after the growth, whereas the original promoter P epo functioned majorly after the exponential growth stage. Tandem repeat engineering on the original promoter P epo remarkably increased epothilone production. The tandem promoter exerted similar expressional pattern as P epo did in M. xanthus. We demonstrated that differential transcriptional modes markedly affected the efficiency of promoters in controlling the gene expressions for the production of the secondary metabolite epothilones. Our study provides an insight into exploiting powerful promoters to produce valuable secondary metabolites, especially in host with limited known promoters.


Asunto(s)
Epotilonas/biosíntesis , Microbiología Industrial , Myxococcus xanthus/genética , Myxococcus xanthus/metabolismo , Regiones Promotoras Genéticas/genética , Transcripción Genética , Familia de Multigenes/genética
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