Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
1.
Neuroscience ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711814

RESUMO

Excessive dietary fat intake is considered a great risk factor for metabolic disorders as well as cognitive dysfunction. However, the potential mechanisms underlying the effects of a high-fat diet (HFD) on the brain remain rather obscure. The purpose of this study was to address how early exposure to HFD induces biochemical changes in different brain regions and affects short- and long-term memory. Mice were fed HFD or normal chow for 4 or 7 weeks beginning in adulthood. Our results showed that oxidative stress and biochemical alterations first appeared in the hippocampus after 4 weeks of exposure and were aggravated by a longer exposure time. Additionally, the HFD-fed mice displayed long-term memory impairments, but the performance of the mice in both the HF-4W and HF-7W groups on behavioral tests relying on short-term memory was not affected. The effect of HFD on the brain was also assessed by electrophysiology, which detected a gradual decrease in long-term potentiation in the CA1 region of the hippocampus. The abnormal expression of proteins associated with synaptic function, e.g. synaptophysin, CaMKII, CaMKIV, calcineurin A, ERK and c-fos, was observed in the hippocampus in response to HFD. These results indicate that HFD elicits rapid biochemical and neurological abnormalities in the hippocampus that contribute to cognitive defects and are potentially connected to the HFD-induced suppression of brain activity.

2.
Biochem Pharmacol ; : 113694, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31706845

RESUMO

Poor bioavailability and limited efficacy are challenges associated with using andrographolide as a therapeutic agent. We recently synthesized AGS-30, a new andrographolide derivative, in our laboratory. In this study we investigated the potential anti-tumor effect of AGS-30 and the underlying mechanisms, particularly those related to angiogenesis. Results from our in vitro experiments showed that AGS-30 exerted anti-angiogenic effects by inhibiting endothelial cell proliferation, migration, invasion, and tube formation. Phosphorylation and activation of angiogenesis-related signaling molecules (e.g., vascular endothelial growth factor [VEGF] receptor 2, mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2, mechanistic target of rapamycin [mTOR], protein kinase B [Akt], and p38) were markedly reduced by AGS-30. Meanwhile, AGS-30 potently inhibited cell proliferation and phosphorylation of cell survival-related proteins (e.g., Akt, mTOR, and ERK1/2) and decreased the expression of VEGF in HT-29 colon cancer cells. AGS-30 blocked microvessel sprouting in a rat aortic ring model and blood vessel formation in zebrafish embryos and a mouse Matrigel plug model. Additionally, AGS-30 suppressed tumor growth and angiogenesis in HT-29 colon cancer cell xenografts in nude mice. These effects were not observed when same concentration of andrographolide, the parent compound of AGS-30, was used. Thus, AGS-30 exerted a strong antitumor effect by inhibiting tumor cell growth and angiogenesis and is a candidate compound for the treatment of cancer.

3.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3391-3398, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602900

RESUMO

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Neoplasias/tratamento farmacológico , Fenantrenos/farmacologia , Tripterygium/química , Apoptose , Autofagia , Pontos de Checagem do Ciclo Celular , Compostos de Epóxi/farmacologia , Humanos
4.
Int J Pharm ; 571: 118707, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31593807

RESUMO

The wound healing effects of pharmaceutic preparations of Periplaneta americana, Kangfuxin liquid, have been widely utilized in clinics. However, its wound repair efficacy is limited due to short retention capability on cutaneous wound location. Herein, Periplaneta americana extract (PAE), which showed pro-fibrogenic and pro-angiogeneic effects, was embedded into hydrogel film (PAE/Film) by solution cast method by blending polyvinyl alcohol, hydroxypropyl chitosan and carbomer at the weight ratio of 78/6/3, with glycerol as plasticizer. PAE/Film exhibited smooth, flexible, and excellent swelling ability (WVTR of 2464 ±â€¯31.5 g/m2/day), characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, meting the condition of ideal wound dressing. The superior wound healing capacity of PAE/Film was demonstrated that it significantly accelerated wound healing process in vivo in both full-thickness skin defect and scald wounded models. Compared to saline, blank vehicle (drug-free) and free PAE group, PAE/Film could accelerate wound healed, promote re-epithelialization and collagen deposition by means of TGF-ß/Smad signal pathway activation. Taken together, this novel hydrogel film-loading PAE would be a useful pharmaceutic candidate for acute cutaneous wound health care.

5.
J Orthop Surg Res ; 14(1): 296, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484533

RESUMO

BACKGROUND: Osteosarcoma is aggressive and prognostic biomarkers are important to predict the outcomes of surgery and chemotherapy. Here, we investigated the potential of transferrin receptor-1 (TfR1) and vascular endothelial growth factor (VEGF) as prognostic markers of osteosarcoma. METHODS: TfR1 and VEGF in osteosarcoma samples from a cohort of 53 osteosarcoma patients were detected by immunohistochemistry analysis. The correlation of TfR1 and VEGF levels with clinicopathological parameters was analyzed by Pearson chi-square and Spearman-rho tests. Overall patient survival was analyzed by the Kaplan-Meier method. RESULTS: We found that TfR1 and VEGF expression levels were low in 20.8% and 18.9%; modest in 35.8% and 35.8%; and high in 43.4% and 45.3% of osteosarcoma patients, respectively. TfR1 and VEGF expression was significantly correlated to histologic grade, Enneking stage, and distant metastasis. TfR1 expression was significantly correlated to VEGF expression and both TfR1 expression and VEGF expression were correlated to shorter overall survival. CONCLUSIONS: TfR1 and VEGF are potential prognostic factors for osteosarcoma.

6.
JAMA Netw Open ; 2(9): e1911970, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539079

RESUMO

Importance: Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood. Objective: To assess the association between metabolomics and lung cancer risk among never-smoking women. Design, Setting, and Participants: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018. Exposures: Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured. Main Outcomes and Measures: Incident lung cancer. Results: Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation. Conclusions and Relevance: This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.

7.
Environ Health Perspect ; 127(9): 97001, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31487206

RESUMO

BACKGROUND: Lung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified. OBJECTIVES: We aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer. METHODS: Using a population-based case-control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables. RESULTS: The strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide ([Formula: see text]) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]) were associated with lung cancer in the multipollutant models. CONCLUSIONS: To our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913.

8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 898-903, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511208

RESUMO

OBJECTIVE: To investigate the effect of miR-186 inhibition on the expression of hypoxia-inducible factor-1α (HIF-α) and mitochondrial function in hypoxic vascular endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) cultured in routine or hypoxic conditions for 6 h were examined for the expression of miR-186. A miR-186 inhibitor was transfected in the HUVECs, and the cells were subsequently cultured in hypoxic condition for 6 h to observe the changes in the mitochondrial structure under an electron microscope. The changes in the mRNA and protein expressions of HIF-1α in response to miR-186 interference were tested using real-time fluorescent quantitative PCR and Western blotting. RESULTS: The expression of miR-18 was mildly increased in HUVECs after hypoxic exposure for 6 h (P=0.0188). Interference of miR-186 expression obviously promoted the mRNA and protein expressions of HIF-1α in HUVECs. In hypoxic conditions, miR-186 interference significantly reduced mitochondrial damage in HUVECs as observed under electron microscope (P=0.0297). CONCLUSIONS: Inhibition of miR-186 protects vascular endothelial cells against hypoxic injuries by promoting HIF-α expression to lessen mitochondrial damage, suggesting the possibility of targeted miR-186 interference for treatment of hemorrhagic shock.


Assuntos
Veias Umbilicais , Hipóxia Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , MicroRNAs , Mitocôndrias
9.
Carbohydr Polym ; 223: 115057, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31427002

RESUMO

It is of vital significance to fabricate high-value-added materials from agricultural wastes by environmentally friendly and cost-effective processes. In this work, we propose an approach to directly and completely convert agricultural straw into multifunctional all-biomass films by introducing an entanglement network of additional cellulose to enhance the strength of the regenerated straw. First, natural wheat straw is dissolved in the ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl). Then, a small amount of cellulose with a high degree of polymerization (DP) is introduced to obtain straw/cellulose/AmimCl solutions, which are subsequently soaked in water for biomass regeneration, washed and dried to obtain straw/cellulose films. Dynamic shear rheological test confirms that after adding high-DP cellulose, an enhanced entanglement network forms in the solutions, which is essential to the processing and mechanical properties of materials. Extensional rheological test indicates that straw/cellulose/AmimCl solutions exhibit excellent spinnability and film-forming properties based on a significant increase in the capillary break-up time. Therefore, after regeneration in water, straw-based all-biomass films with high mechanical strength are obtained. When the content of additional wood pulp (WP, DP = 1300) with respect to total solids is 25 wt%, the obtained straw/WP all-biomass film reaches a tensile strength of 62 MPa. More interestingly, because there is no intentional chemical pretreatment and compositional isolation involved in this process, almost all of the components in straw, such as cellulose, lignin, hemicellulose and inorganic compounds, are retained in the final films. Thus, the resultant films have a superhigh haze of 97% while preventing 97% UVA (320-400 nm) and almost 100% UVB (280-320 nm). In sum, we demonstrate the complete and value-added utilization of low-grade bioresources by a facile, green and economical process to fabricate high-strength, high-haze and UV-shielding all-biomass films, which have great potential in low-cost, biodegradable and environmentally friendly packaging.

10.
J Crohns Colitis ; 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325355

RESUMO

BACKGROUND AND AIMS: Despite the presence of neutrophil extracellular traps (NETs) in inflamed colon has been confirmed, the role of NETs, especially the circulating NETs, in the progression and thrombotic tendency of inflammatory bowel disease (IBD) remains elusive. We extended our previous study to prove that NETs constitute a central component in the progression and prothrombotic state of IBD. METHODS: 48 consecutive patients with IBD were studied. Acute colitis was induced by the treatment of C57BL/6 mice with 3.5% DSS in drinking water for 6 days. Peripheral blood neutrophils and sera were collected from IBD patients and murine colitis models. Exposed phosphatidylserine (PS) was analyzed with flow cytometry and confocal microscopy. Procoagulant activity was evaluated using clotting time, purified coagulation complex and fibrin formation assays. RESULTS: We observed higher plasma NET levels and presence of NETs in colon tissue in patients with active IBD. More importantly, NETs were induced in mice with dextran sulfate sodium (DSS)-colitis and inhibition of NET release attenuated colitis as well as colitis-associated tumorigenesis. NET degradation through DNase administration decreased cytokine levels during DSS-induced colitis. In addition, DNase treatment also significantly attenuated the accelerated thrombus formation and platelet activation observed in DSS-induced colitis. NETs triggered PS-positive microparticle release and PS exposure on platelets and endothelial cells partially through TLR2 and TLR4, converting them to a procoagulant phenotype. CONCLUSIONS: NETs exacerbate colon tissue damage and drive thrombotic tendency during active IBD. Strategies directed against NET formation may offer a potential therapeutic approach for the treatment of IBD.

11.
Food Chem Toxicol ; 131: 110539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158404

RESUMO

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and ß-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.


Assuntos
Fármacos Gastrointestinais/farmacologia , Orchidaceae/química , Polissacarídeos/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Linhagem Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Etanol , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
12.
Carbohydr Polym ; 219: 56-62, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151546

RESUMO

Two new groups of cellulose esters with a substituent, either trifluoromethylbenzoate or methylbenzoate, were synthesized in homogeneous conditions. The actual presence of aromatic substituents was demonstrated by 1H-NMR spectra. The mechanical and structural peculiarities were determined by Depth Sensing Indentation (DSI) and Positron Annihilation Lifetime Spectroscopy (PALS) techniques. The relative position of CH3 and CF3 groups on the aromatic substituents influences the molecular packing differently and affects the formation of free volumes. The hardness characteristics and modulus of the corresponding cellulose esters were the lowest when the CH3 and CF3 groups are in m-position on the aromatic substituents. Meanwhile, they exhibited the highest number density of the free volume holes, as revealed by the o-Ps intensity values. An inverse linear relationship between the hardness, respectively on the modulus, and the o-Ps intensity was found. A simplified scheme of the structural feature of the investigated cellulose esters was proposed.

13.
Epigenetics ; 14(11): 1112-1124, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31241004

RESUMO

Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( ≥ 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis p-value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni p-value < 0.05). We identified a 609 basepair region in the TRIM68 gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (p-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.

14.
Biomed Chromatogr ; 33(11): e4617, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31207665

RESUMO

Siwu decoction (SWD), a traditional Chinese medicinal formula with over 1000 years of clinical history, is widely used for gynecological disease, especially blood deficiency syndrome, which is similar to anemia in modern medicine. In view of metabonomics being useful approach to investigate the potential mechanisms of action from the point of view of systems biology, in this study an ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry method was employed for a holistic evaluation of SWD on a blood-deficiency rat model induced by N-acetylphenylhydrazine and cyclophosphamide via plasma metabonomics study. Routine blood examination results showed that SWD could significantly improve the declining hemogram indices. Meanwhile, the plasma metabonomics profiles in different groups were analyzed and differentiating metabolites were primarily visualized through chemometric analysis. Seven biomarkers were identified in plasma samples of blood-deficiency rat model compared with the normal group. Five main metabolism pathways were suggested using the Kyoto Encyclopedia of Genes and Genomes Pathway Analysis and Pathway Activity Profiling algorithm analysis. This indicated that SWD played a therapeu role in blood deficiency by regulating the aberrant endogenous metabolites. To sum up, this study provides clear evidence that a metabonomics study could serve as a useful tool to elucidate the systematic therapeutic profiles and mechanisms for blood deficiency syndrome of Chinese herbal medicines.

15.
Anal Chim Acta ; 1073: 90-98, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31146840

RESUMO

It is challenging to design and fabricate new and high-performance cellulose-based chiral stationary phases (CSPs), due to the indistinct chiral recognition mechanism and the inherent difficulty to control the structure of cellulose derivatives. Herein, taking advantage of the high regioselective benzoylation of cellulose in 1-allyl-3-methylimidazolium chloride, a series of regioselectively substituted cellulose mixed esters, cellulose 6-benzoate-2,3-phenylcarbamate, are directly obtained by a facile two-steps route without protecting and deprotecting process. The resultant cellulose mixed esters exhibit high chiral recognition capability. In particular, when the benzoate group has an electron-donating substituent on phenyl ring, such as 4-tert-butyl group, the corresponding regioselectively substituted cellulose mixed esters have much better enantioseparation capability than cellulose tri(3,5-dimethylphenylcarbamate), which is commercially available as Chiralcel OD column, one of the most powerful CSPs. More importantly, via adjusting the chemical structure of cellulose derivatives and adding a post-treatment process to optimize their chiral recognition properties, the chiral recognition mechanism is clearly revealed. The synergy of the hydrophobic helical conformation, weak hydrogen-bond donating ability and appropriate distribution of substituents of cellulose derivatives is essential to fabricate high-performance CSPs.

16.
Pharmacol Res ; 146: 104313, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202781

RESUMO

The therapeutic outcomes of doxorubicin (Dox) treatment in breast cancer are limited by decreased drug efficiency and cardiotoxicity. The aim of this study was to investigate whether oridonin (Ori), a natural chemical abundant in the Chinese herb Isodon rubescens, might potentiate the anticancer effects, and decrease the adverse cardiotoxic effects, of Dox. On the basis of the optimized drug ratio determined through combination index calculations, we evaluated the synergistic effects and potential mechanisms of combining Dox with Ori to suppress breast cancer growth and angiogenesis both in vitro and in vivo. Dox plus Ori synergistically induced apoptosis in MDA-MB-231 cells, in a manner involving regulation of the Bcl-2/Bax, PARP, Caspase 3 and Survivin signaling pathways. Additionally, Ori increased the intracellular accumulation of Dox in MDA-MB-231 cells. Moreover, Dox plus Ori significantly decreased the proliferation, migration, invasion and tube formation of HUVECs. The underlying anti-angiogenic mechanism may have been due to the inhibition of VEGFR2-mediated signaling. Computational docking analysis further demonstrated that Dox plus Ori had high affinity toward the ATP-binding domain of VEGFR-2 kinase. Consistently with these findings, in vivo studies indicated that Ori enhanced the antitumor effect of Dox via activating apoptosis and inhibiting blood vessel formation at tumor sites. Moreover, Ori reversed the Dox-induced cardiotoxicity in a mouse model. In conclusion, our findings provide strong evidence that Ori may be highly promising in enhancing the efficacy of Dox and decreasing its adverse cardiotoxic effects, thus suggesting that Ori may serve as a potential adjunct therapy during Dox-based chemotherapy.

17.
Waste Manag ; 87: 326-334, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31109532

RESUMO

The humic-like substances (HLS) are proposed to be formed by biotic and abiotic pathways. The abiotic pathways were neglected in existed composting studies. The present study aims to accelerate the abiotic pathways, and to investigate how MnO2 drives the HLS transformation via changing the contribution of abiotic and biotic pathways during composting with different materials. Parallel factor analysis model (PARAFAC), hetero two-dimensional correlation spectra (hetero-2DCOS) and variance partitioning were used to identify the effects of MnO2 on the formation of humic acid (HA) and fluvic acid (FA) during composting of chicken manure (CM) and corn straw (CS). The addition of MnO2 could change the structures of HLS during CS and CM composting, mainly promoting the formation of complex components in HA and FA during CS composting, as well as the complex components of FA during CM composting. Meanwhile, the addition of MnO2 could reshape the microbial ecology, which enhanced the correlation between microbes and complex components formation during composting, especially in CM composting. Variance partitioning showed that both abiotic and biotic pathways were stimulated in conversion of HLS components after adding MnO2 during CS composting, especially for the abiotic pathways. During CM composting, the MnO2 promoted biotic effects on the conversion of HLS components. Above all, the addition of MnO2 could stimulate pathways of biotic, abiotic or both of them to improve the humification degree of HLS by changing microbial ecology, which could be a promising way for promoting the application value of composting products.


Assuntos
Compostagem , Animais , Substâncias Húmicas , Esterco , Solo , Zea mays
18.
BMJ Open ; 9(4): e024090, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31028035

RESUMO

OBJECTIVE: Engaging in physical activity (PA) plays an important role in promoting physical and mental health, but the PA data for Chinese preschool children are lacking. This study aims to objectively assess the PA levels of preschool children in Shanghai, China and to evaluate their PA levels relative to age-specific recommendations. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study was conducted among preschool children in Shanghai, city of China. There were a total of 303 preschool children (boys, 174; girls, 129) recruited from eight kindergarten classes in the Yangpu and Baoshan Districts of Shanghai. MAIN OUTCOME MEASURES: Daily PA was assessed using ActiGraph GT3X+ accelerometers for seven consecutive days. Children were required to have data from at least 2 weekdays and 1 weekend day, with a minimum daily wear time of 480 min to be included in the analysis. RESULTS: Preschool children in Shanghai accumulated, on average, 70.9 min of moderate-to-vigorous PA (MVPA) and 168.0 min of total PA (TPA) per day (d). Boys engaged in more MVPA and TPA than girls (72.8 min/day vs 68.3 min/day and 171.9 min/day vs 162.9 min/day, respectively). Overall, 72.9% of the participants met the age-specific recommendations of MVPA, while 35.3% met TPA recommendations. CONCLUSIONS: Findings of this study warn of the insufficiency of PA in Shanghai preschool children, suggesting there is substantial room to improve their PA. TRIAL REGISTRATION NUMBER: ChiCTR-OOC-15007439; Results.

20.
J Labelled Comp Radiopharm ; 62(8): 425-437, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30991462

RESUMO

We report the design, synthesis, and evaluation of a new series of benzylpiperazine derivatives as selective σ1 receptor ligands. All seven ligands possessed low nanomolar affinity for σ1 receptors (Ki (σ1 ) = 0.31-4.19 nM) and high subtype selectivity (Ki (σ2 )/Ki (σ1 ) = 50-2448). The fluoroethoxy analogues also exhibited high selectivity toward the vesicular acetylcholine transporter (Ki (VAChT)/Ki (σ1 ) = 99-18252). The corresponding radiotracers [18 F]13, [18 F]14, and [18 F]16 with high selectivity (Ki (σ2 )/Ki (σ1 ) > 100, Ki (VAChT)/Ki (σ1 ) > 1000) were prepared in 42% to 55% radiochemical yields (corrected for decay), greater than 99% radiochemical purity (RCP), and molar activity of about 120 GBq/µmol at the end of synthesis (EOS). All three radiotracers showed high initial brain uptake in mouse (8.37-11.48% ID/g at 2 min), which was not affected by pretreatment with cyclosporine A, suggesting that they are not substrates for permeability-glycoprotein (P-gp). Pretreatment with SA4503 or haloperidol resulted in significantly reduced brain uptake (35%-62% decrease at 30 min). In particular, [18 F]16 displayed high brain-to-blood ratios and high in vivo metabolic stability. Although it may not be an optimal neuroimaging agent because of its slow kinetics in the mouse brain, [18 F]16 can serve as a lead compound for further structural modifications to explore new potential radiotracers for σ1 receptors.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA