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1.
J Pharm Biomed Anal ; 177: 112837, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493746

RESUMO

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.

2.
J Pharm Biomed Anal ; 177: 112873, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539711

RESUMO

A rapid, sensitive and convenient analytical method of ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2) was proposed for the simultaneous determination of characteristic alkaline and acidic components covering many structure types including alkaloids, phenolic acids, phenylpropanoids and flavonoids in Leonurus japonicus Houtt. (LJ). The proposed method was first reported and validated by assessing the matrix effects, linearity, limit of detections, limit of quantifications, precision, repeatability, stability and recovery of target components. The developed UPLC-QTRAP®/MS2 was successfully applied to simultaneously determine all target compounds in 38 batches of LJ from 11 different producing regions in China and five organs (including root, caulis, branch, flower and leaf) of LJ from the same stand planting base in Jiangsu Province (China). The result showed that LJ in different regions with different geographical position would affect the accumulation of different compounds, and the significant discrepancies of some target compounds were also observed in different organs of LJ due to different biosynthetic pathway and enzymes in different organs. Furthermore, both hierarchical clustering analysis and principal components analysis were performed to classify the 38 batches of LJ samples from different producing regions on the basis of target compounds. As a result, the samples could be mainly clustered into different groups, which were similar with areas classification. Overall, the presented method would be helpful for the comprehensive utilization and development of LJ resources.

3.
J Ethnopharmacol ; 247: 112284, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31604137

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair, the most fundamental and simplest form of herb compatibility, serves as the basic building block of traditional Chinese medicine formulae. The Danshen-Honghua herb pair (DH), composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen in Chinese) and Carthami Flos (Honghua in Chinese), has remarkable clinical efficacy to cure cardio-cerebrovascular diseases. This study was designed to investigate the pharmacodynamics of DH in comparison with single herbs and pharmacokinetics of DH relative to Danshen in acute myocardial ischemic injury. MATERIALS AND METHODS: Sixty male Wistar rats were divided into control, model and drug treated groups. The acute myocardial ischemia rat model was induced by administering 85 mg/kg/d isoproterenol (ISO) subcutaneously for two consecutive days. For pharmacodynamic study, histopathological and biochemical analysis were performed to assess the anti-myocardial ischemic effects. While for pharmacokinetic study, a UPLC-MS/MS method was developed for determination of nine main active ingredients, namely danshensu, protocatechuic acid, protocatechualdehyde, caffeic acid, lithospermic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A and salvianolic acid C in rat plasma. RESULTS: The histopathological and biochemical analysis revealed that DH exerted enhanced anti-myocardial ischemic effects against the ISO-induced myocardial ischemia compared with single herbs. The pharmacokinetic study indicated that DH could significantly increase the t1/2z of danshensu, Tmax, AUC0-∞ and MRT0-t of protocatechuic acid in comparison with Danshen alone in normal rats, but more importantly elevate systemic exposure level and prolong t1/2z of protocatechualdehyde, caffeic acid, Tmax of danshensu in acute myocardial ischemia rats. CONCLUSIONS: Our findings demonstrated the greater effects of DH after the compatibility in ISO-induced acute myocardial ischemia rats at pharmacodynamic and pharmacokinetic levels and provided valuable information for clinical application of herb pairs.

4.
Bioresour Technol ; 295: 122175, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31570260

RESUMO

The aim of this study is to reduce nitrogen (N) loss and investigate the role of ammonia (NH3) recycling on N fractions, environmental factors and bacterial communities. In this study, collected NH3 from composting and recycled in it. The results showed that NH3 recycling affected N-cycling processes such as nitrification. Redundancy Analyses (RDA) showed that NH4+-N had significantly negative correlation with denitrifying bacteria in treatment group (p < 0.05), demonstrating that NH3 recycling have influenced on the bacterial community structure. Furthermore, Structural Equation Model (SEM) revealed causal relationships between visual variables. Based on these results, we concluded that NH3 recycling is a novel method to reduce N loss.


Assuntos
Compostagem , Amônia , Nitrogênio , Esgotos , Solo
5.
Opt Lett ; 44(21): 5194-5197, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674966

RESUMO

A scheme of angular velocity measurement with an improved scale factor is proposed and experimentally demonstrated based on the joint operation of a Sagnac loop and an optoelectronic oscillator (OEO). In this scheme, the Sagnac-induced phase difference is mapped into the oscillating frequency shift of the OEO with a large scale factor by making one of the two counter-propagating signals in the Sagnac loop carrier-suppressed modulated and the other just travel through the modulator. The cascaded Sagnac loop and OEO structure can further improve the scale factor by setting a long Sagnac loop and a short OEO loop independently. A sensitivity scale factor as high as 742 kHz/(rad/s) is obtained in our experiment.

6.
Waste Manag ; 102: 452-463, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739279

RESUMO

Sustainable municipal solid waste (MSW) management is regarded as one of the key elements for achieving urban sustainability via mitigating global climate change, recycling resources and recovering energy. Landfill is considered as the least preferable disposal method and the EU Landfill Directive (ELD) announced in 1999 requires member countries to reduce the volume of landfilled biodegradable materials. The enforcement of ELD initiated the evolution of MSW management system UK. This study depicted and assessed the transition and performance of MSW management after the millennium in Nottingham via materials flow analysis (MFA), as well as appropriately selected indicators based on the concept of waste management hierarchy and targets set in waste management regulations. We observed improvements in waste reduction, material recycling, energy recovery, and landfill prevention. During the period 2001/02 to 2016/17, annual waste generation reduced from 463 kg/Ca to 361 kg/Ca, the recycling and composting share increased from 4.6% to 44.4%, and the landfill share reduced from 54.7% to 7.3%. These signs of progress are believed to be driven by the ELD and the associated policies and waste management targets established at the national and local levels. An alternative scenario with food waste and textile separation at source and utilizing anaerobic digestion to treat separately collected organic waste is proposed at the end of this paper to fulfil the high targets set by local government and we further suggest that the recycling share may be improved by educating and supporting the public on waste separation at the sources.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31756417

RESUMO

In recent decades, a growing number of structural neuroimaging studies of grey matter (GM) in trigeminal neuralgia (TN) have reported inconsistent alterations. We carried out a systematic review and meta-analysis to identify consistent and replicable GM volume abnormalities using effect-size signed differential mapping (ES-SDM). Furthermore, we conducted a meta-regression to explore the potential effects of clinical characteristics on GM volume alterations in patients with TN. A total of 13 studies with 15 datasets, representing 407 TN patients and 376 healthy individuals, were included in the present study. The results revealed that TN patients had GM volume abnormalities mainly in the basal ganglia, including the putamen, nucleus accumbens (NAc), caudate nucleus and amygdala, as well as the cingulate cortex (CC), thalamus, insula and superior temporal gyrus (STG). The meta-regression analysis showed that verbal rating scale (VRS) scores were negatively correlated with decreased GM volume in the left striatum and that illness duration was negatively correlated with decreased GM volume in the left STG and left insula. These results provide a thorough profile of GM volume alterations in TN patients and constitute robust evidence that aberrant GM volumes in the brain regions regulating and moderating sensory-motor and affective processing may play an important role in the pathophysiology of TN.

8.
Curr Microbiol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748861

RESUMO

Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.

9.
Dalton Trans ; 48(45): 16952-16960, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31687715

RESUMO

The phosphorescence lifetime approach based on the room temperature phosphorescence (RTP) property has received considerable attention in recent years due to its excellent performance in the precise measurement of oxygen. Herein, a smart nanoprobe, Gd[PC]@ZIF-8, was designed and assembled by homogenously encapsulating a rare-earth complex phosphor Gd[(Pyr)4cyclen] (Pyr = pyrenol) into a zeolitic imidazolate framework (ZIF-8). Because of the restriction of the metal-organic framework (MOF) matrix and host-guest interactions, the nanoprobe Gd[PC]@ZIF-8 exhibited highly enhanced RTP properties, including intensity, quantum yield, and elongated decay lifetime. It displayed an outstanding linear relationship between the phosphorescence decay lifetime, intensity and oxygen concentration, which can be applied in the field of oxygen sensing. Moreover, the complex Gd[(Pyr)4cyclen] in the nanoprobe Gd[PC]@ZIF-8 served as a favorable photosensitizer that resulted in the simultaneous conversion of sufficient oxygen molecules into single state oxygen (1O2) under irradiation during the phosphorescence quenching process, which is conducive to photodynamic therapy (PDT). Thus, the design of the smart nanoprobe Gd[PC]@ZIF-8 in this study provides an ingenious strategy of utilizing a MOF as a matrix to enhance the RTP properties of phosphors for synchronous oxygen sensing and PDT.

10.
Sci Total Environ ; : 134970, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31740057

RESUMO

Remediation of polycyclic aromatic hydrocarbons (PAHs) in oily sludge has become the focus of attention. UV spectrophotometer analysis showed that four types of PAHs were found in sample, which including phenanthrene, anthracene, benzo(a)anthracene and benzo(b)fluoranthene. In order to degrade PAH effectively, the laccase reverse micelles system was proposed. The system protects laccase from being affected by organic phase. Reverse micelles were prepared by using isooctane to simulate oil. The optimum water content W0 was 10 by measuring the electrical conductivity of the system. Under this condition, the effects of pH, temperature and ionic strength on the degradation rate of PAHs were investigated. Also, compared with that of non-immobilized laccase, the ratio between the secondary structures of laccase under different conditions was studied. The results showed that the highest laccase activity was obtained at pH 4.2 and 30 °C with 60 mmol/L KCl. Meanwhile, the structure of α-helix accounts for the largest proportion, and the ratio of α-helix in the laccase secondary structure in the laccase-reverse micelle system was higher than that of the non-immobilized one under this condition. Finally, predicting the reactive site of the degradation of polycyclic aromatic hydrocarbons was simulated by ORCA (Version 4.2.0). The application in oily sludge was further conducted. This study provides an effective method and basis for the degradation of PAHs in oily sludge.

11.
J Ethnopharmacol ; : 112423, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765764

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear. AIM OF THE STUDY: To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota. MATERIALS AND METHODS: MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation. RESULTS: KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg-1, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats. CONCLUSION: KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage.

12.
Biomed Pharmacother ; 121: 109595, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31710896

RESUMO

Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1ß. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 660-665, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762234

RESUMO

OBJECTIVE: To investigate the ability of osteogenic differentiation and the expression of histone demethylases KDM6B in bone marrow mesenchymal stem cells (BMSCs) in diabetic environment. METHODS: Diabetic model rats was successfully established, and BMSCs from diabetic model rats and normal rats were isolated and cultured for further study. When cultured cells, we added high concentration of glucose and advanced glycosylation products (AGE) in the medium to imitating the diabetic environment. BMSCs were divided into 6 groups: diabetes group (derived from diabets SD rats), normal group (derived from normal SD rats), high glucose group (30 mmol/L D-glucose), normal glucose group (5.5 mmol/L D-glucose), AGE group (AGE 300 µg/mL) and BSA group (BSA 300 µg/mL). BMSCs in diabetes group were derived from diabetes SD rats, while others were derived from normal SD rats. After 7 d of osteogenic induction, the cells were examined the ability of osteogenic differentiation by alkaline phosphatase (ALP) staining, the transcription levels of Runt-related transcription factor 2 (Runx2) and KDM6B were determined by RT-PCR, and the expression levels of H3K27Me3 protein were examined by Western bolt. RESULTS: Compared with the control groups, the numbers of ALP stained cells and the mRNA levels of Runx2 and KDM6B in diabetes group, high glucose group and AGE group were all decreased (P < 0.05), while H3K27Me3 protein expression levels were all increased (P < 0.05). CONCLUSION: The ability of osteogenic differentiation of BMSCs in diabetic environment was weakened, and the expression of Runx2 mRNA was inhibited, which may be related to the increased expression of H3K27Me3 after the inhibition of KDM6B expression.

14.
Mikrochim Acta ; 186(11): 721, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655930

RESUMO

A rolling-mediated cascade (RMC) amplification strategy is described for improved visualization of profiling glycans of mucin 1 (MUC 1) on cell surfaces. CdTe quantum dots (QDs) are used as fluorescent labels. The RMC based amplification allows even distinct glycoforms of MUC1 to be visualized on the surface of MCF-7 cell via an amplified Förster resonance energy transfer (FRET) imaging strategy that works at excitation/emission wavelengths of 345/610 nm. This is achieved by utilizing antibody against MUC1 modified with the fluorescent label 7-amino-4-methylcoumarin-3-acetic acid (AMCA) as the energy donor in FRET. The QDs (used to label surface glycans) act as acceptors. N-Azidoacetylgalactosamine-Acetylated (Ac4GalNAz) as a non-natural azido sugar, can be incorporated into the glycans of the cell surface, which can promote further labeling. The method has the advantage of only requiring a small amount of non-natural sugar to be introduced in metabolic glycan labeling since too much of an artificial sugar will interfere with the physiological functions of cells. Graphical abstract Schematic for the DNA rolling-mediated cascade (RMC)-assisted metabolic labeling of cell surface glycans by using CdTe quantum dots as labels and an intramolecular amplified FRET strategy for imaging glycans on a specific glycosylated protein, MUC1.

15.
ACS Appl Mater Interfaces ; 11(43): 39841-39847, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31596067

RESUMO

Developing hollow self-supported nanotube arrays with hierarchical microporous and abundant multiactive sites shows great promise for oxygen evolution reaction (OER) electrocatalysis. Herein, a facile and low-cost strategy of NiCo2S4 hollow nanotubes arrays decorated with CeOx nanoparticles (NPs) assembled on a flexible support carbon cloth (CC) for enhanced OER performance is reported. The obtained hierarchical nanoarrays CeOx/NiCo2S4/CC exhibited excellent activity toward OER with an overpotential (270 mV) at 10 mA cm-2, relatively weak Tafel slope, and distinguished durability. CeOx/NiCo2S4/CC nanoarrays not only provide fast electronic transmission and well-defined connection to the substrate but also defective sites and electron transfer by the introduction of CeOx NPs. This new strategy was offered to construct low-cost and effectively hierarchical structural electrocatalysts containing rare-earth species.

16.
J Sep Sci ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573133

RESUMO

The formation of DNA adducts by genotoxic agents is an early event in cancer development, and it may lead to gene mutations, thereby initiating tumor development. The measurement of DNA adducts can provide critical information about the genotoxic potential of a chemical and its mechanism of carcinogenesis. In recent decades, liquid chromatography coupled with mass spectrometry has become the most important technique for analyzing DNA adducts. The improvements in resolution achievable with new chromatographic separation techniques coupled with the high specificity and sensitivity and wide dynamic range of new mass spectrometry systems have been used for both qualitative and quantitative analyses of DNA adducts. This review discusses the challenges in qualitative and quantitative analyses of DNA adducts by liquid chromatography coupled with mass spectrometry and highlights recent developments towards overcoming the limitations of liquid chromatography coupled with mass spectrometry methods. The key steps and new solutions, such as sample preparation, mass spectrometry fragmentation, and method validation, are summarized. In addition, the fundamental principles and latest advances in DNA adductomic approaches are reviewed.

17.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3116-3122, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602861

RESUMO

The quality marker( Q-maker) of traditional Chinese medicine( TCM) has been the core concept of TCM quality evaluation and control in recent years. Based on the knowledge and long-term practice of the researches on TCM quality,we put forward that " Taking the effectiveness as the core,the measurability and peculiarity as necessary conditions,and considering compatibility for TCM formulae,TCM Q-makers are selected and confirmed,and then the transmission and traceability should be investigated as its functional attributes". Selecting the commonly used representative TCM as the research object,based on the score of TCM effectiveness,measurability and peculiarity,a layered three-dimensional integrated technology was adopted for the quantitative evaluation and grading identification of the Q-markers for TCM. And after Q-markers for TCM are selected and confirmed,the transmission variation of the Q-markers is studied in the whole process from the formation of TCM to its function representation. Based on TCM chemical and biological characteristics as well as effectiveness,and integrating multidisciplinary techniques and methods,researches on innovative methods for system identification and confirmation of the TCM Q-makers are developed emphatically to form representative and exemplary extensive application,which will provide significant theoretical and methodological support for effectively improving the quality control level of TCM.


Assuntos
Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Chinesa/normas , Biomarcadores , Controle de Qualidade
18.
Infect Dis (Lond) ; : 1-10, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31583932

RESUMO

Background: Pneumonia is a common respiratory disease worldwide that can be prevented and treated. However, it is considered to be the leading cause of children death. The present study was aimed to explore the functional role and molecular mechanism of miR-146b in the inflammation injury in pediatric pneumonia. Materials and methods: The lipopolysaccharide (LPS)-induced pulmonary injury cell model was established in WI-38 human lung fibroblasts cells. QRT-PCR and Western blot was applied to detect miR-146b and MyD88 expression. ELISA assay was used to analyze the production of pro-inflammatory factors. Cell viability was evaluated by CCK-8 assay. The apoptosis proteins and the downstream genes of NF-κB pathway were detected by Western blot. Results: we displayed that miR-146b was down-regulated, whereas MyD88 was up-regulated in the serum of children patients with pneumonia and in WI-38 cells treated with LPS. Moreover, re-expression of miR-146b suppressed the production of inflammatory factors in the serum of pneumonia patients and WI-38 cells treated with LPS. In addition, elevating miR-146b expression increased WI-38 cell viability and reduced cell apoptosis. More importantly, bioinformatics analysis revealed that MyD88 was a target of miR-146b and could overturn the protective effect of miR-146b on the inflammation injury in LPS-injured WI-38 cells. Furthermore, miR-146b over-expression inhibited the activation of NF-κB signaling pathway by suppressing MyD88. Conclusion: miR-146b attenuated the inflammation injury in pediatric pneumonia through inhibiting MyD88/NF-κB signaling pathway. These preliminarily findings further deepened our understanding of this mechanism and identified new potential therapeutic targets for pediatric pneumonia.

19.
Molecules ; 24(20)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614806

RESUMO

Limonin is a natural tetracyclic triterpenoid compound, which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron chinense Schneid., and Coptis chinensis Franch. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the pharmacology, toxicity, and pharmacokinetics of limonin. Therefore, this review aimed to provide the latest information on the pharmacology, toxicity, and pharmacokinetics of limonin, exploring the therapeutic potential of this compound and looking for ways to improve efficacy and bioavailability. Limonin has a wide spectrum of pharmacological effects, including anti-cancer, anti-inflammatory and analgesic, anti-bacterial and anti-virus, anti-oxidation, liver protection properties. However, limonin has also been shown to lead to hepatotoxicity, renal toxicity, and genetic damage. Moreover, limonin also has complex impacts on hepatic metabolic enzyme. Pharmacokinetic studies have demonstrated that limonin has poor bioavailability, and the reduction, hydrolysis, and methylation are the main metabolic pathways of limonin. We also found that the position and group of the substituents of limonin are key in affecting pharmacological activity and bioavailability. However, some issues still exist, such as the mechanism of antioxidant activity of limonin not being clear. In addition, there are few studies on the toxicity mechanism of limonin, and the effects of limonin concentration on pharmacological effects and toxicity are not clear, and no researchers have reported any ways in which to reduce the toxicity of limonin. Therefore, future research directions include the mechanism of antioxidant activity of limonin, how the concentration of limonin affects pharmacological effects and toxicity, finding ways to reduce the toxicity of limonin, and structural modification of limonin-one of the key methods necessary to enhance pharmacological activity and bioavailability.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1009-1016, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640961

RESUMO

OBJECTIVE: To investigate the effects of Bifidobacterium on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice. METHODS: Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (n=20) and control group (n=20) for intravenous injection of Bifidobacterium suspension (200 µL, 4 × 108 cfu/mL) and PBS (200 µL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining. RESULTS: In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. Bifidobacterium colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (P=0.01); the acoustic velocity (P=0.001) and the acoustic attenuation (P=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (P=0.0006) and larger coagulative necrosis volume (P=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (P=0.0134). CONCLUSIONS: Bifidobacterium can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.


Assuntos
Bifidobacterium/patogenicidade , Neoplasias da Mama/patologia , Ablação por Ultrassom Focalizado de Alta Intensidade , Acústica , Animais , Colágeno , Técnicas de Imagem por Elasticidade , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Distribuição Aleatória
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