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OBJECTIVES: To investigate the effect of response intensity of allergen skin prick test (SPT) on symptom severity and long-term efficacy of dust mite subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR). METHODS: AR Patients diagnosed with dust mite allergy and completed 3 years of SCIT were collected and classified into three groups: grade 2 (SPT of + +), grade 3 (SPT of + + +) and grade 4 (SPT of + + + +). Comparisons between groups were performed to examine the associations of SPT categories and symptom severity and the long-term efficacy of SCIT in AR. RESULTS: 181 AR patients were included. There was no significant difference in the baseline TNSS, SMS, RQLQ and VAS, and particularly to symptom severity grading among three SPT grade groups (P > 0.05). The moderate-severe AR was more likely to be smoking and accompany with asthma and had higher prevalence of sensitization to cockroach, mixed grass and tree pollen than mild AR (P < 0.05). Prevalence of sensitization to cockroach, mixed grass, ragweed and animal dander was increased in AR patients with asthma and allergic conjunctivitis (P < 0.05). Furthermore, after 3 years of SCIT, no statistical differences in TNSS, SMS, RQLQ, VAS and long-term efficacy were observed among the three SPT grade groups (P > 0.05). Similarly, long-term outcomes of patients with different SPT grades did not differ among different clinical characteristics and different efficacy determination criteria (P > 0.05). CONCLUSIONS: The SPT response intensity cannot be used as an objective evaluation index for symptom severity and the long-term efficacy of SCIT in AR patients.
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Asma , Conjuntivite Alérgica , Rinite Alérgica , Animais , Humanos , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Alérgenos , Imunoterapia , PoaceaeRESUMO
Angiotensin I-converting enzyme (ACE)-inhibiting peptides were isolated from walnut protein isolate (WPI) using ultrasound-assisted extraction. This study aimed to assess the impact of ultrasonic pretreatment on the physicochemical properties of WPI. The optimal extraction conditions for WPI were determined as a 15-min ultrasonic treatment at 400 W. Subsequently, the hydrolysate exhibiting the highest in vitro ACE-inhibiting activity underwent further processing and separation steps, including ultrafiltration, ion exchange chromatography, liquid chromatography-tandem mass spectrometry, ADMET screening, and molecular docking. As a result of this comprehensive process, two previously unidentified ACE-inhibiting peptides, namely Tyr-Ile-Gln (YIQ) and Ile-Tyr-Gln (IYQ), were identified. In addition, a novel peptide, Ile-Lys-Gln (IKQ), was synthesized, demonstrating superior ACE-inhibiting activity and temperature stability. In silico analysis estimated an in vivo utilization rate of 21.7% for IKQ. These peptides were observed to inhibit ACE through an anti-competitive mechanism, with molecular docking simulations suggesting an interaction mechanism involving hydrogen bonding. Notably, both IYQ and IKQ peptides exhibited no discernible toxicity to HUVECs cells and promoted nitric oxide (NO) generation. These findings underscore the potential of ultrasonicated WPI in the separation of ACE-inhibiting peptides and their utility in the development of novel ACE inhibitors for functional food applications.
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Juglans , Juglans/química , Juglans/metabolismo , Peptidil Dipeptidase A/metabolismo , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Hidrolisados de Proteína/químicaRESUMO
BACKGROUND: Elevated body mass index (BMI) has been associated with an increased prevalence of chronic rhinosinusitis (CRS). However, the impact of BMI on the risk of recurrence of CRS is unknown. This study aimed to investigate the association between BMI and the risk of CRS recurrence. MATERIAL AND METHODS: A retrospective cohort study was conducted and recruited 1057 CRS patients who underwent functional endoscopic sinus surgery (FESS). All subjects were classified into four groups: "underweight", "normal weight", "overweight", and "obese". Multivariate regression analysis was performed to examine the associations between BMI categories and other factors and the risk of CRS recurrence. RESULTS: The rate of recurrent CRS was significantly higher in the overweight group and obese group than in the normal weight group (P < 0.05). Unadjusted and adjusted logistic regression analyses demonstrated that overweight and obesity exhibited an increased risk of CRS recurrence as compared to patients with normal weight (P < 0.05). Furthermore, all patients were divided into primary CRS group and recurrent CRS group, and the BMI, duration of disease and rate of allergic rhinitis were vastly increased in the recurrent group than in the primary group (P < 0.05). Univariate and multivariate regression analysis showed that BMI and duration of disease were the dominant risk factors of CRS recurrence (P < 0.05). CONCLUSION: Overweight and obesity presented significant impacts on the CRS recurrence, and elevated BMI were associated with an increased risk of CRS recurrence independently from traditional risk factors. A longer duration of disease was correlated with a higher risk of CRS recurrence.
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Índice de Massa Corporal , População do Leste Asiático , Rinite , Sinusite , Humanos , Doença Crônica , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sinusite/complicações , Sinusite/epidemiologia , Rinite/complicações , Rinite/epidemiologiaRESUMO
OBJECTIVE: Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. METHODS: THP induced immortalized mouse cardiomyocytes HL-1, silenced or overexpressed miR-494-3p. The effects of miR-494-3p on HL-1 contained in THP were investigated by CCK8, flow cytometry, ROS detection, JC-1 mitochondrial membrane potential detection, TUNEL cell apoptosis detection, RT-qPCR, and Western blot. RESULTS: miR-494-3p could reduce cell viability, increase oxidative damage, and promote cell apoptosis; at the same time, it inhibited the expression of MDM4, promoted the activation of p53, and promoted the expression of apoptosis-related proteins. MiR-494-3p inhibitors have the opposite effect. CONCLUSION: miR-494-3p can aggravate THP damage to HL-1, which may be achieved by downregulating MDM4 and promoting p53. miR-494-3p is one of the important miRNAs in THP-induced cardiotoxicity, which provides theoretical support for its possible use as a therapeutic target for THP-induced cardiovascular disease.
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MicroRNAs , Transdução de Sinais , Camundongos , Animais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Miócitos Cardíacos , Cardiotoxicidade/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , ApoptoseRESUMO
BACKGROUND: Native walnut protein is an alkali-soluble protein that seriously limits the application of walnut protein. The pH-shifting method could improve the solubility of walnut proteins and enable the encapsulation of active ingredients. The present study aimed to prepare water-soluble nanoparticles of curcumin using walnut protein and evaluate the process of walnut protein self-assembly, interaction between walnut protein and curcumin, encapsulation properties, and stability of nanoparticles. RESULTS: The solubility of native walnut protein was poor, but the solubility of walnut protein nanoparticles (WPNP) formed by walnut protein after pH-shifting significantly improved to 91.5 ± 1.2%. This is because, during the process of pH changing from 7 to 12 and back to 7, walnut protein first unfolded under alkaline conditions and then refolded under pH drive, finally forming an internal hydrophobic and external hydrophilic shell-core structures. The quenching type of walnut protein and curcumin was static quenching, and the quenching constant was 2.0 × 1014 mol-1 L-1 s-1 , indicating that the interaction between walnut protein and curcumin was non-covalent. Adding curcumin resulted in the formation of nanoparticles with small particle size compared with the no-load. The loading capacity of curcumin-loaded walnut protein nanoparticles (WPNP-C) was 222 mg g-1 walnut protein isolate. Under the same mass, the curcumin equivalent concentration in aqueous solution of WPNP-C was 17 000 times higher than that of the native curcumin. CONCLUSION: The solubility of the self-assembled WPNP significantly increased after pH-shifting treatment. The walnut protein carrier could improve the stability of the encapsulated curcumin. Therefore, walnut proteins could be used as water-soluble carriers for hydrophobic drugs. © 2023 Society of Chemical Industry.
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Curcumina , Juglans , Nanopartículas , Curcumina/química , Portadores de Fármacos/química , Juglans/metabolismo , Nanopartículas/química , Água/química , Tamanho da Partícula , SolubilidadeRESUMO
This study investigated the synergy of ultrasonic and transglutaminase (TGase) treatment on the structural, physicochemical, rheological, gelation properties and controlled release properties of dehulled walnut proteins (DWP). The results showed that after ultrasonic-TGase treatment, the surface hydrophobicity was decreased, indicating the involvement of disulfide bonds in gel formation. Scanning electron microscopy (SEM) showed that ultrasonic-TGase treatment resulted in a more uniform and denser microstructure of DWP gels. Ultrasonic-TGase treatment changed the secondary structure of the DWP gels as determined by Fourier transform infrared spectroscopy, with an increase in α-helix, ß-turn and random coils and a decrease in ß-sheets. In addition, in vitro drug release profiles showed that ultrasonic-TGase treatment promoted the cross-linking of protein molecules and formed a dense network to embed tea polyphenols (TP), thereby slowing down the digestion of TP in simulated gastric fluid and achieving the purpose of slow-release in simulated intestinal fluid. Thus, the synergy of ultrasonic and TGase treatment might be an effective method to improve gel properties and expand the application of protein gels in the food industries. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05756-6.
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This study investigated the effects of the interaction of walnut protein isolate (WPI) with epigallocatechin gallate (EGCG), chlorogenic acid (CLA), (+)-catechin (CA), and ellagic acid (EA) on the structural and functional properties of proteins. The results for polyphenol binding equivalents and content of free amino and sulfhydryl groups as well as those from sodium dodecyl sulfateâpolyacrylamide gel electrophoresis confirmed the covalent interaction between WPI and the polyphenols. The binding capacities of the WPI-polyphenol mixtures and conjugates were as follows: WPI-EGCG > WPI-CLA > WPI-CA > WPI-EA. Fourier transform infrared spectroscopy (FTIR) and fluorescence spectrum analysis identified changes in the protein structure. The conjugation process obviously increased the polyphenols' antioxidant properties and the surface hydrophobicity was substantially reduced. WPI-EGCG conjugates had the best functional properties, followed by WPI-CLA, WPI-CA, and WPI-EA. Lycopene (LYC) was loaded into nanocarriers by WPI-EGCG self-assembly. These results indicated that WPI-polyphenol conjugates can be utilized to develop food-grade delivery systems to protect chemically lipophilic bioactive compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05768-2.
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BACKGROUND: Postoperative major adverse cardiovascular events (MACEs) account for more than one-third of perioperative deaths. Geriatric patients are more vulnerable to postoperative MACEs than younger patients. Identifying high-risk patients in advance can help with clinical decision making and improve prognosis. This study aimed to develop a machine learning model for the preoperative prediction of postoperative MACEs in geriatric patients. METHODS: We collected patients' clinical data and laboratory tests prospectively. All patients over 65 years who underwent surgeries in West China Hospital of Sichuan University from June 25, 2019 to June 29, 2020 were included. Models based on extreme gradient boosting (XGB), gradient boosting machine, random forest, support vector machine, and Elastic Net logistic regression were trained. The models' performance was compared according to area under the precision-recall curve (AUPRC), area under the receiver operating characteristic curve (AUROC) and Brier score. To minimize the influence of clinical intervention, we trained the model based on undersampling set. Variables with little contribution were excluded to simplify the model for ensuring the ease of use in clinical settings. RESULTS: We enrolled 5705 geriatric patients into the final dataset. Of those patients, 171 (3.0%) developed postoperative MACEs within 30 days after surgery. The XGB model outperformed other machine learning models with AUPRC of 0.404(95% confidence interval [CI]: 0.219-0.589), AUROC of 0.870(95%CI: 0.786-0.938) and Brier score of 0.024(95% CI: 0.016-0.032). Model trained on undersampling set showed improved performance with AUPRC of 0.511(95% CI: 0.344-0.667, p < 0.001), AUROC of 0.912(95% CI: 0.847-0.962, p < 0.001) and Brier score of 0.020 (95% CI: 0.013-0.028, p < 0.001). After removing variables with little contribution, the undersampling model showed comparable predictive accuracy with AUPRC of 0.507(95% CI: 0.338-0.669, p = 0.36), AUROC of 0.896(95%CI: 0.826-0.953, p < 0.001) and Brier score of 0.020(95% CI: 0.013-0.028, p = 0.20). CONCLUSIONS: In this prospective study, we developed machine learning models for preoperative prediction of postoperative MACEs in geriatric patients. The XGB model showed the best performance. Undersampling method achieved further improvement of model performance. TRIAL REGISTRATION: The protocol of this study was registered at www.chictr.org.cn (15/08/2019, ChiCTR1900025160).
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Doenças Cardiovasculares , Aprendizado de Máquina , Idoso , Doenças Cardiovasculares/epidemiologia , Humanos , Modelos Logísticos , Prognóstico , Estudos ProspectivosRESUMO
Background: Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients. Methods: We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated. Results: The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT. Conclusions: Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.
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Óxido Nítrico , Rinite Alérgica , Criança , Humanos , Imunoterapia , Óxido Nítrico Sintase Tipo II , Curva ROC , Rinite Alérgica/terapiaRESUMO
This study aimed to encapsulate walnut peptides with different molecular weights (crude peptides, 5-10 kDa and < 5 kDa) within nanoliposomes. The peptides with molecular weight (MW) of 5-10 kDa (F2) was chosen as a representative sample to indicate the formation mechanism of nanoliposomes using scanning electron microscopy (SEM) and transmission electron microscope (TEM). The storage and simulated digestion experiment were carried out to evaluate the protective effect of nanoliposomes loading walnut peptides. Our results indicated that the amino acid composition was affected by peptide MW, and F2 exhibited the highest content of hydrophobic amino acids content. The MW of peptides also affected the distribution of the peptide of nanoliposomes, resulting in changes in particle size, ζ-potential, and encapsulation efficiency. The SEM exhibited that a high concentration of nanoliposomes might result in phospholipid fusion and larger particle diameters. The TEM showed individual nanoliposomes had spherical, smooth and full vesicle structures. The nanoliposomes could improve the stability of walnut peptides during storage. The maximum peptides retention after in vitro digestion was 61.6%, indicating a better sustained release in gastric digestion. The present study suggested that nanoliposomes can offer adequate protection to the walnut peptides during storage and digestion.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated. METHODS: The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein-protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR). RESULTS: In total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival. CONCLUSIONS: SPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
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Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that pyroptosis is associated with the development of cancer; however, the function and mechanism of pyroptosis in NPC remain obscure. In this study, we observed that Taxol treatment caused pyroptotic cell death, along with activation of Caspase-1 and maturation of IL-1ß, as well as cleavage of GSDMD, which is the canonical pyroptosis executor. Furthermore, Taxol-induced pyroptotic cell death could be suppressed by Caspase-1 inhibitor (Z-YVAD-FMK) and GSDMD knockout. Moreover, NPC parental cells demonstrated higher levels of pyroptosis than Taxol-resistant cells, and pyroptosis mediated by Caspase-1/GSDMD suppression induced by a Caspase-1 inhibitor and GSDMD knockout could induce a Taxol-resistant phenotype in vitro and in vivo. By transfecting an siRNA targeting Beclin-1 into NPC Taxol-resistant cells, we discovered that autophagy could negatively regulate pyroptosis by inhibiting Caspase-1/GSDMD activation. Taken together, our results indicated that Caspase-1/GSDMD mediated Taxol-induced pyroptosis and a Taxol-resistant phenotype in NPC cell lines, which may be regulated by autophagy. Thus, we provide novel insight into the mechanisms of Taxol-induced cell death and a promising approach to improve the therapeutic outcomes of patients with advanced NPC.
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Autofagia , Caspase 1/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Carcinoma Nasofaríngeo/patologia , Paclitaxel/farmacologia , Proteínas de Ligação a Fosfato/metabolismo , Piroptose , Autofagia/efeitos dos fármacos , Inibidores de Caspase/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Necrose , Fenótipo , Piroptose/efeitos dos fármacosRESUMO
Processed walnuts including hot air-dried and roasted walnuts were prepared. Volatiles in raw and processed walnuts were analyzed using head-space solid phase microextraction combined with gas chromatography and mass spectrometry. Oxidative stability of hot air-dried walnuts in different antioxidants, with or without vacuum package was studied to find a proper package for oxidation stability of hot air-dried walnuts. The results showed that there were 14 volatiles in raw walnuts, 28 in hot air-dried walnuts and 38 in roasted walnuts. The changes of oil quality indices, total phenols, malondialdehyde and free radical scavenging activities during storage at 60 °C showed that the oil oxidation increased with storage time. The addition of antioxidants and vacuum package could slow down the oxidation. Vacuum aluminum foil package (14 × 20 cm) can delay the oil oxidation and extend the shelf life to ~ 230 days of hot air-dried walnuts at 20 °C. With added antioxidant this was extended to ~ 257 days.
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PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disease of yet unknown etiology. The purpose of this study was to uncover key genes and pathways related to the pathogenesis of CRSwNP via bioinformatics approaches. MATERIALS AND METHODS: The gene expression profile of GSE36830 extracted from Gene Expression Omnibus database was used to screen differentially expressed genes (DEGs) between nasal polyp samples and control samples. Furthermore, functional and pathway enrichment analysis was performed using the clusterProfiler package in R language. In addition, protein-protein interaction (PPI) network was constructed by STRING database and functional modules were detected using Molecular Complex Detection algorithm. RESULTS: A total of 538 DEGs (326 up-regulated and 212 down-regulated) were identified. The most significantly enriched pathways for up-regulated and down-regulated genes were hematopoietic cell lineage and salivary secretion, respectively. Moreover, twenty hub genes with high connectivity degrees were selected from the PPI network, such as TYRO protein tyrosine kinase binding protein (TYROBP), G protein subunit gamma 2 (GNG2), CCR7, and CCR3. Besides, six important modules were obtained, which were highly associated with chemokine signaling pathway, Th1 and Th2 cell differentiation, complement and coagulation cascades, cell cycle, systemic lupus erythematosus, and Staphylococcus aureus infection. CONCLUSIONS: The results of this study may provide new insights into potential molecular mechanisms of CRSwNP. Nevertheless, further experiments are needed to confirm these findings.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Quimiocinas , Biologia Computacional/métodos , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica/métodos , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Pólipos Nasais/complicações , Pólipos Nasais/genética , Receptores CCR3/genética , Receptores CCR7/genética , Rinite/complicações , Rinite/genética , Transdução de Sinais/genética , Sinusite/complicações , Sinusite/genética , Transcriptoma , Regulação para Baixo/genética , Humanos , Regulação para Cima/genéticaRESUMO
BACKGROUND/AIMS: Short-chain fatty acids (SCFAs) are the major energy resources of intestinal epithelial cells. It has been reported that SCFAs can repair the dysfunction of intestinal barrier, however, the underlying mechanisms are still not fully understood. Here, we investigated the stimulative and protective effects of SCFAs on intestinal barrier function and the possible mechanisms. METHODS: To investigate the effects of SCFAs on intestinal barrier function, the Caco-2 monolayers were exposed to acetate, propionate, butyrate respectively or simultaneously without or with lipopolysaccharide (LPS). Next, Caco-2 cells were treated with trichostatin A and etomoxir to identify whether SCFAs act as HDAC inhibitors or energy substances. To activate NLRP3 inflammasome and autophagy, Caco-2 cells were treated with LPS+ATP and rapamycin respectively without or with SCFAs. The transepithelial electrical resistance (TER) and paracellular permeability were respectively detected with a Millicell-ERS voltohmmeter and fluorescein isothiocyanate-labeled dextran. Immunoblotting and immunofluorescence were applied to analyze the expression and distribution of tight junction proteins, and the activation of NLRP3 inflammasome and autophagy. RESULTS: Acetate (0.5mM), propionate(0.01mM) and butyrate (0.01mM) alone or in combination significantly increased TER, and stimulated the formation of tight junction. SCFAs also dramatically attenuated the LPS-induced TER reduction and paracellular permeability increase, accompanying significantly alleviated morphological disruption of ZO-1 and occludin. Meanwhile, the activation of NLRP3 inflammasome and autophagy induced by LPS were significantly inhibited by SCFAs. Trichostatin A imitated the inhibiting action of SCFAs on NLRP3 inflammasome, whereas etomoxir blocked the action of SCFAs on protecting intestinal barrier and inhibiting autophagy. In addition, the activation of autophagy and NLRP3 inflammasome by rapamycin and LPS+ATP resulted in TER reduction, paracellular permeability increase and morphological disruption of both ZO-1 and occludin, which was alleviated by SCFAs. CONCLUSION: It is suggested that SCFAs stimulate the formation of intestinal barrier, and protect the intestinal barrier from the disruption of LPS through inhibiting NLRP3 inflammasome and autophagy. In addition, SCFAs act as energy substances to protect intestinal barrier and inhibit autophagy, but act as HDAC inhibitors to suppress NLRP3 inflammasome. Furthermore, the mutual promoting action between NLRP3 inflammasome and autophagy would destroy intestinal barrier function, which could be alleviated by SCFAs.
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Autofagia/efeitos dos fármacos , Ácidos Graxos Voláteis/farmacologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Beclina-1/metabolismo , Células CACO-2 , Citocinas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirolimo/farmacologia , Junções Íntimas/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
P300 event-related potential component may sensitively predict mild cognitive impairment (MCI) progression. Here, pooled effect size estimates of P300 amplitude and latency were computed at midline electrodes among controls, MCI patients, and Alzheimer's disease (AD) patients. Baseline data were compared to one-year follow-up data. MCI patients showed decreased P300 amplitude and prolonged latency compared to controls. Pooled standardized mean differences (SMDs) were -0.67 (95 % CI -1.12 to -0.23, P = 0.003) and 0.90 (95 % CI 0.66-1.14, P < 0.00001), respectively. P300 latency decreased in MCI compared to AD patients where the pooled SMD was -0.52 (95 % CI -0.85 to -0.18, P = 0.003). Amplitude and latency differed between MCI baseline and follow-up. Pooled SMDs were 0.47 (95 % CI 0.29 to -0.65, P < 0.00001) and -0.52 (95 % CI -0.71 to -0.34, P < 0.00001), respectively. Group differences in MCI P300 latency existed compared to control and AD patients. P300 latency may therefore be a sensitive indicator for early cognitive decline or disease progression in MCI patients and identifying elderly patient progression to MCI and/or AD.
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Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Diagnóstico Diferencial , Potenciais Evocados P300/fisiologia , Doença de Alzheimer/fisiopatologia , Bases de Dados Bibliográficas/estatística & dados numéricos , Progressão da Doença , Eletroencefalografia , Humanos , Estimulação Física , Tempo de Reação/fisiologiaRESUMO
Wild-type p53-induced phosphatase (WIP1) is overexpressed and functionally altered in multiple human malignancies. The present study investigated its abnormal expression and dysfunctions in nasopharyngeal carcinoma (NPC) in vitro. Here, analysis of WIP1 mRNA and protein in human NPC tissues revealed that both WIP1 messenger RNA (mRNA) and protein were elevated and were correlated with NPC clinical stage and metastasis in patients. In vitro experiments further showed that WIP1 inhibition led to a decrease in the proliferative ability of NPC CNE-2 and 5-8F cells accompanied by cell cycle arrest and increased apoptosis. In addition, WIP1 knockdown inhibited the invasiveness of CNE-2 and 5-8F cells and was associated with the down-regulation of the expression of matrix metallopeptidase 9 (MMP-9) mRNA and protein. Taken together, our data demonstrate that WIP1 regulates the proliferation and invasiveness of NPC cells in vitro, and this may be correlated with its modulation of MMP-9 expression, cell cycle progression and apoptosis. WIP1 functioned as a potential therapeutic target in NPC management.
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Neoplasias Nasofaríngeas/patologia , Fosfoproteínas Fosfatases/fisiologia , Adulto , Idoso , Carcinoma , Proliferação de Células , Feminino , Humanos , Metástase Linfática , Masculino , Metaloproteinase 9 da Matriz/fisiologia , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Invasividade Neoplásica , Fosfoproteínas Fosfatases/genética , Proteína Fosfatase 2C , RNA Mensageiro/análiseRESUMO
OBJECTIVES: Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. METHODS: A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. RESULTS: A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (pâ¯<â¯0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (pâ¯<â¯0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (pâ¯<â¯0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (pâ¯<â¯0.05). CONCLUSION: Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. LEVEL OF EVIDENCE: Level 4.
Assuntos
Dislipidemias , Hiperglicemia , Síndrome Metabólica , Pólipos Nasais , Rinite Alérgica , Rinite , Rinossinusite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Rinite/complicações , Rinite/cirurgia , Síndrome Metabólica/complicações , Estudos Retrospectivos , Sobrepeso/complicações , Sinusite/complicações , Sinusite/cirurgia , Rinite Alérgica/complicações , Obesidade/complicações , Dislipidemias/complicações , Hiperglicemia/complicações , Doença Crônica , RecidivaRESUMO
In this research, a novel kind of walnut (Juglans regia L.) peptides-zinc (Zn-WPs) chelate was obtained using the mass ratio of the walnut peptides (WPs) to ZnSO4.7H2O of 3.5:1 at pH 8.5 and 50°C for 84 min, with the chelation rate of 84.5%. In comparison to walnut peptides (WPs), the contents of aspartic acid and glutamic acid in Zn-WPs chelate are approximately 27%, indicating that hydrophilic amino acids predominantly bind with walnut peptides. Following chelation with zinc ions, the ultraviolet-visible (UV) characteristic absorption peak shifted from 213 nm to 210 nm, while the average particle size of the chelate increased to 8.0 ± 0.14 µm, presenting a loose spherical structure under scanning electron microscopy. These findings suggest the formation of new substances. Fourier-transform infrared spectroscopy (FTIR) revealed carboxyl, amino, and peptide bonds as the chelation sites of WPs and zinc. The IC50 of walnut peptides-zinc (Zn-WPs) chelate is 2.91 mg/mL, indicative of a favorable DPPH radical scavenging rate. Furthermore, Zn-WPs chelate microcapsules were produced via the spray drying method, achieving an encapsulation rate of 75.67 ± 0.83% under optimal conditions. These microcapsules demonstrate robust stability across diverse environmental conditions. This study underscores the potential of Zn-WPs and its chelate microcapsules to enhance stability and bioactivity under varying circumstances. PRACTICAL APPLICATION: In this study, a new walnut peptide-zinc (Zn-WPs) chelate was prepared. The presence of zinc ions changes the structure and properties of walnut peptides and improves its stability. The production of Zn-WPs chelate microcapsules enables Zn-WPs to have strong in vitro stability under different pH and simulated gastrointestinal digestion conditions. These results provide novel insights for developing the walnut peptides as bioactive ingredients in functional foods.
RESUMO
Walnut isolate protein (WPI)-epigallocatechin gallate (EGCG) conjugates can be employed to creat food-grade delivery systems for preserving bioactive compounds. In this study, WPI-EGCG nanoparticles (WENPs) were developed for encapsulating lycopene (LYC) using the ultrasound-assisted method. The results indicated successful loading of LYC into these WENPs, forming the WENPs/LYC (cylinder with 200-300 nm in length and 14.81-30.05 nm in diameter). Encapsulating LYC in WENPs led to a notable decrease in release rate and improved stability in terms of thermal, ultraviolet (UV), and storage conditions compared to free LYC. Simultaneously, WENPs/LYC exhibited a synergistic and significantly higher antioxidant activity with an EC50 value of 23.98 µg/mL in HepG2 cells compared to free LYC's 31.54 µg/mL. Treatment with WENPs/LYC led to a dose-dependent restoration of intracellular antioxidant enzyme activities (SOD, CAT, and GSH-Px) and inhibition of intracellular malondialdehyde (MDA) formation. Furthermore, transcriptome analysis indicated that enrichment in glutathione metabolism and peroxisome processes following WENPs/LYC addition. Quantitative real-time reverse transcription PCR (qRT-PCR) verified the expression levels of related genes involved in the antioxidant resistance pathway of WENPs/LYC on AAPH-induced oxidative stress. This study offers novel perspectives into the antioxidant resistance pathway of WENPs/LYC, holding significant potential in food industry.