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1.
Anal Chim Acta ; 1303: 342512, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38609275

RESUMO

BACKGROUND: Various surface-enhanced Raman spectroscopy (SERS) substrate preparation methods have been reported, however, how to tune the "gap" between nanostructures to make more "hot spots" is still a barrier that restricts their application. The gap between nanostructures is usually fixed when the substrates are prepared. In other words, it is hard to tune interparticle distances for maximum electromagnetic coupling during substrate preparation process. Therefore, an in-situ substrate optimization method that could monitor the SERS signal intensity changes, i.e., to find the optimum gap width and particle size, during substrate preparation process is needed. RESULTS: A method based on the galvanic replacement reaction (GRR) is proposed for the in-situ gap width tuning between nanostructures as well as for the optimization of SERS substrates. Noble metal nanoparticles (NPs) form and grow on the sacrificial templates' surface while noble metal ions are reduced by sacrificial metal (oxides) in GRR. Along with the fresh and clean NPs' surface generated, the gap between two noble metal NPs decreases with the growth of the NPs. To demonstrate this strategy, cuprous oxide/Ti (Cu2O/Ti) sacrificial templates were prepared, and then a GRR was carried out with HAuCl4. The real-time SERS detection during GRR show that the optimum reaction time (ORT) is 300 ± 30 s. Furthermore, SERS performance testing was conducted on the optimized substrate, revealing that the detection limit for crystal violet can reach 1.96 × 10-11 M, confirming the feasibility of this method. SIGNIFICANCE AND NOVELTY: By monitoring the in-situ SERS signal of probes during GRR will obtain an "optimal state" of the SERS substrate with optimal gap width and particle size. The SERS substrate preparation and optimization strategy proposed in this article not only provides a simple, efficient, and low-cost method to fabricate surface-clean noble NPs but also paves the way for the in-situ optimization of NPs size and gap width between NPs which could achieve wider applications of SERS.

3.
Heliyon ; 10(7): e28329, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596115

RESUMO

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

4.
Bone Res ; 12(1): 24, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594260

RESUMO

Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.


Assuntos
Ligamentos Longitudinais , Ossificação do Ligamento Longitudinal Posterior , Animais , Ligamentos Longitudinais/metabolismo , Osteogênese/genética , Sorafenibe/farmacologia , Ossificação do Ligamento Longitudinal Posterior/genética , Diferenciação Celular
5.
Int J Biol Macromol ; 265(Pt 1): 130651, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462113

RESUMO

The continuous development of sustainable food-active packaging materials and practices with high performance is a response to the increasing challenges posed by microbial food safety and environmental contamination. In this study, a multifunctional bio-nanocomposite composed primarily of chitosan, cellulose nanomaterials and carvacrol was proposed as a conformal coating for fruit preservation. The coating exhibits excellent antioxidant and antibacterial activities owing to the incorporation of the carvacrol. The inhibition rate of the coating on E. coli and S. aureus is enhanced by 57.13 % and 62.18 %, respectively. And its antioxidant activities is also improved by 77.45 %. In addition, the oxygen permeability (OP) and water vapor permeability (WVP) of this CS/CNC coating are significantly lowered by 67 % and 46 %, respectively, comparing with the CS coating. The coating exhibited excellent biosafety and cytocompatibility because of over 90 % of the HepG2 cells remained alive in each concentration of the coating after 24 h incubation. Additionally, the efficacy of the coating in prolonging the freshness and visual appeal of perishable fruits is substantiated by the experiment involving two fruit specimens. Furthermore, the coating's ease of production, ingestibility, washability, and utilization of cost-effective and easily accessible biomaterials, including renewable waste materials, indicate its potential as a viable economic substitute for commercially accessible fruit coatings.


Assuntos
Quitosana , Cimenos , Nanocompostos , Nanopartículas , Quitosana/química , Frutas/química , Escherichia coli , Celulose/química , Staphylococcus aureus , Antioxidantes/farmacologia , Antioxidantes/análise , Embalagem de Alimentos , Nanopartículas/química , Antibacterianos/farmacologia , Nanocompostos/química
6.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38555474

RESUMO

As key oncogenic drivers in non-small-cell lung cancer (NSCLC), various mutations in the epidermal growth factor receptor (EGFR) with variable drug sensitivities have been a major obstacle for precision medicine. To achieve clinical-level drug recommendations, a platform for clinical patient case retrieval and reliable drug sensitivity prediction is highly expected. Therefore, we built a database, D3EGFRdb, with the clinicopathologic characteristics and drug responses of 1339 patients with EGFR mutations via literature mining. On the basis of D3EGFRdb, we developed a deep learning-based prediction model, D3EGFRAI, for drug sensitivity prediction of new EGFR mutation-driven NSCLC. Model validations of D3EGFRAI showed a prediction accuracy of 0.81 and 0.85 for patients from D3EGFRdb and our hospitals, respectively. Furthermore, mutation scanning of the crucial residues inside drug-binding pockets, which may occur in the future, was performed to explore their drug sensitivity changes. D3EGFR is the first platform to achieve clinical-level drug response prediction of all approved small molecule drugs for EGFR mutation-driven lung cancer and is freely accessible at https://www.d3pharma.com/D3EGFR/index.php.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Mutação , Armazenamento e Recuperação da Informação
7.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426334

RESUMO

OBJECTIVES: The 9th edition of tumour-node-metastasis (TNM) staging for lung cancer was announced by Prof Hisao Asamura at the 2023 World Conference on Lung Cancer in Singapore. The purpose of this study was to externally validate and compare the latest staging of lung cancer. METHODS: We collected 19 193 patients with stage IA-IIIA non-small cell lung cancer (NSCLC) who underwent lobectomy from the Surveillance, Epidemiology and End Results database. Survival analysis by TNM stages was compared using the Kaplan-Meier method and further analysed using univariable and multivariable Cox regression analyses. Receiver operating characteristic curves were used to assess model accuracy, Akaike information criterion, Bayesian information criterion and consistency index were used to compare the prognostic, predictive ability between the current 8th and 9th edition TNM classification. RESULTS: The 9th edition of the TNM staging system can better distinguish between IB and IIA patients on the survival curve (P < 0.0001). In both univariable and multivariable regression analysis, the 9th edition of the TNM staging system can differentiate any 2 adjacent staging patients more evenly than the 8th edition. The 9th and the 8th edition TNM staging have similar predictive power and accuracy for the overall survival of patients with NSCLC [TNM 9th vs 8th, area under the curve: 62.4 vs 62.3; Akaike information criterion: 166 182.1 vs 166 131.6; Bayesian information criterion: 166 324.3 vs 166 273.8 and consistency index: 0.650 (0.003) vs 0.651(0.003)]. CONCLUSIONS: Our external validation demonstrates that the 9th edition of TNM staging for NSCLC is reasonable and valid. The 9th edition of TNM staging for NSCLC has near-identical prognostic accuracy to the 8th edition.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estadiamento de Neoplasias , Teorema de Bayes , Prognóstico
8.
Chemistry ; : e202400121, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538538

RESUMO

It is vital to develop highly efficient non-doped blue organic light-emitting diodes (OLEDs) with high color purity and low-efficiency roll-off for applications in display and lighting. Herein, two blue D-A fluorophores TPA-PO and TPA-DPO are designed and synthesized, in which phenanthro[9,10-d]oxazole (PO) acts as the acceptor and triphenylamine as the donor. TPA-PO and TPA-DPO display good thermal stability and efficient luminescence efficiency in neat film. Results based on photophysical property and theoretical calculation demonstrate that TPA-PO and TPA-DPO possess the hybridized local and charge-transfer (HLCT) feature, which can utilize the triplet exciton to achieve highly efficient electroluminance (EL). The non-doped OLEDs with TPA-PO/TPA-DPO as pure emissive layer show the uniform EL emission peak at 468 nm, corresponding to CIE coordinates of (0.168, 0.187) and (0.167, 0.167), respectively. The TPA-DPO-based non-doped OLEDs provide the maximum external quantum efficiency (EQE) of 7.99% and high exciton utility efficiency of 48.4%~72.6%. Moreover, the TPA-DPO-based device exhibits low-efficiency roll-off, still maintaining the EQE of 6.03% at the high luminance of 5000 cd m-2. Those findings state clearly that PO is a promising building block of blue fluorophore with a potential HLCT feature to be applied in non-doped OLEDs.

9.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38539042

RESUMO

OBJECTIVES: It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes. METHODS: Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort. RESULTS: A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16-0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06-0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15-0.86, P = 0.020, adjusted for clinical TNM stage). CONCLUSIONS: Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Terapia Neoadjuvante/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/etiologia
10.
J Hazard Mater ; 468: 133791, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367438

RESUMO

The prevalence of antibiotic resistance genes (ARGs) in municipal wastewater treatment plants (MWTPs) has emerged as a significant environmental concern. Despite advanced treatment processes, high levels of ARGs persist in the secondary effluent from MWTPs, posing ongoing environmental risks. This study explores the potential of gamma-ray irradiation as a novel approach for sterilizing antibiotic-resistant bacteria (ARB) and reducing ARGs in MWTP secondary effluent. Our findings reveal that gamma-ray irradiation at an absorbed dose of 1.6 kGy effectively deactivates all culturable bacteria, with no subsequent revival observed after exposure to 6.4 kGy and a 96-h incubation in darkness at room temperature. The removal efficiencies for a range of ARGs, including tetO, tetA, blaTEM-1, sulI, sulII, and tetW, were up to 90.5% with a 25.6 kGy absorbed dose. No resurgence of ARGs was detected after irradiation. Additionally, this study demonstrates a considerable reduction in the abundances of extracellular ARGs, with the transformation efficiencies of extracellular tetracycline and sulfadiazine resistance genes decreasing by 56.3-81.8% after 25.6 kGy irradiation. These results highlight the effectiveness of gamma-ray irradiation as an advanced and promising method for ARB sterilization and ARG reduction in the secondary effluent of MWTPs, offering a potential pathway to mitigate environmental risks associated with antibiotic resistance.


Assuntos
Genes Bacterianos , Águas Residuárias , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética
11.
Acta Pharmacol Sin ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383757

RESUMO

Histone deacetylase inhibitors (HDACis) are important drugs for cancer therapy, but the indistinct resistant mechanisms of solid tumor therapy greatly limit their clinical application. In this study we conducted HDACi-perturbated proteomics and phosphoproteomics analyses in HDACi-sensitive and -resistant cell lines using a tandem mass tag (TMT)-based quantitative proteomic strategy. We found that the ribosome biogenesis proteins MRTO4, PES1, WDR74 and NOP16 vital to tumorigenesis might regulate the tumor sensitivity to HDACi. By integrating HDACi-perturbated protein signature with previously reported proteomics and drug sensitivity data, we predicted and validated a series of drug combination pairs potentially to enhance the sensitivity of HDACi in diverse solid tumor. Functional phosphoproteomic analysis further identified the kinase PDK1 and ROCK as potential HDACi-resistant signatures. Overall, this study reveals the potential HDACi-resistant signatures and may provide promising drug combination strategies to attenuate the resistance of solid tumor to HDACi.

12.
Phys Chem Chem Phys ; 26(9): 7794-7807, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375591

RESUMO

The electrochemical corrosion of Ti surfaces is significantly affected by O adsorption, yet the underlying mechanisms remain unexplored. Herein, density functional theory calculations are employed to examine the adsorption energies, structural properties, electronic structures, and thermodynamic stability of atomic O on Ti(0001) surfaces during initial oxidation. Additionally, the impact of O adsorption on Ti dissolution is assessed by introducing a Ti vacancy on the Ti(0001) surface. The passivation of the Ti(0001) surface is predominantly ascribed to the robust adsorption of O atoms. The thermodynamic results reveal that bulk TiO2 easily forms at 300 K, which explains the spontaneous passivation of the Ti(0001) surface. The formation of an O monolayer on the Ti(0001) surface increases the work function (Φ), positively shifting the equilibrium potential and reducing the corrosion rate. The surface vacancy formation energy of Ti on the Ti(0001)/O surface surpasses that on the clean surface. The electrode potential shift for a Ti atom dissolving from the Ti(0001)/O surface is positive, indicating that oxidation impedes the formation of Ti vacancies, rendering Ti atoms less soluble. This study enhances our comprehension of the corrosion mechanism in Ti metal.

13.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38400749

RESUMO

OBJECTIVES: The goal of this project was to evaluate the effect of surgical treatment and the long-term survival of patients with staged IE/IIE pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: From January 2004 to December 2018, we retrospectively analysed 96 patients diagnosed with low-stage primary pulmonary MALT lymphoma according to the modified Ann Arbor staging system (IE/IIE). We compared the outcomes of different treatment modalities for staged IE/IIE MALT lymphoma. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier curves, and the differences were compared using the log-rank test. The Cox proportional hazards model was used in this study. RESULTS: The median PFS time of low-staged MALT lymphomas was 118 months. The overall survival and PFS of the radical surgery group and the biopsy + chemotherapy group suggested no significant difference (P = 0.63, P = 0.65). Patients positive for Blc-2 and Ki-67 suffered from a compromised PFS (P = 0.023, P = 0.006). The Cox adjusted proportional hazards model analysis suggested that surgical procedures were not protective factors for patients with low-staged (IE/IIE) pulmonary MALT lymphoma, whereas being positive for Blc-2 and Ki-67 was a risk factor for patients with low-staged pulmonary MALT lymphoma (hazard ratio: 9.567; P = 0.044; hazard ratio: 6.042, P = 0.049). CONCLUSIONS: Our findings suggested that for staged IE/IIE pulmonary MALT lymphoma, radical surgical resection did not provide a survival benefit compared with chemotherapy after biopsy. Thus, radical surgery may be avoided unless biopsy is necessary for a diagnosis that requires sublobar resection. For those lesions that were Blc-2- or Ki-67-positive, compromised survival may be suggested.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Humanos , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Estudos Retrospectivos , Antígeno Ki-67 , Estadiamento de Neoplasias , Prognóstico
14.
Thorac Cancer ; 15(9): 715-721, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38362771

RESUMO

BACKGROUND: The data of the prognostic role of V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early-stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. METHODS: We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan-Meier method and compared by log-rank test. Cox proportional hazard models, propensity-score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence-free survival (RFS). RESULTS: The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E-mutant patients were detected to have concurrent EGFR mutations, one for 19-del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild-type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). CONCLUSIONS: In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Prognóstico , China , Adenocarcinoma de Pulmão/genética , Mutação , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores ErbB/genética
15.
J Nat Prod ; 87(2): 396-403, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38330072

RESUMO

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.


Assuntos
Dysidea , Poríferos , Sesquiterpenos , Animais , Dysidea/química , Poríferos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Anti-Inflamatórios/farmacologia , NF-kappa B , Estrutura Molecular
16.
RSC Adv ; 14(9): 6085-6095, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38370459

RESUMO

Tyrosinase is a widely distributed copper-containing enzyme found in various organisms, playing a crucial role in the process of melanin production. Inhibiting its activity can reduce skin pigmentation. Hydroquinone is an efficient inhibitor of tyrosinase, but its safety has been a subject of debate. In this research, a scaffold hybridization strategy was employed to synthesize a series of hydroquinone-benzoyl ester analogs (3a-3g). The synthesized compounds were evaluated for their inhibitory activity against mushroom tyrosinase (mTyr). The results revealed that these hydroquinone-benzoyl ester analogs exhibited inhibitory activity against mTyr, with compounds 3a-3e displaying higher activity, with compound 3b demonstrating the highest potency (IC50 = 0.18 ± 0.06 µM). Kinetic studies demonstrated that the inhibition of mTyr by compounds 3a-3e was reversible, although their inhibition mechanisms varied. Compounds 3a and 3c exhibited non-competitive inhibition, while 3b displayed mixed inhibition, and 3d and 3e showed competitive inhibition. UV spectroscopy analysis indicated that none of these compounds chelated with copper ions in the active center of the enzyme. Molecular docking simulations and molecular dynamics studies revealed that compounds 3a-3e could access the active pocket of mTyr and interact with amino acid residues in the active site. These interactions influenced the conformational flexibility of the receptor protein, subsequently affecting substrate-enzyme binding and reducing enzyme catalytic activity, in line with experimental findings. Furthermore, in vitro melanoma cytotoxicity assay of compound 3b demonstrated its higher toxicity to A375 cells, while displaying low toxicity to HaCaT cells, with a dose-dependent effect. These results provide a theoretical foundation and practical basis for the development of novel tyrosinase inhibitors.

17.
BMC Musculoskelet Disord ; 25(1): 118, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336663

RESUMO

BACKGROUND: Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition. CASE PRESENTATION: We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion. CONCLUSIONS: We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.


Assuntos
Calcinose , Condrocalcinose , Degeneração do Disco Intervertebral , Disco Intervertebral , Ossificação do Ligamento Longitudinal Posterior , Humanos , Criança , Ligamentos Longitudinais/diagnóstico por imagem , Osteogênese , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/terapia , Calcinose/complicações , Calcinose/diagnóstico por imagem , Calcinose/terapia , Condrocalcinose/complicações , Vértebras Cervicais/diagnóstico por imagem , Disco Intervertebral/diagnóstico por imagem
18.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38256044

RESUMO

Tyrosinase is vital in fruit and vegetable browning and melanin synthesis, crucial for food preservation and pharmaceuticals. We investigated 6'-O-caffeoylarbutin's inhibition, safety, and preservation on tyrosinase. Using HPLC, we analyzed its effect on mushroom tyrosinase and confirmed reversible competitive inhibition. UV_vis and fluorescence spectroscopy revealed a stable complex formation with specific binding, causing enzyme conformational changes. Molecular docking and simulations highlighted strong binding, enabled by hydrogen bonds and hydrophobic interactions. Cellular tests showed growth reduction of A375 cells with mild HaCaT cell toxicity, indicating favorable safety. Animal experiments demonstrated slight toxicity within safe doses. Preservation trials on apple juice showcased 6'-O-caffeoylarbutin's potential in reducing browning. In essence, this study reveals intricate mechanisms and applications of 6'-O-caffeoylarbutin as an effective tyrosinase inhibitor, emphasizing its importance in food preservation and pharmaceuticals. Our research enhances understanding in this field, laying a solid foundation for future exploration.


Assuntos
Arbutina/análogos & derivados , Ácidos Cafeicos , Monofenol Mono-Oxigenase , Chá , Animais , Simulação de Acoplamento Molecular , Preparações Farmacêuticas
19.
Artigo em Inglês | MEDLINE | ID: mdl-38289442

RESUMO

Time-of-death extrapolation has always been one of the most important issues in forensic practice. For a complicated case in which a corpse is destroyed with little evidence, judging the time of death of the deceased is a major challenge, which also enables criminals to escape legal sanctions. To find a method to roughly judge the time of death of a corpse with only a small amount of skin tissue, in this study, we established an early death model by using mice; furthermore, the postmortem interval was estimated by determining the protein and mRNA levels of Bax and Bcl-2 in the skin. In this process, 0 h after death was used as the control group, and the expression levels of Bax and Caspase-3 reached the maximum value at 8-12 h, while Bcl-2, as an inhibitor of apoptosis protein, peaked after 24 h. The mRNA expression levels of related proteins in postmortem skin tissues were also different. The results of these data indicate that the protein and mRNA levels of Bax and Bcl-2 in the skin have potential application in early time-of-death estimation.

20.
Chin Med ; 19(1): 9, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218825

RESUMO

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism.

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