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1.
Small ; : e2404881, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39440673

RESUMEN

Ammonia (NH3) is regarded as an essential hydrogen storage material in the new energy field, and plasma-electrocatalytic synthesis of NH3 (PESA) is an alternative to the traditional Haber-Bosch process. Here, a bifunctional catalyst CoOOH/CF is proposed to enhance the PESA process. Benefiting from the efficient activation of O2 by CoOOH/CF, NOx - yield rate can reach the highest value of 171.90 mmol h-1 to date. Additionally, CoOOH holds a more negative d-band center, thereby exhibiting weaker adsorption toward NO*, lowering the energy barrier for the rate determining step, resulting in a high NH3 yield rate (302.55 mg h-1 cm-2 at -0.8 V) with ampere-level NH3 current density (2.86 A cm-2 at -0.8 V) and nearly 100% Faraday efficiency (FE, 99.8% at -0.6 V). Moreover, CoOOH/CF achieves an excellent 4.54 g h-1 NH3 yield rate with 97.9% FE in an enlarged electrolyzer, demonstrating the feasibility of PESA on a large scale.

2.
Malar J ; 23(1): 242, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138510

RESUMEN

BACKGROUND: The effects of a diverse spectrum of malaria interventions were evaluated through a deterministic Plasmodium vivax transmission model. This approach aimed to provide theoretical evidence of the performance of these interventions once implemented for achieving malaria elimination. METHODS: An integrated intervention portfolio, including mass drug administration, insecticide treatment, and untreated bed nets, was analyzed through modeling. Additionally, data-driven calibration was implemented to infer coverages that effectively reproduced historical malaria patterns in China from 1971 to 1983. RESULTS: MDA utilizing primaquine emerged as the most effective single intervention, achieving a 70% reduction in malaria incidence when implemented at full coverage. Furthermore, a strategic combination of MDA with primaquine, chloroquine, untreated bed nets, and seasonal insecticide treatments effectively eradicated malaria, attaining elimination at a coverage level of 70%. It was conclusively demonstrated that an integrated approach combining MDA and vector control measures is essential for the successful elimination of malaria. CONCLUSION: High coverage of mass drug administration with primaquine and chloroquine before transmission was the key driver of the malaria decline in China from 1971 to 1983. The best-fit intervention coverage combinations derived from calibration are provided as a reference for malaria control in other countries.


Asunto(s)
Antimaláricos , Malaria Vivax , Malaria Vivax/prevención & control , Malaria Vivax/epidemiología , China/epidemiología , Humanos , Antimaláricos/uso terapéutico , Plasmodium vivax/efectos de los fármacos , Primaquina/uso terapéutico , Administración Masiva de Medicamentos , Cloroquina/uso terapéutico , Control de Mosquitos/métodos
3.
BMC Pediatr ; 24(1): 60, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243213

RESUMEN

NUDT2 is an enzyme important for maintaining the intracellular level of the diadenosine tetraphosphate (Ap4A). Bi-allelic loss of function variants in NUDT2 has recently been reported as a rare cause of intellectual disability (ID). Herein, we describe a Chinese girl with ID, attention deficit hyperactivity disorder (ADHD), and motor delays with abnormal walking posture and difficulty climbing stairs, who bears compound heterozygous variants c.34 C > T (p.R12*) and c.194T > G (p.I65R) in NUDT2. Homozygous variants c.34 C > T (p.R12*) or c.186del (p.A63Qfs*3) in NUDT2 were previously reported to cause ID. This is the first patient with ID due to compound heterozygous variants in NUDT2 and p.I65R is a novel missense variant. This study enriched the genotype and phenotype of NUDT2-related ID and supported the critical developmental involvement of NUDT2.


Asunto(s)
Discapacidad Intelectual , Femenino , Humanos , Discapacidad Intelectual/genética , Genotipo , Fenotipo , Mutación Missense , Homocigoto , Hidrolasas Nudix , Monoéster Fosfórico Hidrolasas/genética
4.
Acta Radiol ; 65(7): 700-707, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38856151

RESUMEN

BACKGROUND: Focal liver lesions (FLLs) are a common form of liver disease, and identifying accurate pathological types is required to guide treatment and evaluate prognosis. PURPOSE: To compare and analyze the application effect of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in the clinical diagnosis of focal liver lesions. MATERIAL AND METHODS: A retrospective analysis was performed on 682 patients with space-occupying liver lesions admitted to our hospital between December 2015 and August 2021. Of these, 280 underwent CEUS-guided biopsies and 402 underwent conventional US biopsies, with the results of each biopsy subsequently compared between the two groups. The success rate and accuracy of the biopsies and their relationship with different pathological features were also analyzed. RESULTS: The success rate, sensitivity, diagnostic accuracy, positive predictive value, and negative predictive value of the CEUS group were significantly higher than those of the US group (P < 0.05). Lesion size accuracy in the CEUS group was significantly higher than that in the US group (89.29% vs. 40.55%; P < 0.05). Lesion type accuracy in the CEUS group was significantly higher than that in the US group (86.49% vs. 43.59%), and the difference between the two groups was statistically significant (P < 0.05). The logistic regression analysis indicated that malignant lesions, lesions ≥5 cm, and lesions ≤1 cm were independent factors affecting the success rate of the puncture procedure (P < 0.05). CONCLUSION: The sensitivity, specificity, and diagnostic accuracy of lesion size and type in the CEUS group were higher than those in the US group.


Asunto(s)
Medios de Contraste , Sensibilidad y Especificidad , Ultrasonografía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Ultrasonografía/métodos , Adulto , Anciano , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Hepatopatías/diagnóstico por imagen , Hepatopatías/patología , Aumento de la Imagen/métodos , Reproducibilidad de los Resultados , Valor Predictivo de las Pruebas , Adulto Joven
5.
World J Surg Oncol ; 22(1): 206, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090636

RESUMEN

BACKGROUND: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance. METHODS: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses. RESULTS: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value. CONCLUSIONS: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis.


Asunto(s)
Anemia , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Masculino , Femenino , Anemia/etiología , Anemia/complicaciones , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Factores de Riesgo , Estudios de Seguimiento , Gastrectomía , Anciano , Estadificación de Neoplasias , Curva ROC , Periodo Preoperatorio , Adulto
6.
BMC Biol ; 21(1): 192, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37697363

RESUMEN

BACKGROUND: Lauraceae is well known for its significant phylogenetic position as well as important economic and ornamental value; however, most evergreen species in Lauraceae are restricted to tropical regions. In contrast, camphor tree (Cinnamomum camphora) is the most dominant evergreen broadleaved tree in subtropical urban landscapes. RESULTS: Here, we present a high-quality reference genome of C. camphora and conduct comparative genomics between C. camphora and C. kanehirae. Our findings demonstrated the significance of key genes in circadian rhythms and phenylpropanoid metabolism in enhancing cold response, and terpene synthases (TPSs) improved defence response with tandem duplication and gene cluster formation in C. camphora. Additionally, the first comprehensive catalogue of C. camphora based on whole-genome resequencing of 75 accessions was constructed, which confirmed the crucial roles of the above pathways and revealed candidate genes under selection in more popular C. camphora, and indicated that enhancing environmental adaptation is the primary force driving C. camphora breeding and dominance. CONCLUSIONS: These results decipher the dominance of C. camphora in subtropical urban landscapes and provide abundant genomic resources for enlarging the application scopes of evergreen broadleaved trees.


Asunto(s)
Cinnamomum camphora , Cinnamomum camphora/genética , Filogenia , Fitomejoramiento , Análisis de Secuencia de ADN , Genómica
7.
Mol Cancer ; 22(1): 95, 2023 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-37316830

RESUMEN

Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting "cold" tumors into "hot" ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.


Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Animales , Ratones , Neoplasias Peritoneales/tratamiento farmacológico , Proteínas HSP90 de Choque Térmico , Proteolisis , Colon
8.
Plant Biotechnol J ; 21(8): 1671-1681, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37155328

RESUMEN

The fungal bioluminescence pathway (FBP) was identified from glowing fungi, which releases self-sustained visible green luminescence. However, weak bioluminescence limits the potential application of the bioluminescence system. Here, we screened and characterized a C3'H1 (4-coumaroyl shikimate/quinate 3'-hydroxylase) gene from Brassica napus, which efficiently converts p-coumaroyl shikimate to caffeic acid and hispidin. Simultaneous expression of BnC3'H1 and NPGA (null-pigment mutant in A. nidulans) produces more caffeic acid and hispidin as the natural precursor of luciferin and significantly intensifies the original fungal bioluminescence pathway (oFBP). Thus, we successfully created enhanced FBP (eFBP) plants emitting 3 × 1011 photons/min/cm2 , sufficient to illuminate its surroundings and visualize words clearly in the dark. The glowing plants provide sustainable and bio-renewable illumination for the naked eyes, and manifest distinct responses to diverse environmental conditions via caffeic acid biosynthesis pathway. Importantly, we revealed that the biosynthesis of caffeic acid and hispidin in eFBP plants derived from the sugar pathway, and the inhibitors of the energy production system significantly reduced the luminescence signal rapidly from eFBP plants, suggesting that the FBP system coupled with the luciferin metabolic flux functions in an energy-driven way. These findings lay the groundwork for genetically creating stronger eFBP plants and developing more powerful biological tools with the FBP system.


Asunto(s)
Ingeniería Metabólica , Plantas , Luciferinas
9.
BMC Cancer ; 23(1): 536, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308852

RESUMEN

BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.


Asunto(s)
Carcinoma , Neoplasias Gástricas , Humanos , Metástasis Linfática , Estudios Retrospectivos , Suplementos Dietéticos
10.
J Nanobiotechnology ; 21(1): 64, 2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36823540

RESUMEN

BACKGROUND: Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT. RESULTS: Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT. CONCLUSIONS: Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.


Asunto(s)
Adenosina Trifosfato , Neoplasias , Terapia Fototérmica , Piroptosis , Humanos , Adenosina Trifosfato/deficiencia , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , Proteínas de Choque Térmico , Nanopartículas , Neoplasias/metabolismo , Neoplasias/terapia , Terapia Fototérmica/métodos , Piroptosis/fisiología , Especies Reactivas de Oxígeno , Temperatura
11.
BMC Med ; 20(1): 17, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-35057816

RESUMEN

BACKGROUND: With the recent certification by World Health Organization that the People's Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People's Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. METHODS: We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People's Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. RESULTS: P. vivax parasites from the seven studies of five southern and central provinces in the People's Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10-19 days) or long-incubation (228-371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman's rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. CONCLUSIONS: Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.


Asunto(s)
Malaria Vivax , Malaria , Animales , China/epidemiología , Erradicación de la Enfermedad , Humanos , Malaria Vivax/tratamiento farmacológico , Malaria Vivax/epidemiología , Malaria Vivax/prevención & control , Plasmodium vivax , Recurrencia , Esporozoítos
12.
Int J Med Sci ; 19(8): 1307-1319, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928717

RESUMEN

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and in vivo mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.


Asunto(s)
Osteogénesis , Proteínas Quinasas p38 Activadas por Mitógenos , Diferenciación Celular , Proliferación Celular/genética , Células Cultivadas , Pulpa Dental/metabolismo , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 3 Activada por Mitógenos , Osteogénesis/genética , Transducción de Señal , Células Madre/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
13.
Acta Clin Croat ; 61(2): 193-197, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36818924

RESUMEN

The aim was to investigate detection of pulmonary alveolar lavage fluid tuberculosis DNA by real-time fluorescent polymerase chain reaction (RT-PCR) combined with clinical application of the sputum smear-negative pulmonary tuberculosis diagnosis with TB interferon-γ release assay (TB-IGRA). From October 2014 to October 2015, 632 outpatients and inpatients treated in our hospital were randomly selected, of which 459 patients as the research group managed with RT-PCR detection combined with TB-IGRA and 173 patients as the control group undergoing electronic bronchoscopy alveolar lavage fluid detection, with detection results statistically evaluated. The positive rate in the research group was 96.51%, i.e. significantly higher than that in the control group (66.47%), yielding a statistically significant difference (χ2=109.68, p=0.00). The true positive rate was 97.7% in the research group and 67.92% in the control group; the true positive rate was significantly higher in the research group patients as compared with the control group, yielding a statistically significant difference (χ2=112.04, p=0.00). The sensitivity and specificity, as well as Youden index were significantly higher in the research group as compared with the control group. In conclusion, TB DNA detection by RT-PCR combined with TB-IGRA is a very good method of diagnosing tuberculosis, and it can be implemented in clinical diagnosis of pulmonary tuberculosis.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Ensayos de Liberación de Interferón gamma/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esputo , Tuberculosis/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Sensibilidad y Especificidad , ADN
14.
Gastroenterology ; 158(6): 1713-1727, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31972238

RESUMEN

BACKGROUND AND AIMS: The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver tumors in mice. METHODS: We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr-/-mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE-/- mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured. RESULTS: C57BL/6J mice on HCD and ApoE-/- mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE-/- mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell-activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr-/- mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr-/- mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs. CONCLUSIONS: Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular/inmunología , Colesterol/sangre , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Pulmonares/inmunología , Animales , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/secundario , Línea Celular Tumoral/trasplante , Colesterol/metabolismo , Dieta Aterogénica , Dietilnitrosamina/toxicidad , Modelos Animales de Enfermedad , Femenino , Humanos , Células Asesinas Naturales/metabolismo , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Noqueados para ApoE , Receptores de LDL/genética
15.
Anal Chem ; 92(5): 3852-3859, 2020 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-32045225

RESUMEN

Quantitative information about protein-ligand interactions is central to drug discovery. To obtain the quintessential reaction dissociation constant, ideally measurements of reactions should be performed without perturbations by molecular labeling or immobilization. The technique of transient induced molecular electrical signal (TIMES) has provided a promising technique to meet such requirements, and its performance in a microfluidic environment further offers the potential for high throughput and reduced consumption of reagents. In this work, we further the development by using integrated TIMES signal (i-TIMES) to greatly enhance the accuracy and reproducibility of the measurement. While the transient response may be of interest, the integrated signal directly measures the total amount of surface charge density resulted from molecules near the surface of electrode. The signals enable quantitative characterization of protein-ligand interactions. We have demonstrated the feasibility of i-TIMES technique using different biomolecules including lysozyme, N,N',N″-triacetylchitotriose (TriNAG), aptamer, p-aminobenzamidine (pABA), bovine pancreatic ribonuclease A (RNaseA), and uridine-3'-phosphate (3'UMP). The results show i-TIMES is a simple and accurate technique that can bring tremendous value to drug discovery and research of intermolecular interactions.


Asunto(s)
Ligandos , Microfluídica , Muramidasa/metabolismo , Ribonucleasa Pancreática/metabolismo , Animales , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Benzamidinas/química , Benzamidinas/metabolismo , Bovinos , Concentración de Iones de Hidrógeno , Muramidasa/química , Ribonucleasa Pancreática/química , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/química , Uridina Monofosfato/metabolismo
16.
BMC Musculoskelet Disord ; 21(1): 603, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32912188

RESUMEN

BACKGROUND: Bone turnover and metabolic indicators are related to age and gender. Age and gender should be matched in subjects in disease control research of bone turnover and metabolism, but strict matching of gender and age increases the difficulty and cost of the research. Therefore, the aim of this study was to solve it is necessary to strictly match age and gender in clinical research in bone metabolism. METHODS: A cross-sectional study was conducted from the data were extracted from the HIS of ZhuJiang Hospital. Data relating to seven bone turnover and metabolic indicators from 1036 patients between January 2018 and October 2019 were analyzed. RESULTS: P1NP, ß-CTx and 25(OH)D were significant different in individuals younger than 20 years of age. ALP was significantly higher in those under 20 years of age and lower at age 20-39 compared with other age groups. The concentrations of Ca and P were different among the groups aged 0-19, 20-39, and 40-59 years of age groups but exhibited no difference above 60 years of age. PTH expression was not dependent on age. P1NP, ß-CTx and PTH concentrations were not significantly different between the genders within the same age group. ALP was significantly different between genders within the age range 20-59 years. Ca and 25(OH)D were significantly different between the genders for those older than 60. Serum P was significantly different in the two genders for those aged 40-79. Patients received both alfacalcidol and calcium treatment differently from the others in P1NP, ß-CTx, Serum Ca, P and ALP. CONCLUSION: P1NP and ß-CTx were highly correlated with age. If these two indictors require analysis in a case control study, the patients and controls should be strictly matched by age under 20 years. The demarcation point for ALP was 40 years of age. Ca and P were strongly recommended strict matching according to age in disease research. The difference in P1NP, ß-CTx, 25(OH)D and ALP between genders depends on age differences. Medication history should be considered in bone turnover and metabolic clinical research.


Asunto(s)
Sistemas de Información en Hospital , Procolágeno , Adolescente , Adulto , Anciano , Biomarcadores , Densidad Ósea , Remodelación Ósea , Estudios de Casos y Controles , Niño , Preescolar , Colágeno Tipo I , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Theor Appl Genet ; 132(5): 1351-1361, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30652203

RESUMEN

KEY MESSAGE: A candidate nicosulfuron sensitivity gene Nss was identified by combining bulked segregant analysis and RNA-seq. Multiple mutations of this gene were discovered in nicosulfuron-sensitive maize compared with the tolerant. It has been demonstrated that variabilities exist in maize response to nicosulfuron. Two nicosulfuron-sensitive inbred lines (HB39, HB41) and two tolerant inbred lines (HB05, HB09) were identified via greenhouse and field trials. Genetic analysis indicated that the sensitivity to nicosulfuron in maize was controlled by a single, recessive gene. To precisely and rapidly map the nicosulfuron sensitivity gene (Nss), two independent F2 segregating populations, Population A (HB41 × HB09) and Population B (HB39 × HB05), were constructed. By applying bulked segregant RNA-Seq (BSR-Seq), the Nss gene was, respectively, mapped on the short arm of chromosome 5 (chr5: 1.1-15.3 Mb) and (chr5: 0.5-18.2 Mb) using two populations, with 14.2 Mb region in common. Further analysis revealed that there were 43 and 119 differentially expressed genes in the mapping intervals, with 18 genes in common. Gene annotation results showed that a cytochrome P450 gene (CYP81A9) appeared to be the candidate gene of Nss associated with nicosulfuron sensitivity in maize. Sequence analysis demonstrated that two common deletion mutations existed in the sensitive maize, which might lead to the nicosulfuron sensitivity in maize. The results will make valuable contributions to the understanding of molecular mechanism of herbicide sensitivity in maize.


Asunto(s)
Herbicidas/toxicidad , Piridinas/toxicidad , Compuestos de Sulfonilurea/toxicidad , Zea mays/genética , Mapeo Cromosómico , Cromosomas de las Plantas , Genes de Plantas , Mutación , Zea mays/efectos de los fármacos
18.
Support Care Cancer ; 27(1): 257-263, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29943153

RESUMEN

BACKGROUND: It is common for central nervous system (CNS) tumor patients to suffer from depressive symptoms. If unrecognized or untreated, CNS tumors may lead to many serious problems in these patients. This study examines the association of social support with depressive symptoms in CNS tumor patients and explores the extent to which hope mediates this relationship. METHODS: A total of 269 CNS tumor patients in China were included in this study. We assessed depressive symptoms using the Epidemiologic Studies Depression Scale (CES-D), social support using the Perceived Social Support Scale (PSSS), and hope using the Herth Hope Index (HHI). Questionnaires were distributed to collect these data. Hierarchical linear regression analyses explored the interrelationship between social support, hope, and depressive symptoms. RESULTS: After adjustment for demographic characteristics, patients with less social support exhibited more depressive symptoms (ß = - 0.452, P < 0.01). Social support explained 19.1% of the variance in depressive symptoms. After adding hope to the regression model, the effect size for social support was reduced by over half but remained significant (from ß = - 0.452 to ß = - 0.218, P < 0.01). In addition, a lower level of hope (ß = - 0.386, P < 0.01) was associated with more depressive symptoms, and this measure explained an additional 9.3% of the variance in depressive symptoms. CONCLUSIONS: Much of the relationship between social support and depressive symptoms is explained by hope. Thus, interventions boosting both social support and hope help to reduce depressive symptoms in patients with CNS tumors.


Asunto(s)
Neoplasias del Sistema Nervioso Central/terapia , Depresión/psicología , Esperanza , Pueblo Asiatico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoyo Social , Encuestas y Cuestionarios
19.
Med Sci Monit ; 25: 8422-8429, 2019 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-31703057

RESUMEN

BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.


Asunto(s)
Proteínas Portadoras/genética , Glioblastoma/genética , Sistema de Señalización de MAP Quinasas/genética , Proteínas Portadoras/metabolismo , Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Flavonoides/farmacología , Glioblastoma/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(2): 157-160, 2019 Feb 10.
Artículo en Zh | MEDLINE | ID: mdl-30703237

RESUMEN

OBJECTIVE: To carry out genome-wide copy number variations (CNVs) analysis for a boy with autism by using single nucleotide polymorphism array (SNP array). METHODS: SNP array analysis was conducted for the boy and his parents, and the data was validated by real-time PCR. Correlation between the deleted genes and the phenotype was analyzed by reviewing the literature. RESULTS: The patient was found to carry a terminal deletion of 18q22.3q23 (7.1 Mb), which involved FBXO15, ZNF407, ZADH2, TSHZ1, MBP and ADNP2 genes. No pathogenic CNVs were found in the parents. Comparison of the patient with cases reported in the literature suggested that the ZNF407 gene probably accounts for the autistic phenotype in these patients. CONCLUSION: The autistic phenotype of the patient may be attributed to the 18q deletion, for which ZNF407 may be a critical candidate. SNP array has provided an useful tool for the study of molecular mechanism underlying autism.


Asunto(s)
Trastorno Autístico , Variaciones en el Número de Copia de ADN , Trastorno Autístico/genética , Humanos , Masculino , Análisis por Micromatrices , Polimorfismo de Nucleótido Simple
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