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1.
J Cell Mol Med ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599396

RESUMO

Although previous studies have explored the gene expression profiles of human oocytes and granulosa cells by single-cell RNA sequencing (scRNA-seq), the dynamic regulatory network at a single-cell resolution during folliculogenesis remains largely unknown. We identified 10 functional modules by WGCNA, four of which were significantly correlated with primary/antral oocyte and antral/pre-ovulatory granulosa cells. Functional enrichment analysis showed that the brown module, which was correlated with antral oocyte, was enriched in oocyte differentiation, and two core subnetworks identified by MCODE were involved in cell cycle (blue subnetwork) and oogenesis (red subnetwork). The cell-specific network (CSN) analysis demonstrated a distinct gene network structure associated with the antral follicular stage, which was notably different from other developmental stages. To our knowledge, this is the first study to explore gene functions during folliculogenesis at single-cell network level. We uncovered two potential gene subnetworks, which may play an important role in oocyte function beginning at the antral stage, and further established their rewiring process at intra-network/whole transcriptome level. The findings provide crucial insights from a novel network perspective to be further explored in functional mechanistic studies.

2.
Nucleic Acids Res ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33561291

RESUMO

Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.

3.
Commun Biol ; 4(1): 72, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452400

RESUMO

Inflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of breast cancer with rapid onset and a strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness and metastatic propensity of IBC are largely unknown. Herein, we report that decorin (DCN), a small leucine-rich extracellular matrix proteoglycan, is downregulated in tumors from patients with IBC. Overexpression of DCN in IBC cells markedly decreased migration, invasion, and cancer stem cells in vitro and inhibited tumor growth and metastasis in IBC xenograft mouse models. Mechanistically, DCN functioned as a suppressor of invasion and tumor growth in IBC by destabilizing E-cadherin and inhibiting EGFR/ERK signaling. DCN physically binds E-cadherin in IBC cells and accelerates its degradation through an autophagy-linked lysosomal pathway. We established that DCN inhibits tumorigenesis and metastasis in IBC cells by negatively regulating the E-cadherin/EGFR/ERK axis. Our findings offer a potential therapeutic strategy for IBC, and provide a novel mechanism for IBC pathobiology.

4.
Sci Rep ; 11(1): 1619, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452336

RESUMO

Numerous population-based studies have documented high prevalence of aflatoxin associated childhood stunting in low income countries. We provide an estimate of the disease burden of aflatoxin related stunting using data from the four African countries. For this empirical analysis, we obtained blood aflatoxin albumin adduct biomarker based exposure data as measured using ELISA technique and anthropometric measurement data from surveys done over a 12-year period from 2001 to 2012 in four low income countries in Africa. We used these data to calculate population attributable risk (PAR), life time disease burden for children under five by comparing two groups of stunted children using both prevalence and incidence-based approaches. We combined prevalence estimates with a disability weight, measuring childhood stunting and co-occurrence of stunting-underweight to produce years lived with disability. Using a previously reported mortality, years of life lost were estimated. We used probabilistic analysis to model these associations to estimate the disability-adjusted life-years (DALYs), and compared these with those given by the Institute for Health Metrics and Evaluation's Global Burden of Disease (GBD) 2016 study. The PAR increased from 3 to 36% for aflatoxin-related stunting and 14-50% for co-occurrence of stunting and underweight. Using prevalence-based approach, children with aflatoxin related stunting resulted in 48,965.20 (95% uncertainty interval (UI): 45,868.75-52,207.53) DALYs per 100,000 individuals. Children with co-occurrence of stunting and underweight due to exposure to aflatoxin resulted in 40,703.41 (95% UI: 38,041.57-43,517.89) DALYs per 100,000 individuals. Uncertainty analysis revealed that reducing aflatoxin exposure in high exposure areas upto non-detectable levels could save the stunting DALYs up to 50%. The burden of childhood all causes stunting is greater in countries with higher aflatoxin exposure such as Benin. In high exposure areas, these results might help guide research protocols and prioritisation efforts and focus aflatoxin exposure reduction. HEFCE Global Challenge Research Fund Aflatoxin project.

5.
Biosensors (Basel) ; 11(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430067

RESUMO

Fumonisin B1 (FB1), a mycotoxin classified as group 2B hazard, is of high importance due to its abundance and occurrence in varied crops. Conventional methods for detection are sensitive and selective; however, they also convey disadvantages such as long assay times, expensive equipment and instrumentation, complex procedures, sample pretreatment and unfeasibility for on-site analysis. Therefore, there is a need for quick, simple and affordable quantification methods. On that note, aptamers (ssDNA) are a good alternative for designing specific and sensitive biosensing techniques. In this work, the assessment of the performance of two aptamers (40 and 96 nt) on the colorimetric quantification of FB1 was determined by conducting an aptamer-target incubation step, followed by the addition of gold nanoparticles (AuNPs) and NaCl. Although MgCl2 and Tris-HCl were, respectively, essential for aptamer 96 and 40 nt, the latter was not specific for FB1. Alternatively, the formation of Aptamer (96 nt)-FB1-AuNP conjugates in MgCl2 exhibited stabilization to NaCl-induced aggregation at increasing FB1 concentrations. The application of asymmetric flow field-flow fractionation (AF4) allowed their size separation and characterization by a multidetection system (UV-VIS, MALS and DLS online), with a reduction in the limit of detection from 0.002 µg/mL to 56 fg/mL.

6.
J Pharm Biomed Anal ; 196: 113903, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33493743

RESUMO

In this research, a comprehensive and innovative method was established for the qualitative and quantitative analysis of the main components in Mahonia fortune (MF). On the one hand, comprehensive insight of the constituents in MF extracts was achieved with a Q­Exactive HF Mass Spectrometer using data-independent acquisition method. The identification of 17 compounds was based on comparison with authentic reference standards and the deduction of 119 additional compounds both in positive and negative modes was using the MS-dial strategy and comparison with literature data. The proportion of alkaloids and phenols were the most in MF. On the other hand, an ultra-performance liquid chromatographic-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method for the quantification of 25 components in MF extract were developed and validated. The method established provided satisfactory precision and accuracy; acceptable recovery and stability; a good linearity and a reasonable limit of detection. The MF samples from 11 different sources were detected, and relative principal component analysis were applied to discriminate these samples. The variations of Columbamine, Jatrorrhizine, Palmatine and Berberine were suggested as important indicators of MF quality. This study supplies a novel and comprehensive method for the quality evaluation of MF. This research presents a MS based analytical strategy which shows an application potential in the analysis of the chemical constituents in Traditional Chinese Medicine (TCM).

7.
IEEE Trans Med Imaging ; PP2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284749

RESUMO

With the development of neuroimaging techniques, a growing amount of multi-modal brain imaging data are collected, facilitating comprehensive study of the brain. In this paper, we jointly analyzed functional magnetic resonance imaging (fMRI) collected under different paradigms in order to understand cognitive behaviors of an individual. To this end, we proposed a novel multi-view learning algorithm called structure-enforced collaborative regression (SCoRe) to extract co-expressed discriminative brain regions under the guidance of anatomical structure of the brain. An advantage of SCoRe over its predecessor collaborative regression (CoRe) lies in its incorporation of group structures in the brain imaging data, which makes the model biologically more meaningful. Results from real data analysis has confirmed that by incorporating prior knowledge of brain structure, SCoRe can deliver better prediction performance and is less sensitive to hyper-parameters than CoRe. After validation with simulation experiments, we applied SCoRe to fMRI data collected from the Philadelphia Neurodevelopmental Cohort and adopted the scores from the wide range achievement test (WRAT) to evaluate an individual's cognitive skills. We located 14 relevant brain regions that can efficiently predict WRAT scores and these brain regions were further confirmed by other independent studies.

8.
Compr Rev Food Sci Food Saf ; 19(4): 1521-1560, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33337083

RESUMO

Contamination of agricultural and food products by some fungi species that produce mycotoxins can result in unsafe food and feed. Mycotoxins have been demonstrated to have disease-causing activities, including carcinogenicity, immune toxicity, teratogenicity, neurotoxicity, nephrotoxicity, and hepatotoxicity. Most of mycotoxins are heat stable and cannot be easily destroyed by conventional thermal food processing or domestic cooking methods. Postharvest approaches to prevent growth of mycotoxin-producing fungi and detoxify mycotoxins from contaminated food are important topics in food safety research. Physical, chemical, and biological methods have been applied to prevent fungal growth or mycotoxin production, or to reduce mycotoxin content in the postharvest period and contribute toward mitigating against the effects of mycotoxins on human health. This literature review aims to evaluate postharvest approaches that have been applied to control both fungi growth and mycotoxin content in food and discuss their potential for upscaling to industrial scale.

10.
Eur J Med Chem ; : 112970, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33153765

RESUMO

To discover novel anticancer agents with potent and low toxicity, we designed and synthesized a range of new thiosemicarbazone-indole analogues based on lead compound 4 we reported previously. Most compounds displayed moderate to high anticancer activities against five tested tumor cells (PC3, EC109, DU-145, MGC803, MCF-7). Specifically, the represented compound 16f possessed strong antiproliferative potency and high selectivity toward PC3 cells with the IC50 value of 0.054 µM, compared with normal WPMY-1 cells with the IC50 value of 19.470 µM. Preliminary mechanism research indicated that compound 16f could significantly suppress prostate cancer cells (PC3, DU-145) growth and colony formation in a dose-dependent manner. Besides, derivative 16f induced G1/S cycle arrest and apoptosis, which may be related to ROS accumulation due to the activation of MAPK signaling pathway. Furthermore, molecule 16f could effectively inhibit tumor growth through a xenograft model bearing PC3 cells and had no evident toxicity in vivo. Overall, based on the biological activity evaluation, analogue 16f can be viewed as a potential lead compound for further development of novel anti-prostate cancer drug.

11.
Eur J Med Chem ; : 112946, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33129590

RESUMO

Identification of potent anticancer agents with high selectivity and low toxicity remains on the way to human health. Pyridazine featuring advantageous physicochemical properties and antitumor potential usually is regarded as a central core in numerous anticancer derivatives. There are several approved pyridazine-based drugs in the market and analogues currently going through different clinical phases or registration statuses, suggesting pyridazine as a promising drug-like scaffold. The current review is intended to provide a comprehensive and updated overview of pyridazine derivatives as potential anticancer agents. In particular, we focused on their structure-activity relationship (SAR) studies, design strategies, binding modes and biological activities in the hope of offering novel insights for further rational design of more active and less toxic anticancer drugs.

12.
Hum Pathol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221342

RESUMO

The Dako 28-8, Dako 22C3, and Ventana SP142 assays are among the approved PD-L1 immunohistochemical companion/complementary diagnostics associated with cancer treatment. To address the concordance of these assays in triple-negative breast cancer (TNBC), we examined PD-L1 expression in 98 TNBC tumors and compared the positive rates using the three assays and three scoring methods: immune cell (IC), tumor cell (TC), and combined tumor cell and immune cell (TCIC) (an equivalent to combined positive score, or CPS). The positive rate for PD-L1 expression with a 1% cutoff was highest with 28-8, followed by the 22C3. These two assays demonstrated almost perfect or substantial agreement in all three scores. There was less agreement between SP142 and the other assays. Using the IC score or the TCIC score at a 1% cutoff (CPS 1), 4% of tumors were positive for PD-L1 with SP142, but negative with the other assays. Using SP142 with a 1% cutoff as a reference, the optimal cutoff for best agreement was at 1% for IC, 30% for TC, and 2% for TCIC (CPS 2) with the other two assays. A 2% cutoff for the 22C3 TCIC (CPS 2) yielded the best agreement with SP142 1% IC cutoff (kappa 0.65). Our study showed the lowest positive rate with SP142 among the three assays. However, the other two assays were not able to identify all tumors that would test positive with SP142 using IC or TCIC/CPS. It is unlikely to achieve high agreement between SP142 and the other two assays by changing the analytical cutoffs.

13.
Cancer Cell Int ; 20: 468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005101

RESUMO

Purpose: Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo. Methods: We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging. Results: SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel. Conclusions: SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

14.
J Sep Sci ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030303

RESUMO

Nowadays, the root of Rose cymosa Tratt. (Rosaceae) is widely used in clinic as one of the sources of Chinese herb medicine Jinyinggen. However, only few studies have been done on its chemical composition and quality control. In this study, 27 monomeric compounds were obtained from the ethanol extract of the roots of R. cymosa Tratt., including two undescribed triterpenes, one of which contains a distinctive contracted five-membered A-ring ursane-type skeleton and the other is a common ursane-type tritepene. Then, triterpenoids, the main components of the R. cymosa root, were qualitatively and quantitatively analyzed by thin-layer chromatography and high-performance liquid chromatography methods. Thin-layer chromatography can identify seven triterpenoids in R. cymosa Tratt. spontaneously. For the high-performance liquid chromatography fingerprint, total of 16 chromatographic peaks were selected as the common peaks of 20 batches of samples, ten of which were identified by reference substances. At the same chromatographic condition, five abundant triterpenoids were quantitatively assayed. R. cymose, as one of the origins of Jinyinggen, was similar to R. laevigata in triterpenoids compounds, which demonstrated that both of them could be used in the clinical medication. These work also laid a foundation for the further research and development of triterpenoids in R. cymosa root.

15.
J Int Med Res ; 48(10): 300060520962292, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33026262

RESUMO

OBJECTIVE: Recessive X-linked ichthyosis (RXLI) caused by deficiency of the steroid sulfatase gene (STS) has a reported prevalence of 1/2000 to 1/6000. The present study aimed to characterize the phenotypes and genotypes of two Chinese families with RXLI. METHODS: The patients were referred to the Family Planning Research Institute of Hunan Province for genetic counseling. Their skin phenotypes were photographed, and venous blood was drawn and used for chromosomal microarray analysis (CMA). RESULTS: The skin phenotype of the proband from the first family was characterized by generalized skin dryness and scaling, with noticeable dark brown, polygonal scales on his trunk and extensor surfaces of his extremities. The proband from the second family had an atypical phenotype showing mild skin dryness over his entire body, slight scaling on his abdomen, and small skin fissures on his arms and legs. No mental disability or developmental anomaly was noted in either proband. CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving four Online Mendelian Inheritance in Man-listed genes including STS. CONCLUSIONS: Our findings add knowledge to the genotype and phenotype spectrum of RXLI, which may be helpful in genetic counseling and prenatal diagnosis.

16.
Eur J Med Chem ; 209: 112861, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045661

RESUMO

CBP/p300, functioning as histone acetyltransferases and transcriptional co-factors, represents an attractive target for various diseases, including malignant tumor. The development of small-molecule inhibitors targeting the bromodomain and HAT domains of CBP/p300 has aroused broad interests of medicinal chemist in expectation of providing new hope for anti-cancer treatment. In particular, the CBP/p300 bromodomain inhibitor CCS1477, identified by CellCentric, is currently undergone clinical evaluation for the treatment of haematological malignancies and prostate cancer. In this review, we depict the development of CBP/p300 inhibitors reported from 2010 to 2020 and particularly highlight their structure-activity relationships (SARs), binding modes, selectivity and pharmacological functions with the aim to facilitate rational design and development of CBP/p300 inhibitors.

17.
J Am Chem Soc ; 142(39): 16723-16731, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32894021

RESUMO

While catalysis is highly dependent on the electronic structure of the catalyst, the understanding of catalytic performance affected by electron spin regulation remains challenging and rare. Herein, we have developed a facile strategy to the manipulation of the cobalt spin state over covalent organic frameworks (COFs), COF-367-Co, by simply changing the oxidation state of Co centered in the porphyrin. Density functional theory (DFT) calculations together with experimental results confirm that CoII and CoIII are embedded in COF-367 with S = 1/2 and 0 spin ground states, respectively. Remarkably, photocatalytic CO2 reduction results indicate that COF-367-CoIII exhibits favorable activity and significantly enhanced selectivity to HCOOH, accordingly much reduced activity and selectivity to CO and CH4, in sharp contrast to COF-367-CoII. The results highlight that the spin-state transition of cobalt greatly regulates photocatalytic performance. Theoretical calculations further disclose that the presence of CoIII in COF-367-Co is preferable to the formation of HCOOH but detrimental to its further conversion, which clearly accounts for its distinctly different photocatalysis over COF-367-CoII. To the best of our knowledge, this is the first report on regulating photocatalysis by spin state manipulation in COFs.

18.
Math Biosci Eng ; 17(4): 3356-3381, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32987533

RESUMO

Fatigue driving is one of the main factors which affect the safety of drivers and passengers in mountain freeway. To improve the driving safety, the application of fatigue driving detection system is a crucial measure. Accuracy, speed and robustness are key performances of fatigue detection system. However, most researches pay attention to one of them, instead of taking care of them all. It has limitation in practical application. This paper proposes a novel three-layered framework, named Real-time and Robust Detection System. Specifically, the framework includes three modules, called facial feature extraction, eyes regions extraction and fatigue detection. In the facial feature extraction module, the paper designs a deep cascaded convolutional neural network to detect the face and locate eye key points. Then, a face tracking sub-module is constructed to increase the speed of the algorithm, and a face validation submodule is applied to improve the stability of detection. Furthermore, to ensure the orderly operation of each sub-module, we designed a recognition loop based on the finite state machine. It can extract facial feature of the driver. In the second module, eyes regions of the driver were captured according to the geometric feature of face and eyes. In the fatigue detection module, the ellipse fitting method is applied to obtain the shape of driver's pupils. According to the relationship between the long and short axes of the ellipse, eyes state (opening or closed) can be decided. Lastly, the PERCLOS, which is defined by calculating the number of closed eyes in a period, is used to determine whether fatigue driving or not. The experimental results show that the comprehensive accuracy of fatigue detection is 95.87%. The average algorithm rate is 32.29 ms/f in an image of 640×480 pixels. The research results can serve the design of a new generation of driver fatigue detection system to mountain freeway.

19.
J Sep Sci ; 43(23): 4247-4262, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32975894

RESUMO

A method of ultra-fast liquid chromatography in series with tandem mass spectrometry for the rapid and sensitive detection of 57 compounds in Spatholobi Caulis (the vine stem of Spatholobus suberectus Dunn) within 35 min was established. This assay can simultaneously determine a variety of compounds without matrix interference in multiple reaction monitoring mode including evaluating the quality of different batches of Spatholobi Caulis from several areas and further identifying the characteristic compounds efficiently. After comprehensive validation, this method can be used to determinate samples rapidly, precisely, accurately, repeatably, and sensitivity. There were significant content differences in 12 batches of Spatholobi Caulis, which were further classified and systematically differentiated applying multivariate statistical analysis. Furthermore, orthogonal partial least squares discrimination analysis results indicated that (-)-gallocatechin (10), (-)-epiafzelechin (20), 4,7,2'-trihydroxy-4'-methoxyisoflavanol (51), and biochanin A (53) characterize compounds to discernment internal quality of Spatholobi Caulis, and recommended as quality control indicators. Hence, presented work provides a method for further study on pharmaceutic preparation, metabolism, as well as for the design, production optimization process, and clinical application.

20.
Toxins (Basel) ; 12(9)2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32932694

RESUMO

There are limited data on exposure to mycotoxins in Pakistan. Here, we measured exposure to deoxynivalenol (DON), a common contaminant of wheat, and aflatoxin B1 (AFB1), a known contaminant of rice, using biomarkers of exposure. Wheat (n = 195) and rice (n = 62) samples were analyzed for AFB1 and DON levels, and the corresponding urinary biomarkers were analyzed in urine samples from a rural population (n = 264, aged 4-80 years, male 58%) using ultra-sensitive liquid chromatography-tandem mass spectrometry. AFB1 was detected in 66% of rice (5.04 ± 11.94 µg/kg) and 3% of wheat samples. AFM1 (hydroxylated form of AFB1)was detected in 69% of urine samples, mean 0.023 ± 0.048 ng/mL and DON was detected in 20% of urine samples, mean 0.170 ± 0.129 ng/mL. The maximum probable daily intake for DON derived from the urinary biomarker was 59.8 ng/kg b.w./day, which is below the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives' tolerable daily intake (1000 ng/kg b.w./day). However, for aflatoxin, the derived margin of exposure (MoE) of (13.2) was well below the safe MoE (10,000) suggested by the European Food Safety Authority. The calculated aflatoxin-associated cancer risk of 0.514/105 individuals/year suggests that measures should be taken to reduce the AFB1 contamination in food, particularly rice, in Pakistan.

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