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1.
Food Res Int ; 195: 114984, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39277245

RESUMO

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.


Assuntos
Antioxidantes , Culinária , Furaldeído , Produtos Finais de Glicação Avançada , Temperatura Alta , Reação de Maillard , Aldeído Pirúvico , Antioxidantes/análise , Antioxidantes/química , Furaldeído/análogos & derivados , Furaldeído/análise , Furaldeído/química , Aldeído Pirúvico/química , Culinária/métodos , Humanos , Glioxal/química , Paladar , Polímeros/química , Pão/análise
2.
Diagn Pathol ; 19(1): 105, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095799

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50-80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Biologia Computacional , Neoplasias Hepáticas , Aprendizado de Máquina , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Humanos , Biomarcadores Tumorais/genética , Vírus da Hepatite B/genética , Proteínas Ativadoras de GTPase/genética , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite B/virologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Bases de Dados Genéticas
4.
Chem Commun (Camb) ; 60(60): 7721-7724, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38967357

RESUMO

A method for the synthesis of furans bearing indoline skeletons was developed via an intramolecular palladium-catalyzed 5-exo-dig cyclization/etherification cascade of N-propargyl arylamines containing a 1,3-dicarbonyl side chain. This method realized the first capture of vinyl carbopalladiums by ketones as O-nucleophiles and showed a wide range of substrate tolerability affording trisubstituted furans in various yields. The enantioselective version for this domino process and diverse derivatizations of the reaction products were also studied.

5.
J Control Release ; 373: 172-188, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38972639

RESUMO

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA257-264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA257-264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA257-264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.


Assuntos
Células Dendríticas , Doxorrubicina , Imunoterapia , Camundongos Endogâmicos C57BL , Nanomedicina , Neoplasias Ovarianas , Feminino , Animais , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/química , Imunoterapia/métodos , Linhagem Celular Tumoral , Nanomedicina/métodos , Células Dendríticas/imunologia , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Humanos , Camundongos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Biomimética/métodos , Materiais Biomiméticos/química , Materiais Biomiméticos/administração & dosagem
6.
Adv Healthc Mater ; : e2401635, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054611

RESUMO

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs.

7.
Food Res Int ; 191: 114674, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39059936

RESUMO

Ultrasonic-assisted extraction using a natural deep eutectic solvent (UAE-NADES) is an efficient method for extracting grape seed polyphenols (GSPs). In this study, response surface methodology was used to optimize the extraction of GSPs with UAE-NADES, and the theoretical extraction rate of GSPs was 139.014 mg GAE/g, the actual extraction rate was 135.78 ± 1.3 mg GAE/g. A pseudo-second-order kinetic extraction fitting was established to simulate the extraction process and mechanism (R2 > 0.99). Analysis of antioxidant capacity, Fourier-infrared spectroscopy and scanning electron microscopy revealed that UAE-NADES works synergetically to maintain the stability of extracted GSPs. The results of high-performance liquid chromatography showed that catechin (41.14 mg/g) is the main component of GSPs in the extract. The UAE-NADES extraction of GSPs can inhibit the growth of Alternaria alternata at 0.25 mg GAE/g, while the GSPs extracted by other methods can effectively inhibit the growth of Alternaria alternata at 0.35 mg GAE/g. Thus, this study demonstrates that UAE-NADES is a high-efficiency means of extracting GSPs and, in a wider sense, is a promising extraction technology for the green utilization of waste resources.


Assuntos
Alternaria , Polifenóis , Sementes , Solventes , Vitis , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Solventes/química , Vitis/química , Sementes/química , Antifúngicos/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/química , Antioxidantes/farmacologia , Antioxidantes/química , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/farmacologia , Cromatografia Líquida de Alta Pressão , Ultrassom/métodos , Espectroscopia de Infravermelho com Transformada de Fourier
8.
J Nanobiotechnology ; 22(1): 337, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886712

RESUMO

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.


Assuntos
Celulose , Dissulfetos , Molibdênio , Regeneração Nervosa , Células de Schwann , Alicerces Teciduais , Regeneração Nervosa/efeitos dos fármacos , Animais , Ratos , Alicerces Teciduais/química , Dissulfetos/química , Dissulfetos/farmacologia , Células de Schwann/efeitos dos fármacos , Molibdênio/química , Molibdênio/farmacologia , Celulose/química , Celulose/farmacologia , Celulose/análogos & derivados , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Proliferação de Células/efeitos dos fármacos , Engenharia Tecidual/métodos , Masculino , Traumatismos dos Nervos Periféricos , Estereoisomerismo
9.
J Biotechnol ; 390: 50-61, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38789049

RESUMO

To reduce food spoilage and deterioration caused by microbial contamination, antimicrobial peptides (AMPs) have gradually gained attention as a biological preservative. Odorranain-C1 is an α-helical cationic antimicrobial peptide extracted from the skin of frogs with broad-spectrum antimicrobial activity. In this study, we achieved the expression of Odorranain-C1 in Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) by employing DNA recombination technology. The recombinant Odorranain-C1 showed broad-spectrum antibacterial activity and displayed a minimum inhibitory concentration within the range of 8-12 µg.mL-1. Meanwhile, Odorranain-C1 exhibited superior stability and lower hemolytic activity. Mechanistically, Odorranain-C1 disrupted the bacterial membrane's integrity, ultimately causing membrane rupture and subsequent cell death. In tilapia fillets preservation, Odorranain-C1 inhibited the total colony growth and pH variations, while also reducing the production of total volatile basic nitrogen (TVB-N) and thiobarbituric acid (TBA). In conclusion, these studies demonstrated the efficient recombinant expression of Odorranain-C1 in P. pastoris, highlighting its promising utilization in food preservation.


Assuntos
Conservação de Alimentos , Saccharomycetales , Animais , Saccharomycetales/genética , Saccharomycetales/metabolismo , Conservação de Alimentos/métodos , Testes de Sensibilidade Microbiana , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Peptídeos Antimicrobianos/genética , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/metabolismo , Antibacterianos/farmacologia , Hemólise/efeitos dos fármacos , Pichia/genética , Pichia/metabolismo , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/farmacologia , Proteínas de Anfíbios/metabolismo , Anuros/metabolismo
10.
ACS Pharmacol Transl Sci ; 7(5): 1278-1290, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751639

RESUMO

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

11.
Biomaterials ; 309: 122607, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38759487

RESUMO

The use of CAR-T cells in treating solid tumors frequently faces significant challenges, mainly due to the heterogeneity of tumor antigens. This study assessed the efficacy of an acidity-targeting transition-aided universal chimeric antigen receptor T (ATT-CAR-T) cell strategy, which is facilitated by an acidity-targeted transition. Specifically, the EGFRvIII peptide was attached to the N-terminus of a pH-low insertion peptide. Triggered by the acidic conditions of the tumor microenvironment, this peptide alters its structure and selectively integrates into the membrane of solid tumor cells. The acidity-targeted transition component effectively relocated the EGFRvIII peptide across various tumor cell membranes; thus, allowing the direct destruction of these cells by EGFRvIII-specific CAR-T cells. This method was efficient even when endogenous antigens were absent. In vivo tests showed marked antigen modification within the acidic tumor microenvironment using this component. Integrating this component with CAR-T cell therapy showed high effectiveness in combating solid tumors. These results highlight the capability of ATT-CAR-T cell therapy to address the challenges presented by tumor heterogeneity and expand the utility of CAR-T cell therapy in the treatment of solid tumors.


Assuntos
Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Microambiente Tumoral , Receptores de Antígenos Quiméricos/imunologia , Humanos , Animais , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Neoplasias/imunologia , Camundongos , Receptores ErbB/metabolismo , Linfócitos T/imunologia , Feminino
12.
Phenomics ; 4(1): 24-33, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38605905

RESUMO

Primary ciliary dyskinesia (PCD) is a rare disorder characterized by extensive genetic heterogeneity. However, in the genetic pathogenesis of PCD, copy number variation (CNV) has not received sufficient attention and has rarely been reported, especially in China. Next-generation sequencing (NGS) followed by targeted CNV analysis was used in patients highly suspected to have PCD with negative results in routine whole-exome sequencing (WES) analysis. Quantitative real-time polymerase chain reaction (qPCR) and Sanger sequencing were used to confirm these CNVs. To further characterize the ciliary phenotypes, high-speed video microscopy analysis (HSVA), transmission electron microscopy (TEM), and immunofluorescence (IF) analysis were used. Patient 1 (F1: II-1), a 0.6-year-old girl, came from a nonconsanguineous family-I. She presented with situs inversus totalis, neonatal respiratory distress, and sinusitis. The nasal nitric oxide level was markedly reduced. The respiratory cilia beat with reduced amplitude. TEM revealed shortened outer dynein arms (ODA) of cilia. chr5:13717907-13722661del spanning exons 71-72 was identified by NGS-based CNV analysis. Patient 2 (F2: IV-4), a 37-year-old man, and his eldest brother Patient 3 (F2: IV-2) came from a consanguineous family-II. Both had sinusitis, bronchiectasis and situs inversus totalis. The respiratory cilia of Patient 2 and Patient 3 were found to be uniformly immotile, with ODA defects. Two novel homozygous deletions chr5:13720087_13733030delinsGTTTTC and chr5:13649539_1 3707643del, spanning exons 69-71 and exons 77-79 were identified by NGS-based CNV analysis. Abnormalities in DNA copy number were confirmed by qPCR amplification. IF showed that the respiratory cilia of Patient 1 and Patient 2 were deficient in dynein axonemal heavy chain 5 (DNAH5) protein expression. This report identified three novel DNAH5 disease-associated variants by WES-based CNV analysis. Our study expands the genetic spectrum of PCD with DNAH5 in the Chinese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00130-0.

13.
Vaccines (Basel) ; 12(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38543883

RESUMO

The gram-negative facultative intracellular pathogen Salmonella enterica serotype Choleraesuis, also known as S. Choleraesuis, is a major financial loss for the pig business. C500 is a vaccine strain that has been used for preventing S. Choleraesuis infection in pigs for many years in China. Although it possessed good immunogenicity and protection efficacy, it still showed severe side effects. The truncation of the key gene rpoS in C500 was believed to take the major responsibility for its attenuation. To achieve a good balance between attenuation and immunogenicity, rpoS was restored to an active state, and other essential virulent genes of crp, fur, phoP, and aroA were evaluated for their effects of deletion on safety and immunogenicity. Animal experiments demonstrated that C5001 (C500 rpoS+ Δcrp10) and C5002 (C500 rpoS+ Δfur9) showed an excellent ability to induce an immune response. To further decrease the endotoxic activity, the combination mutations of ΔpagL7 ΔpagP81::PlpplpxE ΔlpxR9 were introduced into the mutant strains to generate 1'-dephosphorylated lipid A. Animal experiments showed that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) induced higher levels of IgG and secreted IgA antibodies and provided a higher protection rate than SC1 (C500 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) and SC2 (C500 rpoS+ Δcrp10 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9). We also evaluated the ability of SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) as a vaccine carrier to deliver heterologous protein antigens and polysaccharide antigens. The results indicated that SC3 (C500 rpoS+ Δfur9 ΔpagL7 ΔpagP81:: PlpplpxE ΔlpxR9) showed an excellent ability to deliver heterologous antigens and induce the host to produce high levels of antibodies. Together, these results indicate that we constructed a safe and efficient attenuated strain of the S. Choleraesuis vaccine, which demonstrated strong resistance to infection with wild-type S. Choleraesuis and can be employed as a universal vector for the delivery of recombinant antigens.

14.
Biochem Pharmacol ; 222: 116068, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38387529

RESUMO

Non-small cell lung cancer (NSCLC) still lacks effective treatment because of its extensive mutation diversity and frequent drug resistance. Therefore, it is urgent to develop new therapeutic strategies for NSCLC. In this study, we evaluated the inhibitory effect of a new coumarin-furoxan hybrid compound 9, a nitric oxide (NO) donor drug, on NSCLC proliferation and its mechanism. Our results show that compound 9 can inhibit the growth of four NSCLC cell lines and H1975 xenograft model in a dose-dependent manner. Compound 9 effectively releases high concentrations of NO within the mitochondria, leading to cellular oxidative stress, mitochondrial dysfunction, and apoptosis. Moreover, compound 9 inhibits JAK2/STAT3 protein phosphorylation and induces S-nitrosylation modification of STAT3, ultimately resulting in endogenous apoptosis in NSCLC. Additionally, compound 9 significantly induces NSCLC ferroptosis by depleting intracellular GSH, elevating MDA levels, inhibiting SLC7A11/GSH protein expression, and negatively regulating the JAK2/STAT3 pathway. In summary, this study elucidates the inhibitory effects of compound 9 on NSCLC proliferation and provides insights into the underlying mechanisms, offering new possibilities for NSCLC treatment strategies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ferroptose , Neoplasias Pulmonares , Oxidiazóis , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Apoptose , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Janus Quinase 2/metabolismo
15.
Int J Nurs Pract ; 30(3): e13236, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38238976

RESUMO

AIMS: Dehydration is one of the common complications of dysphagia and poses significant risks including hospitalization and mortality, but the relationship between dysphagia and dehydration has received little attention. This study aims to determine the prevalence and risk factors for dehydration of patients with dysphagia in eastern China, and to provide reference for early identification and prevention of dehydration. METHODS: A descriptive, cross-sectional design was conducted. Three hundred and thirty-seven (n = 337) patients with dysphagia participated in the study between August and December 2022. Information relating to participants' demographic variables, nutrition, cognition, functional, hydration status and fluid intake was collected. Univariate analysis was used to examine related impact factors, and then binary logistic regression analysis was conducted to determine reliable impact factors. RESULTS: Among 337 patients with dysphagia, the average age was 63.47 ± 16.96, most participants were male (72.1%) and married (91.7%). The prevalence of dehydration was calculated to be 43.9%, the mean plasma osmolality score was 293.53 mmol/L. Diseases with the highest prevalence were stroke (78.3%), followed by hypertension (63.5%). The risk for dehydration increased with older age, usage of more medicines such as diuretics and beta-blockers, worse functional status and lower fluid intake. CONCLUSION: This study found a high percentage of dehydration in patients with dysphagia. Findings can provide a basis for targeted nursing interventions for clinical prevention and treatment of dehydration.


Assuntos
Transtornos de Deglutição , Desidratação , Humanos , Transtornos de Deglutição/epidemiologia , Estudos Transversais , Masculino , Desidratação/epidemiologia , Feminino , China/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Prevalência , Idoso , Idoso de 80 Anos ou mais , Adulto
16.
Fish Shellfish Immunol ; 146: 109380, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244821

RESUMO

Aeromonas hydrophila (A. hydrophila) is a typical zoonotic pathogenic bacterium that infects humans, animals, and fish. It has been reported that the Fur, a Fe2+ regulatory protein, and the Crp, a cAMP receptor protein, play important roles in bacterial virulence in many bacteria, but no research has been investigated on A. hydrophila. In this study, the Δfur and Δcrp mutant strains were constructed by the suicide plasmid method. These two mutant strains exhibited a slightly diminished bacterial growth and also were observed some alterations in the number of outer membrane proteins, and the disappearance of hemolysis in the Δcrp strain. Animal experiments of crucian carp showed that the Δfur and Δcrp mutant strains significantly decreased virulence compared to the wild-type strain, and both mutant strains were able to induce good immune responses by two kinds of administration routes of intraperitoneal immunization (i.p) and immersion immunization, and the protection rates through intraperitoneal injection of Δfur and Δcrp to crucian carp were as high as 83.3 % and 73.3 %, respectively, and immersion immunization route of Δfur and Δcrp to crucian carp provided protection as high as 40 % and 20 %, respectively. These two mutant strains showed abilities to induce changes in enzymatic activities of the non-specific enzymes SOD, LZM, AKP, and ACP in crucian carp. Together, these results indicated the Δfur and Δcrp mutants were safe and effective candidate vaccine strains, showing good protection against the wild-type A. hydrophila challenge.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Humanos , Animais , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Vacinas Atenuadas , Aeromonas hydrophila
17.
Materials (Basel) ; 16(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38068109

RESUMO

Organic semiconductor materials featuring lightweight, and flexibility may play a significant role in various future applications, such as foldable displays, wearable devices, and artificial skin. For developing high-performance organic devices, organic crystals are highly desired, while a remaining fundamental issue is their contact problem. Here, we have grown a high-quality rubrene single crystal by utilizing a simple in-air sublimation technique. The contact characteristics (barrier height and contact resistance) are detail-studied by resist-free transfer electrodes (Au metal or graphene/Au). The Schottky barrier of the rubrene/graphene interface is lower and can be also modulated by gate bias, which is confirmed by spatial photocurrent mapping. Finally, we demonstrated the zero-bias photocurrent imaging application by constructing the asymmetrical device employing different electrode contacts. Our work would be of significance for studying the contact issue of organic crystals and wireless imaging.

18.
J Am Chem Soc ; 145(49): 26983-26992, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38032103

RESUMO

Employing living cells as carriers to transport transition metal-based catalysts for target-specific bio-orthogonal catalysis represents a cutting-edge approach in advancing precision biomedical applications. One of the initial hurdles in this endeavor involves effectively attaching the catalysts to the carrier cells while preserving the cells' innate ability to interact with biological systems and maintaining the unaltered catalytic activity. In this study, we have developed an innovative layer-by-layer method that leverages a noncovalent interaction between cucurbit[7]uril and adamantane as the primary driving force for crafting polymeric nanostructures on the surfaces of these carrier cells. The strong binding affinity between the host-guest pair ensures the creation of a durable polymer coating on the cell surfaces. Meanwhile, the layer-by-layer process offers high adaptability, facilitating the efficient loading of bio-orthogonal catalysts onto cell surfaces. Importantly, the polymeric coating shows no discernible impact on the cells' physiological characteristics, including their tropism, migration, and differentiation, while preserving the effectiveness of the bio-orthogonal catalysts.


Assuntos
Adamantano , Nanoestruturas , Elementos de Transição , Nanoestruturas/química , Polímeros , Catálise
19.
ACS Appl Mater Interfaces ; 15(41): 48442-48451, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37788404

RESUMO

Organic semiconductors herald new opportunities for fabricating high-performance flexible and wearable optoelectronic devices owing to their intrinsic mechanical flexibility, excellent optical absorption, and cool-free operation. The photocurrent generation mechanisms are of multiple physical origins, including photoconductive, photovoltaic, and photogating effects, and the influence of individual effects on the device figures-of-merit is still not well understood. Here we fabricated a high-performance pentacene single-crystal transistor employing graphene electrodes and demonstrated the modulation from the photogating mechanism to the photoconduction effect by controlling gate bias. Control experiments indicate that the calculation based on transfer curves tends to overestimate the responsivity due to nearby trap states. Using a high frequency-modulated light signal to suppress the trapping process, we successfully measured its intrinsic -3 dB bandwidth of 75 kHz. Finally, high-resolution and UV-NIR high-speed imaging capability was demonstrated. Our work provides new guidelines for understanding the photophysical process and intrinsic performances of organic devices and also confirms the potential of organic single crystals in high-speed imaging applications.

20.
Heliyon ; 9(9): e20169, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809876

RESUMO

Millions of ethnic children in China live without their parents due to financial constraints and the lure of job opportunities elsewhere, staying in their hometowns primarily for education. Yet, current research inadequately addresses the mental health status of these left-behind children from ethnic minority communities in China. This study aimed to explore the effects of the combined identities-ethnic and left-behind-on depression among children in rural ethnic minority areas. We recruited a sample of 1131 children aged 12 to 16 from the Garzê Tibetan Autonomous Prefecture (also known as Ganzi Prefecture) in Sichuan Province. The Children's Depression Inventory was employed to assess depression levels. Results indicated that left-behind children in this region exhibited significantly higher depression levels than their counterparts who lived with their parents. Notably, children of Han ethnicity were more depressed than other ethnic groups. However, no interactive effects were observed between the dual identity factors. Intriguingly, Han children, despite being the majority ethnicity in China, perceived themselves as ethnic minorities in these areas. Their self-perception of ethnic pressure and differences, coupled with a potential lack of acceptance of their ethnic differences from the native minorities, might be subdued. This study underscores that parental relocation poses a risk to the mental health of adolescents in rural China. While policies and programs supporting left-behind children are crucial, further research is imperative to comprehend the nuances of their experiences fully.

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