Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Mol Carcinog ; 63(3): 371-383, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37975495

RESUMEN

Long noncoding RNAs (lncRNAs) are crucial regulators of tumor-initiating cells (TICs) and hold particular importance in triple negative breast cancer (TNBC). Yet, the precise mechanisms by which TIC-associated lncRNAs influence TNBC remain unclear. Our research utilized The Cancer Genome Atlas Breast Cancer (BC) data set to identify prognostic lncRNAs. We then conducted extensive assays to explore their impact on the tumor-initiating phenotype of TNBC cells and the underlying mechanisms. Notably, we found that low expression of lncRNA SEMA3B-AS1 correlated with unfavorable survival in BC patients. SEMA3B-AS1 was also downregulated in TNBC and linked to advanced tumor stage. Functional experiments confirmed its role as a TIC-suppressing lncRNA, curtailing mammosphere formation, ALDH + TIC cell proportion, and impairing clonogenicity, migration, and invasion. Mechanistic insights unveiled SEMA3B-AS1's nuclear localization and interaction with MLL4 (mixed-lineage leukemia 4), triggering H3K4 methylation-associated transcript activation and thus elevating the expression of SEMA3B, a recognized tumor suppressor gene. Our findings emphasize SEMA3B-AS1's significance as a TNBC-suppressing lncRNA that modulates TIC behavior. This study advances our comprehension of lncRNA's role in TNBC progression, advocating for their potential as therapeutic targets in this aggressive BC subtype.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Semaforinas , Neoplasias de la Mama Triple Negativas , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama Triple Negativas/patología , MicroARNs/genética , N-Metiltransferasa de Histona-Lisina/genética , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Línea Celular Tumoral , Glicoproteínas de Membrana/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Semaforinas/uso terapéutico
2.
Nature ; 560(7720): 582-588, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30158607

RESUMEN

The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.

3.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33443222

RESUMEN

Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7-/- mice to determine the role of TLR7 in ALD pathogenesis. In an alcoholic hepatitis (AH) mouse model, hepatic steatosis, injury, and inflammation were induced by chronic binge ethanol feeding in mice, and Tlr7 deficiency exacerbated these effects. Because these results demonstrated that endogenous TLR7 signaling activation is protective in the AH mouse model, we hypothesized that TLR7 activation may be an effective therapeutic strategy for ALD. Therefore, we investigated the therapeutic effect of TLR7 agonistic agent, 1Z1, in the AH mouse model. Oral administration of 1Z1 was well tolerated and prevented intestinal barrier disruption and bacterial translocation, which thus suppressed ethanol-induced hepatic injury, steatosis, and inflammation. Furthermore, 1Z1 treatment up-regulated the expression of antimicrobial peptides, Reg3b and Reg3g, in the intestinal epithelium, which modulated the microbiome by decreasing and increasing the amount of Bacteroides and Lactobacillus, respectively. Additionally, 1Z1 up-regulated intestinal interleukin (IL)-22 expression. IL-22 deficiency abolished the protective effects of 1Z1 in ethanol-induced liver and intestinal damage, suggesting intestinal IL-22 as a crucial mediator for 1Z1-mediated protection in the AH mouse model. Collectively, our results indicate that TLR7 signaling exerts protective effects in the AH mouse model and that a TLR7 ligand, 1Z1, holds therapeutic potential for the treatment of AH.


Asunto(s)
Etanol/toxicidad , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Glicoproteínas de Membrana/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 7/metabolismo , Administración Oral , Animales , Bacteroides/efectos de los fármacos , Modelos Animales de Enfermedad , Hígado Graso/complicaciones , Hígado Graso/genética , Hígado Graso/metabolismo , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/complicaciones , Inflamación/genética , Inflamación/metabolismo , Mucosa Intestinal/efectos de los fármacos , Lactobacillus/efectos de los fármacos , Ligandos , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/fisiopatología , Glicoproteínas de Membrana/agonistas , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs , Proteínas Asociadas a Pancreatitis/genética , Proteínas Asociadas a Pancreatitis/metabolismo , Polietilenglicoles/química , Polietilenglicoles/farmacología , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Transducción de Señal/genética , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/patología , Receptor Toll-Like 7/agonistas , Receptor Toll-Like 7/genética , Interleucina-22
4.
J Sci Food Agric ; 102(4): 1475-1487, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-34402055

RESUMEN

BACKGROUND: The objective was to determine effects of potassium diformate (PD), sodium diacetate (SD) and calcium propionate (CAP) on dynamics of microbial community, fermentation characteristics and aerobic stability of silage comprised of a mixture of alfalfa (AF), rice straw (RS) and wheat bran (MF). Treatments included control (C), PD [5.5 g kg-1 fresh weight (FW)], SD (7 g kg-1 FW), and CAP (10 g kg-1 FW), which were ensiled for 1, 3, 5, 7, 15, 30 and 45 days in vacuum-sealed polythene bags. RESULTS: After day 1 of ensiling, the most dominant bacterial species in all silages was Weissella cibaria, whereas Lactobacillus parabrevis, L. nodensis, L. plantarum and L. paralimentarius were dominant species after 5 and 15 days of ensiling, and ultimately Pseudomonas putida and Stenotrophomonas maltophilia became dominant after 45 days. The positive correlation between PD and L. plantarum supported the lowest pH, butyric acid, ammonia nitrogen, neutral and acid detergent fiber, and hemicellulose content, and high water-soluble carbohydrates and crude protein content in PD silage. In addition, SD and CAP enriched the abundance of L. parabrevis and mainly increased lactic acid (LA) and acetic acid (AA). CAP increased abundance of L. acetotolerans after 45 days of ensiling with more LA and AA than other treatments. CONCLUSIONS: The succession of the bacterial community of mixed silage was modulated by the three fatty acid salts; furthermore, PD and CAP further improved fermentation quality by accelerating the decrease in pH and the increase in LA. The chemical additives prolonged the aerobic stability more than 16 days. © 2021 Society of Chemical Industry.


Asunto(s)
Oryza , Ensilaje , Fibras de la Dieta , Fermentación , Medicago sativa , Sales (Química) , Ensilaje/análisis
5.
Appl Opt ; 60(26): 8016-8021, 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34613062

RESUMEN

A novel, to the best of our knowledge, method is proposed in this study to permit the controllable resolution of a micro-angle measurement by using a Michelson interferometer. The resolution of the proposed system can be adjusted by changing the distances between a pair of parallel mirrors. Through experiments, it was observed that as the distance was changed from 0 to 6 mm, the corresponding resolution was significantly altered from 22.88 to 14.02 µrad. Compared with other small angle measurement methods, the proposed method can realize the conversion of multiple measurement resolutions more easily and conveniently.

6.
Phys Rev Lett ; 124(5): 051301, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32083933

RESUMEN

We improve the test of the gravitational inverse-square law at the submillimeter range by suppressing the vibration of the electrostatic shielding membrane to reduce the disturbance coupled from the residual surface potential. The result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=48 µm. This work establishes the strongest bound on the magnitude α of the Yukawa violation in the range of 40-350 µm, and improves the previous bounds by up to a factor of 3 at the length scale λ≈70 µm. Furthermore, the constraints on the power-law potentials are improved by about a factor of 2 for k=4 and 5.

7.
Phys Rev Lett ; 121(26): 261101, 2018 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-30636147

RESUMEN

Here we present a new test of the equivalence principle designed to search for the possible violation of gravitational parity using test bodies with different chiralities. The test bodies are a pair of left- and right-handed quartz crystals, whose gravitational acceleration difference is measured by a rotating torsion pendulum. The result shows that the acceleration difference towards Earth Δa_{left-right}=[-1.7±4.1(stat)±4.4(syst)]×10^{-15} m s^{-2} (1-σ statistical uncertainty), correspondingly the Eötvös parameter η=[-1.2±2.8(stat)±3.0(syst)]×10^{-13}. This is the first reported experimental test of the equivalence principle for chiral masses and opens a new way to the search for the possible parity-violating gravitation.

8.
J Biol Chem ; 291(36): 18867-79, 2016 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-27417139

RESUMEN

The unique cell wall of mycobacteria is essential to their viability and the target of many clinically used anti-tuberculosis drugs and inhibitors under development. Despite intensive efforts to identify the ligase(s) responsible for the covalent attachment of the two major heteropolysaccharides of the mycobacterial cell wall, arabinogalactan (AG) and peptidoglycan (PG), the enzyme or enzymes responsible have remained elusive. We here report on the identification of the two enzymes of Mycobacterium tuberculosis, CpsA1 (Rv3267) and CpsA2 (Rv3484), responsible for this function. CpsA1 and CpsA2 belong to the widespread LytR-Cps2A-Psr (LCP) family of enzymes that has been shown to catalyze a variety of glycopolymer transfer reactions in Gram-positive bacteria, including the attachment of wall teichoic acids to PG. Although individual cpsA1 and cpsA2 knock-outs of M. tuberculosis were readily obtained, the combined inactivation of both genes appears to be lethal. In the closely related microorganism Corynebacterium glutamicum, the ortholog of cpsA1 is the only gene involved in this function, and its conditional knockdown leads to dramatic changes in the cell wall composition and morphology of the bacteria due to extensive shedding of cell wall material in the culture medium as a result of defective attachment of AG to PG. This work marks an important step in our understanding of the biogenesis of the unique cell envelope of mycobacteria and opens new opportunities for drug development.


Asunto(s)
Proteínas Bacterianas/genética , Pared Celular/metabolismo , Galactanos/metabolismo , Mycobacterium tuberculosis/metabolismo , Peptidoglicano/metabolismo , Ácidos Teicoicos/metabolismo , Proteínas Bacterianas/metabolismo , Pared Celular/genética , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Galactanos/genética , Mycobacterium tuberculosis/genética , Peptidoglicano/genética , Ácidos Teicoicos/genética
9.
J Pharmacol Exp Ther ; 359(2): 247-255, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27543328

RESUMEN

The rennin-angiotensin system (RAS) is crucial in hepatic fibrosis development, and therapies targeting this system may be a promising treatment for hepatic fibrosis. In this study, we investigated the effects of swertiamarin (Swe), an ethanol extract of Gentiana manshurica Kitag, on hepatic fibrosis and its underlying mechanisms through regulating RAS. Primary rat hepatic stellate cells (HSCs) were isolated and treated with angiotensin II (Ang II) with or without Swe and losartan. The proliferation and activation of HSCs were measured. Rat hepatic fibrosis was induced by intraperitoneal dimethylnitrosamine (DMN) injection for 4 weeks. Rats were treated with Swe or losartan from the third week until the end of the experiment. Hydroxyproline content in liver tissue was assayed with Jamall's method, and liver collagen deposition was visualized using Sirius red staining. RAS components were analyzed by Western blot, immunofluorescent staining, and real-time reverse-transcription polymerase chain reaction. The results showed that Swe significantly inhibited Ang II-induced HSC proliferation and activation. Swe also significantly suppressed DMN-induced α-smooth muscle actin production in rat livers and improved liver function. Swe partially inhibited Ang II-induced angiotensin type 1 receptor (AT1R) up-regulation and suppressed Ang II-induced extracellular signal-regulated kinase (ERK) and c-jun phosphorylation in HSCs. In the DMN-treated rats, Swe treatment significantly inhibited the plasma Ang II levels. DMN-induced AT1R up-regulation, and phosphorylation of ERK and c-jun in rat liver were also inhibited by Swe. In conclusion, Swe may attenuate hepatic fibrosis through inhibiting HSC activation by regulating the RAS.


Asunto(s)
Angiotensina II/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucósidos Iridoides/farmacología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Pironas/farmacología , Receptor de Angiotensina Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/patología , Glucósidos Iridoides/uso terapéutico , Cirrosis Hepática/metabolismo , Pironas/uso terapéutico , Ratas , Sistema Renina-Angiotensina/efectos de los fármacos
10.
Phys Rev Lett ; 116(13): 131101, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-27081964

RESUMEN

By using a torsion pendulum and a rotating eightfold symmetric attractor with dual modulation of both the interested signal and the gravitational calibration signal, a new test of the gravitational inverse-square law at separations down to 295 µm is presented. A dual-compensation design by adding masses on both the pendulum and the attractor was adopted to realize a null experiment. The experimental result shows that, at a 95% confidence level, the gravitational inverse-square law holds (|α|≤1) down to a length scale λ=59 µm. This work establishes the strongest bound on the magnitude α of Yukawa-type deviations from Newtonian gravity in the range of 70-300 µm, and improves the previous bounds by up to a factor of 2 at the length scale λ≈160 µm.

11.
Int J Mol Sci ; 17(4): 535, 2016 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-27070591

RESUMEN

miR-155 (microRNA-155) is an important non-coding RNA in regulating host crucial biological regulators. However, its regulatory function in mycobacterium infection remains unclear. Our study demonstrates that miR-155 expression is significantly increased in macrophages after Mycobacterium marinum (M.m) infection. Transfection with anti-miR-155 enhances nitric oxide (NO) synthesis and decreases the mycobacterium burden, and vice versa, in interferon γ (IFN-γ) activated macrophages. More importantly, miR-155 can directly bind to the 3'UTR of CCAAT/enhancer binding protein ß (C/EBPß), a positive transcriptional regulator of nitric oxide synthase (NOS2), and regulate C/EBPß expression negatively. Knockdown of C/EBPß inhibit the production of nitric oxide synthase and promoted mycobacterium survival. Collectively, these data suggest that M.m-induced upregulation of miR-155 downregulated the expression of C/EBPß, thus decreasing the production of NO and promoting mycobacterium survival, which may provide an insight into the function of miRNA in subverting the host innate immune response by using mycobacterium for its own profit. Understanding how miRNAs partly regulate microbicidal mechanisms may represent an attractive way to control tuberculosis infectious.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/inmunología , Interferón gamma/inmunología , MicroARNs/inmunología , Infecciones por Mycobacterium/inmunología , Mycobacterium/inmunología , Óxido Nítrico/inmunología , Animales , Proteína beta Potenciadora de Unión a CCAAT/genética , Células Cultivadas , Regulación de la Expresión Génica , Células HEK293 , Humanos , Inmunidad Innata , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Infecciones por Mycobacterium/genética , Infecciones por Mycobacterium/microbiología , Células RAW 264.7
12.
Infect Immun ; 83(7): 2844-54, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25939506

RESUMEN

LytR-CpsA-Psr family proteins play an important role in bacterial cell wall integrity. Although the pathogenic relevance of LytR-CpsA-Psr family proteins has been studied in a few bacterial pathogens, their function in mycobacteria remains uncharacterized. In this work, a transposon insertion mutant (cpsA::Tn) of Mycobacterium marinum was studied. We found that inactivation of CpsA altered bacterial colony morphology, sliding motility, cell surface hydrophobicity, and cell wall permeability. Besides, the cpsA mutant exhibited a decreased arabinogalactan content, indicating that CpsA plays a role in cell wall assembly. Moreover, the mutant shows impaired growth within macrophage cell lines and is severely attenuated in zebrafish larvae and adult zebrafish. Taken together, our results indicated that CpsA, a previously uncharacterized protein, is important for mycobacterial cell wall integrity and is required for mycobacterial virulence.


Asunto(s)
Proteínas Bacterianas/metabolismo , Pared Celular/fisiología , Mycobacterium marinum/fisiología , Animales , Proteínas Bacterianas/genética , Línea Celular , Pared Celular/química , Pared Celular/metabolismo , Elementos Transponibles de ADN , Interacciones Hidrofóbicas e Hidrofílicas , Larva/microbiología , Locomoción , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Mutagénesis Insercional , Mycobacterium marinum/crecimiento & desarrollo , Mycobacterium marinum/metabolismo , Mycobacterium marinum/patogenicidad , Permeabilidad , Virulencia , Pez Cebra/microbiología
13.
Microbiol Res ; 273: 127393, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37182283

RESUMEN

Many subversive mechanisms promote the occurrence and development of chronic infectious diseases and cancer, among which the down-regulated expression of immune-activating receptors and the enhanced expression of immune-inhibitory receptors accelerate the occurrence and progression of the disease. Recently, the use of immune checkpoint inhibitors has shown remarkable efficacy in the treatment of tumors in multiple organs. However, the expression of immune checkpoint molecules on natural killer (NK) cells by Mycobacterium tuberculosis (Mtb) infection and its impact on NK cell effector functions have been poorly studied. In this review, we focus on what is currently known about the expression of various immune checkpoints in NK cells following Mtb infection and how it alters NK cell-mediated host cytotoxicity and cytokine secretion. Unraveling the function of NK cells after the infection of host cells by Mtb is crucial for a comprehensive understanding of the innate immune mechanism of NK cells involved in tuberculosis and the evaluation of the efficacy of immunotherapies using immune checkpoint inhibitors to treat tuberculosis. In view of some similarities in the immune characteristics of T cells and NK cells, we reviewed the molecular mechanism of the interaction between T cells and Mtb, which can help us to further understand and explore the specific interaction mechanism between NK cells and Mtb.


Asunto(s)
Mycobacterium tuberculosis , Neoplasias , Tuberculosis , Humanos , Linfocitos T , Inhibidores de Puntos de Control Inmunológico , Células Asesinas Naturales/patología , Células Asesinas Naturales/fisiología
14.
Signal Transduct Target Ther ; 8(1): 82, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36828823

RESUMEN

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tuberculosis/metabolismo , Tuberculosis/microbiología , Mycobacterium tuberculosis/metabolismo , Empalme del ARN , Macrófagos/metabolismo , Biomarcadores , Enzimas Ubiquitina-Conjugadoras/metabolismo , Cinesinas/metabolismo , Factores de Empalme Serina-Arginina
15.
Phys Rev Lett ; 108(8): 081101, 2012 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-22463510

RESUMEN

We report a new test of the gravitational inverse square law at millimeter ranges by using a dual-modulation torsion pendulum. An I-shaped symmetric pendulum and I-shaped symmetric attractors were adopted to realize a null experimental design. The non-Newtonian force between two macroscopic tungsten plates is measured at separations ranging down to 0.4 mm, and the validity of the null experimental design was checked by non-null Newtonian gravity measurements. We find no deviations from the Newtonian inverse square law with 95% confidence level, and this work establishes the most stringent constraints on non-Newtonian interaction in the ranges from 0.7 to 5.0 mm, and a factor of 8 improvement is achieved at the length scale of several millimeters.

16.
Artículo en Inglés | MEDLINE | ID: mdl-23243430

RESUMEN

The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs) in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) and α-smooth muscle actin (α-SMA) production in vitro, reduced the gene expression of transforming growth factor beta (TGF-ß), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.

17.
Artículo en Inglés | MEDLINE | ID: mdl-22927877

RESUMEN

In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction Danggui Buxue Tang (DBT; Radix Astragali and Radix Angelicae sinensis in 5 : 1 ratio) in a rat model of liver fibrosis, in order to elucidate its mechanisms of action against liver fibrosis. Liver fibrosis was induced with CCl(4) and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and 8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of VEGF, Ang1 and TGF-ß1 and their signaling mediators, whereas NAC had no effect on VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1α gene and protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1α in fibrotic livers.

18.
Zhong Xi Yi Jie He Xue Bao ; 10(5): 561-8, 2012 May.
Artículo en Zh | MEDLINE | ID: mdl-22587979

RESUMEN

OBJECTIVE: To investigate the mechanism of Fuzheng Huayu recipe (FZHY), a compound traditional Chinese herbal medicine, against liver fibrosis related to transforming growth factor-ß1 (TGF-ß1)/Smads signaling transduction. METHODS: The research consisted of in vitro and in vivo experiments. In the in vivo experiment, 37 male Wistar rats were divided into 3 groups: 5 rats in normal group, 18 and 14 rats respectively in model and FZHY groups. Liver fibrosis was induced in rats of the model group and the FZHY group by intraperitoneal injection of dimethylnitrosamine with a dose of 10µg/kg body weight for 4 weeks. Rats in the FZHY group were administered with FZHY for 4 weeks after liver fibrosis was induced. After the treatment of FZHY, hydroxyproline (Hyp) content in rat liver tissue was assayed by Jamall's method and protein expressions of TGF-ß1, TGF-ß1 receptor I (TßR-I), Smad2, Smad3 and phosphorylated-Smad2/3 were analyzed by Western blotting. In the in vitro experiment, hepatic stellate cells (HSCs) were isolated from normal rats by in situ pronase/collagenase perfusion followed by density gradient centrifugation. On the 4th day of cell culture, HSCs were stimulated by 2.5 ng/mL TGF-ß1 for 24 h, then incubated with the medium containing 10% FZHY-medicated serum or 10µmol/L SB-431542 (a potent and specific inhibitor of TGF-ß1 receptor I kinase) for 24 h. And the HSCs without TGF-ß1 stimulating were used as control group. Protein expressions and location of α-smooth muscle actin (α-SMA) and Smad3 in HSCs were assayed by immunofluorescent staining, and the image was analyzed by Image-Pro Plus 6.1 System. RESULTS: In the in vivo experiment, liver Hyp content in the FZHY group was reduced significantly compared with the model group. FZHY also down-regulated the protein expressions of TGF-ß1, TßR-I and p-Smad2/3 in fibrotic liver tissue. In the in vitro experiment, FZHY-medicated serum incubated with TGF-ß1-stimulated HSCs significantly down-regulated the protein expression of α-SMA. It also inhibited Smad3 nuclear translocation in TGF-ß1-stimulated HSCs. CONCLUSION: The mechanism of FZHY against liver fibrosis is related to the regulation of TGF-ß1 signaling transduction pathway by inhibition of TGF-ß1 and TßR-I expressions and Smads activation in fibrotic liver tissue and HSCs.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Cirrosis Hepática Experimental/tratamiento farmacológico , Cirrosis Hepática Experimental/metabolismo , Fitoterapia , Transducción de Señal , Animales , Masculino , Ratas , Ratas Wistar , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
19.
Front Microbiol ; 13: 858546, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35572702

RESUMEN

The objective of this study was to determine the effect of pre-fermented juice, Lactobacillus plantarum, and L. buchneri on chemical composition, fermentation, aerobic stability, dynamics of microbial community, and metabolic pathway of a mixture of lucerne, wheat bran (WB), and rice straw (RS). All mixtures were ensiled for 1, 3, 5, 7, 15, 30, and 45 days after treatment with uninoculated (control, C); L. plantarum [LP, 1 × 106 cfu/g of fresh weight (FW)]; L. buchneri (LB, 1 × 106 cfu/g of FW); LP + LB (LPB, 1 × 106 cfu/g of FW of each inoculant); and pre-fermented juice (J; 2 × 106 cfu/g of FW). Four lactic acid bacteria (LAB) species from three genera were cultured from the pre-fermented juice, with W. cibaria being dominant. The inoculants increased lactic acid (LA), decreased pH and ammonia nitrogen (AN) compared to C silage at earlier stages of ensiling, and high dry matter (DM) and water-soluble carbohydrate (WSC) content in inoculated silages. Adding LPB increased the abundance of L. plantarum, L. paralimentarius, and L. nodensis, resulting in the lowest pH. Pre-fermented juice enriched W. cibaria, L. sakei, L. parabrevis, Pseudomonas putida, and Stenotrophomonas maltophilia, mainly enhanced accumulation of acetic acid (AA) and LA, and decreased pH, crude protein losses, AN, and hemicellulose contents. L. buchneri and L. brevis had a high abundance in LB-treated and J silages, respectively, inhibited undesirable bacteria, and improved aerobic stability with more than 16 days. In addition, the metabolic pathways changed with time and L. buchneri inoculants promoted global metabolism. In conclusion, inoculations altered bacterial succession and metabolic pathways in silage; LB and pre-fermented juice enhanced ensiling by promoting pH reductions, enhancing concentrations of LA and AA, and extending aerobic stability more than 16 days.

20.
Front Immunol ; 13: 995701, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211395

RESUMEN

Tuberculosis (TB) remains a major global health issue, resulting in around 1.5 million people deaths each year. Better diagnostic and therapeutic tools are urgently needed. Circular RNAs (circRNAs) are a new class of noncoding RNAs with a covalently closed structure, and exhibit a tissue-, cell-, and developmental stage-specific expression pattern. Recently, circRNAs were thought to be regulatory molecules implicated in the onset and progression of a series of human diseases including tuberculosis. In tuberculosis, circRNAs have been shown to regulate host anti-TB immune responses, such as decreasing monocyte apoptosis, enhancing autophagy and promoting macrophage polarization. Importantly, circRNAs are physically stable and abundant in several types of body fluids. Therefore they are considered as promising minimally-invasive biomarkers. In this review, we focus on the recent advances in the immune regulatory roles of circRNAs, as well as their potential diagnostic value in TB.


Asunto(s)
ARN Circular , Tuberculosis , Biomarcadores , Humanos , ARN/genética , ARN/metabolismo , ARN Circular/genética , ARN no Traducido , Tuberculosis/diagnóstico , Tuberculosis/genética , Tuberculosis/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA