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1.
Front Immunol ; 15: 1391524, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38835778

RESUMEN

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.


Asunto(s)
Biomarcadores de Tumor , Inmunoterapia , Proteómica , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/diagnóstico , Biomarcadores de Tumor/sangre , Proteómica/métodos , Pronóstico , Inmunoterapia/métodos , Persona de Mediana Edad , Adulto
2.
J Hazard Mater ; 470: 134122, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38552397

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are a class of toxic organic pollutants commonly detected in the aqueous phase. Traditional biodegradation is inefficient and advanced oxidation technologies are expensive. In the current study, a novel strategy was developed using calcium peroxide (CP) and PAH-degrading bacteria (PDB) to effectively augment PAH degradation by 28.62-59.22%. The PDB consisted of the genera Acinetobacter, Stenotrophomonas, and Comamonas. Applying the response surface model (RSM), the most appropriate parameters were identified, and the predictive degradation rates of phenanthrene (Phe), pyrene (Pyr), and ΣPAHs were 98%, 76%, and 84%, respectively. The constructed mixed system could reduce 90% of Phe and more than 60% of ΣPAHs and will perform better at pH 5-7 and lower salinity. Because PAHs tend to bind to dissolved organic matter (DOM) with larger molecular weights, humic acid (HA) had a larger negative effect on the PAH-degradation efficiency of the CP-PDB mixed system than fulvic acid (FA). The proposed PAH-degradation pathways in the mixed system were based on the detection of intermediates at different times. The investigation constructed and optimized a novel environmental PAH-degradation strategy. The synergistic application of PDB and oxidation was extended for organic contaminant degradation in aqueous environments.


Asunto(s)
Biodegradación Ambiental , Peróxidos , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Peróxidos/química , Peróxidos/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/química , Hidrocarburos Policíclicos Aromáticos/metabolismo , Hidrocarburos Policíclicos Aromáticos/química , Bacterias/metabolismo , Concentración de Iones de Hidrógeno
3.
BMJ Open ; 14(1): e080721, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38199633

RESUMEN

INTRODUCTION: Wearing masks has proven beneficial in preventing respiratory pathogen infections in individuals with chronic obstructive pulmonary disease (COPD). However, the impact of different mask types on physiological indicators and daily physical activity in COPD patients remains uncertain. This study aims to assess the immediate effects of various mask types on cardiopulmonary function indicators, subjective perceptions and the 6-minute walking distance (6MWD) in individuals with COPD. METHODS AND ANALYSIS: This randomised controlled trial will enrol 129 stable COPD patients. Participants will be randomly divided into three groups: control, N95 mask and surgical mask groups. Each group will undergo both a 6-minute seated test and a 6-minute walk test (6MWT), without or with their respective masks. A 10-minute interval will be provided between the two phases. The primary indicators of the study include the 6MWD and blood oxygen saturation. Secondary outcomes encompass blood pressure, pulse rate, Borg score, Rate of Perceived Exertion (RPE) score and subjective perception score. Oxygen saturation, pulse rate and blood pressure will be recorded four times during the trial, while Borg and RPE scores will be compared before and after the 6MWT. Additionally, subjective perception scores will be collected after each mask-wearing stage. ETHICS AND DISSEMINATION: This study has received approval from the Ethics Committee of the Affiliated Hospital of Gansu University of Chinese Medicine (approval number: 202335). We plan to disseminate research results through publication in a peer-reviewed journal or presentation at a conference. TRIAL REGISTRATION NUMBER: ChiCTR2300074554.


Asunto(s)
Comités de Ética , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Presión Sanguínea , Ejercicio Físico , Frecuencia Cardíaca , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Eur J Med Chem ; 266: 116082, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38232462

RESUMEN

Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R-8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R-8i are poor (T1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure-activity relationship study of thiazolidine-4-one sulfone inhibitors from R-8i, which led to the discovery of compound 68. Compound 68 had a potent cellular activity with an IC50 value of 0.217 µM, much higher half-life (T1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile (in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma.


Asunto(s)
Antineoplásicos , Neoplasias Óseas , Osteosarcoma , Humanos , Ratones , Animales , Preparaciones Farmacéuticas , Relación Estructura-Actividad , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Neoplasias Óseas/tratamiento farmacológico , Proliferación Celular , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral
5.
Int J Biol Macromol ; 257(Pt 2): 128623, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070810

RESUMEN

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to human. Since there are still no effective treatment options against the new emerging variants of SARS-CoV-2, it is necessary to devote a continuous endeavor for more targeted drugs and the preparation for the next pandemic. Salvia miltiorrhiza and its active ingredients possess wide antiviral activities, including against SARS-CoV-2. Danshensu, as one of the most important active ingredients in Salvia miltiorrhiza, has been reported to inhibit the entry of SARS-CoV-2 into ACE2 (angiotensin-converting enzyme 2)-overexpressed HEK-293T cells and Vero-E6 cells. However, there is a paucity of information regarding its detailed target and mechanism against SARS-CoV-2. Here, we present Danshensu as a covalent inhibitor of 3-chymotrypsin-like protease (3CLpro) against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. Further molecular docking, site-directed mutagenesis, circular dichroism (CD) and fluorescence spectra revealed that Danshensu covalently binds to C145 of SARS-CoV-2 3CLpro, meanwhile forming the hydrogen bonds with S144, H163 and E166 in the S1 site. Structure-based optimization of Danshensu led to the discovery of the promising compounds with good inhibitory activity and microsomal stability in vitro. Due to Danshensu inhibiting lung inflammation in the mouse model, we found that Danshensu derivatives also showed better anti-inflammatory activity than Danshensu in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Thus, our study provides not only the clue of the efficacy of Salvia miltiorrhiza against SARS-CoV-2, but also a detailed mechanistic insight into the covalent mode of action of Danshensu for design of covalent inhibitors against SARS-CoV-2 3CLpro, highlighting its potential as a bifunctional molecule with antivirus and anti-inflammation.


Asunto(s)
COVID-19 , Lactatos , SARS-CoV-2 , Animales , Ratones , Humanos , Simulación del Acoplamiento Molecular , Proteínas no Estructurales Virales/química , Antivirales/química , Péptido Hidrolasas/farmacología , Inhibidores de Proteasas/farmacología
6.
PLoS One ; 18(9): e0292388, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37768979

RESUMEN

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common, irreversible but preventable disease characterized by persistent respiratory symptoms. The mortality rate of COPD is predicted to reach 5.4 million by the year 2060. Despite its heavy burden on healthcare expenditure worldwide, only 15% of cases are medically identified. The potential benefits of facemask-wearing for COPD patients remain a topic of debate. METHODS: We will conduct a systematic review of all randomized trials and non-randomized controlled trials to evaluate the impact of facemasks on COPD patients. Our review will be based on literature obtained through a comprehensive search strategy across multiple electronic databases, including the Cochrane Library, Embase, PubMed, Web of Science, the Chinese Biomedical Database (SinoMed), and China National Knowledge Infrastructure (CNKI), with no restrictions on language or date of publication. Two independent researchers will extract and assess all relevant data using pre-designed data extraction forms. The included studies will be assessed using the Cochrane RoB2 tool and the suggested risk of bias criteria proposed by the Effective Practice and Organization of Care reviews group of the Cochrane collaboration. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will use Review Manager 5.4 software for statistical analysis. DISCUSSION: In the context of COVID-19, it is important for COPD patients to wear facemasks. This study aims to conduct a comprehensive and systematic assessment of the impact of facemasks on the physiology and activity of COPD patients. TRIAL REGISTRATION: PROSPERO registration number CRD42022326265.


Asunto(s)
COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Máscaras , COVID-19/prevención & control , Revisiones Sistemáticas como Asunto , Equipo de Protección Personal , Enfermedad Pulmonar Obstructiva Crónica/terapia , Metaanálisis como Asunto , Literatura de Revisión como Asunto
7.
J Environ Manage ; 344: 118609, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37473553

RESUMEN

Optimal manure treatment aimed at usage as agricultural soil fertilizers is a prerequisite ecological pollution control strategy. In this work, livestock manure-based fertilizers were collected from 71 animal farms across 14 provinces in China. The contamination levels and potential ecotoxicological risks of residual steroid estrogens (SEs): estrone (E1), estriol (E3), 17α-estradiol (17α-E2), 17ß-estradiol (17ß-E2) and xenoestrogen (XE) bisphenol A (BPA), were investigated. The results showed that the occurrence frequencies for SEs and XE ranged from 66.67% to 100%, and the mean concentration varied considerably across the study locations. The total content of SEs and XE in Hebei province was the highest, and swine manure-based fertilizers concentrations were higher than the levels reported in other animal fertilizers. Compared with farm level manure, manure-based fertilizers are processed by composting, and the micropollutants quantities are significantly reduced (mean: 87.65 - 534.02 µg/kg). The total estradiol equivalent quantity (EEQ) that might migrate to the soil was estimated to be 1.23 µg/kg. Based on the estimated application rate of manure, 38% of the fertilizers risk quotients exceeded 0.1, indicating medium to high risks pressure on terrestrial organisms. Nonetheless, the estrogenic risk was lower in manure-based fertilizers than in manure. This study highlights the significance of proper treatment of livestock manure and designing an optimal manure fertilization strategy to mitigate the risks posed by SEs and XEs to the agroecosystems.


Asunto(s)
Estrógenos , Estiércol , Porcinos , Animales , Estrógenos/análisis , Estiércol/análisis , Fertilizantes/análisis , Estradiol/análisis , Suelo/química , Monitoreo del Ambiente/métodos
8.
J Hazard Mater ; 453: 131328, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37043862

RESUMEN

The situ pollutant residue and microbial characteristics in contaminated environments are crucial for ecological restoration and soil utilization. This work reported the variation of polycyclic aromatic hydrocarbon (PAH) residues and the bacterial community at different depths in an aged-abandoned site. These results unveiled that over 90% of low molecular weight (LMW) and medium molecular weight (MMW), 52.84-76.88% of high molecular weight (HMW) bound-PAH (BP) residues were sequestrated in humin (HM). The stresses of PAH and soil depth enhanced the frequency of bacteria associations, especially positive associations. We enriched and cultured PAH degradation bacteria (PDB) from the sampling site mainly consisting of Pseudomonas and Acinetobacter, which were originally 0.39-0.52% abundant in the sampling site. The abundances of PDB and PAH-degradation genes (PDGs) were higher at shallower depths and increased with high PAH concentration. Simultaneously, Pearson correlation analysis and experimental verification found that the process of PAH binding with SOM limited the further increase of PDB and PDGs in PAH-contaminated sites. These findings may illustrate possible ecological risks of contaminated soils and provide guidance for the isolation and application of PDB.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Suelo/química , Biodegradación Ambiental , Contaminantes del Suelo/metabolismo , Bacterias/metabolismo , Microbiología del Suelo
9.
Front Public Health ; 10: 1027521, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36466486

RESUMEN

Background: Since the emergence of COVID-19, mandatory facemask wearing has been implemented around the world to prevent viral transmission, however, the impact of wearing facemasks on patients with COPD was unclear. Methods: The current study undertakes a systematic review and meta-analysis of a comprehensive literature retrieval from six databases, based on the pre-determined eligibility criteria, irrespective of language. The risk of bias was assessed using an established instrument. We primarily focused on analyzing ETCO2, SpO2, and heart and respiratory rates, and also considered the impacts on physiological and exercise performance. A descriptive summary of the data and possible meta-analysis was performed. Forest plots were generated to pool estimates based on each of the study outcomes. Results: Of the 3,751 publications considered, six publications were selected for a systematic review and two publications were included for meta-analysis, however, the quality of these six studies was relatively low overall. In the case of inactivity, the facemask wearing COPD cohort had higher respiratory rates than that of the non-facemask wearing cohort (MD = 1.00 and 95% CI 0.47-1.53, P < 0.05). There was no significant difference in ETCO2 (MD = 0.10 and 95% CI -1.57-1.78, P > 0.05) and heart rate (MD = 0.40 and 95% CI -3.59-4.39, P > 0.05) nor SpO2 (MD = -0.40 and 95% CI -0.84-0.04, P > 0.05) between the COPD patients with and without facemasks. Furthermore, it was observed that the only significant differences between the COPD patients with and without facemasks undertaking different activities were FEV1 (%) (MD = 3.84 and 95% CI 0.14-7.54, P < 0.05), FEV1/FVC (%) (MD = 3.25 and 95% CI 0.71-5.79, P < 0.05), and blood lactate (MD = -0.90 and 95% CI -1.73 to -0.07, P < 0.05). Conclusion: Wearing facemasks decreased the exercise performance of patients with COPD, however, it had minimal impact on physiological indexes. Further investigations will be performed on the high-quality data from randomized control studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326265, identifier: CRD42022326265.


Asunto(s)
COVID-19 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Máscaras , Equipo de Protección Personal , Conducta Sedentaria
10.
Micromachines (Basel) ; 13(8)2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-36014113

RESUMEN

A chip-level hermetic package for a high-temperature graphene pressure sensor was investigated. The silicon cap, chip and substrate were stacked by Cu-Sn and Au-Au bonding to enable wide-range measurements while guaranteeing a high hermetic package. Prior to bonding, the sample was treated with Ar (5% H2) plasma. The Cu-Sn bonding was firstly performed at 260 °C for 15 min with a pressure of 9.9 MPa, and the corresponding process conditions for Au-Au bonding has increased to 300 °C, 20 min and 19.8 MPa respectively. The average shearing strength was 14.3 MPa, and an excellent leak rate of 1.72 × 10-4 Pa·cm3/s was also achieved. After high-temperature storage (HTS) at 350 °C for 10 h, the resistance of graphene decreased slightly because the dual bonding provided oxygen-free environment for graphene. The leakage rate of the device slightly increased to 2.1 × 10-4 Pa·cm3/s, and the average shear strength just decreased to 13.5 MPa. Finally, under the pressure range of 0-100 MPa, the graphene pressure sensor exhibited a high average sensitivity of 3.11 Ω/MPa. In conclusion, the dual bonding that combined Cu-Sn and Au-Au is extremely suitable for hermetic packaging in high-temperature graphene pressure sensors.

11.
Chemosphere ; 306: 135525, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35779682

RESUMEN

Substituted polycyclic aromatic hydrocarbons (SPAHs) are being intensively investigated, considering their high toxicity. Additionally, the mechanism of the effect of substituents on the removal of SPAHs and the activation of Ce(III) ions on peroxymonosulfate (PMS) have not been explored. Here we evaluated the removal efficiency of SPAHs in the oxidation system constructed by Ce(Ⅲ) ions and PMS, with emphasized the effect of substituents on SPAHs degradation. Ce(Ⅲ) has high catalytic performance for PMS, and the degradation percentage of all pollutants was higher than 92%. The significantly negative correlation between the reaction rate constants of SPAHs and the highest occupied molecular orbital-the lowest unoccupied molecular orbital gap, confirms that substituents lead to the differences in the degradation of SPAHs. The generation of reactive oxygen species (SO4•-, •OH, and 1O2) is based on the electron transfer between Ce(Ⅲ) and PMS, and the contribution of ROS to substituted naphthalene varies due to the role of substituents. The Ce(Ⅳ)/Ce(Ⅲ) cycle accelerates the activation of PMS. Based on the transformation products and condensed Fukui function, the possible degradation pathways are inferred. In addition, inorganic anions and organic matter have little effect on the Ce(Ⅲ)/PMS system, which is a prerequisite for applying this system to real-world waste-water for SPAHs removal. This work demonstrates a new model of the degradation mechanism of SPAHs in the Ce(Ⅲ)/PMS system.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Peróxidos , Hidrocarburos Policíclicos Aromáticos/análisis , Aguas Residuales , Contaminantes Químicos del Agua/análisis
12.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(2): 206-210, 2022 Mar 30.
Artículo en Chino | MEDLINE | ID: mdl-35411752

RESUMEN

Aiming at the medical service robot used in the indoor environment, this study proposes a method to test the pose accuracy of its working surface based on the binocular vision system. This method uses a binocular vision coordinate system to measure targets fixed on the working surface of the service robot, aligns the measurement system with the robot base coordinate system through the nonlinear least squares method, and integrates the multi-eye image data to achieve the accuracy test of the working surface. Finally, the vision test program was tested and verified on a mobile service robot model ABIR X8. According to the accuracy index given in GB/T 38124 Service Robot Performance Test Method, the test results of its pose accuracy were obtained.


Asunto(s)
Dispositivos Ópticos , Robótica , Visión Binocular
13.
Org Lett ; 24(1): 132-136, 2022 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-34928620

RESUMEN

We developed a highly regioselective base-induced synthesis of N2-substituted 1,2,3-triazoles from N-sulfonyl-1,2,3-triazoles and alkyl bromides/alkyl iodides at room temperature. We propose an SN2-like mechanistic pathway to explain the high N2-regioselectivity. The protocol features a broad substrate scope and generates products in good to excellent yields (72-90%).

14.
Water Res ; 192: 116834, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33486288

RESUMEN

The rapid and efficient degradation of polycyclic aromatic hydrocarbon (PAH) derivatives with toxicological properties remains a substantial challenge. In this study, a cost-effective and eco-friendly catalyst, nano-MoO2 (0.05 g L-1), exhibited excellent performance in activating 4.0 mmol L-1 peroxymonosulfate (PMS) for the degradation of naphthalene derivatives with 1 mg L-1 in aqueous systems; these derivatives include 1-methylnaphthalene, 1-nitronaphthalene, 1-chloronaphthalene, 1-naphthylamine and 1-naphthol, with high degradation rates of 87.52%, 86.23%, 97.87%, 99.74%, and 77.16%. Nano-MoO2 acts as an electron donor by transferring an electron causing O-O bond of PMS to cleave producing SO4·-, and later ·OH. Electron paramagnetic resonance (EPR) analysis combined with free radical quenching research indicated that SO4·- and ·OH dominated the degradation of naphthalene derivatives, and O2·- and 1O2 participated in the processes. X-ray photoelectron spectroscopy (XPS) revealed the transformation of Mo(IV) to Mo(V) and Mo(VI), which suggested that the activation process proceeded via electron transfer from nano-MoO2 to PMS. The applicability of the nano-MoO2/PMS system in influencing parameters and stability was explored. The degradation pathways were primarily elucidated for each naphthalene derivative based on the intermediates identified in the systems. The -CH3, -NO2, -Cl, -OH substituents increased the positive electrostatic potential (ESP) on the molecular surface of 1-methylnaphthalene, 1-nitronaphthalene, 1-chloronaphthalene, and 1-naphthol, which reduced the electrophilic reaction and electron transfer between the reactive species and pollutants, leading to a lower degradation rate of naphthalene derivatives than the parent compound. However, the effect of -NH2 substituents is the opposite. These findings suggest that nano-MoO2 may aid as a novel catalyst in the future remediation of environments polluted with PAH derivatives.


Asunto(s)
Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Catálisis , Peróxidos
15.
Nat Commun ; 10(1): 4273, 2019 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-31537782

RESUMEN

Recognition of specific chromatin modifications by distinct structural domains within "reader" proteins plays a critical role in the maintenance of genomic stability. However, the specific mechanisms involved in this process remain unclear. Here we report that the PHD-Bromo tandem domain of tripartite motif-containing 66 (TRIM66) recognizes the unmodified H3R2-H3K4 and acetylated H3K56. The aberrant deletion of Trim66 results in severe DNA damage and genomic instability in embryonic stem cells (ESCs). Moreover, we find that the recognition of histone modification by TRIM66 is critical for DNA damage repair (DDR) in ESCs. TRIM66 recruits Sirt6 to deacetylate H3K56ac, negatively regulating the level of H3K56ac and facilitating the initiation of DDR. Importantly, Trim66-deficient blastocysts also exhibit higher levels of H3K56ac and DNA damage. Collectively, the present findings indicate the vital role of TRIM66 in DDR in ESCs, establishing the relationship between histone readers and maintenance of genomic stability.


Asunto(s)
Daño del ADN/genética , Reparación del ADN/genética , Células Madre Embrionarias/citología , Histonas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Acetilación , Animales , Línea Celular , Cromatina/metabolismo , Cristalografía por Rayos X , Inestabilidad Genómica/genética , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Ratones Noqueados , Dominios Proteicos/fisiología , Sirtuinas/metabolismo
16.
Exp Ther Med ; 16(5): 4058-4062, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30344683

RESUMEN

The aim of the study was to study the serum peroxisome proliferator-activated receptor gamma (PPARγ) level and PPARγ gene polymorphism as well as the severity and prognosis of brain injury in patients with arteriosclotic cerebral infarction (ACI). A total of 246 ACI patients presenting at the Department of Neurology of Zengcheng District People's Hospital of Guangzhou between April 2009 and July 2015 were selected as the case group, and 382 control subjects were enrolled as the control group. The hepatic and renal functions and homocysteine (Hcy) expression levels were measured. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the serum PPARγ levels of the ACI patients. Polymerase chain reaction-restriction fragment length polymorphism method was applied to measure the PPARγ gene polymorphism. The proportions of hypertension patients, diabetes patients and smoking people in the case group were significantly higher than those in the control group. The levels of cholesterol and fasting blood glucose in the case group were elevated obviously compared with those in the control group. The levels of indexes related to the hepatic function and renal function in the case group were remarkably higher than those in the control group. The serum PPARγ levels were increased progressively at acute stage. The distribution frequencies of PPARγ genotypes CC, CT and TT in the case group were higher than those in the control group; compared with that in the control group, the proportion of C allele in the case group was raised obviously, while that of T allele was significantly decreased. The serum PPARγ level has a close correlation with the PPARγ gene polymorphism in ACI patients, and PPARγ is also remarkably related to the severity of brain injury; therefore, PPARγ has great significance in the diagnosis and treatment of cerebral infarction.

17.
Environ Sci Technol ; 52(5): 2694-2703, 2018 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-29415535

RESUMEN

The sorption of polycyclic aromatic hydrocarbons (PAHs) to montmorillonites is largely influenced by their interactions with dissolved organic matter (DOM). However, the role of DOM rather than humic and fulvic acids (e.g., extracellular DNA) in the PAH sorption to soil clays is little known. Here, we demonstrate that extracellular double-stranded salmon testes DNA substantially increased the sorption of phenanthrene and pyrene to Na-, Ca-, and Fe-modified montmorillonites. All PAH sorption isotherms fitted the linear and Freundlich models reasonably well ( R2 = 0.918-0.999). Distribution coefficients were increased from 0.0458-0.103 and 0.0493-0.141 L/g at 0 mg/L DNA to 0.413-0.589 and 0.385-0.560 L/g at 10 mg/L DNA for phenanthrene and pyrene, respectively. Spectroscopic and computational chemistry analyses confirmed that PAHs were first inserted into DNA by binding with the nucleobases via van der Waals and π-π electron donor-acceptor interactions. Compared to PAHs, the DNA-PAH complex can be more easily sorbed to cation-modified montmorillonites by complexation between DNA phosphate and exchangeable cations in addition to intercalation into clay interlayers. This work highlights the importance of understanding the control on contaminant sorption by many organic compounds that are ubiquitous in soils but not represented by humic and fulvic acids.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Adsorción , Bentonita , ADN , Suelo
18.
Org Biomol Chem ; 15(16): 3423-3426, 2017 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-28393959

RESUMEN

The concise synthesis of 2,3-dihydro-4H-benzo[e][1,3]oxazin-4-ones has been accomplished by copper-catalyzed tandem reactions of o-halobenzamides, LiOH and dichloromethane. The aryl-halogen bond hydroxylation and subsequent N,O-acetalization on CH2Cl2 are enabled under catalytic conditions which allows the generation of C(sp2)-O, C(sp3)-O and C(sp3)-N bonds to give the target products.

19.
Structure ; 22(5): 756-68, 2014 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-24726341

RESUMEN

Trypanosoma brucei protein arginine methyltransferase 7 (TbPRMT7) exclusively generates monomethylarginine (MMA), which directs biological consequences distinct from that of symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). However, determinants controlling the strict monomethylation activity are unknown. We present the crystal structure of the TbPRMT7 active core in complex with S-adenosyl-L-homocysteine (AdoHcy) and a histone H4 peptide substrate. In the active site, residues E172, E181, and Q329 hydrogen bond the guanidino group of the target arginine and align the terminal guanidino nitrogen in a position suitable for nucleophilic attack on the methyl group of S-adenosyl-L-methionine (AdoMet). Structural comparisons and isothermal titration calorimetry data suggest that the TbPRMT7 active site is narrower than those of protein arginine dimethyltransferases, making it unsuitable to bind MMA in a manner that would support a second turnover, thus abolishing the production of SDMA and ADMA. Our results present the structural interpretations for the monomethylation activity of TbPRMT7.


Asunto(s)
Proteína-Arginina N-Metiltransferasas/química , Proteína-Arginina N-Metiltransferasas/metabolismo , Trypanosoma brucei brucei/metabolismo , Secuencia de Aminoácidos , Arginina/análogos & derivados , Arginina/química , Arginina/metabolismo , Dominio Catalítico , Cristalografía por Rayos X , Guanidina/metabolismo , Histonas/química , Histonas/metabolismo , Metilación , Modelos Moleculares , Datos de Secuencia Molecular , Multimerización de Proteína , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , S-Adenosilhomocisteína/química , S-Adenosilhomocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Trypanosoma brucei brucei/química
20.
Zhonghua Er Ke Za Zhi ; 50(3): 222, 2012 Mar.
Artículo en Chino | MEDLINE | ID: mdl-22801209
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