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1.
Clin Cancer Res ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674273

RESUMO

PURPOSE: Gemcitabine is most commonly used for pancreatic cancer (PC). However, the molecular features and mechanisms of the frequently occurred resistance remain unclear. This work aims at exploring the molecular features of gemcitabine resistance and identifying candidate biomarkers and combinatorial targets for the treatment. EXPERIMENTAL DESIGN: In present study, we established 66 patient-derived xenografts (PDXs) based on clinical PC specimens and treated them with gemcitabine. We generated multi-omics data (including whole exome-seq, RNA-seq, miRNA-seq and DNA methylation array) of 15 drug sensitive and 13 resistant PDXs before and after the gemcitabine treatment. We performed integrative computational analysis to identify the molecular networks related to gemcitabine intrinsic and required resistance. Then, shRNA-based high-content screening was implemented to validate the function of the de-regulated genes. RESULTS: The comprehensive multi-omics analysis and functional experiment revealed that MRPS5 and GSPT1 had strong effects on cell proliferation, and CD55 and DHTKD1 contributed to gemcitabine resistance in PC cells. Moreover, we found miR-135a-5p was significantly associated with the prognosis of PC patients and could be a candidate biomarker to predict gemcitabine response. Comparing the molecular features before and after the treatment, we found that PI3K-Akt, p53, HIF-1 pathways were significantly altered in multiple patients, providing candidate target pathways for reducing the acquired resistance. CONCLUSIONS: This integrative genomic study systematically investigated the predictive markers and molecular mechanisms of chemoresistance in PC and provide potential therapy targets for overcoming gemcitabine resistance.

2.
Phys Chem Chem Phys ; 23(11): 6880-6887, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33725039

RESUMO

Tuning the work functions of materials is of practical interest for maximizing the performance of microelectronic and (photo)electrochemical devices, as the efficiency of these systems depends on the ability to control electronic levels at surfaces and across interfaces. Perovskites are promising compounds to achieve such control. In this work, we examine the work functions of more than 1000 perovskite oxide surfaces (ABO3) using data-driven (machine-learning) analysis and identify the factors that determine their magnitude. While the work functions of the BO2-terminated surfaces are sensitive to the energy of the hybridized oxygen p bands, the work functions of the AO-terminated surfaces exhibit a much less trivial dependence with respect to the filling of the d bands of the B-site atom and of its electronic affinity. This study shows the utility of interpretable data-driven models in analyzing the work functions of cubic perovskites from a limited number of electronic-structure descriptors.

3.
Ann Palliat Med ; 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33548995

RESUMO

BACKGROUND: To explore the prognostic role of ovarian endometriosis in symptomatic adenomyosis patients underwent uterine artery embolization (UAE). METHODS: This was a retrospective, single-center study. A total of 76 patients with adenomyosis who underwent UAE in The First Affiliated Hospital of Sun Yat-sen University between May 2009 and July 2016 were enrolled in this study. These patients were divided into two groups based on whether complicated with ovarian endometriosis. After UAE, the patients were followed up for 12 months. The improvements of dysmenorrhea and menorrhagia were evaluated according to the symptom relief criteria. The improvement rates in both groups were analyzed and compared. RESULTS: Among the 76 patients with adenomyosis, 17 (22.3%) were diagnosed with OE and 59 (77.6%) were non-OE. In the OE group, all patients (17/17, 100%) had dysmenorrhea and 11 (11/17, 64.7%) had menorrhagia. In non-OE group, 57 patients (57/59, 96.6%) had dysmenorrhea and 50 (50/59, 84.7%) had menorrhagia. The improvement rates of dysmenorrhea in the two groups were 47.1% (OE group) and 86.0% (non-OE group), respectively (P<0.05). The improvement rates of menorrhagia in the two groups were 63.6% (OE group) and 84.0% (non-OE group), respectively (P=0.263). CONCLUSIONS: Patients without OE showed a lower incidence of dysmenorrhea and may have an advantage in the improvement of dysmenorrhea compared with those with OE when they underwent UAE. However, no significant difference was observed in the improvement of menorrhagia.

4.
Environ Health Prev Med ; 26(1): 10, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461491

RESUMO

BACKGROUND: Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions. METHODS: This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei. RESULTS: The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods. CONCLUSION: Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.


Assuntos
/epidemiologia , Período de Incubação de Doenças Infecciosas , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Quarentena , Estudos Retrospectivos , Adulto Jovem
5.
J Hazard Mater ; 403: 123923, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33264974

RESUMO

Microplastics (MPs) are an environmental hazard of growing concern, including their potential toxic effects on the biota of different trophic levels. Nevertheless, the molecular mechanisms underlying MP-induced toxicity remain largely unknown. In the present study, Tetrahymena thermophila was exposed to polystyrene nanoplastics (PS-NPs) and the responses of this relatively sensitive ciliate were then followed using transcriptome analysis together with several other verification methods. The results showed that PS-NPs perturbed calcium (Ca) homeostasis, by inducing the inositol-1,4,5-trisphosphate-dependent liberation of Ca from the endoplasmic reticulum into the cytosol. The high cytosolic concentration of Ca induced Ca accumulation in mitochondria, which increased mitochondrial permeability and the generation of reactive oxygen species, finally leading to growth inhibition. Such toxicity is the so-called direct effects of PS-NPs. By contrast, PS-NPs also inhibited the activity of multixenobiotic resistance transporter, by down-regulating the ATP-binding cassette transporter genes Abcb15 and Abcc52. This additional effect may alter cellular responses to other pollutants and implicates PS-NPs in the risks to the organism posed by subsequent toxic exposures, which was named as the indirect effects of PS-NPs. Our study highlights the importance of considering both direct and indirect biological effects of MPs in evaluations of their environmental and health risks.

6.
Anal Methods ; 13(2): 192-201, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33331361

RESUMO

An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous determination of 15 mycotoxins, including aflatoxins (B1, B2, G1, and G2), ochratoxins (A, B, and C), citrinin, patulin, and emerging Alternaria toxins (alternariol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid, and altenusin) in orange, grape and apple juices. Different extraction approaches, sorbents, chromatographic columns and mobile phases were investigated for establishment of an optimal QuEChERS procedure and UHPLC-MS/MS conditions. Recoveries were in the range of 74-110%, and the limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.05 to 0.1 ng mL-1 and from 0.1 to 5.0 ng mL-1, respectively. Matrix effects were evaluated and matrix-matched calibration curves were used to compensate for matrix effects and achieve accurate quantification. The correlation coefficients (R2) of linearity were higher than 0.99 and the relative standard deviations (RSDs) of intra- and inter-day precision were under 13%. The method was subsequently applied to 22 fruit juice samples. The high frequencies (90.9%) of mycotoxins not only proved the reliability and sensitivity of the currently established method, but also demonstrated that fruit juices are susceptible to different mycotoxins, which need to be continuously monitored in the future.

7.
Invest New Drugs ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006020

RESUMO

Purpose Hepatic arterial infusion chemotherapy (HAIC) is one of the options to treat unresectable hepatocellular carcinoma (HCC). The majority of HCC patients suffer great pain in the course of HAIC treatment. To improve the quality of life and the efficacy of HAIC treatment, the causes of pain, the choice of an analgesic regimen, and the relationship between pain and prognosis of HCC were analyzed. Methods A total of 376 HCC patients under HAIC in our hospital were recriuted between March 2017 and September 2019. Multivariate linear regression analysis (stepwise) was used to calculate the potential factors related to the severe pain in HCC patients under HAIC. Analgesics treatments were carried out based on the results of the visual analogue scale (VAS) score which was used to evaluate the pain. Results The mean value of the VAS score is 3.604, which indicates that the pain in most patients is mild and endurable. Intra-arterial lidocaine injection is an effective method in most patients (96%, 361 of 376), and the total score of VAS is reduced from 1355 to 195 following lidocaine injection. Multivariate analysis suggestes that oxaliplatin (OXA) preparation time, hepatic artery diameter and OXA manufacturers (R2 = 0.859) are influential factors for pain scores. Conclusion This study demonstrates an effective way to systematically assess and ease pain in HCC patients with HAIC treatment. OXA preparation time, hepatic artery diameter, and OXA manufacturers are the potential influencing factors for pain. This work presented here will provide a detailed understanding of the clinical application of HAIC in advanced HCC patients.

8.
Technol Cancer Res Treat ; 19: 1533033820965587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33089769

RESUMO

OBJECTIVE: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone. METHODS: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan-Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant. RESULTS: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment. CONCLUSION: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.

9.
Acta Pharm Sin B ; 10(9): 1784-1795, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33088696

RESUMO

The application of nanotechnology for antimicrobial delivery has capacity to improve antibacterial efficacy. Currently, the usage of various inorganic and organic carriers, such as metal ions, nano-silicon and surfactants, might increase the potential toxicity of nanoparticles and make their clinical transformation more difficult. Herein, a nano-delivery system was constructed by direct self-assembly of antibacterial phytochemicals (berberine and rhein) originated from traditional Chinese medicine Coptis chinensis Franch. and Rheum palmatum L., respectively. Combining X-ray single crystal diffraction, nuclear magnetic resonance and other spectra characterizations, the stacked structure of nanoparticles was profoundly demonstrated. Briefly, rhein acted as the layered backbone and berberine embedded in it. In vitro bacteriostasis experiment showed the minimum bactericidal concentration of nanoparticles was 0.1 µmol/mL, which was lower than that of berberine and rhein. The results of confocal laser scanning microscope, biofilm quantitive assay and scanning electron microscopy indicated that nanoparticles had strong inhibitory effects on Staphylococcus aureus biofilm. More importantly, transmission electron microscopy and mass spectra indicated the further bacteriostatic mechanism of nanoparticles. Meanwhile, the nanoparticles had well biocompatibility and safety. Current study will open up new prospect that the design of self-assemblies between active phytochemicals can be originated from traditional Chinese medicine combination.

10.
Opt Express ; 28(18): 26882-26897, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32906954

RESUMO

Phase-shifting profilometry has been increasingly sought and applied in dynamic three-dimensional (3D) shape measurement. However, the object motion will lead to extra phase shift error and thus measurement error. In this paper, a real-time 3D shape measurement method based on dual-frequency composite phase-shifting grating and motion-induced error reduction is proposed for a complex scene containing dynamic and static objects. The proposed method detects the motion region of a complex scene through the phase relations of the dual-frequency composite grating and reduces the motion-induced error with the combination of the phase calculated by a phase-shifting algorithm and the phase extracted by Fourier fringe analysis. It can correctly reconstruct the 3D shape of a complex dynamic scene and ensure high measurement accuracy of its static object as well. With the aid of the phase-shifting image ordering approach, the dynamic 3D shape of complex scenes can be reconstructed and the motion-induced error can also be suppressed in real time. Experimental results well proved that the proposed method is effective and practical.

12.
JGH Open ; 4(3): 477-483, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32514457

RESUMO

Purpose: The aim of this study was to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen combined with transarterial embolization (TAE + HAIC) in patients with unresectable hepatocellular carcinoma (HCC). Methods: Unresectable HCC patients treated with TAE + HAIC and conventional transcatheter arterial chemoembolization (TACE), respectively, between January 2015 and October 2016 in China were retrospectively assessed. The primary outcome was progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), the disease control rate (DCR), and main complications. Propensity score matching (PSM) was estimated by multiple logistic regression using caliper matching (caliper 0.2). A Cox proportional hazards model was used to identify those factors shown to be associated with PFS. Results: A total of 113 patients were analyzed, with 41 and 72 receiving TAE + HAIC and TACE, respectively. After PSM, 35 pairs of patients were assessed. The median PFS was 7.93 months (95% confidence interval [CI], 4.44-11.42) for the TAE + HAIC group, which was higher compared with 2.60 months (95% CI, 0.93-4.27, P = 0.003) for TACE. The subgroup with Barcelona clinic liver cancer (BCLC) stage C obtained more PFS benefit from TAE + HAIC (P = 0.002). ORRs in the TAE + HAIC and TACE groups were 37.14% (13/35) and 20.00% (7/35, P = 0.112), respectively; DCRs were 88.57% (31/35) and 60.00% (21/35, P = 0.006), respectively. Abundant blood supply (hazard ratio [HR] =0.327, 95% CI 0.173-0.615, P < 0.001) and TAE + HAIC (HR = 0.332, 95% CI 0.177-0.621, P < 0.001) were associated with longer PFS in multivariate analysis. Conclusions: Compared with conventional TACE, TAE + HAIC provides more PFS benefits to patients with unresectable HCC, especially in those with BCLC stage C.

13.
J Infect Dev Ctries ; 14(4): 323-327, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32379707

RESUMO

INTRODUCTION: Current studies estimated a general incubation period distribution of COVID-19 based on early-confirmed cases in Wuhan, and have not examined whether the incubation period distribution varies across population segments with different travel histories. We aimed to examine whether patients infected by community transmission had extended incubation periods than the early generation patients who had direct exposures to Wuhan. METHODOLOGY: Based on 4741 patient case reports from municipal centers of disease control by February 21, 2020, we calculated the incubation periods of 2555 patients with clear epidemiological survey information and illness development timeline. All patients were categorized into five groups by their travel histories. Incubation period distributions were modeled for each group by the method of the posterior Weibull distribution estimation. RESULTS: Adults aged 30 to 59 years had the most substantial proportion of confirmed cases in China. The incubation period distribution varied slightly across patient groups with different travel histories. Patients who regularly lived in Wuhan and left to other locations before January 23, 2020 had the shortest posterior median value of 7.57 days for the incubation period, while the incubation periods for persons affected by local community transmission had the largest posterior median of incubation periods, 9.31 days. CONCLUSIONS: The median incubation period for all patients infected outside Wuhan was 9 days, a bit of more extended than the early estimated 5-day incubation period that was based on patients in Wuhan. Our findings may imply the decreases of virulence of the COVID-19 virus along with intergenerational transmission.


Assuntos
Infecções por Coronavirus/epidemiologia , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/epidemiologia , Viagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias
14.
Food Chem Toxicol ; 139: 111277, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32217092

RESUMO

T-2 toxin, one of the most toxic mycotoxins, is commonly presented along with its metabolites, HT-2 toxin, neosolaniol (NEO), T-2 triol, and T-2 tetraol in foodstuff and feed. The aim of this study was to evaluate the cytotoxic effects of T-2 toxin alone and in combination with its metabolites on porcine Leydig cells. Based on the determination of cell viability with CCK-8, toxicological interactions were investigated using Combination Index method. The cytotoxic potency of five tested mycotoxins individual and their mixtures all showed with a dose-dependent manner. In view of IC50 values, the decreasing cytotoxicity of mycotoxins was ranking: T-2 toxin > HT-2 toxin > T-2 triol > NEO > T-2 tetraol. Combinations of T-2+HT-2, T-2+NEO, and HT-2+NEO displayed synergism at low doses but antagonism at high doses, while the ternary combination of T-2+HT-2+NEO revealed adverse situation from antagonism to synergism. All binary and ternary combinations of T-2 toxin, T-2 triol, and T-2 tetraol exhibited antagonistic interactions. Our results suggest that the co-occurrence of T-2 toxin and its metabolites might pose a slight threat to reproductive health due to antagonistic interactions. However, the synergy observed should be not ignored especially at low doses of mycotoxins co-occurrence in the diet.

15.
Mycotoxin Res ; 36(3): 269-276, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32016807

RESUMO

This study was conducted to investigate the exposure to ochratoxin A (OTA) of populations living in Nanjing, China. Plasma samples were collected from 147 healthy adults (age 18-63 years) and analyzed for OTA by a reliable and sensitive ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method (limit of detection 0.04 ng/mL). After enzymatic hydrolysis by ß-glucuronidase/arylsulfatase, OTA was detected in 80.9% plasma samples with mean concentration of 0.26 ± 0.59 ng/mL (range 0.04-6.59 ng/mL). The estimated daily intakes of OTA based on plasma concentrations (mean 0.51 ng/kg bw/day, max 12.99 ng/kg bw/day) were lower than the tolerable daily intake published by European Food Safety Authority (EFSA) or Joint FAO/WHO Expert Committee on Food Additives (JFECFA) indicative of rare risks related to the OTA exposure in the investigated area. This study provides a valuable insight on human exposure to OTA in China. Further studies in children and elder people and in adult cohorts from other regions are recommended.


Assuntos
Exposição Dietética/análise , Ocratoxinas/sangue , Adolescente , Adulto , China , Cromatografia Líquida , Exposição Dietética/estatística & dados numéricos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Ocratoxinas/metabolismo , Plasma/química , Espectrometria de Massas em Tandem , Adulto Jovem
16.
Toxins (Basel) ; 12(1)2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936883

RESUMO

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 µg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.

17.
Environ Pollut ; 259: 113852, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887592

RESUMO

The widespread use of nanoparticles (NPs) has drawn considerable attention because of their potential toxicity and the environmental consequences thereof. However, the effects of the exposure route and life stage of an organism on the bioaccumulation and toxicity of NPs are largely unknown. In the present study, we investigated the accumulation kinetics (uptake, assimilation, and efflux) and tissue distribution of waterborne and dietary hematite NPs (HemNPs) during three life stages (embryo, larva, and adult) of the zebrafish Danio rerio. For all zebrafish life stages, the waterborne accumulation of well-dispersed HemNPs increased linearly with exposure time but decreased after reaching a maximum. The increase in HemNPs accumulation followed the order embryo > larva > adult. Compared with the waterborne route, the dietary accumulation of HemNPs in larval and adult zebrafish fluctuated, reaching a maximum after each food refreshment and then decreasing until the next food addition. Similar to waterborne exposure, adult fish accumulated less dietary HemNPs than did larvae. Nevertheless, dietary HemNPs mostly accumulated in the intestinal tract, with smaller amounts in the truncus, head, and gills, as compared with their waterborne counterparts. Moreover, in the gonad no dietary HemNPs were detected whereas accumulation via waterborne HemNPs was significant. Despite the low assimilation efficiency of dietary HemNPs, biodynamic modeling showed that the diet was the main source of particle accumulation in zebrafish. Thus, both the life stage and the exposure route should be considered in evaluations of the environmental risks of NPs.


Assuntos
Dieta , Compostos Férricos , Nanopartículas , Poluentes Químicos da Água , Peixe-Zebra , Animais , Compostos Férricos/metabolismo , Nanopartículas/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
18.
Crit Rev Food Sci Nutr ; 60(9): 1523-1537, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30806521

RESUMO

Masked mycotoxins are biologically modified phase II metabolites formed by plant defense mechanisms through glucosylation catalyzed by uridine diphosphate -glucosyltransferases. Most of the current reports focus on the occurrence of masked mycotoxins in Europe, America, Africa, and cover other geographic regions, e.g. China and Japan. High proportions of masked mycotoxins co-occurring with their parent forms in various cereal-based food and feedstuff could clearly increase total exposures and pose additional health risks to humans and animals. In contrast to the parent mycotoxins, the data on the toxicity of masked mycotoxins are still scarce, however, the poor existing information showed that masked mycotoxins generally exhibit significant in vitro and in vivo toxicities lower than those of their parent forms, especially for deoxynivalenol-3-glucoside, which is the only thoroughly investigated masked mycotoxin. Although the lower toxicity level of masked mycotoxins, these are probably hydrolyzed into their free forms by intestinal microorganisms in the digestive tract of mammals and thus contribute to unpredicted toxicity. The metabolic characteristics of reported masked mycotoxins are species-specific. The most relevant animal model of human sensitivity, the pig, is most sensitive to masked mycotoxins. This review focuses on updates in the current knowledge on country-specific natural-occurrence data in global surveys, as well as in vitro and in vivo toxicology and metabolic investigations of masked mycotoxins.


Assuntos
Micotoxinas/metabolismo , Micotoxinas/toxicidade , Plantas/química , Animais , Contaminação de Alimentos/análise , Microbioma Gastrointestinal/fisiologia , Humanos , Micotoxinas/análise , Micotoxinas/química
19.
Eur J Med Chem ; 185: 111839, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31708185

RESUMO

The ligustrazine - betulin derivative (TB), TB amino acids derivatives (TB-01 - TB-09) and TB dipeptide derivatives (TB-10 - TB-18) were designed and synthesized. And their in vitro cytotoxic activities were evaluated against four cancer cell lines (Hela, HepG2, BGC-823 and HT-29) and normal cells MDCK by standard methylthiazol tetrazolium (MTT) assay. Most of them demonstrated better antitumor activity than the relevant material betulin. Among them, compound TB-01 showed the best anti-tumor effect on the cancer cells and the lowest toxicity on the normal cells. For example, the cytotoxicity of TB-01 against the cancer cells (mean IC50 = 4.86 ±â€¯1.16 µM) was 3-fold higher than that against the normal cells MDCK (IC50 = 16.11 ±â€¯2.29 µM). Moreover, TB-01 showed better cytotoxic than positive drug cisplatin (DDP) on tumor cells. Besides, the Zebrafish toxicity evaluation test showed that TB-01 demonstrated high biosafety. Subsequently, fluorescent staining, apoptosis detection and cell cycle analysis indicated that TB-01 induced early apoptosis in HepG2 cells and blocked the cell cycle in the G1 phase. In addition, the structure-activity relationships of these derivatives were briefly discussed.


Assuntos
Aminoácidos/farmacologia , Antineoplásicos/farmacologia , Dipeptídeos/farmacologia , Desenho de Fármacos , Pirazinas/farmacologia , Triterpenos/farmacologia , Aminoácidos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Estrutura Molecular , Pirazinas/química , Relação Estrutura-Atividade , Triterpenos/química , Peixe-Zebra
20.
ACS Appl Mater Interfaces ; 12(1): 227-237, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829617

RESUMO

S. aureus is resistant to various first-line antibiotics, and seeking multifarious strategies aimed at effective control of antibiotic-resistant behavior is urgently needed. Here, we report a two-component directed self-assembly mode: the phytochemicals berberine and cinnamic acid can directly self-assemble into nanoparticles (NPs) displaying good bacteriostastic activity. Compared with several first-line antibiotics, the obtained nanostructures have a better inhibitory effect on multidrug-resistant S. aureus (MRSA) and stronger ability for biofilm removal. These qualities are attributed to the fact that organic assemblies can first spontaneously adhere to the surface of the bacteria, infiltrate into the cell, and then lead to converging attack against MRSA; thereafter, multipath bactericidal mechanisms of NPs on MRSA are found by both transcriptomic analysis and quantitative Polymerase Chain Reaction analysis. Moreover, when combined with spectral data and single crystal X-ray diffraction, the NPs' self-assembly mechanism governed by hydrogen bonds and π-π stacking interactions is clearly elucidated. These non-covalent interactions induce the NPs' formation of butterfly-like one-dimensional self-assembled units and finally layered three-dimensional spatial configuration. In addition, biocompatibility tests show that the NPs are nonhemolytic with little toxicity in vitro and in vivo. This directed self-assembly mode can offer a new perspective toward the design of biocompatible antimicrobial nanomedicines for clinical translation.


Assuntos
Antibacterianos , Berberina , Cinamatos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Nanopartículas/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Berberina/química , Berberina/farmacologia , Cinamatos/química , Cinamatos/farmacologia , Cães , Células Madin Darby de Rim Canino , Ratos , Peixe-Zebra
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