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1.
J Asian Nat Prod Res ; 26(8): 1001-1008, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38607260

RESUMO

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.


Assuntos
Ganoderma , Óxido Nítrico , Ganoderma/química , Camundongos , Células RAW 264.7 , Animais , Estrutura Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Carpóforos/química
2.
Asia Pac J Clin Nutr ; 33(1): 111-117, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494693

RESUMO

BACKGROUND AND OBJECTIVES: While the health promoting effects of green tea polyphenols have been identi-fied among adult, research on children is scarce probably due to safety concerns about caffeine. This study aims to evaluate the safety of decaffeinated green tea polyphenols (DGTP) supplementation in girls with obesity and lay the foundation for its application in children population. METHODS AND STUDY DESIGN: This 12-week randomized, double-blinded, parallel-controlled trial was performed among 62 girls with obesity aged 6 to 10 years old. Participants were allocated to take 400 mg/d DGTP (DGTP group, n = 31) or isodose placebo (Control group, n = 31) at random. Anthropometric measurements and biochemical parameters including hepatic and renal function indicators, serum minerals concentrations, and routine blood parameters, were measured at baseline and the end of this trial. DGTP intake diary was required for each participant to record any abnormal reactions. RESULTS: After the 12-week supplementation, compared to Control group, the uric acid concentration in DGTP group showed a significant decrease (-48.0 ± 83.2 vs -0.01 ± 69.1, µmol/L), within the normal range. Regarding other biochemical indicators, there were no significant differences in changed values between the two groups. Throughout the trial, no adverse effects were reported in either group. CONCLUSIONS: This study indicated that the supplementation of 400 mg/d DGTP for 12 weeks had no adverse health effects in girls with obesity, providing evidence for the DGTP adoption in children research.


Assuntos
Polifenóis , Chá , Criança , Feminino , Humanos , Antioxidantes , Suplementos Nutricionais , Método Duplo-Cego , Obesidade/tratamento farmacológico , Polifenóis/farmacologia
3.
J Multidiscip Healthc ; 17: 1-9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38192739

RESUMO

Neonatal respiratory distress syndrome (NRDS) is a common critical disease in neonates. Early diagnosis and timely treatment are crucial. Historically, X-ray imaging was the primary method for diagnosing NRDS. However, this method carries radiation exposure risks, making it unsuitable for dynamic lung condition monitoring. In addition, neonates who are critically ill require bedside imaging, but diagnostic delays are often unavoidable due to equipment transportation and positioning limitations. These challenges have been resolved with the introduction of lung ultrasound (LUS) in neonatal intensive care. The diagnostic efficacy and specificity of LUS for NRDS is superior to that of X-ray. The non-invasive, dynamic, and real-time benefits of LUS also allow for real-time monitoring of lung changes throughout treatment for NRDS, yielding important insights for guiding therapy. In this paper, we examine the ultrasonographic characteristics of NRDS and the recent progress in the application of ultrasound in the diagnosis and treatment of NRDS while aiming to promote wider adoption of this method.

4.
J Allergy Clin Immunol ; 153(3): 718-731.e11, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38056634

RESUMO

BACKGROUND: Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. METHODS: Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. RESULTS: S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. CONCLUSIONS: S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/metabolismo , Rinite/complicações , Staphylococcus aureus , Células B de Memória , Imunoglobulina E , Interleucina-13 , Imunidade Inata , Interleucina-5 , Sinusite/complicações , Linfócitos/metabolismo , Doença Crônica
5.
Artigo em Inglês | MEDLINE | ID: mdl-38088514

RESUMO

BACKGROUND: Itching is a troublesome symptom that disturbs patients with allergic rhinitis (AR). The molecular mechanisms underlying itching in AR need to be further illuminated. The aim of this study was to investigate the role of epithelial cell-derived interleukin-31 (IL-31) in nasal itching in AR. METHODS: A total of 33 patients and 20 healthy control subjects were enrolled in this prospective study. The disease severity of patients with AR was assessed by the total visual analog scale score. The levels of IL-31, cysteinyl leukotriene receptor 1 (CysLT1R), and CysLT2R in the nasal brush specimens from the enrolled subjects were measured by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining. The expression of CysLT2R in a human nasal epithelial cell line (HNEpC) was assessed by immunofluorescence staining. RESULTS: Compared with the control subjects, the protein and mRNA levels of IL-31 and CysLT2R were significantly increased in patients with AR. Higher levels of IL-31 and CysLT2R in nasal epithelial cells were associated with itching but not nasal congestion, rhinorrhea, or sneezing in AR. A significant relationship was found between IL-31 and CysLT2R in nasal epithelial cells, with a correlation coefficient of 0.93. Furthermore, RT-PCR and immunofluorescence staining revealed that IL-31 directly induced CysLT2R expression in HNEpCs. Nasal steroid treatment inhibited IL-31 and CysLT2R expression in 13 patients with AR in vivo. CONCLUSIONS: Nasal epithelial cell-derived IL-31 might be associated with itching symptoms via CysLT2R in AR.

6.
Front Immunol ; 14: 1275999, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942332

RESUMO

Accurate structural information plays a crucial role in comprehending biological processes and designing drugs. Indeed, the remarkable precision of the AlphaFold2 has facilitated significant advancements in predicting molecular structures, encompassing antibodies and antigens. This breakthrough has paved the way for rational drug design, ushering in new possibilities in the field of pharmaceutical development. Within this study, performing analysis and humanization guided by the structures predicted by AlphaFold2. Notably, the resulting humanized antibody, h3D5-hIgG1, demonstrated exceptional binding affinity to the PD-L1 protein. The KD value of parental antibody 3D5-hIgG1 was increased by nearly 7 times after humanization. Both h3D5-hIgG1 and 3D5-hIgG1 bound to cells expressing human PD-L1 with EC50 values of 5.13 and 9.92nM, respectively. Humanization resulted in a twofold increase in the binding capacity of the antibody, with h3D5-hIgG1 exhibiting superior performance compared to the parental antibody 3D5-hIgG1. Furthermore, h3D5-hIgG1 promoted cytokine secretion of T cells, and significantly suppressed MC38-hPD-L1 tumor growth. This study highlights the potential for artificial intelligence-assisted drug development, which is poised to become a prominent trend in the future.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Inteligência Artificial , Anticorpos , Estrutura Molecular
7.
Artigo em Inglês | MEDLINE | ID: mdl-38033197

RESUMO

Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.

8.
Clin Lab ; 69(5)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37145070

RESUMO

BACKGROUND: Altered anti-CD25 antibody levels in plasma have been observed in patients with various solid malignancies. The present study aimed to determine whether circulating anti-CD25 antibody levels were altered in bladder cancer (BC). METHODS: An enzyme-linked immunosorbent assay was developed in-house to detect plasma IgG antibodies against three CD25-derived linear peptide antigens in 132 patients with BC and 120 control subjects. RESULTS: The Mann-Whitney U-test indicated that the plasma levels of anti-CD25a (Z = -10.11, p < 0.001), anti-CD25b (Z = -12.79, p < 0.001), and anti-CD25c IgG (Z = -11.95, p < 0.001) were significantly lower in BC patients than in the control group. Further analysis indicated that the plasma levels of anti-CD25a IgG antibody were stage-dependent and associated with different postoperative histological grades (U = 977.5, p = 0.003). The receiver operating characteristic curve analysis showed that the area under the ROC curve (AUC) was 0.869 for anti-CD25a IgG (95%, 0.825 - 0.913), 0.967 for anti-CD25b IgG (95%, 0.945 - 0.988), and 0.936 for anti-CD25c IgG (95%, 0.905 - 0.967), with a sensitivity of 91.3% for the anti-CD25a IgG assay, 98.8% for the anti-CD25b IgG assay, and 96.7% for the anti-CD25c IgG assay, against a specificity of 95%. CONCLUSIONS: The present study suggests that circulating anti-CD25 IgG may have a potential predictive value for clinical staging and histological grading of BC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias da Bexiga Urinária , Humanos , Neoplasias Pulmonares/patologia , Peptídeos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G
9.
Artigo em Inglês | MEDLINE | ID: mdl-36716512

RESUMO

Zanthoxyli Radix, the dried root of Zanthozylum nitidum (Roxb.) DC, one of traditional Chinese medicines (TCMs), exhibits various pharmacological activities such as anti-bacterial, anti-inflammatory, anti-tumor, analgesic activity. A sustainable vortex-enhanced magnetic solid phase extraction (VE-MSPE) method combined with ultra-high performance liquid chromatography (UHPLC) was established to enrich and analyze the bioactive quaternary ammonium alkaloids (QAAs) of Zanthoxyli Radix. Fe3O4@C@CMCS magnetic nanoparticles (MNPs) was first synthesized for selectively adsorbing target QAAs (magnolinine, sanguinarine, nitidine chloride and chelerythrine), which possess excellent adsorption performance after being reused 10 times. The results revealed that the great adsorption rate of Fe3O4@C@CMCS MNPs for the four QAAs could reach 55.1-78.7 %. In addition, a reliable linear relationship (r ≥ 0.9995) and good recovery (97.5-104 %) was obtained. Consequently, the VE-MSPE method applying Fe3O4@C@CMCS MNPs as a sustainable adsorbent exhibited great potential in the selective enrichment of QAAs in TCM.


Assuntos
Alcaloides , Compostos de Amônio , Anti-Inflamatórios não Esteroides , Adsorção , Extração em Fase Sólida/métodos , Fenômenos Magnéticos , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção
10.
J Asian Nat Prod Res ; 25(1): 44-52, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35113741

RESUMO

One new 6a,11a-dehydropterocarpan derivative, 6-O-methyl-anhydrotuberosin (1), one new 6a-hydroxypterocarpan, (6aR,11aR,11bR)-hydroxytuberosone (7), and seven known compounds including two 6a,11a-dehydropterocarpans (2 and 4), two coumestans (3 and 5), one isoflavonoid (6) and two other phenolic compounds (8 and 9) were isolated from the roots of Pueraria lobata. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1 D and 2DNMR, HRESIMS). Compounds 1, 2, 4-5 showed potent LSD1 inhibitory activities with IC50 values ranging from 1.73 to 4.99 µM. Furthermore, compound 2 showed potent cytotoxicity against gastric cancer cell lines MGC-803 and BGC-823, and lung cancer cell lines H1299 and H460.


Assuntos
Isoflavonas , Pueraria , Pueraria/química , Linhagem Celular , Fenóis , Histona Desmetilases/análise , Raízes de Plantas/química , Isoflavonas/farmacologia , Isoflavonas/química
11.
Chem Biol Interact ; 369: 110302, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36512946

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The entire 'Reason' text must be identical to that in the XML version Box 6).

12.
J Pediatr Nurs ; 68: e87-e95, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36437132

RESUMO

PURPOSE: To determine the needs of informal caregivers during the long-term health management of minors who have undergone craniopharyngioma surgery. Design and methodology This is a qualitative and descriptive research study. Purposive sampling was used to select participants, and semi-structured interviews were conducted to explore the needs of 21 informal caregivers for postoperative minors. Due to the COVID-19 pandemic, the respondents were provided with the options of online video call or offline one-on-one interviews. Following this, a content analysis method was conducted. RESULTS: Four themes and 14 sub-themes were extracted from the results of the study, including needs for relieving psychological stress (including psychological pressure on both minors and on caregivers); requirement for on-campus assistance (physical activity, eliminating verbal violence in schools, special education needs for child, healthcare services provided by school hospitals); demands for medical help (acquiring medical knowledge, need for medication management, convenience and reliable access to medical services, need for technological development, expectations of multidisciplinary cooperation, the necessity of health review reminders); and the desire for financial aid (charity platform assistance, inclination of government policy). CONCLUSIONS: In China, informal caregivers of young patients with onset craniopharyngioma require both the multidisciplinary cooperation of medical institutions and the multi-departmental cooperation of society. Information and medical technology advancements may benefit families with young patients. Improving community hospitals' medical services and encouraging the practical use of online medical treatment and prescriptions are both necessary in the context of COVID-19. PRACTICE IMPLICATIONS: By identifying the needs of informal caregivers, medical professionals are able to develop care plans and interventions aimed at reducing the burden of care for minors who have undergone craniopharyngioma surgery.


Assuntos
COVID-19 , Craniofaringioma , Neoplasias Hipofisárias , Criança , Humanos , Cuidadores/psicologia , Craniofaringioma/cirurgia , População do Leste Asiático , Menores de Idade , Pandemias , Pesquisa Qualitativa , Neoplasias Hipofisárias/cirurgia
13.
Cancer Med ; 12(6): 6811-6824, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36420689

RESUMO

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects. CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.


Assuntos
Cisplatino , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Cisplatino/efeitos adversos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/uso terapêutico
14.
J Allergy Clin Immunol ; 151(2): 458-468, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36272582

RESUMO

BACKGROUND: Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated. OBJECTIVE: We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors. METHODS: Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining. RESULTS: Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5. CONCLUSION: Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/terapia , Citocinas/metabolismo , Sinusite/terapia , Inflamação , Mucosa Nasal/metabolismo , Doença Crônica
15.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5574-5583, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471975

RESUMO

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.


Assuntos
Neoplasias , Pueraria , Pueraria/química , Histona Desmetilases/genética , Histona Desmetilases/análise , Raízes de Plantas/química , Transição Epitelial-Mesenquimal
16.
Iran J Basic Med Sci ; 25(6): 781-788, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35949313

RESUMO

Objectives: Lysine-specific demethylase1 (LSD1), an important class of histone demethylases, plays a crucial role in regulation of mammalian biology. The up-regulated LSD1 expression was frequently associated with progress and oncogenesis of multiple human cancers, including non-small cell lung cancer (NSCLC). Therefore, inhibition of LSD1 may provide an attractive strategy for cancer treatment. We investigated the effect of sanguinarine against lung cancer cells as a natural alkaloid LSD1 inhibitor. Materials and Methods: The inhibition properties of sanguinarine to the recombinant LSD1 were evaluated by a fluorescence-based method. Subsequently, assays such as viability, apoptosis, clonogenicity, wound healing, and transwell were performed on H1299 and H1975 cells after treatment with sanguinarine. Results: Upon screening our in-house natural chemical library toward LSD1, we found that sanguinarine possessed a potent inhibitory effect against LSD1 with the IC50 value of 0.4 µM in a reversible manner. Molecular docking simulation suggested that sanguinarine may inactivate LSD1 by inserting into the binding pocket of LSD1 to compete with the FAD site. In H1299 and H1975 cells, sanguinarine inhibited the demethylation of LSD1, validating its cellular activity against the enzyme. Further studies showed that sanguinarine exhibited a strong capacity to suppress colony formation, inhibit migration and invasion, as well as induce apoptosis of H1299 and H1975 cells. Conclusion: Our findings present a new chemical scaffold for LSD1 inhibitors, and also provide new insight into the anti-NSCLC action of sanguinarine.

17.
Chem Biol Interact ; 365: 110088, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35940278

RESUMO

Ferroptosis is crucial for tumor growth inhibition. Moreover, ferroptosis has been considered as a potential strategy against cancer. The present study focused on the mechanism of ferroptosis induction by ß-elemene during the lung cancer (extracted from the Chinese medicine Curcuma Wen yujin). CCK-8 assay, flow cytometry and biochemical assays including intracellular ROS, MDA, GSH, iron and 8-OHdG level were performed. DNA polymerase epsilon subunit 2 (Pole2) and the ferroptosis-related proteins were studied by utilizing western blotting. The study results showed that the ß-elemene reduced the viability of lung cancer cells via ferroptosis. Furthermore, multiple experiments confirmed that Pole2 knockdown enhanced the production of lipid ROS, MDA and iron, leading to the iron-dependent ferroptosis in lung cancer cells. Overexpression of Pole2 inhibited ß-elemene-induced ferroptosis through reduction of iron-dependent oxidative damage. Mechanically, Pole2 reduced the upregulation of p53 expression, and increased the phosphorylation levels of PI3K and AKT in ß-elemene-induced cells. Overexpression of TP53 or the inhibitor of PI3K/AKT pathway reversed the effects of Pole2. Together, ß-elemene evoked ferroptosis through the Pole2-regulated p53 or PI3K/AKT signalling, and might be an effective therapy for lung carcinogenesis.


Assuntos
Ferroptose , Neoplasias Pulmonares , Sesquiterpenos , Linhagem Celular Tumoral , DNA Polimerase II/metabolismo , Humanos , Ferro/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Proteína Supressora de Tumor p53
18.
Phytochemistry ; 202: 113297, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35803306

RESUMO

Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1ß,2ß:4ß,5ß-diepoxy-10ß-hydroxy-6ßH,7αH,11ßH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 µM. Moreover, achigermalide D decreased the expression of IL-1ß and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.


Assuntos
Achillea , Resistência à Insulina , Sesquiterpenos , Achillea/metabolismo , Glucose , Células Hep G2 , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Palmítico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano
19.
Sci Total Environ ; 847: 157681, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35908708

RESUMO

Although straw mulching and nitrogen applications are extensively practiced in the agriculture sector, large uncertainties remain about their impacts on crop yields and especially the environment. The responses of summer maize yields, fertilizer use efficiency, and greenhouse gas (GHG) emissions including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in the North China Plain (NCP) to two straw management practices (S0: no straw and S1: straw mulching) and two nitrogen application rates (N1: 180 and N2: 210 kg N ha-1) were investigated in field tests in 2018, 2019, and 2020. The highest yields and partial factor productivity (PFP) were obtained by S1N1, followed by S1N2, S0N1, and S0N2. S1N2 had the highest CO2 emissions and greatest CH4 uptake, S0N1 had the lowest CO2 emissions, and S0N2 had the smallest CH4 uptake. The highest and lowest N2O emissions were found in S0N1 and S1N1, respectively. The S1N2 treatment, an extensively applied practice, had the greatest global warming potential (GWP), which was 70.3 % larger than S1N1 and two times more than S0N1 and S0N2. The largest GHG emission intensity (GHGI) of 19.4 was found in the S1N2 treatment, while the other three treatments, S0N1, S0N2, and S1N1, had a GHGI of 10.1, 10.7, and 10.7, respectively according to three tested results. In conclusion, S1N1 treatment achieved a better trade-off between crop yields and GHG emissions of summer maize in NCP.


Assuntos
Fertilizantes , Gases de Efeito Estufa , Agricultura/métodos , Dióxido de Carbono , China , Fertilizantes/análise , Gases de Efeito Estufa/análise , Metano/análise , Nitrogênio , Óxido Nitroso/análise , Solo , Zea mays
20.
Environ Pollut ; 309: 119747, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35835280

RESUMO

Agricultural tillage practices have a significant impact on the generation and consumption of greenhouse gases (GHGs), the primary causes of global warming. Two tillage systems, conventional tillage (CT) and no-tillage (NT), were compared to evaluate their effects on GHG emissions in this study. Averaged from 2018 to 2020, significant decreases of CO2 and N2O emissions by 7.4% and 51.1% were observed in NT as compared to those of CT. NT was also found to inhibit the soil CH4 uptake. In this study, soil was a source of CO2 and N2O but a sink for CH4. The effect of soil temperature on the fluxes of CO2 was more pronounced than that of soil moisture. However, soil temperature and soil moisture had a weak correlation with CH4 and N2O flux variations. As compared to CT, NT did not affect maize yields but significantly reduced global warming potential (GWP) by 8.07%. For yield-scaled GWP, no significant difference was observed in NT (9.63) and CT (10.71). Taken together, NT was an environment-friendly tillage practice to mitigate GHG emissions in the soil under the tested conditions.


Assuntos
Gases de Efeito Estufa , Agricultura , Dióxido de Carbono/análise , Metano/análise , Óxido Nitroso/análise , Solo , Zea mays
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