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1.
Mikrochim Acta ; 191(7): 397, 2024 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877314

RESUMEN

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.


Asunto(s)
Aflatoxina B1 , Técnicas Biosensibles , Exodesoxirribonucleasas , Límite de Detección , Liposomas , Polímero Poliacetilénico , Polímero Poliacetilénico/química , Liposomas/química , Exodesoxirribonucleasas/química , Exodesoxirribonucleasas/metabolismo , Técnicas Biosensibles/métodos , Aflatoxina B1/análisis , Aptámeros de Nucleótidos/química , Técnicas de Amplificación de Ácido Nucleico/métodos , Poliinos/química , Espectrometría de Fluorescencia/métodos , Zea mays/química , Triticum/química , Oryza/química , Polímeros/química , Contaminación de Alimentos/análisis
2.
Small Methods ; : e2301644, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38593356

RESUMEN

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis.

3.
Heliyon ; 10(2): e24906, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38312545

RESUMEN

Objective: Osteoporosis is a common clinical bone disease that occurs most frequently in middle-aged and elderly people. Various traditional herbal medicine formulations have shown significant benefits in models of osteoporosis. In this study, we aim to investigate the osteogenic efficacy of naringin (NRG) in the osteoporotic state. Design: We treated Bone marrow stromal cells (BMSCs) with various concentrations of NRG for 3 and 7 days. BMSC proliferation was measured by the MTT assay. The effect of NRG on the osteogenic differentiation of BMSCs was detected by ALP and alizarin red staining. The effect of NRG on the BMP2/Runx2/Osterix signaling pathway was analyzed by using real-time PCR. The effect of NRG on the oestrogen receptor was measured by Enzyme-linked immunosorbent assay. In vivo animal experiments were performed by micro-computed tomography and ALP immunohistochemistry to determine the ectopic osteogenic effect of NRG sustained-release nanoparticles in a mouse model of osteoporosis. Results: NRG promoted the proliferation and osteogenic differentiation of BMSCs. Moreover, it also activated the BMP2/Runx2/Osterix signaling pathway. When NRG sustained-release nanoparticles were added in vivo in animal experiments, we found that NRG sustained-release nanoparticles had better ectopic osteogenic effects in a mouse model of osteoporosis. Conclusions: NRG induced osteoblastic differentiation of BMSCs by activating the BMP2/Runx2/Osterix signaling pathway and promoted the regulation of oestrogen receptor pathway protein expression, and NRG sustained-release nanoparticles exerted a more significant in vivo ectopic osteogenic effect in an osteoporosis mouse model. Therefore, naringin is expected to be developed as a novel treatment for inducing osteogenesis, because of its ubiquitous, cost-efficient, and biologically active characteristics. However, further research is needed on how to improve the pharmacokinetic properties of naringin and its specific mechanism.

4.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37894822

RESUMEN

Chemotherapy is commonly used clinically to treat colorectal cancer, but it is usually prone to drug resistance, so novel drugs need to be developed continuously to treat colorectal cancer. Neocryptolepine derivatives have attracted a lot of attention because of their good cytotoxic activity; however, cytotoxicity studies on colorectal cancer cells are scarce. In this study, the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b] quinoline (MMNC) in colorectal cells was evaluated. The results showed that MMNC inhibits the proliferation of HCT116 and Caco-2 cells, blocks the cell cycle in the G2/M phase, decreases the cell mitochondrial membrane potential and induces apoptosis. In addition, the results of western blot experiments suggest that MMNC exerts cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Based on these results, MMNC is a promising lead compound for anticancer activity in the treatment of human colorectal cancer.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Quinolinas , Humanos , Antineoplásicos/farmacología , Apoptosis , Células CACO-2 , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinolinas/farmacología , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
5.
Theranostics ; 13(10): 3188-3203, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37351171

RESUMEN

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, and there is an urgent need to discover reliable biomarkers for early diagnosis. Here, we established an effective urine multi-omics platform and integrated metabolomics and peptidomics to investigate the biological changes during DKD pathogenesis. Methods: Totally 766 volunteers (221 HC, 198 T2DM, 175 early DKD, 125 overt DKD, and 47 grey-zone T2DM patients with abnormal urinary mALB concentration) were included in this study. Non-targeted metabolic fingerprints of urine samples were acquired on matrix-free LDI-MS platform by the tip-contact extraction method using fluorinated ethylene propylene coated silicon nanowires chips (FEP@SiNWs), while peptide profiles hidden in urine samples were uncovered by MALDI-TOF MS after capturing urine peptides by porous silicon microparticles. Results: After multivariate analysis, ten metabolites and six peptides were verified to be stepwise regulated in different DKD stages. The altered metabolic pathways and biological processes associated with the DKD pathogenesis were concentrated in amino acid metabolism and cellular protein metabolic process, which were supported by renal transcriptomics. Interestingly, multi-omics significantly increased the diagnostic accuracy for both early DKD diagnosis and DKD status discrimination. Combined with machine learning, a stepwise prediction model was constructed and 89.9% of HC, 75.5% of T2DM, 69.6% of early DKD and 75.7% of overt DKD subjects in the external validation cohort were correctly classified. In addition, 87.5% of grey-zone patients were successfully distinguished from T2DM patients. Conclusion: This multi-omics platform displayed a satisfactory ability to explore molecular information and provided a new insight for establishing effective DKD management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/metabolismo , Silicio , Metabolómica/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Péptidos , Diabetes Mellitus Tipo 2/metabolismo
6.
J Proteome Res ; 22(6): 1855-1867, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37218629

RESUMEN

Cholangiocarcinoma (CCA) is an aggressive malignant tumor with a poor prognosis. Carbohydrate antigen 19-9 is an essential biomarker for CCA diagnosis, but its low sensitivity (72%) makes the diagnosis unreliable. To explore potential biomarkers for the diagnosis of CCA, a high-throughput nanoassisted laser desorption ionization mass spectrometry technique was constructed. We performed serum lipidomics and peptidomics analyses from 112 patients with CCA and 123 patients with benign biliary diseases. Lipidomics analysis showed that various lipids, such as glycerophospholipids, glycerides, and sphingolipids, were perturbed. Peptidomics analysis revealed perturbations of multiple proteins involved in the coagulation cascade, lipid transport, and so on. After data mining, 25 characteristic molecules including 20 lipids and 5 peptides were identified as potential diagnostic biomarkers. After screening various machine learning algorithms, artificial neural network was selected to construct a multiomics model for CCA diagnosis with 96.5% sensitivity and 96.4% specificity. The sensitivity and specificity of the model in the independent test cohort were 93.8 and 87.5%, respectively. Furthermore, integrated analysis with transcriptomic data in the cancer genome atlas confirmed that genes altered in CCA significantly affected multiple lipid- and protein-related pathways. Data are available via MetaboLights with the identifier MTBLS6712.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Biomarcadores de Tumor , Multiómica , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/genética , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Espectrometría de Masas , Conductos Biliares Intrahepáticos/metabolismo , Lípidos
7.
Front Cell Infect Microbiol ; 13: 1104932, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36896188

RESUMEN

Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells that are abundant in the human body, recognize microbial-derived vitamin B metabolites presented by MHC class I-related protein 1 (MR1), and rapidly produce proinflammatory cytokines, which are widely involved in the immune response to various infectious diseases. In the oral mucosa, MAIT cells tend to accumulate near the mucosal basal lamina and are more inclined to secrete IL-17 when activated. Periodontitis is a group of diseases that manifests mainly as inflammation of the gums and resorption of the alveolar bone due to periodontal tissue invasion by plaque bacteria on the dental surface. The course of periodontitis is often accompanied by a T-cell-mediated immune response. This paper discussed the pathogenesis of periodontitis and the potential contribution of MAIT cells to periodontitis.


Asunto(s)
Enfermedades Transmisibles , Células T Invariantes Asociadas a Mucosa , Periodontitis , Humanos , Células T Invariantes Asociadas a Mucosa/metabolismo , Antígenos de Histocompatibilidad Clase I , Citocinas/metabolismo , Periodontitis/metabolismo
8.
J Leukoc Biol ; 113(4): 365-375, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36843303

RESUMEN

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and its etiology is related to several systemic factors. At present, the destruction of periodontal tissues is considered to be the result of inflammation resolution disorders. Efferocytosis plays an important role in the resolution of inflammation, and defective efferocytosis is an essential factor in the persistence of many chronic inflammatory diseases. Therefore, this review will describe the mechanisms involved in the efferocytosis of macrophages in the pathogenesis of periodontitis and highlight emerging therapeutic strategies to provide new ideas for future periodontal treatment.


Asunto(s)
Neutrófilos , Periodontitis , Humanos , Fagocitosis , Periodontitis/etiología , Periodontitis/terapia , Inflamación , Macrófagos , Apoptosis
9.
Eur J Pharmacol ; 938: 175408, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36442620

RESUMEN

Gastric cancer is highly heterogeneous and there is still a lack of efficient, low-toxicity small molecule compounds for the treatment of gastric cancer. Natural products are important sources for the development of antitumor compounds. Therefore, it is promising strategy to find the lead compound of anti-gastric cancer agents by structural modification of natural products. The aim of this study was to synthesize a novel neocryptolepine derivative CFNC and explore its potential anti-gastric cancer effect and molecular mechanism. The MTT assay showed that the IC50 of CFNC on AGS cells reached 148 nM. CFNC arrested AGS cells in the G2/M phase of the cell cycle. Furthermore, CFNC inhibited cell proliferation and migration, leading to the loss of membrane potential by causing mitochondrial dysfunction, which induced the apoptosis of AGS cells. Western blot assay suggested that CFNC could inhibit the expression of important proteins in the PI3K/AKT/mTOR signaling pathway. These results showed that CFNC exhibited strong cytotoxic activity in gastric cancer cell lines by regulating the PI3K/AKT/mTOR signaling pathway. Taken together, CFNC could be a promising lead compound for the clinical treatment of gastric cancer.


Asunto(s)
Antineoplásicos , Productos Biológicos , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal , Neoplasias Gástricas/patología , Apoptosis , Proliferación Celular , Antineoplásicos/uso terapéutico , Productos Biológicos/farmacología
10.
Front Endocrinol (Lausanne) ; 13: 963451, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36482997

RESUMEN

Nuclear factor E2-related factor 2(Nrf2) is a transcription factor that mainly regulates oxidative stress in the body. It initiates the expression of several downstream antioxidants, anti-inflammatory proteins and detoxification enzymes through the Kelch-like ECH-associating protein 1 (Keap1) -nuclear factor E2-related factor 2(Nrf2) -antioxidant response element (ARE) signaling pathway. Its anti-apoptosis, anti-oxidative stress and anti-inflammatory effects have gradually become the focus of periodontal disease research in recent years. In this paper, the structure and function of Nrf2 pathway and its mechanism of action in the treatment of periodontitis in recent years were analyzed and summarized, so as to further clarify the relationship between Nrf2 pathway and oxidative stress in the occurrence and development of periodontitis, and to provide ideas for the development of new treatment drugs targeting Nrf2 pathway.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Enfermedades Periodontales , Humanos , Peroxidación de Lípido , Proteína 1 Asociada A ECH Tipo Kelch , Antiinflamatorios
11.
Cells ; 11(21)2022 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-36359745

RESUMEN

Periodontitis is a chronic inflammatory disease associated with bacterial biofilm. It is characterized by loss of periodontal support tissue and has long been considered as a "silent disease". Because it is difficult to prevent and has a health impact that can not be ignored, researchers have been focusing on a mechanism-based treatment model. Ferroptosis is an iron-dependent regulatory form of cell death, that directly or indirectly affects glutathione peroxidase through different signaling pathways, resulting in a decrease in cell antioxidant capacity, accumulation of reactive oxygen species and lipid peroxidation, which cause oxidative cell death and tissue damage. Recently, some studies have proven that iron overload, oxidative stress, and lipid peroxidation exist in the process of periodontitis. Based on this, this article reviews the relationship between periodontitis and ferroptosis, in order to provide a theoretical reference for future research on the prevention and treatment of periodontal disease.


Asunto(s)
Ferroptosis , Sobrecarga de Hierro , Periodontitis , Humanos , Peroxidación de Lípido/fisiología , Sobrecarga de Hierro/complicaciones , Especies Reactivas de Oxígeno/metabolismo
12.
Int J Mol Sci ; 23(19)2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36233226

RESUMEN

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.


Asunto(s)
Antineoplásicos , Productos Biológicos , Quinolinas , Neoplasias Gástricas , Alcaloides , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Productos Biológicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Humanos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinolinas/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo
13.
Front Cell Infect Microbiol ; 12: 933833, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35979090

RESUMEN

Aim: There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis. Materials and Methods: Unstimulated whole saliva samples were collected from the periodontitis with diabetes group (TC), chronic periodontitis group (CP), and periodontally healthy and systemically healthy group (H) by spitting method. Bacterial genomic DNA was PCR-amplified at the V4 variable region of 16S rRNA gene. The library was constructed according to the obtained sequence results, and biological analysis and statistical analysis were carried out. Functional prediction of three groups of microbial communities was performed by the PICRUSt algorithm. Results: There was no significant difference in bacterial diversity between the TC and CP groups. Compared with the H group, the TC group and CP group presented a higher diversity of salivary flora. Firmicutes, Streptococcus, Haemophilus, Veillonella, and Haemophilus parainfluenzae dominated the H group. Corynebacterium, Leptotrichia, Dialister, Comamonas, Capnocytophaga, Catonella, Filifactor, Campylobacter, Treponema, Campylobacter concisus, Prevotella oralis, and Porphyromonas gingivalis were significantly enriched in the TC and CP groups. Among them, Treponema and P. oralis were the most abundant in the TC group. The PICRUSt results showed that many pathways related to cell motility and functional metabolism of the salivary microbial flora changed in the TC group and the CP group. Conclusions: Diabetes was not the main factor causing the altered diversity of salivary microbiota in patients with periodontitis; however, the presence of diabetes altered the abundance of some microbiota in saliva.


Asunto(s)
Periodontitis Crónica , Diabetes Mellitus , Microbiota , China , Periodontitis Crónica/microbiología , ADN Bacteriano/genética , Humanos , Microbiota/genética , Porphyromonas gingivalis/genética , ARN Ribosómico 16S/genética , Saliva/microbiología
14.
Int J Mol Sci ; 23(14)2022 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-35887375

RESUMEN

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 µM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.


Asunto(s)
Alcaloides , Antineoplásicos , Neoplasias Gástricas , Alcaloides/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Quinazolinas/farmacología , Transducción de Señal , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo
15.
Curr Microbiol ; 79(9): 270, 2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35881202

RESUMEN

Serofluid dish is a traditional fermented food that contains rich microbial populations. To gain insight into the environmental variables shaping the microbial diversity patterns, serofluid dish samples were collected from different areas, and 16S rRNA sequencing was performed. Analyses revealed both species and community diversity, including phylotype richness, Shannon index and phylogenetic diversity, were mostly influenced by pH. Additionally, such effects were corroborated by the Mantel test of pairwise UniFrac distances and variable selection of multiple linear regression models. Eventually, correlations between dominant lineages and the pH of serofluid dish other than geographical distance explained a large portion of the changes in microbial composition and diversity. Lactobacillus and related genera, Pediococcus and Acetobacter were largely driven by the variability of pH, and higher richness was observed under moderate pH ranges. Collectively, the results demonstrated that a microbial diversity pattern in serofluid dish is predictable by natural environmental variation and can be better understood through pH conditions.


Asunto(s)
Alimentos Fermentados , Verduras , China , Filogenia , ARN Ribosómico 16S/genética
16.
Anal Chem ; 94(24): 8570-8579, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35670384

RESUMEN

Serum lipid metabolites have been emerging as ideal biomarkers for disease diagnosis and prediction. In the current stage, nontargeted or targeted lipidomic research mainly relies on a liquid chromatography-mass spectrometry (LC-MS) platform, but future clinical applications need more robust and high-speed platforms. Surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) has shown excellent advantages in the high-speed analysis of lipid metabolites. However, the platform in the positive ion mode is more inclined to target a certain class of lipids, leading to the low coverage of lipid detection and limiting its practical translation to clinical applications. Herein, we proposed a dual-mechanism-driven strategy for high-coverage detection of serum lipids on a novel SALDI-MS target, which is a composite nanostructure comprising vertical silicon nanowires (VSiNWs) decorated with AuNPs and polydopamine (VSiNW-Au-PDA). The performance of laser desorption and ionization on the target can be enhanced by charge-driven desorption coupled with thermal-driven desorption. Simultaneous detection of 236 serum lipids (S/N ≥ 5) including neutral and polar lipids can be achieved in the positive ion mode. Among these, 107 lipid peaks were successfully identified. When combined with VSiNW-Au-PDA and VSiNW chips, 479 lipid peaks can be detected in serum samples in positive and negative ion modes, respectively. Based on the platform, serum samples from 57 hepatocellular carcinoma (HCC) patients and 76 healthy controls were analyzed. After data mining, 14 lipids containing different lipid types (TAG, CE, PC) were selected as potential lipidomic biomarkers. With the assistance of an artificial neural network, a diagnostic model with a sensitivity of 92.7% and a specificity of 96% was constructed for HCC diagnosis.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas del Metal , Carcinoma Hepatocelular/diagnóstico , Oro , Humanos , Lípidos/análisis , Neoplasias Hepáticas/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos
17.
Front Bioeng Biotechnol ; 10: 898240, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35677304

RESUMEN

Cancer is second only to heart disease as a cause of death, despite improvements in its early diagnosis and precision medicine. Due to the limitations of commonly used anticancer methods such as surgery, radiotherapy and chemotherapy, biological therapy, especially probiotics such as lactic acid bacteria, has received widespread attention. Lactobacillus has been proven to inhibit the proliferation of a variety of cancer cells. In this work, the effects of the cell-free culture supernatant of serofluid dish (CCS1) and the cell-free culture supernatant of Lactiplantibacillus plantarum YT013 (CCS2) isolated from serofluid dish on AGS, HCT116, HepG2 and PANC-1 cells were investigated. Based on the CCK-8 assay, CCS1 and CCS2 were shown to suppress the growth of cancer cells in a concentration-dependent manner. The IC50 values of CCS2 of AGS, HCT116, HepG2 and PANC-1 cells were 346.51 ± 35.28, 1207.69 ± 333.18, 650.94 ± 123.78 and 808.96 ± 126.27 µg/ml, respectively. In addition, the results of fluorescence microscopy showed that CCS2 changed cell morphology and treated with CCS2 (200, 400 and 800 µg/ml) for 48 h, AGS cell apoptosis was quantitatively surveyed by flow cytometry, showing 25.0, 34.1, and 42.6% total apoptotic cells. Moreover, western blotting confirmed that BAX, BAD and Caspase-3/8/9 were significantly upregulated and that BCL-2 was significantly downregulated in AGS cells treated with CCS2. These results indicated that CCS2 might lead to apoptosis via the endogenous mitochondrial apoptotic pathway. In summary, Lactiplantibacillus plantarum YT013 may be considered a good candidate for anticancer therapies.

18.
Eur J Pharmacol ; 928: 175120, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35753402

RESUMEN

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 µM and 2 µM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Células HCT116 , Humanos , Imidazoles/farmacología , Imidazoles/uso terapéutico , Simulación del Acoplamiento Molecular , Fenantrolinas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo
19.
J Enzyme Inhib Med Chem ; 37(1): 1212-1226, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35450499

RESUMEN

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1-26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 µM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.


Asunto(s)
Antineoplásicos , Neoplasias Gástricas , Humanos , Alcaloides , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/farmacología , Quinazolinas , Neoplasias Gástricas/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo
20.
ACS Nano ; 16(4): 6916-6928, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35416655

RESUMEN

Spatially resolved tissue lipidomics is essential for accurate intraoperative and postoperative cancer diagnosis by revealing molecular information in the tumor microenvironment. Matrix-free laser desorption ionization mass spectrometry imaging (LDI-MSI) is an emerging attractive technology for label-free visualization of metabolites distributions in biological specimens. However, the development of LDI-MSI technology that could conveniently and authentically reveal molecular distribution on tissue samples is still a challenge. Herein, we present a tissue imprinting technology by retaining tissue lipids on 2D nanoflakes-capped silicon nanowires (SiNWs) for further mass spectrometry imaging and cancer diagnosis. The 2D nanoflakes were prepared by liquid exfoliation of molybdenum disulfide (MoS2) with nitrogen-doped graphene quantum dots (NGQDs), which serve as both intercalation agent and dispersant. The obtained NGQD@MoS2 nanoflakes were then decorated on the tip of vertical SiNWs, forming a hybrid NGQD@MoS2/SiNWs nanostructure, which display excellent lipid extraction ability, enhanced LDI efficiency and molecule imaging capability. The peak number and total ion intensity of different lipids species on animal lung tissues obtained by tissue imprinting LDI-MSI on NGQD@MoS2/SiNWs were ∼4-5 times greater than those on SiNWs substrate. As a proof-of-concept demonstration, the NGQD@MoS2/SiNWs nanostructure was further applied to visualize phospholipids on sliced non small cell lung cancer (NSCLC) tissue along with the adjacent normal tissue. On the basis of selected feature lipids and machine learning algorithm, a prediction model was constructed to discriminate NSCLC tissues from the adjacent normal tissues with an accuracy of 100% for the discovery cohort and 91.7% for the independent validation cohort.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Nanocables , Animales , Lipidómica , Silicio/química , Nanocables/química , Molibdeno , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Imagen Molecular , Lípidos/análisis , Microambiente Tumoral
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