Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 236
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Gastroenterol Hepatol ; 39(3): 596-607, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38059880

RESUMEN

BACKGROUND AND AIM: Circular ubiquitin-like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1-G9a-ubiquitin-like, containing PHD and ring finger domains 1 (UHRF1) mRNA-eukaryotic translation initiation factor 4A3 (EIF4A3)-PDZ and LIM domain 1 (PDLIM1) network in HCC. METHODS: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial-mesenchymal transition (EMT)-related proteins, and Hippo-Yap pathway components was determined by quantitative polymerase chain reaction (Q-PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit-8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull-down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co-immunoprecipitation was performed to examine the binding between UHRF1 and G9a. RESULTS: Circular ubiquitin-like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. CONCLUSION: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo-Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1-G9a-UHRF1 mRNA-EIF4A3-PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , ARN Helicasas DEAD-box , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/tratamiento farmacológico , ARN Mensajero/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/uso terapéutico , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina/uso terapéutico , Dominios RING Finger , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/uso terapéutico , Proteínas Potenciadoras de Unión a CCAAT/química , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Factores de Iniciación de Péptidos/genética , Factores de Iniciación de Péptidos/metabolismo , Factores de Iniciación de Péptidos/uso terapéutico , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo
2.
J Nat Prod ; 87(2): 322-331, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38334086

RESUMEN

A strategy integrating in silico molecular docking with LXRα and phenotypic assays was adopted to discover anti-hypercholesterolemia agents in a small library containing 205 marine microorganism-derived natural products, collected by our group in recent years. Two fumitremorgin derivatives, 12R,13S-dihydroxyfumitremorgin C (1) and tryprostatin A (3), were identified as potential LXRα agonists, by real-time qPCR and Western blot (WB) analysis, together with a surface plasmon resonance (SPR) assay. The anti-hypercholesterolemic effects of 1 and 3, together with their mechanisms, were investigated in depth using different cell and mouse models, among which the study of LXRα is of crucial importance. Compound 1 or 3 exhibited the capacity to effectively reverse excessive lipid accumulation in a hepatic steatosis cell model and significantly reduce liver damage and blood cholesterol levels in high cholesterol diet (HCD)-fed wild-type mice, whereas those beneficial effects were completely nullified in HCD-fed LXRα-knockout mice. Furthermore, 1 and 3 outperformed common LXRα agonists by suppressing the expression of sterol regulatory element-binding protein 1 (SREBP1) in HCD-fed mice, mitigating lipotoxicity. Thus, this study highlights the discovery of two marine microorganism-derived anti-hypercholesterolemia agents targeting LXRα.


Asunto(s)
Hipercolesterolemia , Receptores Nucleares Huérfanos , Animales , Ratones , Colesterol/metabolismo , Hipercolesterolemia/tratamiento farmacológico , Hígado , Receptores X del Hígado/metabolismo , Ratones Noqueados , Simulación del Acoplamiento Molecular , Receptores Nucleares Huérfanos/metabolismo , Receptores Nucleares Huérfanos/farmacología
3.
Pharmacol Res ; 188: 106666, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36657504

RESUMEN

Pregnane X receptor (PXR) plays an important role in the regulation of metabolic homeostasis. Yes-associated protein (YAP) is a critical regulator of liver size and liver regeneration. Recently, we reported that PXR-induced liver enlargement and regeneration depend on YAP signalling, but the underlying mechanisms remain unclear. This study aimed to reveal how PXR regulates or interacts with YAP signalling during PXR-induced hepatomegaly and liver regeneration. Immunoprecipitation (IP), Co-IP and GST pull-down assays were performed in vitro to reveal the regulatory mechanisms involved in the PXR-YAP interaction. The roles of YAP-TEAD binding and Sirt2-driven deacetylation and polyubiquitination of YAP were further investigated in vitro and in vivo. The results showed that the ligand-binding domain (LBD) of PXR and the WW domain of YAP were critical for the PXR-YAP interaction. Furthermore, disruption of the YAP-TEAD interaction using the binding inhibitor verteporfin significantly decreased PXR-induced liver enlargement and regeneration after 70 % partial hepatectomy (PHx). Mechanistically, PXR activation significantly decreased YAP acetylation, which was interrupted by the sirtuin inhibitor nicotinamide (NAM). In addition, p300-induced YAP acetylation contributed to K48-linked YAP ubiquitination. Interestingly, PXR activation remarkably inhibited K48-linked YAP ubiquitination while inducing K63-linked YAP polyubiquitination. Sirt2 interference abolished the deacetylation and K63-linked polyubiquitination of YAP, suggesting that the PXR-induced deacetylation and polyubiquitination of YAP are Sirt2 dependent. Taken together, this study demonstrates that PXR induce liver enlargement and regeneration via the regulation of YAP acetylation and ubiquitination and YAP-TEAD binding, providing evidences for using PXR as potential target to promote hepatic development and liver repair.


Asunto(s)
Hepatomegalia , Hígado , Receptor X de Pregnano , Sirtuina 2 , Proteínas Señalizadoras YAP , Animales , Ratones , Hepatomegalia/metabolismo , Receptor X de Pregnano/metabolismo , Sirtuina 2/metabolismo , Ubiquitinación , Proteínas Señalizadoras YAP/metabolismo , Hígado/fisiología
4.
Environ Sci Technol ; 57(47): 18550-18562, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36474357

RESUMEN

The efficient and selective removal of refractory antibiotics from high-strength antibiotic production wastewater is crucial but remains a substantial challenge. In this study, a novel ozone micronano-bubble (MNB)-enhanced treatment system was constructed for antibiotic production wastewater treatment. Compared with conventional ozone, ozone MNBs exhibit excellent treatment efficiency for oxytetracycline (OTC) degradation and toxicity decrease. Notably, this study identifies the overlooked singlet oxygen (1O2) for the first time as a crucial active species in the ozone MNB system through probe and electron paramagnetic resonance methods. Subsequently, the oxidation mechanisms of OTC by ozone MNBs are systematically investigated. Owing to the high reactivity of OTC toward 1O2, ozone MNBs enhance the selective and anti-interference performance of OTC degradation in raw OTC production wastewater with complex matrixes. This study provides insights into the mechanism of ozone MNB-enhanced pollutant degradation and a new perspective for the efficient treatment of high-concentration industrial wastewater using ozone MNBs. In addition, this study presents a promising technology with scientific guidance for the treatment of antibiotic production wastewater.


Asunto(s)
Oxitetraciclina , Ozono , Oxitetraciclina/análisis , Aguas Residuales , Oxígeno Singlete , Antibacterianos
5.
Pharmacol Res ; 178: 106188, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35338002

RESUMEN

Hyperbilirubinemia is a serious hazard to human health due to its neurotoxicity and lethality. So far, successful therapy for hyperbilirubinemia with fewer side effects is still lacking. In this study, we aimed to clarify the effects of oridonin (Ori), an active diterpenoid extracted from Rabdosia rubescens, on hyperbilirubinemia and revealed the underlying molecular mechanism in vivo and in vitro. Here, we showed that liver X receptor alpha (LXRα) deletion eliminated the protective effect of Ori on phenylhydrazine hydrochloride-induced hyperbilirubinemia mice, indicating that LXRα acted as a key target for Ori treatment of hyperbilirubinemia. Ori significantly increased the expression of LXRα and UDP-glucuronosyltransferase 1A1 (UGT1A1) in the liver of wild-type (WT) mice, which were lost in LXRα-/- mice. Ori or LXR agonist GW3965 also reduced lipopolysaccharide/D-galactosamine-induced hyperbilirubinemia via activating LXRα/UGT1A1 in WT mice. Liver UGT1A1 enzyme activity was elevated by Ori or GW3965 in WT mice. Further, Ori up-regulated LXRα gene expression, increased its nuclear translocation and stimulated UGT1A1 promoter activity in HepG2 cells. After silencing LXRα by siRNA, Ori-induced UGT1A1 expression was markedly reduced in HepG2 cells and primary mouse hepatocytes. Taken together, Ori stimulated the transcriptional activity of LXRα, resulting in the up-regulation of UGT1A1. Therefore, Ori or its analogs might have the potential to treat hyperbilirubinemia-related diseases through modulating LXRα-UGT1A1 signaling.


Asunto(s)
Bilirrubina , Hiperbilirrubinemia , Animales , Diterpenos de Tipo Kaurano , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Hiperbilirrubinemia/inducido químicamente , Hiperbilirrubinemia/tratamiento farmacológico , Hiperbilirrubinemia/genética , Receptores X del Hígado , Ratones
6.
Molecules ; 27(7)2022 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-35408555

RESUMEN

Hericium erinaceus, a culinary and medicinal mushroom, is widely consumed in Asian countries. Chemical investigation on the fruiting bodies of Hericium erinaceus led to the isolation of one new ergostane-type sterol fatty acid ester, erinarol K (1); and eleven known compounds: 5α,8α -epidioxyergosta-6,22-dien-3ß-yl linoleate (2); ethyl linoleate (3); linoleic acid (4); hericene A (5); hericene D (6); hericene E (7); ergosta-4,6,8(14),22-tetraen-3-one (8); hericenone F (9); ergosterol (10); ergosterol peroxide (11); 3ß,5α,6α,22E-ergosta-7,22-diene-3,5,6-triol 6-oleate (12). The chemical structures of the compounds were determined by 1D and 2D NMR (nuclear magnetic resonance) spectroscopy, mass spectra, etc. Anti-inflammatory effects of the isolated aromatic compounds (5-7, 9) were evaluated in terms of inhibition of pro-inflammatory mediator (TNF-α, IL-6 and NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. The results showed that compounds 5 and 9 exhibited moderate activity against TNF-α (IC50: 78.50 µM and 62.46 µM), IL-6 (IC50: 56.33 µM and 48.50 µM) and NO (IC50: 87.31 µM and 76.16 µM) secretion. These results supply new information about the secondary metabolites of Hericium erinaceus and their anti-inflammatory effects.


Asunto(s)
Agaricales , Factor de Necrosis Tumoral alfa , Agaricales/química , Animales , Antiinflamatorios/farmacología , Hericium , Interleucina-6 , Ratones
7.
Molecules ; 27(21)2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36364166

RESUMEN

(R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanamine, a key chiral intermediate of selective tetrodotoxin-sensitive blockers, was efficiently synthesized by a bienzyme cascade system formed by with R-ω-transaminase (ATA117) and an alcohol dehydrogenase (ADH) co-expression system. Herein, we report that the use of ATA117 as the biocatalyst for the amination of 3,5-bistrifluoromethylacetophenone led to the highest efficiency in product performance (enantiomeric excess > 99.9%). Moreover, to further improve the product yield, ADH was introduced into the reaction system to promote an equilibrium shift. Additionally, bienzyme cascade system was constructed by five different expression systems, including two tandem expression recombinant plasmids (pETDuet-ATA117-ADH and pACYCDuet-ATA117-ADH) and three co-expressed dual-plasmids (pETDuet-ATA117/pET28a-ADH, pACYCDuet-ATA117/pET28a-ADH, and pACYCDuet-ATA117/pETDuet-ADH), utilizing recombinant engineered bacteria. Subsequent studies revealed that as compared with ATA117 single enzyme, the substrate handling capacity of BL21(DE3)/pETDuet-ATA117-ADH (0.25 g wet weight) developed for bienzyme cascade system was increased by 1.50 folds under the condition of 40 °C, 180 rpm, 0.1 M pH9 Tris-HCl for 24 h. To the best of our knowledge, ours is the first report demonstrating the production of (R)-1-[3,5-bis(trifluoromethyl)phenyl]ethanamine using a bienzyme cascade system, thus providing valuable insights into the biosynthesis of chiral amines.


Asunto(s)
Alcohol Deshidrogenasa , Transaminasas , Alcohol Deshidrogenasa/genética , Transaminasas/genética , Transaminasas/metabolismo , Plásmidos/genética , Aminación , Estereoisomerismo
8.
Cancer Cell Int ; 21(1): 103, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579299

RESUMEN

PURPOSE: Glioma is the most prevalent malignant form of brain tumors, with a dismal prognosis. Currently, cancer immunotherapy has emerged as a revolutionary treatment for patients with advanced highly aggressive therapy-resistant tumors. However, there is no effective biomarker to reflect the response to immunotherapy in glioma patient so far. So we aim to assess the clinical predictive value of FCER1G in patients with glioma. METHODS: The expression level and correlation between clinical prognosis and FER1G levels were analyzed with the data from CGGA, TCGA, and GEO database. Univariate and multivariate cox regression model was built to predict the prognosis of glioma patients with multiple factors. Then the correlation between FCER1G with immune cell infiltration and activation was analyzed. At last, we predict the immunotherapeutic response in both high and low FCER1G expression subgroups. RESULTS: FCER1G was significantly higher in glioma with greater malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio of FCER1G expression (Low versus High) was 0.66 and 95 % CI is 0.54 to 0.79 (P < 0.001), whereas age (HR = 1.26, 95 % CI 1.04-1.52), grade (HR = 2.75, 95 % CI 2.06-3.68), tumor recurrence (HR = 2.17, 95 % CI 1.81-2.62), IDH mutant (HR = 2.46, 95 % CI 1.97-3.01) and chemotherapeutic status (HR = 1.4, 95 % CI 1.20-1.80) are also included. Furthermore, we illustrated that gene FCER1G stratified glioma cases into high and low FCER1G expression subgroups that demonstrated with distinct clinical outcomes and T cell activation. At last, we demonstrated that high FCER1G levels presented great immunotherapeutic response in glioma patients. CONCLUSIONS: This study demonstrated FCER1G as a novel predictor for clinical diagnosis, prognosis, and response to immunotherapy in glioma patient. Assess expression of FCER1G is a promising method to discover patients that may benefit from immunotherapy.

9.
Bioorg Chem ; 112: 104927, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33932772

RESUMEN

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo2(OAc)4-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRß and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (KD) value of 6.2 µM, demonstrated 6 could act as a new potential LXR agonist.


Asunto(s)
Cromonas/farmacología , Receptores X del Hígado/metabolismo , Neglecta/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromonas/química , Cromonas/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Humanos , Receptores X del Hígado/genética , Estructura Molecular , Relación Estructura-Actividad
10.
BMC Pulm Med ; 21(1): 182, 2021 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-34051779

RESUMEN

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) encompasses a rare and agnogenic group of diffuse alveolar capillary hemorrhagic diseases. Corticosteroid treatment is the globally preferred therapeutic strategy for IPH; however, it can cause immunodeficiency. Nocardia infection often occurs in immunocompromised patients and primarily involves the pleura and lungs. Herein, we describe a case of pediatric pulmonary Nocardia infection after the corticosteroid treatment of IPH. CASE PRESENTATION: A 7-year-old girl presented with chief complaints of pale complexion persisting for 1 year and a cough for 20 days. Abundant hemosiderin-laden macrophages were detected in the gastric juice, which supported the diagnosis of IPH. Uninterrupted doses of corticosteroids were administered during the last hospitalization. After nearly 2 months of corticosteroids therapy, the patient began to cough and produce a purulent sputum. Next-generation sequencing of the bronchoalveolar lavage fluid revealed Nocardia abscessus (N. abscessus) DNA. Linezolid was administered with good response, and the patient was discharged after 18 days of hospitalization. Her symptoms and pulmonary lesions had recovered, and the IPH appeared to be well-controlled with low dose of corticosteroids in follow-up. CONCLUSIONS: Nocardia infection should be considered in the differential diagnoses for IPH patients receiving corticosteroid therapy, especially in patients with poor response to conventional empirical antibiotic therapy. Next-generation sequencing of bronchoalveolar lavage fluid may be used to quickly identify the Nocardia. Sulfonamides or linezolid are effective for pediatric pulmonary Nocardia infection.


Asunto(s)
Hemosiderosis/complicaciones , Hemosiderosis/diagnóstico , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico , Nocardiosis/complicaciones , Nocardiosis/diagnóstico , Nocardia/genética , Corticoesteroides/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Niño , Diagnóstico Diferencial , Femenino , Hemosiderosis/tratamiento farmacológico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Huésped Inmunocomprometido , Enfermedades Pulmonares/tratamiento farmacológico , Macrófagos/patología , Nocardiosis/etiología , Hemosiderosis Pulmonar
11.
BMC Musculoskelet Disord ; 22(1): 686, 2021 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-34384393

RESUMEN

BACKGROUND: Total two-stage exchange is commonly used in clinical practice as a treatment for infected total hip arthroplasty (THA); however, this approach involves considerable limitations, including significant bone loss and severe trauma. This retrospective cohort study was conducted to evaluate clinical outcomes following the use of partial two-stage exchange (PTE) for infected THA. METHODS: We performed a retrospective analysis of 28 patients with infected THA who were treated by PTE between September 2000 and June 2019. Eligibility for PTE was limited to patients with a well-fixed femoral stem prosthesis. In the first stage of the operation, the femoral stem prosthesis was preserved; subsequently, the acetabular prosthesis, liner, and head were replaced with an antibiotic-loaded spacer. The new prosthesis was then implanted into patients and monitored for at least 3 months to ensure freedom from infection. RESULTS: Patients were followed for an average of 4 years (range, 2-11 years), with an overall success rate of 85.7% (24/28). The mean Harris hip score at the final follow-up was 76.2 ± 11.7 points. CONCLUSIONS: The findings of this study suggest that PTE could be an acceptable option for a subset of patients with infected THA, offering a satisfactory infection control rate and clinical outcomes comparable to those of total two-stage exchange, but with less harm.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Infecciones Relacionadas con Prótesis , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Humanos , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
12.
Drug Dev Res ; 82(4): 575-580, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33377532

RESUMEN

Acute liver injury (ALI) is a serious syndrome that is associated with high mortality, but there are few effective treatments. The activation of NLRP3 inflammasome is associated with ALI. Oridonin is a natural substance with an anti-inflammatory effect and has been reported to be an inhibitor of NLRP3. The aim of this study was to investigate the protective effect of oridonin on d-galactosamine (d-GalN)/lipopolysaccharide (LPS)-induced ALI and whether the effect is mediated by NLRP3. Mice were pretreated with oridonin (5 or 10 mg/kg) for 3 days. Then, they were injected with d-GalN (400 mg/kg) and LPS (40 µg/kg). The levels of inflammatory factors were measured by RT-PCR, Western blot, and enzyme-linked immunosorbent assay. We confirmed that oridonin significantly alleviated ALI induced by d-GalN/LPS in mice. Oridonin markedly decreased the inflammatory response by reducing the levels of inflammatory cytokines. More importantly, oridonin markedly reduced the expression of NLRP3, caspase-1, IL-18, and IL-1ß. This study showed that oridonin has a protective effect on d-GalN/LPS-induced ALI, and the underlying mechanisms may be associated with the inhibition of the NLRP3 inflammatory pathways.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Diterpenos de Tipo Kaurano/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Animales , Galactosamina , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos C57BL
13.
Entropy (Basel) ; 23(3)2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33668394

RESUMEN

Obstructive sleep apnea (OSA) is associated with reduced heart rate variability (HRV) and autonomic nervous system dysfunction. Sample entropy (SampEn) is commonly used for regularity analysis. However, it has limitations in processing short-term segments of HRV signals due to the extreme dependence of its functional parameters. We used the nonparametric sample entropy (NPSampEn) as a novel index for short-term HRV analysis in the case of OSA. The manuscript included 60 6-h electrocardiogram recordings (20 healthy, 14 mild-moderate OSA, and 26 severe OSA) from the PhysioNet database. The NPSampEn value was compared with the SampEn value and frequency domain indices. The empirical results showed that NPSampEn could better differentiate the three groups (p < 0.01) than the ratio of low frequency power to high frequency power (LF/HF) and SampEn. Moreover, NPSampEn (83.3%) approached a higher OSA screening accuracy than the LF/HF (73.3%) and SampEn (68.3%). Compared with SampEn (|r| = 0.602, p < 0.05), NPSampEn (|r| = 0.756, p < 0.05) had a significantly stronger association with the apnea-hypopnea index (AHI). Hence, NPSampEn can fully overcome the influence of individual differences that are prevalent in biomedical signal processing, and might be useful in processing short-term segments of HRV signal.

14.
J Cell Mol Med ; 24(18): 10444-10457, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32681612

RESUMEN

Over-activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti-inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose-dependent manner, significantly decreased osteoclast-related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor-kappaB (NF-κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency-induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down-regulating the NF-κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.


Asunto(s)
Resorción Ósea/patología , Estrógenos/deficiencia , Glucósidos/farmacología , Taninos Hidrolizables/farmacología , FN-kappa B/metabolismo , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/farmacología , Actinas/metabolismo , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Glucósidos/química , Taninos Hidrolizables/química , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoprotegerina/metabolismo , Ovariectomía , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
15.
Chem Res Toxicol ; 33(7): 1798-1808, 2020 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-32538071

RESUMEN

Emodin is the main toxic component in Chinese medicinal herbs such as rhubarb. Our previous studies demonstrated that genetic polymorphisms of UDP-glucuronosyltransferase 2B7 (UGT2B7) had an effect on the glucuronidation and detoxification of emodin. This study aimed to reveal the transcriptional regulation mechanism of UGT2B7 on emodin glucuronidation and its effect on toxicity. Emodin glucuronic activity and genome and transcriptome data were obtained from 36 clinical human kidney tissues. The genome-wide association studies (GWAS) identified that four single nucleotide polymorphisms (SNPs) (rs6093966, rs2868094, rs2071197, and rs6073433), which were located on the hepatocyte nuclear factor 4α (HNF4A) gene, were significantly associated with the emodin glucuronidation (p < 0.05). Notably, rs2071197 was significantly associated with the gene expression of HNF4A and UGT2B7 and the glucuronidation of emodin. The gene expression of HNF4A showed a high correlation with UGT2B7 (R2 = 0.721, p = 5.83 × 10-11). The luciferase activity was increased 7.68-fold in 293T cells and 2.03-fold in HepG2 cells, confirming a significant transcriptional activation of UGT2B7 promoter by HNF4A. The knockdown of HNF4A in HepG2 cells (36.6%) led to a significant decrease of UGT2B7 (19.8%) and higher cytotoxicity (p < 0.05). The overexpression of HNF4A in HepG2 cells (31.2%) led to a significant increase of UGT2B7 (24.4%) and improved cell viability (p < 0.05). Besides, HNF4A and UGT2B7 were both decreased in HepG2 cells and rats after treatment with emodin. In conclusion, emodin used long term or in high doses could inhibit the expression of HNF4A, thereby reducing the expression of UGT2B7 and causing hepatotoxicity.


Asunto(s)
Emodina/farmacocinética , Glucurónidos/metabolismo , Glucuronosiltransferasa/genética , Factor Nuclear 4 del Hepatocito/genética , Animales , Línea Celular , Emodina/farmacología , Estudio de Asociación del Genoma Completo , Glucuronosiltransferasa/metabolismo , Factor Nuclear 4 del Hepatocito/metabolismo , Humanos , Riñón/metabolismo , Masculino , Polimorfismo de Nucleótido Simple , Ratas Sprague-Dawley
16.
J Nat Prod ; 83(4): 1258-1264, 2020 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-32283019

RESUMEN

Seven unusual new ene-yne hydroquinones (1-3, 5-8), including three rare glycosylated derivatives named pestalotioquinosides A-C (6-8), were obtained from the marine-derived strain SCSIO41403 of the fungus Pestalotiopsis neglecta. Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and in vitro surface plasmon resonance studies showed that pestalotioquinoside C (8) could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene ABCA1 was significantly upregulated by 8, which revealed 8 as a potential LXRα agonist.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/química , Hidroquinonas/química , Receptores X del Hígado/química , Transportador 1 de Casete de Unión a ATP/aislamiento & purificación , Transportador 1 de Casete de Unión a ATP/farmacocinética , Receptores X del Hígado/aislamiento & purificación , Receptores X del Hígado/metabolismo , Simulación del Acoplamiento Molecular , Estructura Molecular , Neglecta/química , Pestalotiopsis/química , Xylariales/química
17.
BMC Pediatr ; 20(1): 61, 2020 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-32039717

RESUMEN

BACKGROUND: Plastic bronchitis (PB) frequently occurs as a serious postoperative complication of the Fontan procedure. The definitive causes of PB are unknown. CASE PRESENTATION: Herein, we report a pediatric case of PB secondary to adenoviral infection. A 4-year-old girl was admitted to the general pediatric ward for cough since 2 weeks and fever since 11 days. Consolidated lesions were noted in the right upper and both lower lung lobes. Extracorporeal membrane oxygenation was performed because the patient's respiratory failure remained unalleviated despite the use of a ventilator. Bronchial dendritic casts were extracted using flexible bronchoscopy, and the patient's breathing improved. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. The exfoliated cells of sputum and cells from bronchoalveolar lavage fluid were positive for adenoviral antigen. Human adenovirus 7 was detected by next-generation sequencing of the bronchoalveolar lavage fluid. The patient recovered and was discharged 39 days after admission without recurrence of cough or wheezing. CONCLUSIONS: PB due to human adenovirus 7 infection should be considered in children with persistent respiratory failure. Flexible bronchoscopy should be performed early to confirm diagnosis and to remove any airway obstruction.


Asunto(s)
Infecciones por Adenoviridae , Antibacterianos , Bronquitis , Infecciones por Adenoviridae/complicaciones , Bronquitis/diagnóstico , Bronquitis/virología , Broncoscopía , Niño , Preescolar , Femenino , Humanos , Plásticos , ARN Ribosómico 16S
18.
Clin Anat ; 33(5): 637-642, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31573096

RESUMEN

External fixation is a common, efficient technique used for humeral shaft stabilization and elbow fractures. There are reports of radial nerve injuries associated with this procedure. In this study, we investigated the course and variability of the radial nerve along the lateral humerus in relation to the elbow joint to determine a relatively safe zone for lateral pin placement in external fixation. Twenty upper extremities from 10 cadavers were studied. The nerve branches and course of the radial nerve along the lateral humerus were carefully dissected. Straight lines (a, b, and c) were made connecting three landmarks (the acromion, coracoid process, and anterior wall of the axilla) in the proximal upper extremity to the lateral condyle (LC) of the humerus; their intersections with the radial nerve (A, B, and C) were marked. We analyzed whether the intersection positions were correlated with the connecting line lengths. The mean lengths of the connecting lines were (a) 27.24 ± 2.57, (b) 26.18 ± 2.79, and (c) 20.95 ± 1.44 cm; the distance between the intersection points and the LC of the humerus were (Aa) 7.56 ± 1.31, (Bb) 6.90 ± 2.27, and (Cc) 5.01 ± 0.83 cm; and the measured intersection points of the radial nerve in the lateral aspect of the humerus were (A) 18.48%-34.82%, (B) 13.48%-40.00%, and (C) 19.27%-28.05% of the lengths of lines a, b, and c, respectively. Our data provide a more reliable reference to predict the course of the radial nerve on the lateral humerus and define a safe zone for pin placement. Clin. Anat., 33:637-642, 2020. © 2019 Wiley Periodicals, Inc.


Asunto(s)
Clavos Ortopédicos , Articulación del Codo/inervación , Húmero/inervación , Nervio Radial/anatomía & histología , Anciano , Anciano de 80 o más Años , Puntos Anatómicos de Referencia , Cadáver , Femenino , Fijación de Fractura/métodos , Humanos , Masculino , Persona de Mediana Edad
19.
Hemoglobin ; 44(2): 131-133, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32281892

RESUMEN

ß-Thalassemia (ß-thal) is a common hematological disorder in the Guangxi Zhuang Autonomous Region of Southern China. Heterozygous ß-thal is usually associated with reduced hematological indices and increased Hb A2 levels. However, the preventive program of the regional government only conducts the screening of hematological indices [complete blood count (CBC)] especially at primary hospitals. In this study, we describe a male ß-thal patient presenting normal hematological indices but with a high Hb A2 level. We proposed that hemoglobin (Hb) analysis and CBC should be performed together in the preventive screening program in regions with a high thalassemia incidence to avoid misdiagnosis.


Asunto(s)
Hemoglobina A2/análisis , Talasemia beta/sangre , Adulto , Pueblo Asiatico/genética , Recuento de Células Sanguíneas , China/epidemiología , Humanos , Masculino , Talasemia beta/diagnóstico , Talasemia beta/epidemiología , Talasemia beta/genética
20.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1357-1362, 2020 Mar.
Artículo en Zh | MEDLINE | ID: mdl-32281348

RESUMEN

The aim of this paper was to evaluate the key production processes of Schizonepetae Herba formula granules based on the new model of combining characteristic chromatogram with quantitative transfer relationship. The rationality of production process design was evaluated by studying the intermediates in different processes of formula granules, analyzing the loss of index component pulegone in each step, and establishing the characteristic chromatogram. The content of pulegone in 10 batches of standard decoction ranged between 0.067% and 0.124%(70%-130% of the average value), and the transfer rate of pulegone was 44.58%-93.97%. After the improvement of the production process, the content of pulegone in Schizonepetae Herba formula granules was 0.093%, and the transfer rate of pulegone was 68.38%, which was consistent with the parameters range of standard decoction. This study emphasized the integrality of the research process of traditional Chinese medicine(TCM) formula granules, and provided a new idea for the quality control of TCM with content determination as the main evaluation index for a long time.


Asunto(s)
Medicamentos Herbarios Chinos/química , Lamiaceae/química , Control de Calidad , Cromatografía Líquida de Alta Presión , Medicina Tradicional China
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA