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1.
J Transl Med ; 22(1): 507, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802851

RESUMO

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.


Assuntos
Fibronectinas , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-myc , RNA Circular , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Proteólise , Camundongos Nus , Sequência de Bases , Movimento Celular/genética , Feminino , Camundongos
2.
Chem Biodivers ; 21(5): e202400098, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38462532

RESUMO

Curcumae Radix (CuR) is a traditional Chinese medicine that has been used in China for more than 1,000 years. It has the traditional efficacy of activating blood and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood, and promoting gallbladder and removing jaundice. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, pharmacological effects, toxicity and quality control. Currently, 250 compounds, mainly including terpenoids and curcuminoids, have been isolated and identified from CuR, which has pharmacological activities, including antitumor, anti-inflammatory and analgesic, antidepressant, hepatoprotective, hemostatic, hematopoietic, and treatment of diabetes mellitus. In modern clinical practice, CuR is widely used in the treatment of tumors, breast hyperplasia, hepatitis, and stroke. However, the generation of toxicity and clinical application of CuR and Caryophylli Flos, the determination of the concoction process of artifacts, the determination of specific Quality Marker, and the establishment of the quality control system of CuR, are problems that need to be solved urgently at present.


Assuntos
Curcuma , Controle de Qualidade , Humanos , Curcuma/química , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Animais , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação
3.
Anal Chem ; 96(5): 2008-2021, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38276876

RESUMO

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.


Assuntos
Lipídeos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Lipídeos/análise , Cromatografia Líquida/métodos , Algoritmos , Simulação por Computador
4.
Int J Mol Med ; 53(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214365

RESUMO

Following the publication of this article, a concerned reader drew to the Editor's attention that, in Fig. 9C on p. 2478 showing the results of Transwell invasion assay experiments, unexpected areas of similarity were identified in terms of the cellular patterns revealed both within the data panels for the six different experiments portrayed in this figure, and comparing among them. After having conducted an internal investigation, the Editor of International Journal of Molecular Medicine has reached the conclusion that the overlapping sections of data shown in this figure were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [International Journal of Molecular Medicine 42: 2469­2480, 2018; DOI: 10.3892/ijmm.2018.3853].

5.
Food Chem ; 415: 135717, 2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-36848832

RESUMO

Microplastics (MPs) released from food packaging have attracted widespread attention. In this study, drip bags made from polyethylene (PE), polypropylene (PP), polyester (PET), and rayon selected from eight brands were employed to investigate MPs releasing. Fourier-transform infrared microspectroscopy (µ-FTIR), optical microscope and scanning electron microscope (SEM) were used to study the effects of brewing time and temperature on the release of MPs. The results showed that a single plastic coffee bag steeped at 95 ℃ for 5 min could release more than 10,000 MPs particles into a cup of coffee. Irregular blocks, long strips, and size range of 10-500 µm MPs were easier to be released, implying that consuming 3-4 cups of coffee will lead to an intake of 50 thousand MPs particles daily. Rayon was the primary type of released MPs, accounting for over 80% of the total amount of the released MPs. Our results are hoped to provide evaluation standards of material selection for processing coffee bags.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Água
6.
Chin J Nat Med ; 20(1): 67-73, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35101251

RESUMO

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 µmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Apoptose , Caspases , Humanos , Osteossarcoma/tratamento farmacológico , Penicillium
7.
Angew Chem Int Ed Engl ; 61(21): e202116865, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35132759

RESUMO

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than BIII . In the case of Al-preoccupation, the bulk diffusion of BIII is hindered. In this way, a B-rich surface and Al-rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.

8.
Orthop Surg ; 13(5): 1662-1672, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34105258

RESUMO

OBJECTIVE: To assess the effects of PTH (1-34) on bone and cartilage metabolism in a collagenase-induced mouse model of osteoarthritis (OA) and examine whether PTH (1-34) affects the expression of JAK2/STAT3 and WNT5A/ROR2 in this process. METHODS: Eighteen 12-week-old male C57Bl/6 mice were randomly assigned into three groups as follows: sham group (Group A), the collagenase + saline injection group (Group B), and the collagenase + PTH (1-34) treatment group (Group C). Collagenase was injected (intra-articular) into the knee joint of Group B and C. The PTH (1-34)-treatment was started at 6 weeks after the operation and lasted for 6 weeks. Cartilage pathology was evaluated by gross visual, histological, and immunohistochemical assessments. Subchondral bone was evaluated by microcomputed tomography (micro-CT) and immunohistochemical analyses. RESULTS: The OARSI macroscopic and microscopic scores of Group B were higher than those of Group A (P = 0.026; P = 0.002, respectively). Group C showed statistically significant differences in macroscopic and microscopic scores from Group B (P = 0.041; P = 0.008, respectively). The results showed that the Col-II and AGG expression levels in the cartilage tissue were significantly lower in Group B than Group A (P < 0.001; P = 0.008, respectively). The Col-II and AGG expression levels were significantly higher in Group C than Group B (P = 0.009; P = 0.014, respectively). MMP-13, ADAMTS-4, Caspase-3, P53, and Bax expression levels were significantly higher in Group B than the Group A (P < 0.001; P < 0.001; P = 0.04; P < 0.001; P = 0.005, respectively); however, the cartilage tissue in Group C showed significantly less ADAMTS-4, MMP-13, Caspase-3, P53, and Bax expression than Group B (P < 0.001, P < 0.001, P = 0.044; P = 0.002; P = 0.005, respectively). Over-expressed JAK2/STAT3 and WNT5A/ROR2 were observed in both cartilage and subchondral bone in this model; however, these changes were prevented by PTH (1-34) treatment. These parameters (bone mineral density, bone volume ratio, trabecular bone pattern factor, and structure model index) of micro-CT indicated subchondral bone loss and architecture changes in Group B, but improvements in these parameters in Group C. CONCLUSIONS: PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a collagenase-induced OA mouse model, and it may be involved in down-regulating the expression of JAK2/STAT3 and WNT5A/ROR2.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Janus Quinase 2/metabolismo , Osteoartrite do Joelho/tratamento farmacológico , Hormônio Paratireóideo/farmacologia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína Wnt-5a/metabolismo , Animais , Colagenases , Modelos Animais de Doenças , Regulação para Baixo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 969-974, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105502

RESUMO

OBJECTIVE: To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism. METHODS: The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed. RESULTS: In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05). CONCLUSION: The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.


Assuntos
Leucopenia , Baço , Animais , Epirubicina , Fator Estimulador de Colônias de Granulócitos , Contagem de Leucócitos , Leucopenia/induzido quimicamente , Leucopenia/tratamento farmacológico , Camundongos , Peso Molecular , Extratos Vegetais , Proteínas Recombinantes
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 430-437, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34018361

RESUMO

OBJECTIVE: To investigate the effect of E74-like factor 5 (ELF5) overexpression on the growth and invasion ability of colorectal cancer cells and its effect on tumor formation in nude mice. METHODS: Human colorectal cancer SW480 and HT-29 cells were divided into 5 groups: the lentivirus (LV)- GFP group transfected with empty vector LV- GFP, the LV- ELF5 group transfected with recombinant LV- ELF5, the shRNA-NC group transfected with empty vector shRNA-NC, the shRNA- ELF5 group transfected with recombinant shRNA- ELF5, and the control group, not transfected with any vector. Seventy-two h after transfection, the cell supernatant containing lentivirus was collected. The mRNA expression level of ELF5 in each group was examined by real-time fluorescent quantitative PCR (RT-qPCR). The protein expression levels of ELF5, apoptosis-related cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9, and invasion-related E-cadherin and N-cadherin were checked with Western blot. CCK-8 was used to check cell viability. Colony formation experiment was done to evaluate colony formation rate. Flow cytometry was used to assess cell apoptosis. Transwell migration assay was used to examine cell invasion. TUNEL assay was used to examine the apoptosis of tissues cells. Immunohistochemistry test was done to determine the expression of E-cadherin and N-cadherin in tissues. 20 BALB/c nude mice were put into 4 groups (5 in each group): LV- GFP group, shRNA-NC group, LV- ELF5 group, and shRNA- ELF5 group. Recombinant lentiviral SW480 cell supernatants were subcutaneously injected into nude mice to construct nude mice tumorigenesis models and the volume changes of transplanted tumors were monitored. On the 30th day, transplanted tumor tissues from the nude mice were extracted and the tumor mass was measured. Western blot was done to measure the expression of ELF4 protein in the transplanted tumors. TUNEL staining was used to check cell apoptosis in the tissues, and the positive expression of N-cadherin in the transplanted tumor was measured by immunohistochemical tests. RESULTS: Compared with the control group, there was no statistically significant difference in the indicators of the two cell lines in the LV- GFP group and shRNA-NC group. The results of Western blot and RT-qPCR showed that the ELF5 protein and mRNA of the LV- ELF5 group of the two cell lines were up-regulated ( P<0.05, compared with those of the LV- GFP group), and the ELF5 protein and mRNA of the shRNA- ELF5 group were down-regulated ( P<0.05). The ELF5 overexpression system and interference system were successfully constructed. Compared with the LV- GFP group, data from the LV- ELF5 group showed that cell viability and colony formation rate ( P<0.05) were reduced, SW480 and HT-29 cell apoptosis was promoted, cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9 protein expression was up-regulated ( P<0.05), cell invasion was inhibited, and the expression of E-cadherin protein was up-regulated while the expression of N-cadherin protein was down-regulated ( P<0.05). After ELF5 interference, the above-mentioned expression of cells demonstrated an opposite trend ( P<0.05, comparing shRNA- ELF5 group with shRNA-NC group). In vivo experimental results indicated that ELF5 overexpression reduced tumor volume and tumor mass ( P<0.05), promoted cell apoptosis in tissues ( P<0.05), and inhibited N-cadherin protein expression ( P<0.05). When ELF5 expression was inhibited, the above mentioned experimental results showed the opposite trend. CONCLUSION: In vivo and in vitro experiments showed that ELF5 overexpression could promote the apoptosis of colorectal cancer cells and inhibit the growth and invasion of colorectal cancer cells.


Assuntos
Neoplasias do Colo , Fator V , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/genética , Proteínas de Ligação a DNA , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fatores de Transcrição , Transfecção
11.
Arch Gynecol Obstet ; 304(1): 163-170, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33555431

RESUMO

OBJECTIVE: To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. METHODS: Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. RESULTS: The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05). CONCLUSION: The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis.


Assuntos
Povo Asiático/genética , Endometriose/cirurgia , Endométrio/metabolismo , Interleucina-6/sangue , Fator Inibidor de Leucemia/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , China/epidemiologia , Endometriose/sangue , Endometriose/etnologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Células Estromais
12.
Bone Joint Res ; 9(10): 675-688, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33101657

RESUMO

AIMS: Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. METHODS: Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 µg/kg/day or 40 µg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. RESULTS: Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 µg, and PTH 40 µg groups, but these parameters were significantly higher in the PTH 40 µg group than in the PTH 10 µg group. CONCLUSION: Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway.Cite this article: Bone Joint Res 2020;9(10):675-688.

13.
Bioorg Med Chem Lett ; 30(17): 127373, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738985

RESUMO

In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1-29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.


Assuntos
Anti-Inflamatórios/farmacologia , Oxidiazóis/química , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/síntese química , Sobrevivência Celular , Desenho de Fármacos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
J Asian Nat Prod Res ; 22(11): 1018-1023, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566431

RESUMO

Two new naphthoate derivatives, including a symmetrical dimer (1) and a monomer (2), were separated from the roots of Morinda officinalis var. hirsuta. Their structures were characterized on the basis of spectroscopic means especially MS and NMR methods. Biological evaluations revealed that the two compounds did not show inhibition against both cholinesterases AChE and BChE, while the dimer (1) did exhibit moderate growth inhibitory activity toward one human osteosarcoma cell line U2OS with an IC50 value of 18.5 ± 1.1 µM.


Assuntos
Morinda , Rubiaceae , Acetilcolinesterase , Inibidores da Colinesterase/farmacologia , Humanos , Estrutura Molecular , Raízes de Plantas
15.
J Chromatogr A ; 1616: 460787, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31864723

RESUMO

Automatic data analysis for gas chromatography-mass spectrometry (GC-MS) is a challenging task in untargeted metabolomics. In this work, we provide a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (autoGCMSDataAnal) by developing a new automatic strategy for performing TIC peak detection and resolution and proposing a novel time-shift correction and component registration algorithm. autoGCMSDataAnal uses original acquired GC-MS datafiles as input to automatically perform TIC peak detection, component resolution, time-shift correction and component registration, statistical analysis, and compound identification. We utilize standards and complex plant samples to comprehensively investigate the performance of autoGCMSDataAnal. The results suggest that the developed strategy is comparable with several state-of-the-art methods that are widely used in GC-MS-based untargeted metabolomics. Based on the proposed strategy, we develop a user-friendly MATLAB GUI for users who are unfamiliar with programming languages to facilitate their routine analysis, which can be freely downloaded at: http://software.tobaccodb.org/software/autogcmsdataanal.


Assuntos
Análise de Dados , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metabolômica/métodos , Algoritmos , Automação , Plantas/química , Análise de Componente Principal , Padrões de Referência , Fatores de Tempo
16.
Bioorg Chem ; 92: 103196, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31445194

RESUMO

Eleven new highly oxygenated germacrane-type sesquiterpenoids (1-11) and 16 known analogues (12-27) were isolated from the aerial parts of Sigesbeckia orientalis. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially NMR and ECD analyses. Compounds 13, 21 and 23 possessing an 8-methacryloxy group showed stronger in vitro cytotoxicity against human A549 and MDA-MB-231 cancer cell lines than other co-metabolites, with IC50 values ranging from 6.02 to 10.77 µM comparable to the positive control adriamycin.


Assuntos
Antineoplásicos Fitogênicos/química , Asteraceae/química , Extratos Vegetais/química , Sesquiterpenos de Germacrano/química , Sesquiterpenos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade
17.
J Ovarian Res ; 12(1): 60, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277702

RESUMO

OBJECTIVE: To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3ß/Snail signaling pathway. METHODS: The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3ß/Snail pathway-related proteins were assessed by Western blotting. RESULTS: Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM. Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3ß/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor. CONCLUSION: miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3ß/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Adulto , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno , Fatores de Transcrição da Família Snail/genética
18.
J Agric Food Chem ; 67(25): 7174-7182, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240931

RESUMO

Intake of endocrine-disrupting chemicals (EDCs) by humans could disturb the metabolism of hormones, induce cancer, and damage the liver and other organs. Phthalate acid esters (PAEs) and alkylphenols (APs) are important EDCs and environmental contaminants. With the increasing use of plastics and nonionic surfactants worldwide, PAEs and APs have entered environmental water and accumulated in edible fish, which are finally consumed by humans. In this study, a coated direct inlet probe (CDIP) based on an atmospheric solid analysis probe, which can rapidly and simultaneously extract both PAEs and APs in fish, was developed. Twelve PAEs and APs were quantified by using a stable-isotope-labeled internal standard. Standard curves of the PAEs and APs having correlation coefficients of R2 ≥ 0.9837 were obtained. The limit of detection of the PAEs and APs was distributed from 0.01 to 40 ng g-1. The relative recovery of the method was 78-120% between low, medium, and high spiked levels. Combined with principal component analysis, PAE- and AP-contaminated Carassius auratus from different habitats could be identified. Multiple sample analysis mode allowed the extraction of up to 12 samples at once, and the total analysis time (including sample pretreatment, extraction, and analysis time) was less than 10 min per sample, which indicates that CDIP is useful for rapid quantitative analysis.


Assuntos
Ésteres/análise , Carpa Dourada , Ensaios de Triagem em Larga Escala/métodos , Fenóis/análise , Ácidos Ftálicos/análise , Animais , Disruptores Endócrinos/análise , Disruptores Endócrinos/isolamento & purificação , Ésteres/isolamento & purificação , Carpa Dourada/metabolismo , Ensaios de Triagem em Larga Escala/instrumentação , Limite de Detecção , Fenóis/isolamento & purificação , Ácidos Ftálicos/isolamento & purificação , Extração em Fase Sólida
19.
J Chromatogr A ; 1601: 300-309, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31047656

RESUMO

Gas chromatography-mass spectrometry (GCMS) has been extensively used in complex sample analysis for the high-throughput characterization of volatile and semivolatile compounds. However, the accurate extraction of compound information remains challenging. Here, we present a combined algorithm strategy for GCMS data analysis to accurately screen metabolites across groups. First, chromatographic peaks in a total ion chromatogram (TIC) are extracted by using a Gaussian smoothing strategy and aligned on the basis of their mass spectra by a dynamic programing algorithm. The aligned TIC peaks are then registered into a component list table by applying a nearest-neighbor clustering algorithm. Significantly expressed TIC peaks among groups are screened through statistical analysis, such as ANOVA. Second, a chemometric method of multivariate curve resolution-alternating least squares for the peak resolution of the screened TIC peaks is utilized to retrieve the chromatographic and mass spectral profiles of coeluted components. The developed strategy is employed for the analysis of standard and complex plant sample datasets. Results indicate that our methodology is comparable with several state-of-the-art methods that are widely used in GC-MS-based metabolomics.


Assuntos
Algoritmos , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica/métodos , Análise por Conglomerados , Análise dos Mínimos Quadrados , Distribuição Normal
20.
Food Chem ; 286: 241-249, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30827602

RESUMO

This study aimed to determine the changes in the flavor profile during different operating units when making cold-smoked Spanish mackerel. Sensory evaluation and instrumental analysis of tenderness were applied to optimize the processing parameters. For the overall odor perception, distinct odor among fresh and processed samples could be distinguished using electronic nose (e-Nose). Purge-and-trap (P&T) extraction combined with gas chromatography-mass spectrometry (GC-MS) was used to identify volatile compounds. Alcohols were the major volatiles in Spanish mackerel over the whole processing, while 2-butanol was found in the highest concentration. Curing was an effective way to remove fishy odor. Drying decreased the concentration of volatiles, especially sulfur compounds. Odor formation in cold-smoked mackerel could be divided into four steps (curing, drying, cold smoking and heating) as a result of partial least squares discriminant analysis (PLS-DA).


Assuntos
Manipulação de Alimentos , Perciformes/metabolismo , Compostos Orgânicos Voláteis/análise , Álcoois/análise , Animais , Dessecação , Análise Discriminante , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Análise dos Mínimos Quadrados , Odorantes/análise , Temperatura , Compostos Orgânicos Voláteis/química
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