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1.
PLoS One ; 19(7): e0305572, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954711

RESUMO

Green leafy vegetables are an essential component of Chinese leafy vegetables. Due to their crisp stems and tender leaves, orderly harvester generally causes significant mechanical clamping damage. The physical and mechanical properties of green leafy vegetables are one of the important basis to design the orderly harvester. At the same time, they provide important parameters for the simulation and optimization of harvester. So, this paper measured the physical characteristic parameters of roots and stems of green leafy vegetables. Then, based on the TMS-Pro texture analyzer, the elasticity modulus of the roots and stems of green leafy vegetables were measured. The static friction coefficient, dynamic friction coefficient, and restitution coefficient of green leafy vegetables root-root, stem-stem, root-steel, and stem-steel were measured separately using a combination method of inclined plane and high-speed photography. Uniaxial compression creep experiments were carried out on whole and single leaf of green leafy vegetables using the TA.XT plus C universal testing machine. The constitutive equation of the four-element Burgers model was used to fit the deformation curve of the sample with time during the constant-pressure loading stage. The fitting determination coefficients R2 were all higher than 0.996, which verified the reasonable validity of the selected model. The above experimental results provide a parameter basis and theoretical support for the design and discrete element simulation optimization of orderly harvester critical components of green leafy vegetables.


Assuntos
Folhas de Planta , Raízes de Plantas , Verduras , Viscosidade , Folhas de Planta/química , Elasticidade , Caules de Planta/fisiologia
2.
J Biochem Mol Toxicol ; 38(7): e23762, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967723

RESUMO

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.


Assuntos
Antineoplásicos , Benzimidazóis , Sistema de Sinalização das MAP Quinases , Espécies Reativas de Oxigênio , Neoplasias Gástricas , Benzimidazóis/farmacologia , Benzimidazóis/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose/efeitos dos fármacos , Camundongos Nus
3.
Arch Biochem Biophys ; 758: 110051, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851368

RESUMO

Colorectal cancer (CRC) is an aggressive cancer type globally. Surgery and chemotherapy are often ineffective at curing CRC. Dictamnine is a natural product derived from Dictamnus dasycarpus Turcz. root bark and possesses multi-pharmacological properties, including anticancer effects. Nevertheless, the biological roles and the possible mechanism of dictamnine in CRC are still unclear. Here, we demonstrated that dictamnine blocked cell viability and proliferation in DLD-1 human colorectal adenocarcinoma cells and LoVo human colon cancer cells. Dictamnine triggered CRC cell ferroptosis, as evidenced by enhanced levels of reactive oxygen species, malondialdehyde, and Fe2+ levels, alongside downregulation of glutathione peroxidase 4 protein expression. In addition, CD163 (HPA ID: HPA046404) was highly expressed and CD68 (HPA ID: CAB000051) was lowly expressed in CRC tissues and CRC cell culture medium-cultured THP-1 monocytes-derived macrophages. The patients with CD163 low-expression lived much longer than those with CD163 high-expression, indicating that M2 polarization of macrophages was related to poor prognosis of CRC. Dictamnine markedly inhibited CD163 protein expression, transforming growth factor-ß and arginase 1 mRNA expressions and IL-10 production in macrophages with CRC cell co-culture, suggesting that dictamnine impeded M2 polarization of macrophages. Mechanistically, dictamnine repressed ERK phosphorylation in CRC cells. The treatment with the ERK activator tBHQ counteracted the effects of dictamnine on CRC cell proliferation and ferroptosis, as well as its inhibitory effect on M2 polarization of macrophages. Results of a xenograft model showed that dictamnine effectively hindered CRC tumor growth in vivo. Collectively, these data provide evidence for the clinical trials of dictamnine as a novel drug for CRC therapy.


Assuntos
Neoplasias Colorretais , Ferroptose , Sistema de Sinalização das MAP Quinases , Macrófagos , Ferroptose/efeitos dos fármacos , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Masculino
4.
J Opt Soc Am A Opt Image Sci Vis ; 40(11): 2068-2077, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038073

RESUMO

Optical coherence tomography (OCT) is a noninvasive optical imaging technique that can be used to produce three-dimensional images of fingerprints. However, the low quality and poor resolution of the regions of interest (ROIs) in OCT images make it challenging to segment small tissues accurately. To address this issue, a super-resolution (SR) network called ESRNet has been developed to enhance the quality of OCT images, facilitating their applications in research. Firstly, the performance of the SR images produced by ESRNet is evaluated by comparing it to those generated by five other SR methods. Specifically, the SR performance is evaluated using three upscale factors (2×, 3×, and 4×) to assess the quality of the enhanced images. Based on the results obtained from the three datasets, it is evident that ESRNet outperforms current advanced networks in terms of SR performance. Furthermore, the segmentation accuracy of sweat glands has been significantly improved by the SR images. The number of sweat glands in the top view increased from 102 to 117, further substantiating the performance of the ESRNet network. The spiral structure of sweat glands is clear to human eyes and has been verified by showing similar left-right-handed spiral numbers. Finally, a sweat gland recognition method for the SR 3D images is proposed.


Assuntos
Glândulas Sudoríparas , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Glândulas Sudoríparas/diagnóstico por imagem , Imageamento Tridimensional , Algoritmos , Olho
5.
Biomed Eng Online ; 22(1): 103, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907955

RESUMO

To classify early endometrial cancer (EC) on sagittal T2-weighted images (T2WI) by determining the depth of myometrial infiltration (MI) using a computer-aided diagnosis (CAD) method based on a multi-stage deep learning (DL) model. This study retrospectively investigated 154 patients with pathologically proven early EC at the institution between January 1, 2018, and December 31, 2020. Of these patients, 75 were in the International Federation of Gynecology and Obstetrics (FIGO) stage IA and 79 were in FIGO stage IB. An SSD-based detection model and an Attention U-net-based segmentation model were trained to select, crop, and segment magnetic resonance imaging (MRl) images. Then, an ellipse fitting algorithm was used to generate a uterine cavity line (UCL) to obtain MI depth for classification. In the independent test datasets, the uterus and tumor detection model achieves an average precision rate of 98.70% and 87.93%, respectively. Selecting the optimal MRI slices method yields an accuracy of 97.83%. The uterus and tumor segmentation model with mean IOU of 0.738 and 0.655, mean PA of 0.867 and 0.749, and mean DSC of 0.845 and 0.779, respectively. Finally, the CAD method based on the calculated MI depth reaches an accuracy of 86.9%, a sensitivity of 81.8%, and a specificity of 91.7% for early EC classification. In this study, the CAD method implements an end-to-end early EC classification and is found to be on par with radiologists in terms of performance. It is more intuitive and interpretable than previous DL-based CAD methods.


Assuntos
Neoplasias do Endométrio , Imageamento por Ressonância Magnética , Feminino , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Diagnóstico por Computador , Computadores
6.
Sci Rep ; 13(1): 7798, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37179376

RESUMO

Aiming at the problems of low fertilization efficiency, mainly the process operation and inconsistent fertilization depth of domestic tea garden fertilizer machines, a single-spiral fixed depth ditching and fertilizing machine is appropriately designed. This machine is capable of performing the integrated operation of ditching, fertilization, and covering soil at the same time through the operation mode of single-spiral ditching and fertilization. The theoretical analysis and design of the structure of the main components are properly carried out. The fertilization depth can be adjusted through the established depth control system. The performance test reveals that the single-spiral ditching and fertilizing machine exhibits a maximum stability coefficient of 96.17% and a minimum of 94.29% in terms of trenching depth and a maximum of 94.23% and a minimum of 93.58% in terms of fertilization uniformity, meeting the production requirements of tea plantations.

7.
Future Med Chem ; 15(4): 333-344, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36946221

RESUMO

Aim: Because of the severe morbidity and mortality of gastric cancer, discovering new candidate drugs has been an urgent issue. The close association between histone deacetylase 6 (HDAC6) and gastric cancer makes the development of HDAC6-targeted anti-gastric cancer drugs a viable idea. Methods & results: Carbenoxolone disodium was identified as a novel HDAC6 inhibitor. Cellular thermal shift assay, surface plasmon resonance assay and molecular docking confirmed its binding ability to HDAC6. Cell viability, wound healing and transwell assays as well as animal studies have demonstrated that carbenoxolone disodium could block the proliferation and migration of gastric cancer cells MGC-803 in vitro and in vivo. Conclusion: This is the first report to indicate that carbenoxolone disodium could be an HDAC6 inhibitor with potential for treatment of gastric cancer.


Assuntos
Histona Desacetilases , Neoplasias , Animais , Desacetilase 6 de Histona , Histona Desacetilases/metabolismo , Carbenoxolona , Simulação de Acoplamento Molecular , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química
8.
Environ Geochem Health ; 45(7): 4703-4717, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36905567

RESUMO

Groundwater is susceptible to arsenic contamination by sediment with high arsenic content, which is the primary culprit of regional arsenic pollution and poisoning. To explore the influence of the change in hydrodynamic conditions caused by changes in the sedimentary environment over time on arsenic content in sediments during the Quaternary, the hydrodynamic characteristics and arsenic content enrichment of borehole sediments were studied in typical high-arsenic groundwater areas of the Jianghan-Dongting Basin, China. The regional hydrodynamic conditions represented by each borehole location were analyzed, the correlation between the variation in groundwater dynamics characteristics and arsenic content in different hydrodynamic periods was analyzed, and the relationship between arsenic content and grain size distribution was quantitatively investigated using grain size parameter calculation, elemental analysis, and statistical estimates of arsenic content in borehole sediments. We observed that the relationship between arsenic content and hydrodynamic conditions differed between sedimentary periods. Furthermore, arsenic content in the sediments from the borehole at Xinfei Village was significantly and positively correlated with a grain size of 127.0-240.0 µm. For the borehole at Wuai Village, arsenic content was significantly and positively correlated with a grain size of 1.38-9.82 µm size (at 0.05 level of significance). However, arsenic content was inversely correlated with grain sizes of 110.99-716.87 and 133.75-282.07 µm at p values of 0.05 and 0.01, respectively. For the borehole at Fuxing Water Works, arsenic content was significantly and positively correlated with a grain size of 409.6-655.0 µm size (at 0.05 level of significance). Arsenic tended to be enriched in transitional and turbidity facies sediments with normal corresponding hydrodynamic strength but poor sorting. Furthermore, continuous and stable sedimentary sequences were conducive to arsenic enrichment. Fine-grain sediments provided abundant potential adsorption sites for high-arsenic sediments, but finer particle size was not correlated with higher arsenic levels.


Assuntos
Arsênio , Água Subterrânea , Poluentes Químicos da Água , Arsênio/análise , Hidrodinâmica , Sedimentos Geológicos/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Água Subterrânea/análise
9.
PLoS One ; 17(12): e0277824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36516157

RESUMO

In response to the problems of low fertilizer application efficiency, poor operation quality, and uneven application of fertilizer by domestic tea garden trenching and fertilizing machines, an automatic depth-adjusting double screw trenching and fertilizing machine was designed. The machine uses a double spiral furrowing and fertilizer application method, which can complete the integrated operation of furrowing, fertilizer application, and mulching at one time. The key components of the machine such as the screw-type fertilizer discharger, trenching, and fertilizer application mechanism are designed using theoretical analysis, and the trenching depth is automatically adjusted through the hydraulic control system to maintain a consistent depth. A single-factor test and a quadratic regression rotary orthogonal test were conducted to select the diameter of the spiral fertilizer discharger, the rotational speed of the spiral fertilizer discharger, and the rotational speed of the trenching and fertilizer application mechanisms. Based on these tests, the fertilizer application performance of the fertilizer machine was evaluated, and a mathematical model of the fertilizer application volume and coefficient of variation was established. The influence of the test factors on the coefficient of variation was also analyzed. In the study, 58.36 and 480.35 r/min were found to be the optimal rotational speeds for spiral fertilizer discharge and trenching and fertilizer application, respectively, while 88.90 mm was found to be the optimal diameter for spiral fertilizer discharge. The coefficient of variation for the spiral fertilizer discharge was 3.95%, which meets the tea plantation's fertilizer application requirements.


Assuntos
Agricultura , Fertilizantes , Fertilizantes/análise , Agricultura/métodos , Nitrogênio/análise , Chá , Parafusos Ósseos , Solo
10.
Cell Biosci ; 12(1): 171, 2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36210463

RESUMO

BACKGROUND: Chemokine CXC motif receptor 7 (CXCR7) is an atypical G protein-coupled receptor (GPCR) that signals in a biased fashion. CXCL12/CXCR7 biased signal has been reported to play crucial roles in multiple stages of colorectal cancer (CRC). However, the mechanism of CXCL12/CXCR7 biased signal in promoting CRC progression and metastasis remains obscure. RESULTS: We demonstrate that CXCR7 activation promotes EMT and upregulates the expression of Vimentin and doublecortin-like kinase 1 (DCLK1) in CRC cells with concurrent repression of miR-124-3p and miR-188-5p through YAP1 nuclear translocation. Cell transfection and luciferase assay prove that these miRNAs regulate EMT by targeting Vimentin and DCLK1. More importantly, CXCL12/CXCR7/ß-arrestin1-mediated biased signal induces YAP1 nuclear translocation, which functions as a transcriptional repressor by interacting with Yin Yang 1 (YY1) and recruiting YY1 to the promoters of miR-124-3p and miR-188-5p. Pharmacological inhibitor of YAP1 suppresses EMT and tumor metastasis upon CXCR7 activation in vivo in tumor xenografts of nude mice and inflammatory colonic adenocarcinoma models. Clinically, the expression of CXCR7 is positively correlated with nuclear YAP1 levels and EMT markers. CONCLUSIONS: Our studies reveal a novel mechanism and clinical significance of CXCL12/CXCR7 biased signal in promoting EMT and invasion in CRC progression. These findings highlight the potential of targeting YAP1 nuclear translocation in hampering CXCL12/CXCR7 biased signal-induced metastasis of colorectal cancer.

11.
Front Plant Sci ; 13: 1011859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311065

RESUMO

Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Fo), is a severe soil-borne disease affecting cucumber production worldwide, particularly under monocropping in greenhouses. Silicon (Si) plays an important role in improving the resistance of crops to Fusarium wilt, but the underlying mechanism is largely unclear. Here, an in vitro study showed that 3 mmol·l-1 Si had the best inhibitory effect on the mycelial growth of F. oxysporum in potato dextrose agar (PDA) culture for 7 days. Subsequently, the occurrence of cucumber wilt disease and its mechanisms were investigated upon treatments with exogenous silicon under soil culture. The plant height, stem diameter, root length, and root activity under Si+Fo treatment increased significantly by 39.53%, 94.87%, 74.32%, and 95.11% compared with Fo only. Importantly, the control efficiency of Si+Fo was 69.31% compared with that of Fo treatment. Compared with Fo, the activities of peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) significantly increased by 148.92%, 26.47%, and 58.54%, while the contents of H2O2, O 2 · - , and malondialdehyde (MDA) notably decreased by 21.67%, 59.67%, and 38.701%, respectively, in roots of cucumber plants treated with Si + Fo. Compared with Fo treatment, the net photosynthesis rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), maximum RuBisCO carboxylation rates (Vcmax), maximum RuBP regeneration rates (Jmax), and activities of ribulose-1,5-bisphosphate carboxylase (RuBisCO), fructose-1,6-bisphosphatase (FBPase), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the expression of FBPA, TPI, SBPase, and FBPase in Si+Fo treatment increased significantly. Furthermore, Si alleviated stomatal closure and enhanced endogenous silicon content compared with only Fo inoculation. The study results suggest that exogenous silicon application improves cucumber resistance to Fusarium wilt by stimulating the antioxidant system, photosynthetic capacity, and stomatal movement in cucumber leaves. This study brings new insights into the potential of Si application in boosting cucumber resistance against Fusarium wilt with a bright prospect for Si use in cucumber production under greenhouse conditions.

12.
Sci Rep ; 12(1): 8336, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585115

RESUMO

The construction of check dams is an important measure to prevent soil erosion on the Loess Plateau and reduce the amount of sediment entering the Yellow River. Based on an analysis of the current situation of soil and water conservation on the Loess Plateau and the three major problems faced by the traditional homogeneous soil check dam construction, the study of anti-scouring materials, hydrological calculation methods, dam design and construction technology and soil and water conservation monitoring are carried out in this paper. The results showed that the current soil and water conservation measures on the Loess Plateau have achieved remarkable outcomes. The new design and application concept of check dams with anti-burst and multi-sand interceptions is innovatively proposed in this paper. The new materials of solidified loess have good durability and anti-scouring characteristics and could meet the overflow and anti-scouring requirements of the new check dam. The small watershed high sand content of hydrological calculation can establish the upper limit of the flood sediment boundary for the anti-scouring protection layer of the check dam. The new technology of dam design and construction can achieve no collapse or slow collapse when encountering floods exceeding the standard. Intelligent monitoring systems can realize real-time dynamic monitoring for soil and water conservation on the Loess Plateau. The results will eventually contribute to the national strategy of the Ecological Protection and High Quality Development in the Yellow River basin.


Assuntos
Conservação dos Recursos Hídricos , Solo , China , Conservação dos Recursos Naturais/métodos , Monitoramento Ambiental/métodos , Rios , Areia
13.
Insect Mol Biol ; 31(3): 377-390, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35141960

RESUMO

Laodelphax striatellus is a sap-feeding pest and the main insect vector of rice stripe virus (RSV). There is an urgent need to identify molecular targets to control this insect pest and plant arboviruses. In this study, we identified a L. striatellus gene (named LsGrpE) encoding a GroP-E-like protein. We found that the LsGrpE protein localized to mitochondria. Using gene-specific dsRNA to interfere with the expression of LsGrpE led to a significant increase in insect mortality, and most of the surviving insects could not develop into adults. Further analyses revealed that LsGrpE deficiency caused mitochondrial dysfunction and inhibited the insulin pathway, resulting in diabetes-like symptoms such as elevated blood sugar, inactive behaviour, developmental delay, and death. In addition, LsGrpE deficiency significantly reduced the RSV titre in surviving L. striatellus, and indirectly prevented viral vertical transmission by reducing the number of adults. We generated transgenic rice plants expressing LsGrpE-specific dsRNA, and the dsRNA was acquired by L. striatellus during feeding, resulting in increased insect mortality and the prevention of arboviral transmission. This study clarifies the function of LsGrpE and demonstrates that LsGrpE can be used as a molecular target of plant-generated dsRNA to resist this sap-feeding pest, a17nd therefore, its transmitted arboviruses.


Assuntos
Arbovírus , Hemípteros , Oryza , Tenuivirus , Animais , Arbovírus/genética , Arbovírus/metabolismo , Hemípteros/genética , Hemípteros/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos/genética , Mitocôndrias/genética , Oryza/genética , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , Tenuivirus/genética
14.
Sci Rep ; 11(1): 13941, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230568

RESUMO

Odorant-binding proteins (OBPs) are prevalent in the antennal transcriptomes of different orders of insects. Studies on OBPs have focused on their role in the insect chemosensory system, but knowledge of their functions in the insect testis is limited. We sequenced the transcriptomes of the Athetis dissimilis reproductive organs and analyzed the expression of AdisOBP genes in different tissues. We identified 23 OBPs in the testis and ovaries and 31 OBPs in antennal transcriptomes. The results of real-time quantitative PCR revealed that 23 of the 54 OBP genes were highly expressed in both female and male antennae, including three that exhibited male-biased expression and 15 that exhibited female-biased expression. A total of 24 OBPs were highly expressed in the testis of A. dissimilis, while expression of OBPs in the ovaries was very low. These findings highlight the functional diversity of OBPs in insects and can facilitate further studies on the OBPs in A. dissimilis and lepidopteran species.


Assuntos
Antenas de Artrópodes/metabolismo , Regulação da Expressão Gênica , Genitália/metabolismo , Lepidópteros/genética , Receptores Odorantes/genética , Animais , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Masculino , Anotação de Sequência Molecular , Ovário/metabolismo , Filogenia , Receptores Odorantes/metabolismo , Análise de Sequência de DNA , Testículo/metabolismo , Transcriptoma/genética
15.
Front Pharmacol ; 12: 640949, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935733

RESUMO

Lysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibitors, while none of them has entered into market. With the help of compound library, monobenzone, a local depigmentor using as a treating over-pigmentation in clinic, was characterized as an effective KDM1A inhibitor (IC50 = 0.4507 µM), which may competitively inhibit KDM1A reversibly. Further cellular study confirmed that monobenzone could inhibit the proliferation of gastric cancer cell lines MGC-803 and BGC-823 with IC50 as 7.82 ± 0.55 µM and 6.99 ± 0.51 µM, respectively, and erase the substrate of KDM1A, H3K4me1/2 and H3K9 me2, and inhibit the migration of gastric cancer cell by reversing epithelial-mesenchymal transition (EMT). As the structure of monobenzone is very simple and small, this study provides a novel backbone for the further optimization of KDM1A inhibitor and gives monobenzone potential new application.

16.
Life Sci ; 276: 119399, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33781830

RESUMO

AIMS: Exosomal transfer of miRNAs affects recipient cell proliferation and chemoresistance. Here, we aimed to investigate the role of exosomal miRNAs in controlling cisplatin resistance in non-small cell lung carcinoma (NSCLC). MAIN METHODS: Paired tumor and normal tissue-derived exosomes were collected from NSCLC patients with low or high responsiveness to cisplatin treatment. The results showed that the microRNA-4443 (miR-4443) level was upregulated in cisplatin-resistant NSCLC tumor tissue-derived exosomes compared with cisplatin-sensitive tissue-derived exosomes. Cisplatin-resistant cells (A549-R) were generated from the parental cells (A549-S). Resistant exosomes conferred cisplatin resistance by transferring miR-4443 to sensitive cells. Moreover, overexpression of miR-4443 inhibited FSP1-mediated ferroptosis induced by cisplatin treatment in vitro and enhanced tumor growth in vivo. KEY FINDINGS: Through bioinformatics analysis and luciferase assays, METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3. SIGNIFICANCE: Our findings provide more in-depth insight into the chemoresistance of NSCLC and support the therapeutic potential of targeting ferroptosis.


Assuntos
Adenosina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Ferroptose , MicroRNAs/genética , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Adenosina/química , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Metilação de DNA , Epigênese Genética , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Proteína A4 de Ligação a Cálcio da Família S100/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Bioorg Chem ; 103: 104161, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889380

RESUMO

Capsaicinoids are plant secondary metabolites, and capsaicin is the main principal that responsible to the pungency of chili peppers, with widely application as food additive. In our study, capsaicin was characterized as lysine specific demethylase 1A (KDM1A/LSD1) inhibitor with IC50 of 0.6 ± 0.0421 µM in biochemical level, and can bind KDM1A recombinant directly and reversibly. Further cellular study confirmed that capsaicin can bind and inhibit KDM1A in gastric cancer cell line BGC-823 and further inhibit cell invasion and migration by reversing epithelial-mesenchymal transition (EMT). In sum, our findings identified KDM1A as a target of capsaicin and reveals capsaicin as a modifier of histone methylation for the first time, which may provide a new skeleton for further optimization of KDM1A inhibitor.


Assuntos
Capsaicina/uso terapêutico , Histona Desmetilases/antagonistas & inibidores , Capsaicina/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
18.
Oncogene ; 38(28): 5747, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31182792

RESUMO

A correction to this paper has been published and can be accessed via a link at the top of the paper.

19.
Eur J Med Chem ; 174: 9-15, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31022552

RESUMO

Myricetin is a natural dietary flavonoid compound with multiple activities, such as anti-oxidant, anti-inflammatory, anti-carcinogenic and anti-proliferative effects. However, myricetin exhibited substantial limitations, such as poor water-solubility, and low stability in body when it was administrated by oral. To solve these problems, we designed and synthesized a series of derivatives based on the structure of myricetin. M10 was produced by adding a hydrophilic glycosylation group and then forming a sodium salt derivative, which exhibited excellent water-solubility (>100 mg/mL), and better stability in Wistar rat plasma and liver microsomes. In vivo study, M10 exhibited higher efficacy than myricetin and mesalazine in a dextran sulfate sodium (DSS) induced mice model with ulcerative colitis. In addition, M10 also exhibited high safety (LD50 > 5 g/kg) in mice. Based on these results, M10 could be developed as a potential therapeutic agent for treatment of ulcerative colitis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Flavonoides/uso terapêutico , Lactose/análogos & derivados , Lactose/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Colite Ulcerativa/induzido quimicamente , Colo/patologia , Sulfato de Dextrana , Estabilidade de Medicamentos , Feminino , Flavonoides/síntese química , Flavonoides/química , Flavonoides/farmacocinética , Glicosilação , Meia-Vida , Lactose/síntese química , Lactose/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/metabolismo , Ratos Wistar , Solubilidade
20.
Iran J Biotechnol ; 17(3): e2219, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32195285

RESUMO

BACKGROUND: Salinity is a major environmental limiting factor, which affect agricultural production. The two Manilkara seedlings (M. roxburghiana and M. zapota) with high economic importance, could not adapt well to higher soil salinity and little is known about their proteomic mechanisms. OBJECTIVES: The mechanisms responsible for the effects of salinity on the two Manilkara species leaves were examined by means of proteomic analysis. MATERIAL AND METHODS: The seedlings were cultivated in a greenhouse and treated with NaCl. Leaves of control and the salt-stressed seedlings were sampled for phenol protein extraction. Proteins were separated by two-dimensional gel electrophoresis coupled with mass spectroscopy to study the change of proteins under different NaCl concentration. RESULTS: For M. roxburghiana leaves, 21 protein spots exhibited significant abundance variations between the control and the 6‰, 8‰ NaCl treatments, of these 13 proteins were identified. They included L-ascorbate peroxidase, chloroplast carbonic anhydrase, phosphoglycerate kinase, 5 heat-shock proteins(HSPs) which were all down- regulated; For M. zapota leaves, 35 protein spots exhibited significant abundance variations, then 24 proteins were identified, including 7 down-regulated HSPs as well as glyceraldehyde-3-phosphate dehydrogenase, Cell division protein, putative mitochondrial NAD-dependent malate dehydrogenase, ATP synthase, Rubisco large subunit-binding protein, Cytochrome c peroxidase. CONCLUSIONS: Based on the common identified proteins between the two M. species, our results indicated that the identificated proteins in the two Manilkara species were involved in carbohydrate metabolism, photosynthesis, defense and stress. HSPs exhibited variation strictly related to NaCl stress. The down-regulated HSPs meant the function to repair cells that have suffered damage weaken during stress process. Furthermore, except for HSP70 in M. zapota leaves, the HSPs in the two species were all small heat shock proteins (sHSPs) with molecular weights ranging from 15 to 42 kDa.

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