GPR39-mediated ERK1/2 signaling reduces permethrin-induced proliferation of estrogen receptor α-negative cells.

Certain insecticides are known to have estrogenic effects by activating estrogen receptors through genomic transcription. This has led researchers to associate specific insecticide use with an increased breast cancer risk. However, it is unclear if estrogen receptor-dependent pathways are the only way in which these compounds induce carcinogenic effects. The objective of this study was to determine the impact of the pyrethroid insecticide permethrin on the growth of estrogen receptor negative breast cancer cells MDA-MB-231. Using tandem mass spectrometric techniques, the effect of permethrin on cellular protein expression was investigated, and gene ontology and pathway function enrichment analyses were performed on the deregulated proteins. Finally, molecular docking simulations of permethrin with the candidate target protein was performed and the functionality of the protein was confirmed through gene knockdown experiments. Our findings demonstrate that exposure to 10-40 µM permethrin for 48 h enhanced cell proliferation and cell cycle progression in MDA-MB-231. We observed deregulated expression in 83 upregulated proteins and 34 downregulated proteins due to permethrin exposure. These deregulated proteins are primarily linked to transmembrane signaling and chemical carcinogenesis. Molecular docking simulations revealed that the overexpressed transmembrane signaling protein, G protein-coupled receptor 39 (GPR39), has the potential to bind to permethrin. Knockdown of GPR39 partially impeded permethrin-induced cellular proliferation and altered the expression of proliferation marker protein PCNA and cell cycle-associated protein cyclin D1 via the ERK1/2 signaling pathway. These findings offer novel evidence for permethrin as an environmental breast cancer risk factor, displaying its potential to impact breast cancer cell proliferation via an estrogen receptor-independent pathway.

A social theory-enhanced graph representation learning framework for multitask prediction of drug-drug interactions.

Current machine learning-based methods have achieved inspiring predictions in the scenarios of mono-type and multi-type drug-drug interactions (DDIs), but they all ignore enhancive and depressive pharmacological changes triggered by DDIs. In addition, these pharmacological changes are asymmetric since the roles of two drugs in an interaction are different. More importantly, these pharmacological changes imply significant topological patterns among DDIs. To address the above issues, we first leverage Balance theory and Status theory in social networks to reveal the topological patterns among directed pharmacological DDIs, which are modeled as a signed and directed network. Then, we design a novel graph representation learning model named SGRL-DDI (social theory-enhanced graph representation learning for DDI) to realize the multitask prediction of DDIs. SGRL-DDI model can capture the task-joint information by integrating relation graph convolutional networks with Balance and Status patterns. Moreover, we utilize task-specific deep neural networks to perform two tasks, including the prediction of enhancive/depressive DDIs and the prediction of directed DDIs. Based on DDI entries collected from DrugBank, the superiority of our model is demonstrated by the comparison with other state-of-the-art methods. Furthermore, the ablation study verifies that Balance and Status patterns help characterize directed pharmacological DDIs, and that the joint of two tasks provides better DDI representations than individual tasks. Last, we demonstrate the practical effectiveness of our model by a version-dependent test, where 88.47 and 81.38% DDI out of newly added entries provided by the latest release of DrugBank are validated in two predicting tasks respectively.

miR-96-5p attenuates malathion-induced apoptosis of human kidney cells by targeting the ER stress marker DDIT3.

Micro RNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, their functions in organophosphate-induced cytotoxicity remain unclear. This study investigated the involvement of miR-96-5p in the non-cholinergic toxicity of malathion in normal human kidney cells (HK-2 cells). Malathion decreased HK-2 cell viability and the expression of miR-96-5p in a dose- and time-dependent manner. In addition, transfection with miR-96-5p mimics attenuated malathion-induced HK-2 cell apoptosis, whereas transfection with a miR-96-5p inhibitor increased HK-2 cell apoptosis. Luciferase assays indicated that miR-96-5p could bind directly to the 3'-untranslated region of DDIT3, a well-known marker of endoplasmic reticulum stress. Further analyses of the expression of apoptosis-related genes and proteins indicated that miR-96-5p may function to reduce malathion-induced HK-2 cell apoptosis via regulation of the DDIT3/B-cell lymphoma (BCL)-2/caspase-3 signaling pathway. In summary, the results of the present study indicate that miR-96-5p protects HK-2 cells from malathion-induced ER stress-dependent apoptosis by targeting DDIT3.

[Determination of common dyes in dyed safflower by near infrared spectroscopy].

Because the red and bright color of corolla is the main indicator for the quality assessment of good safflower,the dyed safflower is sometimes found at the herbal market,what is influence on this herb quality and efficacy. A total of 127 safflower samples was therefore collected from different cultivating areas and herbal markets in China to develop a rapid method to identify the dyed safflower. Near-infrared spectroscopy(NIRS) combined with characteristic identification,high performance liquid chromatography(HPLC),principal component analysis(PCA) and partial least squares regression analysis(PLS) were employed to differentiate safflower from dyed safflower samples,and further quantify the levels of the 6 dyes,i.e. tartrazine,carmine,sunset yellow,azorubine,acid red 73 and orange Ⅱ in the dyed safflower. The results indicated that the 50 safflower samples and 77 dyed safflower samples were located at different regions in PCA cluster diagram by NIR spectra. Tartrazine,carmineand and sunset yellow were found in the 77 dyed safflower samples with the amounts of 0. 60-3. 66,0. 11-1. 37,0. 10-0. 71 mg·g-1,respectively. It indicated that the three dyes were the common and main dyes in the dyed safflower. However,azorubine,acid red 73 and orange Ⅱ were not detected in all herb samples. A total of 62 dyed safflower samples were chosen as calibration samples to develop the model for estimating the amount of dyes in dyed safflower. The estimating accuracy was verified by another 15 dyed safflower samples. The values of tartrazine,carmine and sunset yellow in dyed safflower samples were compared between the NIRS and HPLC methods. Each value of mean absolute difference(MAD) was less than 5%. The correlation coefficients of tartrazine,carmineand and sunset yellow were 0. 970,0. 975,0. 971,respectively. It indicated the data quantified by NIRS and HPLC were consistence. It is concluded that NIRS can not only differentiate safflower from dyed safflower,but also quantify the amount of the dyes. NIRS is suitable for rapidly identify the quality of safflower.

[Research on spectral reflectance characteristics for Glycyrrhizae Radix].

In order to study the spectral reflectance differences of Glycyrrhizae Radix under different growth conditions and lay the foundation for quantitative monitoring of Glycyrrhizae Radix remote sensing images, spectra of Glycyrrhiza species under different growth period and different varieties and different regions were measured by a portable spectrometer. The results showed that the reflectivity of annual G. uralensis was obviously higher than that of the two years plant in the visible light band own to the contents of crown layer chlorophyll. The reflectivity of two years G. pallidiflora was higher than that of G. uralensis in the near infrared band own to the leaf area index and the content of leaf water. The red edge spectrum of annual plant fluctuated largely than that of two years plant due to vegetation coverage and leaf area index. G. pallidiflora grew well than G. uralensis. Under different regions of the Glycyrrhiza species, spectral data analysis showed that within a certain range, the average annual precipitation and average annual evaporation were the major factors to affect the differences of Glycyrrhiza species spectral data under different regions owe to the leaf water content, the higher leaf water content, the lower spectral reflectance. The principal component analysis and continuum-removed method of the spectral data under different regions found that, within a certain range, the average annual precipitation and average annual evaporation were the major factors caused by the differences of Glycyrrhiza species spectral data under the different regions, Glycyrrhiza species spectral similarity related to the spatial distance.

[HPLC fingerprint spectrum of xinjiang uyghur medicine Nigella glandulifera seed].

OBJECTIVE: To establish the HPLC fingerprint spectrum of Nigella glandulifera seed identification. METHODS: The chromatographic system consisted of a Shim-pack ODS C18 column (150 mm x 4.6 mm, 5 microm) and a mobile phase of acetonitrile-0.1% formic acid in condition of gradient elution,The detection wavelength was 280 nm. The column temperature was 30 degrees C. RESULTS: Detected the HPLC fingerprint spectrum of 10 batches samples Nigella glandulifera seed from Xinjiang; Calibrated 18 characteristic peaks. The result was in accordance with the technical requirement of fingerprint spectrum. The similarity calculation software showed that the similarity was higher than 0. 95. CONCLUSION: The HPLC fingerprint spectrum of Nigella glandulifera seed can be used as an identification method. It may provide the basis for quality control of Nigella glandulifera seed.

[Simultaneous determination of contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora alopecuroides by HPLC].

OBJECTIVE: To develop a HPLC method for simultaneous determination of the contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora alopecuroides. METHOD: Chromatographic condition included a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) column and thmobile phase consisting of a mixture of methanol-0.2% phosphatic acid (7:93). The detection wavelength was at 205 nm. The flow rate was 1.0 mL x min(-1) and column temperature was set at 30 degrees C. RESULT: All calibration curves showed good linearity (r > or = 0.9997) within test ranges. The mean recoveries were 100.0%, 97.0% and 97.0% respectively. CONCLUSION: This method is simple, rapid and accurate, and suitable for quality control of S. alopecuroides seed.