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1.
J Environ Manage ; 366: 121766, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38986373

RESUMEN

Based on city-level panel data spanning 2008 to 2021, this study investigates the impact of government environmental attention (GEA) on green total factor productivity (GTFP). The findings suggest that increased GEA substantially enhances the growth of GTFP. After conducting robustness and endogeneity tests, the study's results consistently show reliability and robustness. Further analysis elucidates several mechanisms through which GEA influences GTFP, including fostering green technology innovation, optimizing resource allocation, and promoting upgrades in industrial structure. Heterogeneity analyses reveal that the impact of GEA on GTFP is notably pronounced in eastern cities, as well as in cities characterized by low resource dependency, mature industrial development, and high market competition. Conversely, the influence of GEA on GTFP is less discernible in cities prioritizing economic development goals, possibly due to differing policy orientations and resource allocation strategies. This study offers a novel perspective on understanding how GEA shape green development and provides empirical support for policy formulation.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38864839

RESUMEN

A Gram-stain-positive, strictly anaerobic, endospore-forming and rod-shaped (0.6-0.8×2.7-13.1 µm) bacterium, designated as 5 N-1T, was isolated from a yellow water sample collected from the manufacturing process of Nongxiangxing baijiu in the Yibin region of Sichuan, PR China. Growth occurred at 15-40 °C (optimum growth at 37 °C), at pH 6.0-9.0 (optimum growth at pH 7.0) and in NaCl concentrations of 0-1 % (w/v) and ethanol concentrations of 0-2 % (v/v). The major fatty acids in strain 5 N-1T were C16 : 0, C18 : 0 and C14 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified lipid. Phylogenetic analysis of its 16S rRNA gene sequence indicated that strain 5 N-1T was most closely related to Clostridium weizhouense YB-6T (97.70 %) and Clostridium uliginosum DSM 12992T (97.56 %). The average nucleotide identity and digital DNA‒DNA hybridization values between strain 5 N-1T and the above two type strains were 80.89 and 80.05 % and 25.80 and 25.30 %, respectively, which were all below the species thresholds. The genome size of strain 5 N-1T was 3.5 Mbp and the DNA G+C content was 27.5 mol%. Based on the results of phenotypic and genotypic analyses, strain 5 N-1T represents a novel species of the genus Clostridium, for which the name Clostridium aquiflavi sp. nov. is proposed. The type strain is Clostridium aquiflavi 5 N-1T (=CICC 24886T=JCM 35355T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , Clostridium , ADN Bacteriano , Ácidos Grasos , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , China , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , Clostridium/genética , Clostridium/aislamiento & purificación , Clostridium/clasificación , Microbiología del Agua , Fosfolípidos/análisis
3.
Angew Chem Int Ed Engl ; : e202405423, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758011

RESUMEN

In recent years, enantioselective electrocatalysis has surfaced as an increasingly-effective platform for sustainable molecular synthesis. Despite indisputable progress, strategies that allow the control of two distinct stereogenic elements with high selectivity remain elusive. In contrast, we, herein, describe electrochemical cobalt-catalyzed C-H activations that enable the installation of chiral stereogenic centers along with a chiral axis with high levels of enantio- and diastereoselectivities. The developed electrocatalysis strategy allowed for C-H/N-H activations/annulations with cyclic and non-cyclic alkenes providing expedient access to various central as well as atropo-chiral dihydroisoquinolinones paired to the valuable hydrogen evolution reaction. Studies on the atropo-stability of the obtained compounds demonstrated that the exceedingly mild conditions ensured by the electrocatalytic process were key for the achieved high stereoselectivities.

4.
Front Microbiol ; 15: 1341884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38298895

RESUMEN

The identification and quantification of viable bacteria at the species/strain level in compound probiotic products is challenging now. Molecular biology methods, e.g., propidium monoazide (PMA) combination with qPCR, have gained prominence for targeted viable cell counts. This study endeavors to establish a robust PMA-qPCR method for viable Lacticaseibacillus rhamnosus detection and systematically validated key metrics encompassing relative trueness, accuracy, limit of quantification, linear, and range. The inclusivity and exclusivity notably underscored high specificity of the primers for L. rhamnosus, which allowed accurate identification of the target bacteria. Furthermore, the conditions employed for PMA treatment were fully verified by 24 different L. rhamnosus including type strain, commercial strains, etc., confirming its effective discrimination between live and dead bacteria. A standard curve constructed by type strain could apply to commercial strains to convert qPCR Cq values to viable cell numbers. The established PMA-qPCR method was applied to 46 samples including pure cultures, probiotics as food ingredients, and compound probiotic products. Noteworthy is the congruity observed between measured and theoretical values within a 95% confidence interval of the upper and lower limits of agreement, demonstrating the relative trueness of this method. Moreover, accurate results were obtained when viable L. rhamnosus ranging from 103 to 108 CFU/mL. The comprehensive appraisal of PMA-qPCR performances provides potential industrial applications of this new technology in quality control and supervision of probiotic products.

5.
Eur J Med Chem ; 265: 116121, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38194777

RESUMEN

TP53, also known as the "guardian of the genome," is an important tumor suppressor gene. It is encoded by the human genome and is associated with the development of diverse cancers. The p53 protein, encoded by TP53, functions in the cell to monitor DNA damage and prompts the cell to respond appropriately. When DNA is damaged, p53 halts the cell cycle, allowing cells to enter the repair state. If the repair is ineffective, p53 induces cell death via apoptosis. This prevents DNA damage transmission during cell division and reduces cancer risk. However, the p53 gene mutation compromises its function. This leads to the inability of cells to respond properly to DNA damage, which may result in cancer development. Mutations in p53 are widespread in diverse cancers, especially highly prevalent cancers, including breast, colon, and lung cancers. Despite the association between p53 mutations and cancer, researchers have discovered drugs and treatments that may reactivate mutated p53 function. Therefore, p53 remains an important area of research in cancer treatment and holds promise as a new direction for cancer therapy. In summary, TP53 is a vital tumor suppressor gene responsible for monitoring DNA damage and prompting cells to respond appropriately. This article summarizes drugs related to p53 and diverse strategies for discovering drugs that act on either wide or mutant p53. Herein, p53 is categorized into two types: wild and mutant type. Drugs are also classified according to diverse treatment strategies, enabling readers to differentiate between the two types of p53 and aiding in selecting the appropriate research direction. Additionally, this review offers a valuable reference for drug design.


Asunto(s)
Neoplasias , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Mutación , Daño del ADN , Apoptosis
6.
Heliyon ; 9(12): e20030, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38125457

RESUMEN

Physalis Calyx seu Fructus is the dry calyx or the calyx with fruit of the Solanaceae plant Physalis alkekengi L. var. franchetii (Mast.) Makino, with a long history of use in medicine and food. However, despite its many potential therapeutic and culinary applications, P. alkekengi is not being exploited for these applications on a large scale. This study analysed various research related to the different chemical components of P. alkekengi, including steroids, flavonoids, alkaloids, phenylpropanoids, sucrose esters, piperazines, volatile oils, polysaccharides, amino acids, and trace elements. In addition, research related to the pharmacological activities of P. alkekengi, including its anti-inflammatory, anti microbial, antioxidative, hypoglycaemic, analgesic, anti-tumour, and immunomodulatory effects were investigated. Research articles from 1974 to 2023 were obtained from websites such as Google Scholar, Baidu Scholar, and China National Knowledge Infrastructure, and journal databases such as Scopus and PubMed, with the keywords such as Physalis alkekengi, components, effects, and activities. This study aims to provide a comprehensive understanding of the progress of phytochemical and pharmacological research on the phytochemical and pharmacological aspects of P. alkekengi and a reference for the better exploitation of P. alkekengi in the food and pharmaceutical industries.

7.
J Magn Reson Imaging ; 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37795920

RESUMEN

BACKGROUND: Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), whether anomalous NVC would be present is unclear. PURPOSE: To investigate NVC changes and potential neural basis in MELAS by combining resting-state functional MRI (rs-fMRI) and arterial spin labeling (ASL). STUDY TYPE: Prospective. SUBJECTS: Twenty-four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. FIELD STRENGTH/SEQUENCE: 3.0 T, resting-state gradient-recalled echo-planar imaging and pseudo-continuous 3D ASL sequences. ASSESSMENT: Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS. Regional NVC was also evaluated by voxel-wise and lesion-wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. STATISTICAL TESTS: Two-sample t-test, paired-sample t-test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. RESULTS: Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF-ALFF, CBF-fALFF, CBF-ReHo, and CBF-FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke-like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. DATA CONCLUSIONS: This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

8.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4302-4319, 2023 Aug.
Artículo en Chino | MEDLINE | ID: mdl-37802857

RESUMEN

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.


Asunto(s)
Medicamentos Herbarios Chinos , Scrophularia , Medicina Tradicional China , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión , Raíces de Plantas/química , Scrophularia/química
9.
Artículo en Inglés | MEDLINE | ID: mdl-36142003

RESUMEN

This paper investigates the relationship between fiscal expenditure on health care (FE) and the pharmaceutical industry stock index (SP) by using full-sample and sub-sample rolling-window bootstrap causality tests. It can be observed that there is both a positive and negative relationship between FE and SP. FE will promote the rise of the pharmaceutical stock market, which proves the Keynesian theory, while the result that FE negatively affects SP supports the classical theory. In turn, SP positively impacts FE, which indicates that the development of the pharmaceutical industry and the increase in medical and health expenditures can promote each other. In addition, the negative influence of SP on FE suggests that the impact of the pharmaceutical index on fiscal expenditure needs to be judged in conjunction with other events and market conditions. In complex economic conditions, investors can rationally consider the industry situation of the pharmaceutical market and benefit by optimising their investment portfolios. The government can regulate and guide the pharmaceutical industry by adjusting the fiscal expenditure on health care, thereby promoting the sustainable and stable development of the financial market.


Asunto(s)
Gastos en Salud , Inversiones en Salud , China , Industria Farmacéutica , Preparaciones Farmacéuticas
10.
Front Surg ; 9: 877038, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35865039

RESUMEN

Background: Severe traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients. Methods: One hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups. Results: Absorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group, P = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group, P = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation (P = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate (P = 0.008), lower KPS scores (P < 0.001) and lower functionally independent rate (P = 0.049) in one year after surgery than patients without TCH. Conclusions: In terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.

11.
Front Surg ; 9: 789118, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35284472

RESUMEN

Background: The mixed density hematoma (MDH) has a high recurrence rate in chronic subdural hematoma (CSDH). This study adopted rigid neuroendoscopy assisted hematoma resection to evacuate CSDH and investigated its efficacy as compared with the traditional burr-hole craniostomy (BHC) in CSDH with mixed density. Methods: A retrospective cohort study was conducted at two centers between January 2015 and December 2020. The data of 124 patients who underwent BHC for CSDH with mixed density were collected and analyzed. A total of 41 patients underwent rigid neuroendoscopy assisted hematoma resection (neuroendoscopy group) and 83 patients were treated by the traditional BHC (control group). Follow-ups were conducted 6 months after the surgery. Results: There was no significant difference in the baseline characteristics and preoperative CT features between the two groups (p > 0.05). The neuroendoscopy group had a lower recurrence rate than the control group (p = 0.043). Besides the neuroendoscopy group had a higher rate of hematoma evacuation (p < 0.001), less pneumocephalus volume (p < 0.001), shorter hospital stay (p < 0.001) and better Markwalder score (p < 0.001) than the control group within 24-48 h after operation. However, there was no significant difference between the two groups in the incidence of pneumocephalus, Markwalder score (at discharge and 6 months after surgery) and mortality. Moreover, the operation time was longer in the neuroendoscopy group (p < 0.001). Conclusions: When compared with the traditional BHC, rigid neuroendoscopy assisted hematoma resection can better reduce the recurrence rate of CSDH with mixed density. Also, it surpassed the results obtained from BHC in reducing the volume of pneumocephalus, improving hematoma evacuation rate, promoting short-term neurological recovery, and shortening hospital stays.

12.
Biomed Res Int ; 2020: 9380965, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32724821

RESUMEN

The effects of acupuncture on osteoarthritis (OA) pathogenesis have been demonstrated in vitro and in animal models. However, the potential for acupuncture to mediate protective effects on obese-induced OA has not been examined. Here, we investigated the effects of different acupuncture patterns on OA pathogenesis in high-fat diet- (HFD-) induced obese rats. After 12-week diet-induced obesity, obese rats were treated with three acupuncture protocols for 2 weeks, including ST36, GB34, and ST36+GB34. The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Obesidad/complicaciones , Osteoartritis/etiología , Osteoartritis/terapia , Animales , Bacteroidetes/crecimiento & desarrollo , Electroacupuntura/métodos , Heces/microbiología , Firmicutes , Microbioma Gastrointestinal/fisiología , Inflamación/terapia , Metabolismo de los Lípidos/fisiología , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley
13.
Antonie Van Leeuwenhoek ; 113(5): 663-676, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31897851

RESUMEN

Using electrophoretic karyotyping, RAPD fingerprinting and phylogenetic analysis of ribosomal RNA gene sequences, twenty-six Vanderwaltozyma strains were studied. Out of 19 strains isolated in mountainous areas of Taiwan, eighteen strains were isolated from soil and one strain was isolated from the fruiting body of mushroom, six were identified as V. polyspora and three as V. verrucispora. Based on the results of a multigene sequence analysis (D1/D2, ITS and mitochondrial COX II gene) and DNA-DNA reassociation, three new ascosporic members of the genus Vanderwaltozyma are formally described: V. huisunica sp. nov. (GA1S06T = CBS 12250T = BCRC 23260T), V. meishanica sp. nov. (EN4S02T = CBS 12249T = BCRC 23255T) and V. molinica sp. nov. (GJ8S05T = CBS 12251T = BCRC 23264T), and the holotypes of these novel species are assigned as BCRC 23260T, BCRC 23255T and BCRC 23264T, respectively.


Asunto(s)
Saccharomycetales , Clasificación , Complejo IV de Transporte de Electrones/genética , Genes Fúngicos , Genes de ARNr , Técnicas de Tipificación Micológica , Técnica del ADN Polimorfo Amplificado Aleatorio , Saccharomycetales/clasificación , Saccharomycetales/genética , Saccharomycetales/aislamiento & purificación , Análisis de Secuencia de ADN , Microbiología del Suelo , Taiwán
14.
Int J Syst Evol Microbiol ; 70(3): 2103-2107, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31995468

RESUMEN

Four strains of anamorphic yeasts isolated from the fruiting bodies of mushrooms collected in Taiwan were found to represent two novel yeast species belonging to the genus Teunomyces, which was formally known as the Candida kruisii clade. Strains NY13M09T and NY14M14 were related to the type strains of Teunomyces panamensis, T. pallodes, T. tritomae and T. lycoperdinae, and strains GG4M07T and GG6M14 were related to T. kruisii NRRL Y-17087T and T. cretensis NRRL Y-27777T. However, strains NY13M09T and NY14M14 differed from their closest phylogenetic neighbours by 2.9-3.7 % in the D1/D2 domain sequence of the LSU rRNA gene and by 6.6-13.7 % in the internal transcribed spacer (ITS); GG4M07T and GG6M14 differed from their closest known species by 2.4 % in the D1/D2 domain sequence of the LSU rRNA gene and by 8.7-10.0 % in the ITS. Meanwhile, these strains were also clearly distinguished from their closest relatives based on the results of physiological tests. Based on the characteristics described above, the strains could be regarded as representing two novel species of the genus Teunomyces, for which the names Teunomyces basidiocarpi sp. nov. and Teunomyces luguensis sp. nov. are proposed. The holotypes are Teunomyces basidiocarpi BCRC 23475T and Teunomyces luguensis BCRC 23476T.


Asunto(s)
Agaricales , Filogenia , Saccharomycetales/clasificación , Composición de Base , ADN de Hongos/genética , Técnicas de Tipificación Micológica , ARN Ribosómico/genética , ARN Ribosómico 16S/genética , Saccharomycetales/aislamiento & purificación , Análisis de Secuencia de ADN , Taiwán
15.
Anal Bioanal Chem ; 411(21): 5519-5530, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31147761

RESUMEN

A novel fluorescent probe based on molecularly imprinted polymers (MIPs) coupled with carbon quantum dots (CQDs) was fabricated and successfully used for selective recognition of mesotrione. In this probe, the biomass-derived CQDs were prepared through a hydrothermal method using mango peels as carbon source, and the whole synthesis procedure was green without chemical reagents. The CQDs were encapsulated into MIPs by using sol-gel technology. After removal of the template molecule mesotrione, specific binding sites are formed and there is electrostatic attraction between the probe and the template molecule. The synthetic CQDs@MIPs were able to selectively capture the target mesotrione with fluorescence quenching via the specific interaction between mesotrione and the recognition cavities. The probe was used for determination of mesotrione in corn to verify the practicality of the proposed method. The detection limit of mesotrione was 4.7 nmol L-1, and the linear range was 15 nmol L-1 to 3000 nmol L-1. Meanwhile, the recoveries of this method for mesotrione were 91.4-96.2%, and the relative standard deviations (RSDs) were 3.2-6.1%. This work provides a novel research method to synthesize CQDs@MIPs with high selectivity (imprinting factor = 5.6), and which can be used for convenient, rapid recognition and sensitive detection of trace compounds from complex matrices.


Asunto(s)
Biomasa , Ciclohexanonas/análisis , Colorantes Fluorescentes/química , Impresión Molecular , Puntos Cuánticos , Límite de Detección , Reproducibilidad de los Resultados
16.
J Pathol ; 236(3): 337-47, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25775999

RESUMEN

Although hepatitis B virus (HBV) has been established to cause hepatocellular carcinoma (HCC), the exact mechanism remains to be clarified. Type II ground glass hepatocytes (GGHs) harbouring the HBV pre-S2 mutant large surface protein (LHBS) have been recognized as a morphologically distinct hallmark of HCC in the advanced stages of chronic HBV infection. Considering its preneoplastic nature, we hypothesized that type II GGH may exhibit high genomic instability, which is important for the carcinogenic process in chronic HBV carriers. In this study we found that pre-S2 mutant LHBS directly interacted with importin α1, the key factor that recognizes cargos undergoing nuclear transportation mediated by the importin α/ß-associated nuclear pore complex (NPC). By interacting with importin α1, which inhibits its function as an NPC factor, pre-S2 mutant LHBS blocked nuclear transport of an essential DNA repair and recombination factor, Nijmegen breakage syndrome 1 (NBS1), upon DNA damage, thereby delaying the formation of nuclear foci at the sites of DNA double-strand breaks (DSBs). Pre-S2 mutant LHBS was also found to block NBS1-mediated homologous recombination repair and induce multi-nucleation of cells. In addition, pre-S2 mutant LHBS transgenic mice showed genomic instability, indicated by increased global gene copy number variations (CNVs), which were significantly higher than those in hepatitis B virus X mice, indicating that pre-S2 mutant LHBS is the major viral oncoprotein inducing genomic instability in HBV-infected hepatocytes. Consistently, the human type II GGHs in HCC patients exhibited increased DNA DSBs representing significant genomic instability. In conclusion, type II GGHs harbouring HBV pre-S2 mutant oncoprotein represent a high-risk marker for the loss of genome integrity in chronic HBV carriers and explain the complex chromosome changes in HCCs. Mouse array CGH raw data: GEO Accession No. GSE61378 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61378).


Asunto(s)
Carcinoma Hepatocelular/genética , Transformación Celular Viral/genética , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Neoplasias Hepáticas/genética , Precursores de Proteínas/genética , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Hibridación Genómica Comparativa , Roturas del ADN de Doble Cadena , Variaciones en el Número de Copia de ADN , Daño del ADN , Reparación del ADN , Femenino , Inestabilidad Genómica , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/metabolismo , Hepatitis B Crónica/metabolismo , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Hepatocitos/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación , Precursores de Proteínas/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo
17.
Oxid Med Cell Longev ; 2014: 901315, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24723997

RESUMEN

Toona sinensis is one of the most popular vegetarian cuisines in Taiwan and it has been shown to possess antioxidant, antiangiogenic, and anticancer properties. In this study, we investigated the antiatherosclerotic potential of aqueous leaf extracts from Toona sinensis (TS; 25-100 µg/mL) and its major bioactive compound, gallic acid (GA; 5 µg/mL), in LPS-treated rat aortic smooth muscle (A7r5) cells. We found that pretreatment with noncytotoxic concentrations of TS and GA significantly inhibited inflammatory NO and PGE2 production by downregulating their precursors, iNOS and COX-2, respectively, in LPS-treated A7r5 cells. Furthermore, TS and GA inhibited LPS-induced intracellular ROS and their corresponding mediator, p47(phox). Notably, TS and GA pretreatment significantly inhibited LPS-induced migration in transwell assays. Gelatin zymography and western blotting demonstrated that treatment with TS and GA suppressed the activity or expression of MMP-9, MMP-2, and t-PA. Additionally, TS and GA significantly inhibited LPS-induced VEGF, PDGF, and VCAM-1 expression. Further investigation revealed that the inhibition of iNOS/COX-2, MMPs, growth factors, and adhesion molecules was associated with the suppression of NF-κB activation and MAPK (ERK1/2, JNK1/2, and p38) phosphorylation. Thus, Toona sinensis may be useful for the prevention of atherosclerosis.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Inflamación/tratamiento farmacológico , Meliaceae/química , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Dinoprostona/biosíntesis , Regulación hacia Abajo/efectos de los fármacos , Proteínas del Ojo/metabolismo , Ácido Gálico/farmacología , Proteínas I-kappa B/metabolismo , Lipopolisacáridos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/enzimología , NADPH Oxidasas/metabolismo , Inhibidor NF-kappaB alfa , Factores de Crecimiento Nervioso/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/uso terapéutico , Ratas , Serpinas/metabolismo , Transducción de Señal/efectos de los fármacos , Activador de Tejido Plasminógeno/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
J Gen Virol ; 94(Pt 12): 2750-2758, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24062531

RESUMEN

Elevated levels of antibodies against Epstein-Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV.


Asunto(s)
Herpesvirus Humano 4/fisiología , Microtúbulos/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteína Quinasa C/metabolismo , Activación Viral , Carcinoma , Línea Celular , Activación Enzimática , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Microtúbulos/genética , Carcinoma Nasofaríngeo , Nocodazol/farmacología , Polimerizacion , Proteína Quinasa C/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
Appl Environ Microbiol ; 79(21): 6604-16, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23974132

RESUMEN

Lysobacter enzymogenes is a ubiquitous environmental bacterium that is emerging as a potentially novel biological control agent and a new source of bioactive secondary metabolites, such as the heat-stable antifungal factor (HSAF) and photoprotective polyene pigments. Thus far, the regulatory mechanism(s) for biosynthesis of these bioactive secondary metabolites remains largely unknown in L. enzymogenes. In the present study, the diffusible signal factor (DSF) and diffusible factor (DF)-mediated cell-cell signaling systems were identified for the first time from L. enzymogenes. The results show that both Rpf/DSF and DF signaling systems played critical roles in modulating HSAF biosynthesis in L. enzymogenes. Rpf/DSF signaling and DF signaling played negative and positive effects in polyene pigment production, respectively, with DF playing a more important role in regulating this phenotype. Interestingly, only Rpf/DSF, but not the DF signaling system, regulated colony morphology of L. enzymgenes. Both Rpf/DSF and DF signaling systems were involved in the modulation of expression of genes with diverse functions in L. enzymogenes, and their own regulons exhibited only a few loci that were regulated by both systems. These findings unveil for the first time new roles of the Rpf/DSF and DF signaling systems in secondary metabolite biosynthesis of L. enzymogenes.


Asunto(s)
Toxinas Bacterianas/biosíntesis , Regulación Bacteriana de la Expresión Génica/fisiología , Lysobacter/fisiología , Interacciones Microbianas/fisiología , Pigmentos Biológicos/biosíntesis , Metabolismo Secundario/fisiología , Escherichia coli , Lysobacter/genética , Análisis por Micromatrices , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Metabolismo Secundario/genética , Xanthomonas
20.
Cell Transplant ; 21(5): 971-84, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22449499

RESUMEN

Transplant arteriosclerosis (TA) remains the major limitation of long-term graft survival in heart transplantation despite the advances in immunosuppressants. Mesenchymal stem cells (MSCs) have been demonstrated to suppress allogeneic immune responses by numerous in vitro studies. However, the immunomodulatory effects of MSCs in vivo are controversial and the underlying molecular mechanisms are not conclusive. In this study, we investigated the therapeutic potential of autologous bone marrow-derived MSCs on TA in a porcine model of femoral artery transplantation. MSCs or saline were injected into the soft tissue surrounding the arterial grafts immediately postanastomosis. Four weeks after transplantation, neointimal formation increased significantly in untreated allografts compared with the MSC-treated grafts as assessed by intravascular ultrasound (maximum luminal area stenosis: 40 ± 12% vs. 18 ± 6%, p < 0.001). Grafts harvested at 4 weeks showed dense perivascular lymphocyte infiltration accompanied by significant intimal hyperplasia in the untreated but not in the MSC-treated allografts. Serial angiographic examination showed that all of the untreated allografts became occluded at the 8th week whereas the majority of the MSC-treated grafts remained patent at the 12th week posttransplantation (n = 12 each group, p < 0.001). Quantitative PCR analysis revealed that Foxp3 expression was comparable between the untreated and the MSC-treated groups. However, expression of interleukin-10 (IL-10), interferon-γ (IFN-γ), and indoleamine 2,3-dioxygenase (IDO) was increased significantly in the MSC-treated allografts compared with that in the allograft controls (p = 0.021 for IL-10, p = 0.003 for IFN-γ, and p = 0.008 for IDO). In conclusion, local delivery of autologous MSCs alleviates TA by inducing allograft tolerance via enhanced expression of IL-10, IFN-γ, and IDO but not Foxp3-positive cells in the vessel wall. These results suggest that MSCs induce immune tolerance by activating the type 1 regulatory T-like cells.


Asunto(s)
Arteriosclerosis/prevención & control , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Animales , Células de la Médula Ósea/citología , Modelos Animales de Enfermedad , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/metabolismo , Arteria Femoral/trasplante , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Vectores Genéticos/genética , Vectores Genéticos/metabolismo , Supervivencia de Injerto , Terapia de Inmunosupresión , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Interferón gamma/genética , Interleucina-10/genética , Células Madre Mesenquimatosas/metabolismo , Porcinos , Transfección , Trasplante Autólogo , Trasplante Homólogo , Ultrasonografía
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