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1.
Cell ; 186(13): 2748-2764.e22, 2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37267948

RESUMEN

Ferroptosis, a cell death process driven by iron-dependent phospholipid peroxidation, has been implicated in various diseases. There are two major surveillance mechanisms to suppress ferroptosis: one mediated by glutathione peroxidase 4 (GPX4) that catalyzes the reduction of phospholipid peroxides and the other mediated by enzymes, such as FSP1, that produce metabolites with free radical-trapping antioxidant activity. In this study, through a whole-genome CRISPR activation screen, followed by mechanistic investigation, we identified phospholipid-modifying enzymes MBOAT1 and MBOAT2 as ferroptosis suppressors. MBOAT1/2 inhibit ferroptosis by remodeling the cellular phospholipid profile, and strikingly, their ferroptosis surveillance function is independent of GPX4 or FSP1. MBOAT1 and MBOAT2 are transcriptionally upregulated by sex hormone receptors, i.e., estrogen receptor (ER) and androgen receptor (AR), respectively. A combination of ER or AR antagonist with ferroptosis induction significantly inhibited the growth of ER+ breast cancer and AR+ prostate cancer, even when tumors were resistant to single-agent hormonal therapies.


Asunto(s)
Ferroptosis , Masculino , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Peroxidación de Lípido , Peróxidos , Fosfolípidos
2.
Nature ; 616(7955): 56-60, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36949191

RESUMEN

Quantum error correction (QEC) aims to protect logical qubits from noises by using the redundancy of a large Hilbert space, which allows errors to be detected and corrected in real time1. In most QEC codes2-8, a logical qubit is encoded in some discrete variables, for example photon numbers, so that the encoded quantum information can be unambiguously extracted after processing. Over the past decade, repetitive QEC has been demonstrated with various discrete-variable-encoded scenarios9-17. However, extending the lifetimes of thus-encoded logical qubits beyond the best available physical qubit still remains elusive, which represents a break-even point for judging the practical usefulness of QEC. Here we demonstrate a QEC procedure in a circuit quantum electrodynamics architecture18, where the logical qubit is binomially encoded in photon-number states of a microwave cavity8, dispersively coupled to an auxiliary superconducting qubit. By applying a pulse featuring a tailored frequency comb to the auxiliary qubit, we can repetitively extract the error syndrome with high fidelity and perform error correction with feedback control accordingly, thereby exceeding the break-even point by about 16% lifetime enhancement. Our work illustrates the potential of hardware-efficient discrete-variable encodings for fault-tolerant quantum computation19.

3.
Nature ; 582(7810): 100-103, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32461694

RESUMEN

Cancers develop as a result of driver mutations1,2 that lead to clonal outgrowth and the evolution of disease3,4. The discovery and functional characterization of individual driver mutations are central aims of cancer research, and have elucidated myriad phenotypes5 and therapeutic vulnerabilities6. However, the serial genetic evolution of mutant cancer genes7,8 and the allelic context in which they arise is poorly understood in both common and rare cancer genes and tumour types. Here we find that nearly one in four human tumours contains a composite mutation of a cancer-associated gene, defined as two or more nonsynonymous somatic mutations in the same gene and tumour. Composite mutations are enriched in specific genes, have an elevated rate of use of less-common hotspot mutations acquired in a chronology driven in part by oncogenic fitness, and arise in an allelic configuration that reflects context-specific selective pressures. cis-acting composite mutations are hypermorphic in some genes in which dosage effects predominate (such as TERT), whereas they lead to selection of function in other genes (such as TP53). Collectively, composite mutations are driver alterations that arise from context- and allele-specific selective pressures that are dependent in part on gene and mutation function, and which lead to complex-often neomorphic-functions of biological and therapeutic importance.


Asunto(s)
Carcinogénesis/genética , Modelos Genéticos , Mutación , Neoplasias/genética , Oncogenes/genética , Alelos , Animales , Femenino , Genes p53/genética , Humanos , Ratones , Selección Genética , Telomerasa/genética
4.
Phys Rev Lett ; 132(20): 203602, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38829095

RESUMEN

Fock states with a well-defined number of photons in an oscillator have shown a wide range of applications in quantum information science. Nonetheless, their usefulness has been marred by single and multiphoton losses due to unavoidable environment-induced dissipation. Though several dissipation engineering methods have been developed to counteract the leading single-photon-loss error, averting multiple-photon losses remains elusive. Here, we experimentally demonstrate a dissipation engineering method that autonomously stabilizes multiphoton Fock states against losses of multiple photons using a cascaded selective photon-addition operation in a superconducting quantum circuit. Through measuring the photon-number populations and Wigner tomography of the oscillator states, we observe a prolonged preservation of nonclassical Wigner negativities for the stabilized Fock states |N⟩ with N=1, 2, 3 for a duration of about 10 ms. Furthermore, the dissipation engineering method demonstrated here also facilitates the implementation of a nonunitary operation for resetting a binomially encoded logical qubit. These results highlight potential applications in error-correctable quantum information processing against multiple-photon-loss errors.

5.
J Hepatol ; 75(3): 547-556, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33961940

RESUMEN

BACKGROUND & AIMS: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention. METHODS: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described. RESULTS: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH. CONCLUSIONS: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH. LAY SUMMARY: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.


Asunto(s)
Carga Global de Enfermedades/tendencias , Hepatitis Viral Humana/diagnóstico , Clase Social , Países en Desarrollo/estadística & datos numéricos , Años de Vida Ajustados por Discapacidad/tendencias , Hepatitis Viral Humana/epidemiología , Humanos , Incidencia , Años de Vida Ajustados por Calidad de Vida
6.
J Immunol ; 199(9): 3280-3292, 2017 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-28954889

RESUMEN

Host innate immunity is crucial for cellular responses against viral infection sensed by distinct pattern recognition receptors and endoplasmic reticulum (ER) stress. Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and neurological diseases. However, the exact mechanism underlying the link between ER stress induced by EV71 infection and host innate immunity is largely unknown. In this study, we demonstrated that EV71 infection induces the homocysteine-induced ER protein (HERP), a modulator of the ER stress response which is dependent on the participation of MAVS. Virus-induced HERP subsequently stimulates host innate immunity to repress viral replication by promoting type-I IFNs (IFN-α and IFN-ß) and type-III IFN (IFN-λ1) expression. Through interacting with TANK-binding kinase 1, HERP amplifies the MAVS signaling and facilitates the phosphorylation and nuclear translocation of IFN regulatory factor 3 and NF-κB to enhance the expression of IFNs, which leads to a broad inhibition of the replication of RNA viruses, including EV71, Sendai virus, influenza A virus, and vesicular stomatitis virus. Therefore, we demonstrated that HERP plays an important role in the regulation of host innate immunity in response to ER stress during the infection of RNA viruses. These findings provide new insights into the mechanism underlying the replication of RNA viruses and the production of IFNs, and also demonstrate a new role of HERP in the regulation of host innate immunity in response to viral infection.


Asunto(s)
Estrés del Retículo Endoplásmico/inmunología , Inmunidad Innata , Proteínas de la Membrana/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Infecciones por Virus ARN/inmunología , Virus ARN/fisiología , Replicación Viral/inmunología , Animales , Estrés del Retículo Endoplásmico/genética , Femenino , Humanos , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/inmunología , Interferones/genética , Interferones/inmunología , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Proteínas Serina-Treonina Quinasas/genética , Infecciones por Virus ARN/genética , Infecciones por Virus ARN/patología
7.
Materials (Basel) ; 16(18)2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37763489

RESUMEN

Different sands have significant influences on MICP reinforcement effects. Using calcium carbonate production and bioflocculation lag period as evaluation criteria, this study investigates the optimal theoretical pH values of bacterial solutions with different concentrations. We reinforced four different sands using MICP at the optimal theoretical pH, and based on permeability, moisture retention, raindrop erosion, wind erosion, penetration, and SEM tests, the influence of sand properties on low-pH MICP reinforcement was analyzed and the low-pH MICP mechanism was revealed. The results indicate the following: (1) The optimal theoretical pH values for bacterial solutions with concentrations of 0.67 × 108 cells/mL, 3 × 108 cells/mL, and 10 × 108 cells/mL are 4.5, 3, and 4, respectively. (2) With 0.67 × 108, 3 × 108, and 10 × 108 cells/mL bacterial solutions, the strength of tailings sand containing calcium salt was 21.15%, 44.42%, and 13.61% higher than that of quartz sand, respectively. The effective reinforcement depth of alkaline reclaimed sand was 10, 8, and 6 mm lower than that of neutral calcareous sand, respectively. The strength of fine tailings sand was 70.41%, 58.04%, and 22.6% higher than that of coarse reclaimed sand. The effective reinforcement depth of fine quartz sand was 6, 4, and 4 mm lower than that of coarse calcareous sand. (3) Low pH temporarily suppresses urease activity, delaying calcium carbonate flocculation and enhancing reinforcement uniformity. To achieve optimal reinforcement effects, adjusting the actual optimal pH values of bacterial solution based on sand properties is essential in engineering applications.

8.
Front Bioeng Biotechnol ; 11: 1109265, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36741750

RESUMEN

With societal development, the growing scale of engineering construction, and the increase in environmental protection requirements, the necessity of engineering waste mud disposal is becoming increasingly prominent. In this study, microbially induced struvite precipitation (MISP) was introduced to treat engineering waste mud. The study mainly focused on: i) the optimal mineralization scheme for microbially induced struvite precipitation, ii) the feasibility of the process and the effect of reaction parameters on treating engineering waste mud with microbially induced struvite precipitation, and iii) the mechanism of microbially induced struvite precipitation in treating engineering waste mud. The results showed that the waste mud could be well treated with 8.36 × 10 6   c e l l ⋅ m L - 1 bacteria, 10 mM urea, 20 mM phosphate buffer, and 25 mM M g C l 2 at pH 7. The kaolin suspension could be effectively flocculated. The flocculation rate reached approximately 87.2% under the optimum mineralization conditions. The flocculation effect was mainly affected by the concentrations of reactants and heavy metals and the suspension pH. The X-ray diffraction (XRD) patterns showed a strong struvite (MAP) diffraction peak. Scanning electron microscopy (SEM) images indicated that under the optimal mineralization conditions, the crystals were large and showed prismatic shapes tilted at both ends with adhered kaolin particles. In summary, this manuscript provides an effective way to treat engineering waste mud, and the findings should have a positive effect on enhancing soil fertility and preventing secondary pollution.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(4): 427-430, 2023 Apr.
Artículo en Zh | MEDLINE | ID: mdl-37308201

RESUMEN

OBJECTIVE: To track analysis of viral nucleic acid test results in patients with re-positive SARS-CoV-2 infection, and provide clinical reference for nucleic acid test of re-positive cases. METHODS: A retrospective study was conducted. The multiple nucleic acid results of 96 cases with SARS-CoV-2 infection tested by medical laboratory of Shenzhen Luohu Hospital Group from January to September in 2022 were analyzed. The test dates and cycle threshold (Ct) values of detectable positive virus nucleic acid in the 96 cases were summarized and analyzed. RESULTS: A total of 96 patients with SARS-CoV-2 infection were retested re-sampled for nucleic acid testing at least 12 days after the initial positive screening. Among them, 54 cases (56.25%) had Ct value of < 35 for nucleocapsid protein gene (N) and/or open reading frame 1ab gene (ORF 1ab), 42 cases (43.75%) had Ct value ≥ 35. In the re-sampling of infected patients, N gene titers were 25.08 to 39.98 Ct cycles, and ORF 1ab gene titers were 23.16 to 39.56 Ct cycles. Compared with the positive results of the initial screening, the Ct values of N gene and/or ORF 1ab gene positive were increased in 90 cases (93.75%). Among them, the patients with the longest duration of nucleic acid positive could still be positive for double targets (the Ct value of N gene was 38.60, and the Ct value of ORF 1ab gene was 38.11) at an interval of 178 days after the initial positive screening. CONCLUSIONS: Patients infected with SARS-CoV-2 can be sustained or repeatedly tested positive for nucleic acid for a long period of time, and most of them had Ct values < 35. But whether it is infectious needs to be comprehensively evaluated by combining epidemiology, variant type, samples with the alive virus, and clinical symptoms and signs.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Unidades Hospitalarias
10.
Medicine (Baltimore) ; 101(50): e32271, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36550916

RESUMEN

RATIONALE: Diabetic foot ulcers (DFUs) present with different grades of ischemia and infection and are associated with high mortality and disability rates with little effective treatment. We used Fu Subcutaneous Needling (FSN) to treat 2 cases with DFUs and achieved satisfactory results. PATIENT CONCERNS: Two cases of DFUs showed poor recovery after conventional wound care treatment, and case 2 was confronted with the risk of amputation. DIAGNOSIS: Two patients with history of diabetes were diagnosed with DFUs, presenting with lower leg and foot ulcers. INTERVENTIONS: Case 1 received 6 sessions of FSN treatment in 8 days, and case 2 received 10 sessions of FSN treatment in 14 days. OUTCOMES: Case 1 completely healed from a 1 × 0.5-cm blister and a 0.5 × 0.5-cm ulcer of the right lower leg 14 days after the first FSN treatment. The ulcer area of the left foot in case 2 decreased from 6 × 7 cm to 4 × 3.5 × 0.2 cm. Three months of follow-up revealed full wound closure. LESSONS: FSN is effective for healing with DFUs, and it may be used as an adjunctive healing strategy for DFUs patients when conventional treatments such as infection, glycemic control, and local ulcer care are not available.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Humanos , Pie Diabético/terapia , Pie Diabético/diagnóstico , Cicatrización de Heridas , Pie , Tejido Subcutáneo , Resultado del Tratamiento
11.
Am J Transl Res ; 14(11): 7820-7830, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36505330

RESUMEN

OBJECTIVE: To identify the abnormal expression profile of miRNA in peripheral blood of children with Kawasaki disease (KD) and explore its diagnostic value for Kawasaki disease. METHODS: From January 2020 to June 2021, 62 children with KD (KD group) and 158 children with febrile disease (Con group) were selected as subjects. Peripheral blood was collected before treatment, and differentially expressed miRNAs in peripheral blood were identified by next generation sequencing, and the identified targets were verified by RT-PCR. The diagnostic value of miRNAs in KD was analyzed by ROC curves and linear SVM model. RESULTS: Compared to Con group, a total of 163 differentially expressed miRNAs were detected in peripheral blood of children in the KD group, including 126 up-regulated miRNAs and 37 down-regulated miRNAs. Hierarchical clustering showed that miRNA profiles of children in the KD group and Con group were significantly different, among which 3 miRNAs wereup-regulated and 3 miRNAs were down-regulated (P<0.05). The results of miRanda and TargetScanS software showed that a total of 17159 target genes were predicted. GO function and KEGG signal pathway enrichment analysis showed that target genes were involved in a wide range of biological functions; ROC curve results showed that the sensitivity of miR-355 and miR-2911 in diagnosing KD were 73.8% and 71.2%, the specificity was 72.4% and 73.9%, and the AUC was 0.793 and 0.757, respectively. The AUC for combined detection of miR-355 and miR-2911 was increased to 0.806. A linear SVM model further verified the diagnostic value of joint detection of miR-355 and miR-2911. CONCLUSION: Expression levels of miR-355 and miR-2911 were significantly up-regulated in peripheral blood of children with Kawasaki disease. miR-355 and miR-2911 could serve as biomarkers for diagnosis of Kawasaki disease.

12.
Geospat Health ; 17(s1)2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-35735947

RESUMEN

Coronavirus disease 2019 (COVID-19) has strongly impacted society since it was first reported in mainland China in December 2020. Understanding its spread and consequence is crucial to pandemic control, yet difficult to achieve because we deal with a complex context of social environment and variable human behaviour. However, few efforts have been made to comprehensively analyse the socio-economic influences on viral spread and how it promotes the infection numbers in a region. Here we investigated the effect of socio-economic factors and found a strong linear relationship between the gross domestic product (GDP) and the cumulative number of confirmed COVID-19 cases with a high value of R2 (between 0.57 and 0.88). Structural equation models were constructed to further analyse the social-economic interaction mechanism of the spread of COVID-19. The results show that the total effect of GDP (0.87) on viral spread exceeds that of population influx (0.58) in the central cities of mainland China and that the spread mainly occurred through its interplay with other factors, such as socio-economic development. This evidence can be generalized as socio-economic factors can accelerate the spread of any infectious disease in a megacity environment. Thus, the world is in urgent need of a new plan to prepare for current and future pandemics.


Asunto(s)
COVID-19 , COVID-19/epidemiología , China/epidemiología , Producto Interno Bruto , Humanos , Pandemias , Factores Socioeconómicos
13.
Materials (Basel) ; 16(1)2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36614589

RESUMEN

Calcareous sand is a special soil formed by the accumulation of carbonate fragments. Its compressibility is caused by a high void ratio and breakable particles. Because of its high carbonate content and weak cementation, its load-bearing capacity is limited. In this study, the optimal stimulation solution was obtained with response surface methodology. Then, the effect of reinforcing calcareous sand was analysed with unconfined compressive strength (UCS) tests, calcium carbonate content tests, microscopy and microbial community analyses. The components and concentrations of the optimal stimulation solution were as follows: sodium acetate (38.00 mM), ammonium chloride (124.24 mM), yeast extract (0.46 g/L), urea (333 mM), and nickel chloride (0.01 mM), and the pH was 8.75. After the calcareous sand was treated with the optimal stimulation scheme, the urease activity was 6.1891 mM urea/min, the calcium carbonate production was 8.40%, and the UCS was 770 kPa, which constituted increases of 71.41%, 35.40%, and 83.33%, respectively, compared with the initial scheme. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses showed that calcium carbonate crystals were formed between the particles of the calcareous sand after the reaction, and the calcium carbonate crystals were mainly calcite. Urease-producing microorganisms became the dominant species in calcareous sand after treatment. This study showed that biostimulation-induced mineralization is feasible for reinforcing calcareous sand.

14.
Environ Pollut ; 303: 119057, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35231542

RESUMEN

Reliable attribution is crucial for understanding various climate change issues. However, complicated inner-interactions between various factors make causation inference in atmospheric environment highly challenging. Taking PM2.5-Meteorology causation, which involves a large number of non-Linear and uncertain interactions between many meteorological factors and PM2.5, as a case, we examined the performance of a series of mainstream statistical models, including Correlation Analysis (CA), Partial Correlation Analysis (PCA), Structural Equation Model (SEM), Convergent Cross Mapping (CCM), Partial Cross Mapping (PCM) and Geographical Detector (GD). From a coarse perspective, the Top 3 major meteorological factors for PM2.5 in 190 cities across China extracted using different models were generally consistent. From a strict perspective, the extracted dominant meteorological factor for PM2.5 demonstrated large model variations and shared a limited consistence. Such models as SEM and PCM, which are capable of further separating direct and indirect causation in simple systems, performed poorly to identify the direct and indirect PM2.5-Meteorology causation. The notable inconsistence denied the feasibility of employing multiple models for better causation inference in atmospheric environment. Instead, the sole use of CCM, which is advantageous in dealing with non-linear causation and removing disturbing factors, is a preferable strategy for causation inference in complicated ecosystems. Meanwhile, given the multi-direction, uncertain interactions between many variables, we should be more cautious and less ambitious on the separation of direct and indirect causation. For better causation inference in the complicated atmospheric environment, the combination of statistical models and atmospheric models, and the further exploration of Deep Neural Network can be promising strategies.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Ecosistema , Monitoreo del Ambiente , Material Particulado/análisis
15.
NPJ Breast Cancer ; 8(1): 96, 2022 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35999225

RESUMEN

Estrogen receptor alpha (ERα) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs. We now identify the induction of an ERα isoform, ERα-LBD, that is encoded by an alternative ESR1 transcript and lacks the activation function and DNA binding domains. Despite lacking the transcriptional activity, ERα-LBD is found to promote breast cancer growth and resistance to the ERα antagonist fulvestrant. ERα-LBD is predominantly localized to the cytoplasm and mitochondria of BC cells and leads to enhanced glycolysis, respiration and stem-like features. Intriguingly, ERα-LBD expression and function does not appear to be restricted to cancers that express full length ERα but also promotes growth of triple-negative breast cancers and ERα-LBD transcript (ESR1-LBD) is also present in BC samples from both ERα(+) and ERα(-) human tumors. These findings point to ERα-LBD as a potential mediator of breast cancer progression and therapy resistance.

16.
Biochem Biophys Res Commun ; 416(3-4): 379-84, 2011 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-22120627

RESUMEN

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths globally. Chronic hepatitis B virus (HBV) infection accounts for over 75% of all HCC cases; however, the molecular pathogenesis of HCC is not well understood. In this study, we found that the expression of the newly identified gene melanoma inhibitory activity 2 (MIA2) was reduced by HBV infection in vitro and in vivo, and that HBV X protein (HBx) plays a major role in this regulation. Recent studies have revealed that MIA2 is a potential tumor suppressor, and that, in most HCCs, MIA2 expression is down-regulated or lost. We found that the knock-down of MIA2 in HepG2 cells activated cell growth and proliferation, suggesting that MIA2 inhibits HCC cell growth and proliferation. In addition, the over-expression of HBx alone induced cell proliferation, whereas MIA2 over-expression impaired the HBx-mediated induction of proliferation. Taken together, our results suggest that HBx activates hepatoma cell growth and proliferation through repression of the potential tumor suppressor MIA2.


Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Virus de la Hepatitis B/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Transactivadores/metabolismo , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Antígenos de Neoplasias , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Proteínas de Neoplasias , Proteínas Supresoras de Tumor/genética , Proteínas Reguladoras y Accesorias Virales
17.
Anal Biochem ; 414(2): 196-201, 2011 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-21435334

RESUMEN

A label-free amperometric immunosensor for fast and sensitive assay of human serum chorionic gonadotropin (hCG) is presented. hCG was immobilized on nanoporous gold (NPG) foils and using hydroquinone (HQ) redox species as indicator. The variation of amperometric response to the concentration of hCG, the target antigen, was evaluated by cyclic voltammetry in phosphate-buffered solution. Taking advantage of dual-amplification effects of the NPG foils and graphene sheets (GSs), the immunosensor exhibited a specific response to hCG in the range of 0.5-40.00 ng ml(-1) with a detection limit of 0.034 ng ml(-1) under optimal conditions. It was demonstrated that our proposed method possesses good accuracy, acceptable precision, and reproducibility. The NPG showed a better sensitizing effect and stability as immobilization matrices.


Asunto(s)
Gonadotropina Coriónica/sangre , Técnicas Electroquímicas/métodos , Oro/química , Grafito/química , Inmunoensayo/métodos , Nanoporos/ultraestructura , Técnicas Biosensibles/métodos , Humanos , Hidroquinonas/química , Oxidación-Reducción , Porosidad
18.
Biochem Genet ; 49(3-4): 190-201, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21165767

RESUMEN

Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) A49G is a polymorphism that is extensively studied in various cancers. To investigate whether it is associated with the occurrence of glioma in Chinese patients, we performed a case-control research study with 670 patients and 680 controls. In this group, we found that the genotype at this locus is significantly associated with glioma risk (GG vs. AA: P = 0.045; GG + AG vs. AA: P = 0.013). In some subgroups, G allele carriers are significantly less represented. We also observed significant correlations between the polymorphism genotype and glioma risk in patients with WHO histologic stages. We conclude that CTLA4 A49G might be a potential clinical biomarker for distinguishing persons with a high risk for developing gliomas.


Asunto(s)
Antígenos CD/genética , Neoplasias del Sistema Nervioso Central/genética , Glioma/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Pueblo Asiatico , Antígeno CTLA-4 , Estudios de Casos y Controles , Neoplasias del Sistema Nervioso Central/etnología , Niño , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Glioma/etnología , Humanos , Modelos Logísticos , Masculino , Riesgo , Factores de Riesgo , Adulto Joven
19.
Luminescence ; 26(6): 629-33, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21465633

RESUMEN

Based on the inhibition effect of transferrin (Tf) on the reaction of the luminol-hydrogen peroxide (H(2)O(2)) chemiluminescence (CL) system, catalysed by meso-tetra-(3-methoxyl-4-hydroxyl) phenyl manganese porphyrin (MnP) as a mimetic enzyme of peroxides, a sensitive flow-injection CL method has been developed for the determination of Tf in an alkaline medium. The CL reaction was carefully investigated by examining the variations of reaction conditions. Under optimum conditions, the linear range for the determination of transferrin was 0.04-20.0 µg/mL and the detection limit was 1.62 ng/mL. This proposed method was sensitive, convenient and simple, and has been successfully applied to the determination of transferrin in a serum sample.


Asunto(s)
Análisis de Inyección de Flujo/métodos , Peróxido de Hidrógeno/química , Luminol/química , Metaloporfirinas/química , Transferrina/análisis , Concentración de Iones de Hidrógeno , Luminiscencia
20.
Hepatol Commun ; 5(1): 12-23, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32838104

RESUMEN

Although abnormal liver chemistries are linked to a higher risk of coronavirus disease 2019 (COVID-19)-related death, liver manifestations may be diverse and even confusing. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in patients with COVID-19 who died or discharged alive. We searched PubMed, Google Scholar, medRxiv, bioRxiv, the Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19, using a fixed or random-effects model. In our meta-analysis of 19 studies, which included a total of 4,103 patients, the pooled mean alanine aminotransferase and aspartate aminotransferase levels were, respectively, 31.7 IU/L and 51.0 IU/L in the patients with COVID-19 who died and 27.7 IU/L and 32.9 IU/L in those discharged alive (both P < 0.0001). Compared with the patients discharged alive, those who died tended to have lower albumin levels but longer prothrombin time and higher international normalized ratio. Conclusion: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively describe three patterns of liver impairment related to COVID-19: hepatocellular injury, cholestasis, and hepatocellular disfunction. The patients who died from COVID-19 tended to have different liver chemistries from those discharged alive. Special caution should be given to the patients with a relatively higher index of liver chemistries.

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