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1.
Int Immunopharmacol ; 136: 112330, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38823180

ABSTRACT

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

2.
Food Chem ; 454: 139718, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38795620

ABSTRACT

N-lauroyl-L-tryptophan (LT), which has the strongest potential flavor-presenting activity, was skillfully screened from numerous N-Lau-AAs docked to different taste receptors by molecular simulation techniques. Subsequently, LT was synthesized employing food-grade commercial enzymes and structurally characterized, the optimized yields of LT could reach 69.08%, 76.16%, and 50.40%, respectively. Sensory and E-tongue evaluations showed that LT at 1 mg/L significantly benefited the performance of different taste sensations and exhibited different bitter taste masking effects: L-Ile (68.42%), L-Trp (68.18%), D-salicylic acid (48.48%) and quinine (35.00%). The molecular docking results illustrated that LT had a high affinity for various taste receptors, dominated by hydrogen bonding and hydrophobic interactions. This work provided a rare systematic elucidation of the potential and mechanism of enzymatically synthesized LT in enhancing taste properties. It provides novel insights into the directions and strategies for the excavation and innovation of flavor enhancers and food flavors.

3.
Food Chem ; 454: 139670, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38820630

ABSTRACT

Recently, amino acid derivatives gradually gained attention, but studies on N-lactoyl-leucine (Lac-Leu) and N-lactoyl-isoleucine (Lac-Ile) are limited. This study aims to explore the contributions of Lac-Leu and Lac-Ile to soy sauce. Lac-Leu and Lac-Ile were synthesized via enzymatic synthesis method catalyzed by Tgase. The mixed solutions containing Lac-Leu were found to have greater taste improvement than those containing Lac-Ile. Sensory evaluation indicated the sour, bitter, and astringent taste of Lac-Leu in water as well as its kokumi, astringent, and umami-enhancing taste in MSG solution. The taste threshold and umami-enhancing threshold of Lac-Leu measured by TDA and cTDA, respectively, were 0.08 mg/mL and 0.16 mg/mL. Molecular docking of Lac-Leu and Lac-Ile with the kokumi receptor CaSR and the umami receptors T1R1 and T1R3 indicated that Lac-Leu had higher affinities with receptors than Lac-Ile. These findings demonstrated the underlying contribution Lac-Leu made to soy sauce, indicating its potential to improve the flavor quality of soy sauce.

4.
Food Chem ; 453: 139661, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38772310

ABSTRACT

The present study aimed to explore the similarity and difference in taste enhancement properties of N-succinyl-L-phenylalanine (N-Suc-Phe), N-succinyl-L-tryptophan (N-Suc-Trp), and N-succinyl-L-tyrosine (N-Suc-Tyr) using temporal dominance of sensations (TDS), temporal check-all-that-apply (TCATA), and time-intensity (TI) techniques. Meanwhile, leading taste enhancers in the market, such as N'-[(2,4-dimethoxyphenyl)methyl]-N-(2-pyridin-2-ylethyl) oxamide (DE) was chosen to conduct a comparative analysis with the aforementioned three compounds. Findings from TDS and TCATA revealed that all compounds under investigation notably enhanced umami and saltiness while reducing bitterness in a concentration-dependent fashion (0.25-1 mg/L). Additionally, the TI results indicated that the duration of umami was extended by 50-75%, and the duration of bitterness was decreased by 20-40% upon addition of DE, N-Suc-Phe, N-Suc-Trp, and N-Suc-Tyr (1 mg/L). Among these, N-Suc-Trp was identified as the most effective in augmenting umami and mitigating bitterness, whereas N-Suc-Tyr excelled in enhancing saltiness intensity. Partial least squares regression (PLSR) pinpointed the carbon­carbon double bond as the important structure influencing the enhancement of umami and reduction of bitterness, whereas the phenolic hydroxyl group was identified as critical for enhancing saltiness. This investigation provided insights into the different characteristics of taste enhancement of N-Suc-AAs and the impact of chemical structure on such specificity.


Subject(s)
Flavoring Agents , Taste , Humans , Flavoring Agents/chemistry , Adult , Male , Female , Amino Acids/chemistry , Young Adult , Molecular Structure , Phenylalanine/chemistry
5.
Nat Commun ; 15(1): 4519, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806474

ABSTRACT

Protein ubiquitination regulates a wide range of cellular processes. The degree of protein ubiquitination is determined by the delicate balance between ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase (DUB)-mediated deubiquitination. In comparison to the E3-substrate interactions, the DUB-substrate interactions (DSIs) remain insufficiently investigated. To address this challenge, we introduce a protein sequence-based ab initio method, TransDSI, which transfers proteome-scale evolutionary information to predict unknown DSIs despite inadequate training datasets. An explainable module is integrated to suggest the critical protein regions for DSIs while predicting DSIs. TransDSI outperforms multiple machine learning strategies against both cross-validation and independent test. Two predicted DUBs (USP11 and USP20) for FOXP3 are validated by "wet lab" experiments, along with two predicted substrates (AR and p53) for USP22. TransDSI provides new functional perspective on proteins by identifying regulatory DSIs, and offers clues for potential tumor drug target discovery and precision drug application.


Subject(s)
Deubiquitinating Enzymes , Proteome , Ubiquitination , Humans , Proteome/metabolism , Deubiquitinating Enzymes/metabolism , Deubiquitinating Enzymes/genetics , Deep Learning , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/chemistry , Substrate Specificity , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Machine Learning , Protein Binding , Amino Acid Sequence , Thiolester Hydrolases
6.
Nat Commun ; 15(1): 2974, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582895

ABSTRACT

Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.


Subject(s)
Ubiquitin-Protein Ligases , Ubiquitin , Animals , Mice , Homeostasis , NF-kappa B/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
7.
Brain Sci ; 14(4)2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38671952

ABSTRACT

Parkinson's disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

8.
Brain Sci ; 14(3)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38539626

ABSTRACT

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson's disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

9.
Molecules ; 29(6)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38542861

ABSTRACT

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27-1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.


Subject(s)
Antineoplastic Agents , Neoplasms , Mice , Animals , Focal Adhesion Protein-Tyrosine Kinases , Molecular Docking Simulation , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Radiopharmaceuticals/chemistry , Biological Transport , Protein Kinase Inhibitors/chemistry , Cell Line, Tumor , Structure-Activity Relationship , Antineoplastic Agents/chemistry
10.
Ultrasonics ; 139: 107294, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479109

ABSTRACT

In the field of structure health monitoring (SHM), the use of Lamb wave to locate damage is a common method. Energy focusing is beneficial for damage localization because of higher SNR and higher resolution. Optimization design of elastic metamaterials is promising for energy focusing based on speed modulation. However, current design scheme is effective only for narrowband Lamb waves. Compared to narrowband waves, broadband Lamb waves with a larger frequency range carry richer structural information. In this study, an energy focusing method based on broadband Lamb waves by simultaneous designing excitation waveforms and elastic metamaterials is proposed. Firstly, COMSOL finite element simulation software is used to calculate the relationship between the metamaterial structure and the excitation wave. Subsequently, the metamaterial structure and the excitation signal form are designed according to the relationship. Finally, the metamaterial structure is bonded with the aluminum plate using 3D printing PA2200 nylon to verify the effectiveness of the method.

11.
Comput Biol Med ; 172: 108214, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508057

ABSTRACT

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.


Subject(s)
Aortic Valve Stenosis , Aortic Valve/pathology , Calcinosis , Heart Valve Diseases , Humans , Aortic Valve Stenosis/genetics , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/epidemiology , Heart Valve Diseases/genetics , Calcinosis/genetics
12.
Water Res ; 252: 121251, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38324983

ABSTRACT

Nanofiltration (NF) membranes play a pivotal role in water treatment; however, the persistent challenge of membrane fouling hampers their stable application. This study introduces a novel approach to address this issue through the creation of a poly(3,4-ethylenedioxythiophene) (PEDOT)-based conductive membrane, achieved by synergistically coupling interfacial polymerization (IP) with in situ self-polymerization of EDOT. During the IP reaction, the concurrent generation of HCl triggers the protonation of EDOT, activating its self-polymerization into PEDOT. This interwoven structure integrates with the polyamide network to establish a stable selective layer, yielding a remarkable 90 % increase in permeability to 20.4 L m-2 h-1 bar-1. Leveraging the conductivity conferred by PEDOT doping, an electro-assisted cleaning strategy is devised, rapidly restoring the flux to 98.3 % within 5 min, outperforming the 30-minute pure water cleaning approach. Through simulations in an 8040 spiral-wound module and the utilization of the permeated salt solution for cleaning, the electro-assisted cleaning strategy emerges as an eco-friendly solution, significantly reducing water consumption and incurring only a marginal electricity cost of 0.055 $ per day. This work presents an innovative avenue for constructing conductive membranes and introduces an efficient and cost-effective electro-assisted cleaning strategy to effectively combat membrane fouling.


Subject(s)
Membranes, Artificial , Organic Chemicals , Polymerization , Permeability , Electric Conductivity
13.
Exp Ther Med ; 27(2): 72, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38234625

ABSTRACT

In contrast to prior findings that have illustrated the conversion of non-neuronal cells into functional neurons through the specific targeting of polypyrimidine tract-binding protein 1 (PTBP1), accumulated evidence suggests the impracticality of inducing neuronal transdifferentiation through suppressing PTBP1 expression in pathological circumstances. Therefore, the present study explored the effect of knocking down PTBP1 under physiological conditions on the transdifferentiation of mouse hippocampal neuron HT22 cells and mouse astrocyte (MA) cells. A total of 20 µM negative control small interfering (si)RNA and siRNA targeting PTBP1 were transfected into HT22 and MA cells using Lipo8000™ for 3 and 5 days, respectively. The expression of early neuronal marker ßIII-Tubulin and mature neuronal markers NeuN and microtubule-associated protein 2 (MAP2) were detected using western blotting. In addition, ßIII-tubulin, NeuN and MAP2 were labeled with immunofluorescence staining to evaluate neuronal cell differentiation in response to PTBP1 downregulation. Under physiological conditions, no significant changes in the expression of ßIII-Tubulin, NeuN and MAP2 were found after 3 and 5 days of knockdown of PTBP1 protein in both HT22 and MA cells. In addition, the immunofluorescence staining results showed no apparent transdifferentiation in maker levels and morphology. The results suggested that the knockdown of PTBP1 failed to induce neuronal differentiation under physiological conditions.

14.
Cancer Cell ; 42(3): 464-473.e3, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38242125

ABSTRACT

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.


Subject(s)
Carcinoma , Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Neoplasm Staging , Herpesvirus 4, Human , Prognosis , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/pathology , Epstein-Barr Virus Infections/pathology , Carcinoma/pathology , Retrospective Studies
15.
Laryngoscope ; 134(1): 148-153, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37243347

ABSTRACT

Hearing improvement is another basic requirement for microtia patients in addition to aesthetic needs. This quantitative framework fabrication method can reduce the learning curve, obtain satisfactory aesthetic results with few complications, and reserve a certain space for future canalplasty. Laryngoscope, 134:148-153, 2024.


Subject(s)
Congenital Microtia , Costal Cartilage , Plastic Surgery Procedures , Humans , Costal Cartilage/transplantation , Ear, External/surgery , Congenital Microtia/surgery , Cartilage/transplantation
16.
Food Chem ; 439: 138090, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38043280

ABSTRACT

This study was the first to compare the structural features, functional properties and in vitro digestibility of two protein concentrates produced from defatted sunflower meal via two different three-stage processes (chlorogenic acid removal-alkaline extraction-isoelectric precipitation versus chlorogenic acid removal-alkaline extraction-ultrafiltration; concentrates termed AI-SPC and AU-SPC, respectively). Compared with AI-SPC, AU-SPC with a darker brown color had much higher protein recovery yield and purity, much higher solubility at pH 4-7, higher oil-holding capacity, greater emulsifying and foaming capacities at pH 7 and 9, and slightly lower foaming capacity at pH 3. The bioavailability was higher for AU-SPC after oral-gastric-intestinal digestion. Moreover, AI-SPC occurred as clumps/lumps of particles, whilst AU-SPC appeared as flat blocks with continuous surfaces. AU-SPC was more negatively charged, and had a smaller particle size, less ß-sheet, more ß-turn, slightly more α-helix structure. These results confirmed the close relationship between protein production methods and its functional properties and digestibility.


Subject(s)
Helianthus , Ultrafiltration , Chlorogenic Acid , Plant Proteins/chemistry , Solubility
17.
J Sci Food Agric ; 104(6): 3477-3486, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38133859

ABSTRACT

BACKGROUND: Enzymatic modification is an effective means of improving the functional properties, digestive properties, and in vitro digestion product physiological activity of proteins, thus significantly expanding protein uses in various food applications. RESULTS: In this study, the addition of chymotrypsin (CT) at pH 9.0 and 11.0 was found to significantly improve the functional properties (solubility, foaming properties, water holding capacity, oil holding capacity, etc.) and digestive properties of extruded corn gluten meal (ECGM). Similar changes were observed when treating ECGM with glutaminase, protein glutaminase, and papain. These changes were likely due to the increase in number of carboxyl groups and the multiple effects of change in protein net charge and conformation caused by enzymatic deamidation. Of note, ECGM deamidated by CT showed the highest degree of deamidation, solubility, and gastrointestinal digestibility at pH 11.0, up to 44.92%, 43.75%, and 82.22%, respectively. In addition, CT-ECGM digestion product exhibited strong antioxidant activity and potential to promote alcohol metabolism in both a static digestion model and dynamic digestion model, even comparable to commercial corn peptides (CCP), while being inexpensive and of low bitterness compared to CCP. Meanwhile, the physiological activity enhanced as the molecular weight of digestion product decreased with the digested component having strongest activity. CONCLUSION: This study may promote the application of ECGM as a food component in the food industry or even as a substitute for CCP. © 2023 Society of Chemical Industry.


Subject(s)
Glutaminase , Glutens , Glutens/chemistry , Zea mays/chemistry , Peptides/chemistry , Digestion
18.
J Sci Food Agric ; 104(2): 716-726, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37658829

ABSTRACT

BACKGROUND: The demand for food-based anti-photoaging products is surging because of the rising recognition of health and beauty, as well as enhanced comprehension of the detrimental impact of ultraviolet (UV) radiation. This study aimed to investigate the potential of bioactive peptides derived from bovine elastin, specifically focusing on identifying novel elastase inhibitory peptides and assessing their photoprotective properties using bioinformatics techniques. RESULTS: A total of 48 bioactive peptides were screened in bovine elastin hydrolysate (EH) utilizing Peptide Ranker analysis. Three novel elastase inhibitory peptides, GAGQPFPI, FFPGAG and FPGIG (in descending order of activity), exhibited potent inhibitory effects on elastase in vitro, surpassing the inhibitory effect of EH by a factor of 1-2 and reaching significantly lower concentrations (8-15 times lower) than EH. The cumulative inhibitory effect of GAGQPFPI, FFPGAG, and FPGIG reached 91.5%. Further analysis revealed that FFPGAG and FPGIG exhibited mixed inhibition, whereas GAGQPFPI displayed non-competitive inhibition. Molecular simulations showed that these peptides interacted effectively with the elastase active site through hydrogen bonding and hydrophobic interactions. Furthermore, GAGQPFPI, FFPGAG, and FPGIG demonstrated high stability in gastrointestinal digestion, demonstrated transcellular permeability across Caco-2 cell monolayers, and exhibited remarkable photoprotective properties against UVB-irradiated HaCaT cells. CONCLUSION: GAGQPFPI showed the most promising potential as a functional food with photoprotective effects against UVB damage and inhibitory properties against elastase. © 2023 Society of Chemical Industry.


Subject(s)
Pancreatic Elastase , Skin Diseases , Humans , Animals , Cattle , Caco-2 Cells , Peptides/pharmacology , Peptides/chemistry , Elastin
19.
BMC Med ; 21(1): 500, 2023 12 18.
Article in English | MEDLINE | ID: mdl-38110931

ABSTRACT

BACKGROUND: More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. METHODS: Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. RESULTS: PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70-0.83) than the LDA (AUC = 0.7506; 95% CI 0.68-0.82) and ANN models (AUC = 0.7425; 95% CI 0.67-0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71-0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71-0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74-0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75-0.87). CONCLUSIONS: The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.


Subject(s)
Epilepsy , Tuberous Sclerosis , Humans , Fluorodeoxyglucose F18 , Tuberous Sclerosis/complications , Tuberous Sclerosis/diagnostic imaging , Tuberous Sclerosis/metabolism , Reproducibility of Results , Glycolysis , Retrospective Studies
20.
J Agric Food Chem ; 71(49): 19694-19704, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38016698

ABSTRACT

Previous studies have demonstrated that thermal processing in the presence of lactate and amino acids can produce taste-active N-lactoyl amino acids. This study aimed to investigate the impact of lactate and thermal processing on the sensory characteristics of acid-hydrolyzed vegetable proteins (aHVP). The results showed that the processed aHVP exhibited enhanced kokumi, a milder umami taste, and reduced bitterness on treatment with 1% lactate at 110 °C for 3 h or 3% lactate at 120 °C for 2 h compared to the unprocessed samples. Partial or orthogonal least-squares discriminant analysis and variable importance in projection (VIP) analyses revealed the significant contributions of N-,l-Lac-l-hydrophobic AAs [-Met, -Ile, -Leu, -Val, and -Phe (VIP > 1.2)] to the observed differences between the processed and unprocessed samples. Electronic tongue analysis confirmed the sensory findings and indicated a decrease in the aftertaste of bitterness in the processed samples. Furthermore, the study identified the sensory characteristics of N-l-Lac-l-Met, -Ile, and -Leu, highlighting their potential to enhance salty, umami, and kokumi perception in simulated broth. Furthermore, the study incorporated the addition of bitter amino acids (Val, Ile, Leu, Tyr, Phe, Lys, His, and Arg) and the aforementioned N-l-Lac-l-AAs to aHVP, providing further evidence for their contributions to bitterness and aftertaste-B as well as the kokumi differences, respectively. This study provides valuable insights into the sensory effects of lactate and thermal processing on aHVP, facilitating the development of improved taste-enhancing strategies.


Subject(s)
Lactic Acid , Taste , Lactic Acid/analysis , Vegetables , Amino Acids/analysis , Plant Proteins, Dietary/pharmacology
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