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1.
Med Chem ; 20(1): 2-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37038674

RESUMO

Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.


Assuntos
Praguicidas , Praguicidas/toxicidade , Praguicidas/análise , Medição de Risco , Algoritmos , Redes Neurais de Computação , Aprendizado de Máquina
2.
J Sep Sci ; 46(10): e2200969, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36932879

RESUMO

A novel chiral group functionalized metal-organic framework, Cyclodextrin-NH-MIL-53, was synthesized and modified on the inner wall of a capillary column via a post-synthetic process. The prepared chiral metal-organic framework was utilized as a chiral capillary stationary phase and used in an open-tubular capillary electrochromatography method to enantioseparate several racemic amino acids. Excellent enantioseparation of five pairs of enantiomers was obtained in this chiral separation system (Resolutions of D/L-Alanine = 16.844, D/L-Cysteine = 3.617, D/L-Histidine = 9.513, D/L-Phenylalanine = 8.133, and D/L-Tryptophan = 2.778). The prepared Cyclodextrin-NH-MIL-53 and the Cyclodextrin-NH-MIL-53-based capillary columns were characterized by scanning electron microscopy, X-ray diffraction, Fourie-transform infrared spectroscopy, and circular dichroism. The chiral capillary electrochromatography conditions, such as separation conditions, amount of Cyclodextrin-NH-MIL-53, and electroosmotic flow, were optimized. This research is estimated to present a novel insight and method for the design and use of metal-organic framework-based capillaries for enantioseparation.

3.
Eur J Pharmacol ; 936: 175377, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347320

RESUMO

Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated a diabetic model in mice with LB, and the results showed that LB lowered blood glucose and alleviated islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated mice with LB in a diabetic model and showed that LB lowered blood glucose and reduced islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Further, after inhibiting GLP-1R activity, the results showed that LB promoted insulin secretion, Ins-1 cell proliferation and reduced Ins-1 cell apoptosis with reduced effect, indicating that LB achieved the above effects by activating GLP-1Ra. Meanwhile, cellular cAMP levels increased when GLP-1R was overexpressed, which also demonstrated the interaction between LB and GLP-1R. Subsequently, the effect of LB on cellular potassium channels was examined by membrane clamp, and the results showed that LB increased intracellular Ca2+ concentration and stimulated insulin secretion by activating GLP-1R and thus closing the ATP-sensitive potassium channels. On the other hand, the activation effect of LB on AKT/PDX1 signaling pathway was verified.


Assuntos
Produtos Biológicos , Diabetes Mellitus Experimental , Animais , Camundongos , Secreção de Insulina , Proteínas Proto-Oncogênicas c-akt , Glicemia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
4.
World J Clin Cases ; 10(21): 7314-7323, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36157993

RESUMO

BACKGROUND: The pathophysiological characteristics of severe pneumonia complicated by respiratory failure comprise pulmonary parenchymal changes leading to ventilation imbalance, alveolar capillary injury, pulmonary edema, refractory hypoxemia, and reduced lung compliance. Prolonged hypoxia can cause acid-base balance disorder, peripheral circulatory failure, blood-pressure reduction, arrhythmia, and other adverse consequences. AIM: To investigate sequential mechanical ventilation's effect on severe pneumonia complicated by respiratory failure. METHODS: We selected 108 patients with severe pneumonia complicated by respiratory failure who underwent mechanical ventilation between January 2018 and September 2020 at the Luhe Hospital's Intensive Care Unit and divided them into sequential and regular groups according to a randomized trial, with each group comprising 54 patients. The sequential group received invasive and non-invasive sequential mechanical ventilation, whereas the regular group received invasive mechanical ventilation. Blood-gas parameters, hemodynamic parameters, respiratory mechanical parameters, inflammatory factors, and treatment outcomes were compared between the two groups before and after mechanical-ventilation treatment. RESULTS: The arterial oxygen partial pressure and stroke volume variation values of the sequential group at 24, 48, and 72 h of treatment were higher than those of the conventional group (P < 0.05). The carbon dioxide partial pressure value of the sequential group at 72 h of treatment and the Raw value of the treatment group at 24 and 48 h were lower than those of the conventional group (P < 0.05). The pH value of the sequential group at 24 and 72 h of treatment, the central venous pressure value of the treatment at 24 h, and the Cst value of the treatment at 24 and 48 h were higher than those of the conventional group (P < 0.05). The tidal volume in the sequential group at 24 h of treatment was higher than that in the conventional group (P < 0.05), the measured values of interleukin-6 and tumor necrosis factor-α in the sequential group at 72 h of treatment were lower than those in the conventional group (P < 0.05), and the total time of mechanical ventilation in the sequential group was shorter than that in the conventional group, with a statistically significant difference (P < 0.05). CONCLUSION: Treating severe pneumonia complicated by respiratory failure with sequential mechanical ventilation is more effective in improving respiratory system compliance, reducing inflammatory response, maintaining hemodynamic stability, and improving patient blood-gas levels; however, from this study's perspective, it cannot reduce patient mortality.

5.
Adv Sci (Weinh) ; 9(31): e2203173, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36031407

RESUMO

A recently developed synthetic retinoid abrogates proliferation and induces apoptosis of drug-resistant malignant-cancer-stem-cell-like cells. However, the underlying mechanisms of how the synthetic retinoid induces cancer-stem-cell-like cell tumor-repopulating cell (TRC) apoptosis are elusive. Here, it is shown that although the retinoid and conventional anticancer drugs cisplatin, all-trans retinoic acid, and tazarotene all inhibit cytoskeletal tension and decondense chromatin prior to inducing TRC apoptosis, half-maximal inhibitory concentration of the retinoid is 20-fold lower than those anticancer drugs. The synthetic retinoid induces retinoic acid receptor gamma (RARγ) translocation from the nucleus to the cytoplasm, leading to reduced RARγ binding to Cdc42 promoter and Cdc42 downregulation, which decreases filamentous-actin (F-actin) and inhibits cytoskeletal tension. Elevating F-actin or upregulating histone 3 lysine 9 trimethylation decreases retinoid-induced DNA damage and apoptosis of TRCs. The combinatorial treatment with a chromatin decondensation molecule and the retinoid inhibits tumor metastasis in mice more effectively than the synthetic retinoid alone. These findings suggest a strategy of lowering cell tension and decondensing chromatin to enhance DNA damage to abrogate metastasis of cancer-stem-cell-like cells with high efficacy.


Assuntos
Antineoplásicos , Neoplasias , Células-Tronco Neoplásicas , Retinoides , Medicamentos Sintéticos , Animais , Camundongos , Actinas , Antineoplásicos/farmacologia , Cromatina , Células-Tronco Neoplásicas/efeitos dos fármacos , Retinoides/farmacologia , Resistencia a Medicamentos Antineoplásicos
6.
Ecotoxicol Environ Saf ; 243: 114001, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36027710

RESUMO

Heavy metal pollution is a major threat to agricultural produce and it can pose potential ecological risks which subsequently impacts on human health. Strawberries are an economically important produce of China. The intrinsic link of heavy metal pollution risk in the soil-strawberry ecosystem is of concern. In this study, the pollution index of heavy metal pollutants in farmlands of different provinces were evaluated, and the results showed significantly high levels of cadmium. In addition, Nemerow integrated pollution index analysis showed that low-pollution farmlands only accounted for 14.07% of the total arable land area. Then, the transfer factors were used to calculate the migration of heavy metals from the soil into strawberries. The results showed that cadmium and nickel were relatively high in strawberries from the Guangxi province. Similar results were found for mercury in Jiangxi Province. The pollution index of single food pollution also showed that mercury in strawberries from Jiangxi Province was at a moderate pollution level. The comprehensive pollution index indicated that heavy metal pollution in strawberries in Central China may be severe. In addition, spatial clustering analysis showed that cadmium, chromium, lead, arsenic and zinc in strawberries had significant hotspot clustering in central, south and southwest China. Finally, our studies also suggested that the risk of carcinogenic and non-carcinogenic diseases was higher in the (2, 4] years age group than in other age groups. People in Yunnan Province were also found to have a higher non-carcinogenic risk than those in other provinces and cities in China. This study provides a comprehensive view of the potential risks of heavy metal contamination in strawberries, which could provide assistance in the design of regulatory and risk management programs for chemical pollutants in strawberries, thus ensuring the safety of consumption of these edible fruits.


Assuntos
Poluentes Ambientais , Fragaria , Mercúrio , Metais Pesados , Poluentes do Solo , Cádmio/análise , China , Ecossistema , Monitoramento Ambiental , Poluentes Ambientais/análise , Humanos , Mercúrio/análise , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
7.
Eur J Pharmacol ; 910: 174481, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34481876

RESUMO

Insulin resistance (IR) is the main cause of type 2 diabetes. The liver is the organ where insulin is secreted from the pancreas, and it regulates the storage and release of glucose according to the body's demand. Althouth Loureirin B (LB) has been reported to promote insulin secretion and decrease blood glucose, the effects of LB on glucose metabolism in the liver and the mechanism is still unclear. Different concentrations of LB were applied to treat on insulin resistance model (IR-HepG2) cells. The research results showed that LB inhibited the production of ROS (Reactive oxygen species) in IR-HepG2 cells, promoted the phosphorylation of AKT, down-regulated the expression of FoxO1, and up-regulated the expression of IRS1 and GLUT4. In addition, LB also down regulated the glucose metabolism related genes PEPCK and GSK3ß. The glucose uptake, consumption and glycogen content were increased. Moreover, LB-treated diabetic mice also showed hypoglycaemic effects. In summary, LB may ameliorate type 2 diabetes by preventing the inactivation of IRS1/AKT pathway in IR-HepG2 cells, increasing insulin sensitivity, and regulating glucose uptake and production.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gluconeogênese/efeitos dos fármacos , Resistência à Insulina , Resinas Vegetais/farmacologia , Animais , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/diagnóstico , Células Hep G2 , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resinas Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/administração & dosagem , Estreptozocina/toxicidade
8.
J Exp Clin Cancer Res ; 40(1): 280, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34479623

RESUMO

BACKGROUND: Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance. METHODS: Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs). RESULTS: Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an IC50 superior to that of acyclic retinoid and sorafenib, to which the recurrent HCC exhibits significant resistance at advanced stage. Sulfarotene promoted the expression and activation of RARα, which down-regulated SOS2, a key signal mediator associated with RAS activation and signal transduction involved in multiple downstream pathways. Moreover, sulfarotene selectively inhibited tumorigenesis of HCC PDXs with high expression for SOS2. CONCLUSIONS: Our study identified sulfarotene as a selective inhibitor for the TRCs of HCC, which targets a novel RARα-SOS2-RAS signal nexus, shedding light on a new, promising strategy of target therapy for advanced liver cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Retinoides/uso terapêutico , Proteínas Son Of Sevenless/efeitos dos fármacos , Sorafenibe/uso terapêutico , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Retinoides/farmacologia , Transdução de Sinais , Sorafenibe/farmacologia
9.
Curr Top Med Chem ; 21(13): 1139-1155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34109910

RESUMO

ANO1, anoctamin 1(also known as TMEM16A), is the molecular basis of calcium-activated chloride channels with ten transmembrane segments which are widely expressed in mammalian cells, including epithelial cells, vascular smooth muscle tissues, electro-excitatory cells, and some tumor cells. To date, multiple studies have shown that many natural and synthetic compounds have regulatory effects on ANO1. Therefore, ANO1 could be a potential new drug target for the treatment of cancer, pain, diarrhea, hypertension, and asthma. In this study, we review the structure of ANO1 and its involvement in cancer, pain, diarrhea, hypertension, and asthma.


Assuntos
Anoctamina-1/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas/química , Animais , Anoctamina-1/metabolismo , Asma/tratamento farmacológico , Asma/metabolismo , Química Farmacêutica , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Neoplasias/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo
10.
J Sci Food Agric ; 101(13): 5325-5336, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33650104

RESUMO

BACKGROUND: Roasted peanut is widely loved as a kind of food with rich taste. However, peanut allergy is one of the major threats to human health, which affects about 5% of children and 1.4-2% of adults in the world. RESULTS: To evaluate the sensitization mechanism of peanut allergen Ara h 3, Caco-2 cells as the model, which has the similar structure and function to differentiated small intestinal epithelial cells. Compared with Ara h 3-raw (purified from raw peanut) group, more significant results such as the inhibited Caco-2 cell viability and proliferation, the increased secretion of reactive oxygen species (ROS) and the decreased transepithelial electrical resistance were obtained in Ara h 3-roasted (purified from roasted peanut) group. Accordingly, oxidative stress and NF-κB signaling pathway were more imbalanced, which lead to the increased of thymic stromal lymphopoietin (TSLP), interleukin 6 (IL-6), IL-8 and monocyte chemotactic protein 1 (MCP-1). Then, the gene expression of tight junction proteins ZO-1, occludin and JAM-1 were reduced, which proved that the integrity of the Caco-2 monolayer barrier is severely damaged. CONCLUSION: These finding identify the mechanisms of the allergenicity of roasted peanut allergy proteins are probably associated with intestinal uptake and cytokine dependent allergies. The aggravated allergic reaction might be caused by the increment of TSLP, IL-6, IL-8 and MCP-1 due to the activated NF-κB signaling pathway, and the enhanced transport of Ara h 3-roasted protein by Caco-2 monolayer. © 2021 Society of Chemical Industry.


Assuntos
Antígenos de Plantas/imunologia , Arachis/imunologia , Células Epiteliais/imunologia , Hipersensibilidade a Amendoim/imunologia , Proteínas de Plantas/imunologia , Alérgenos/química , Alérgenos/imunologia , Antígenos de Plantas/química , Arachis/química , Células CACO-2 , Moléculas de Adesão Celular/imunologia , Quimiocina CCL2/imunologia , Humanos , Interleucina-6/imunologia , Interleucina-8/imunologia , Intestino Delgado/imunologia , NF-kappa B/imunologia , Proteínas de Plantas/química , Receptores de Superfície Celular/imunologia , Sementes/química , Sementes/imunologia , Proteína da Zônula de Oclusão-1/imunologia
11.
Clin Transl Med ; 11(3): e373, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33783986

RESUMO

BACKGROUND: Blood transfusion, a common basic supporting therapy, can lead to acute hemolytic transfusion reaction (AHTR). AHTR poses a great risk to patients through kidney function damage in a short time. Previous reports found that heme from destroyed red blood cells impaired kidney function, and NLR family pyrin domain containing 3 (NLRP3) inflammasome was augmented in case of kidney injury. However, the detailed mechanism regarding whether NLRP3 inflammasome is involved in kidney function injury in AHTR is not fully understood yet. METHODS: Hemolysis models were established by vein injection with human blood plasma or mouse heme from destroyed red blood cells. The injured renal tubular epithelial cells (RTECs) were evaluated by tubular damage markers staining in hemolysis models and in primary RTECs in vitro. The activation of NLRP3 inflammasome in RTECs by hemes was investigated by Western blot, ELISA, scanning electron microscopy, immunofluorescent staining, flow cytometry, and hemolysis models. NLRP3 gene knockout mice were employed to confirm these observations in vitro and in vivo. The binding between a novel inhibitor (66PR) and NLRP3 was affirmed by molecule docking and co-immunoprecipitation. The rescue of 66PR on kidney function impairment was explored in murine hemolysis models. RESULTS: We found that heme could activate NLRP3 inflammasome in RTECs to induce kidney function injury. NLRP3 gene knockout could prevent the damage of RTECs caused by hemes and recover kidney function in AHTR. Moreover, NLRP3 inflammasome chemical inhibitor, 66PR, could bind to NLRP3 protein and inhibit inflammasome activation in RTECs, which consequently relieved the injury of RTECs caused by hemes, and alleviated kidney function damage in the AHTR model. CONCLUSIONS: Hemes could activate NLRP3 inflammasome in RTECs, and a novel NLRP3 inflammasome inhibitor named 66PR relieved kidney function damage in AHTR. Our findings provided a new possible strategy to treat kidney function failure in AHTR.


Assuntos
Injúria Renal Aguda/metabolismo , Células Epiteliais/metabolismo , Inflamassomos/metabolismo , Túbulos Renais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Reação Transfusional/metabolismo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/genética , Animais , Modelos Animais de Doenças , Inflamassomos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Reação Transfusional/complicações , Reação Transfusional/genética
12.
J Cell Mol Med ; 25(2): 855-866, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33300675

RESUMO

Loureirin B (LB) is a natural product derived from Sanguis draconis, which has hypoglycaemic effects. In order to research the possible target of LB in the treatment of diabetes, molecular docking was used to simulate the interaction between LB and potential targets, and among them, glucagon-like peptide-1 receptor (GLP-1R) had the optimal results. Further, spectroscopy and surface plasmon resonance (SPR) experiments were applied to detect the interaction between LB and GLP-1R. Ultimately, after GLP-1R siRNA interfering the expression of GLP-1R in Ins-1 cell, the promoting insulin secretion of LB was weaken, which directly proved that GLP-1R plays an important role. These results show that LB promotes insulin secretion of Ins-1 cells through GLP-1R. Hence, the strategy of LB as a prodrug will provide a potential approach for non-peptide GLP-1R agonist.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Resinas Vegetais/farmacologia , Animais , Produtos Biológicos , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ratos
13.
Biotech Histochem ; 96(1): 76-81, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32619110

RESUMO

Gastric cancer (GC) is characterized by infrequent early diagnosis, poor prognosis and high mortality. Signal transducer and activator of transcription 3 (Stat3) and signal transducer and activator of transcription 5b (Stat5b) play multiple roles in the development and progression of many human cancers. We investigated the effects of silencing Stat3 and Stat5b on the viability and apoptosis of the human gastric cancer cell line, BGC-823. We found that Stat3 and Stat5b were expressed in both the nucleus and cytoplasm of BGC-823 cells. Silencing of Stat3 caused significantly decreased viability and increased apoptosis, as well as attenuated B-cell lymphoma-2 (Bcl-2) expression in BGC-823 cells. Silencing of Stat5b, however, had no significant effect on these events. Stat3, but not Stat5b, plays an important role in the viability and apoptosis of human gastric cancer cell line, BGC-823, which suggests that Stat3 is a potential target for gastric cancer therapy.


Assuntos
Apoptose , Fator de Transcrição STAT3 , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células , Inativação Gênica , Humanos , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-32640694

RESUMO

Epidemiological studies have corroborated that respiratory diseases, including lung cancer, are related to fine particulate matter (<2.5 µm) (PM2.5) exposure. The toxic responses of PM2.5 are greatly influenced by the source of PM2.5. However, the effects of PM2.5 from Beijing on bronchial genotoxicity are scarce. In the present study, PM2.5 from Beijing was sampled and applied in vitro to investigate its genotoxicity and the mechanisms behind it. Human bronchial epithelial cells 16HBE were used as a model for exposure. Low (67.5 µg/mL), medium (116.9 µg/mL), and high (202.5 µg/mL) doses of PM2.5 were used for cell exposure. After PM2.5 exposure, cell viability, oxidative stress markers, DNA (deoxyribonucleic acid) strand breaks, 8-OH-dG levels, micronuclei formation, and DNA repair gene expression were measured. The results showed that PM2.5 significantly induced cytotoxicity in 16HBE. Moreover, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cellular heme oxygenase (HO-1) were increased, and the level of glutathione (GSH) was decreased, which represented the occurrence of severe oxidative stress in 16HBE. The micronucleus rate was elevated, and DNA damage occurred as indicators of the comet assay, γ-H2AX and 8-OH-dG, were markedly enhanced by PM2.5, accompanied by the influence of 8-oxoguanine DNA glycosylase (OGG1), X-ray repair cross-complementing gene 1 (XRCC1), and poly (ADP-ribose) polymerase-1 (PARP1) expression. These results support the significant role of PM2.5 genotoxicity in 16HBE cells, which may occur through the combined effect on oxidative stress and the influence of DNA repair genes.


Assuntos
Dano ao DNA , Pequim , China , Células Epiteliais , Humanos , Estresse Oxidativo , Material Particulado , Espécies Reativas de Oxigênio , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
15.
J Sci Food Agric ; 100(15): 5617-5626, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32608517

RESUMO

BACKGROUND: Ara h 1 is a major food allergen in peanuts. Recently, many studies have revealed that the Maillard reaction (MR) affects the allergenicity of food proteins. RESULTS: To investigate the influence of the MR on the allergenicity of Ara h 1, R-Ara h 1 was processed with glucose in dry heating conditions for different periods. The extent of the MR was assessed by four methods. The changes in secondary and tertiary structures were characterized through spectroscopy assays. Advanced glycation end products (AGE) structures were identified by protein sample dry heating for 60 min, indicating the formation of AGE-Ara h 1. Simulated gastric fluid (SGF) digestion analysis showed that AGE-Ara h 1 has higher resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model was also utilized to explore the effect of the MR on the allergenicity of Ara h 1, and the results showed that the Th2-type cytokines, antibodies, and histamine content increased, and there was a greater degree of degranulation of rat basophilic leukemia (RBL) cells in the AGE-Ara h 1 group compared with the R-Ara h 1 group. CONCLUSION: During the process of dry heating, proteins participated in the MR with changes in secondary and tertiary structures. The condition applying a temperature of 100 °C for 60 min caused the formation of AGE-Ara h 1. Simulated gastric fluid digestion analysis showed that AGE-Ara h 1 had a greater resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model showed that AGE-Ara h 1 had more allergenicity, indicating that the MR could enhance the allergenicity of Ara h 1. © 2020 Society of Chemical Industry.


Assuntos
Antígenos de Plantas/química , Antígenos de Plantas/imunologia , Arachis/química , Proteínas de Membrana/química , Proteínas de Membrana/imunologia , Hipersensibilidade a Amendoim/imunologia , Proteínas de Plantas/química , Proteínas de Plantas/imunologia , Animais , Arachis/imunologia , Basófilos/imunologia , Manipulação de Alimentos , Temperatura Alta , Humanos , Imunoglobulina E/imunologia , Reação de Maillard , Camundongos , Camundongos Endogâmicos BALB C , Conformação Proteica , Ratos
16.
Genomics ; 112(1): 837-847, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150762

RESUMO

BACKGROUND: Glioma is the most lethal nervous system cancer. Recent studies have made great efforts to study the occurrence and development of glioma, but the molecular mechanisms are still unclear. This study was designed to reveal the molecular mechanisms of glioma based on protein-protein interaction network combined with machine learning methods. Key differentially expressed genes (DEGs) were screened and selected by using the protein-protein interaction (PPI) networks. RESULTS: As a result, 19 genes between grade I and grade II, 21 genes between grade II and grade III, and 20 genes between grade III and grade IV. Then, five machine learning methods were employed to predict the gliomas stages based on the selected key genes. After comparison, Complement Naive Bayes classifier was employed to build the prediction model for grade II-III with accuracy 72.8%. And Random forest was employed to build the prediction model for grade I-II and grade III-VI with accuracy 97.1% and 83.2%, respectively. Finally, the selected genes were analyzed by PPI networks, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the results improve our understanding of the biological functions of select DEGs involved in glioma growth. We expect that the key genes expressed have a guiding significance for the occurrence of gliomas or, at the very least, that they are useful for tumor researchers. CONCLUSION: Machine learning combined with PPI networks, GO and KEGG analyses of selected DEGs improve our understanding of the biological functions involved in glioma growth.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioma/genética , Glioma/metabolismo , Aprendizado de Máquina , Mapeamento de Interação de Proteínas , Neoplasias Encefálicas/diagnóstico , Expressão Gênica , Ontologia Genética , Glioma/diagnóstico , Estadiamento de Neoplasias
17.
Curr Pharm Des ; 25(40): 4287-4295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696805

RESUMO

BACKGROUND: Nilatinib is an irreversible tyrosine kinase inhibitor, which is used in the treatment of some kinds of cancer. To study the interaction between Neratinib and MAD2L1, a potential tumor target, is of guiding significance for enriching the medicinal value of Neratinib. METHOD: The binding mechanism between Mitotic arrest deficient 2-like protein 1 (MAD2L1) and Neratinib under simulative physiological conditions was investigated by molecule simulation and multi-spectroscopy approaches. RESULTS: Molecular docking showed the most possible binding mode of Neratinib-MAD2L1 and the potential binding sites and interaction forces of the interaction between MAD2L1 and Neratinib. Fluorescence spectroscopy experiments manifested that Neratinib could interact with MAD2L1 and form a complex by hydrogen bond and van der Waals interaction. These results were consistent with the conclusions obtained from molecular docking. In addition, according to Synchronous fluorescence and three-dimensional fluorescence results, Neratinib might lead to the conformational change of MAD2L1, which may affect the biological functions of MAD2L1. CONCLUSION: This study indicated that Neratinib could interact with MAD2L1 and lead to the conformational change of MAD2L1. These works provide helpful insights for the further study of biological function of MAD2L1 and novel pharmacological utility of Neratinib.


Assuntos
Proteínas Mad2/metabolismo , Simulação de Acoplamento Molecular , Quinolinas/metabolismo , Sítios de Ligação , Humanos , Ligação de Hidrogênio , Ligação Proteica , Estrutura Terciária de Proteína , Espectrometria de Fluorescência
18.
Curr Top Med Chem ; 19(25): 2301-2317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622219

RESUMO

In recent years, the successful implementation of human genome project has made people realize that genetic, environmental and lifestyle factors should be combined together to study cancer due to the complexity and various forms of the disease. The increasing availability and growth rate of 'big data' derived from various omics, opens a new window for study and therapy of cancer. In this paper, we will introduce the application of machine learning methods in handling cancer big data including the use of artificial neural networks, support vector machines, ensemble learning and naïve Bayes classifiers.


Assuntos
Aprendizado de Máquina , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Teorema de Bayes , Humanos , Neoplasias/diagnóstico , Máquina de Vetores de Suporte
19.
Se Pu ; 37(7): 712-722, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31271010

RESUMO

A liquid chromatography-tandem mass spectrometry method for the identification of marker peptides of aquatic product allergens and quantitative detection of multiple allergens in meat products and seasonings was developed. The samples were prepared by protein extraction, protein purification, and trypsin hydrolysis. The proteins and peptides were identified using ProteinPilot by the data analysis of the ion spectrum of polypeptide fragments using ultra-performance liquid chromatography-quadrupole/electrostatic orbitrap high-resolution mass spectrometry (UPLC-Q/Exactive-HRMS). The identification of 30 species-specific marker peptides in Penaeus vannamei, Eriocheir, Scylla serrata, Thunnus thynnus, and Atlantic salmon by comparison of the basic local alignment search tool (BLAST) with the UniProt database was achieved. The verification and multiple reaction monitoring (MRM) quantitative studies of these marker peptides were performed using a triple quadrupole mass spectrometry (UPLC-QqQ-MS) system. The proposed method showed a good linear relationship in the range of 5-250 mg/kg. The limits of quantitation and observed recoveries were in the range of 2-3.5 mg/kg and 88.7%-110.2%, respectively. This method presents various advantages such as good repeatability and high throughput, suitability for rapid screening, and quantitative analysis of seven aquatic allergens in meat products and seasonings.


Assuntos
Alérgenos/análise , Proteínas de Peixes/análise , Contaminação de Alimentos/análise , Produtos da Carne/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Espectrometria de Massas em Tandem
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