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BACKGROUND AND AIMS: The efficacy and safety of colonoscopy performed by artificial intelligence (AI)-assisted novices remain unknown. The aim of this study was to compare the lesion detection capability of novices, AI-assisted novices, and experts. METHODS: This multicenter, randomized, noninferiority tandem study was conducted across 3 hospitals in China from May 1, 2022, to November 11, 2022. Eligible patients were randomized into 1 of 3 groups: the CN group (control novice group, withdrawal performed by a novice independently), the AN group (AI-assisted novice group, withdrawal performed by a novice with AI assistance), or the CE group (control expert group, withdrawal performed by an expert independently). Participants underwent a repeat colonoscopy conducted by an AI-assisted expert to evaluate the lesion miss rate and ensure lesion detection. The primary outcome was the adenoma miss rate (AMR). RESULTS: A total of 685 eligible patients were analyzed: 229 in the CN group, 227 in the AN group, and 229 in the CE group. Both AMR and polyp miss rate were lower in the AN group than in the CN group (18.82% vs 43.69% [P < .001] and 21.23% vs 35.38% [P < .001], respectively). The noninferiority margin was met between the AN and CE groups of both AMR and polyp miss rate (18.82% vs 26.97% [P = .202] and 21.23% vs 24.10% [P < .249]). CONCLUSIONS: AI-assisted colonoscopy lowered the AMR of novices, making them noninferior to experts. The withdrawal technique of new endoscopists can be enhanced by AI-assisted colonoscopy. (Clinical trial registration number: NCT05323279.).
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Pólipos , Humanos , Inteligência Artificial , Estudos Prospectivos , Colonoscopia/métodos , Projetos de Pesquisa , Adenoma/diagnóstico , Adenoma/patologia , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnósticoRESUMO
BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5 mm adenomas and should undergo an early repeat colonoscopy. In this study, we used artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system to accurately identify patients who are at high risk of having >5 mm adenomas missed due to inadequate bowel preparation. METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University, from October 8, 2021, to November 9, 2022. Eligible patients who underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using the e-Boston Bowel Preparation Scale (e-BBPS) while endoscopists made evaluations using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy; otherwise, the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 adenomas >5 mm in size were detected; 27 adenomas >5 mm in size were missed. In unqualified-AI patients, the >5 mm adenoma miss rate (AMR) was significantly higher than in qualified-AI patients (35.71% vs 13.19% [P = .0056]; odds ratio [OR], .2734 [95% CI, .1139-.6565]), as were the AMR (50.89% vs 20.79% [P < .001]; OR, .2532 [95% CI, .1583-.4052]) and >5 mm polyp miss rate (35.82% vs 19.48% [P = .0152]; OR, .4335 [95% CI, .2288-.8213]). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI exhibited an unacceptable >5 mm AMR, providing key evidence for implementing AI in guiding bowel re-cleansing and potentially standardizing future colonoscopy screening. (Clinical trial registration number: NCT05145712.).
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BACKGROUND: The choice of polypectomy device and surveillance intervals for colorectal polyps are primarily decided by polyp size. We developed a deep learning-based system (ENDOANGEL-CPS) to estimate colorectal polyp size in real time. METHODS: ENDOANGEL-CPS calculates polyp size by estimating the distance from the endoscope lens to the polyp using the parameters of the lens. The depth estimator network was developed on 7297 images from five virtually produced colon videos and tested on 730 images from seven virtual colon videos. The performance of the system was first evaluated in nine videos of a simulated colon with polyps attached, then tested in 157 real-world prospective videos from three hospitals, with the outcomes compared with that of nine endoscopists over 69 videos. Inappropriate surveillance recommendations caused by incorrect estimation of polyp size were also analyzed. RESULTS: The relative error of depth estimation was 11.3% (SD 6.0%) in successive virtual colon images. The concordance correlation coefficients (CCCs) between system estimation and ground truth were 0.89 and 0.93 in images of a simulated colon and multicenter videos of 157 polyps. The mean CCC of ENDOANGEL-CPS surpassed all endoscopists (0.89 vs. 0.41 [SD 0.29]; P<0.001). The relative accuracy of ENDOANGEL-CPS was significantly higher than that of endoscopists (89.9% vs. 54.7%; P<0.001). Regarding inappropriate surveillance recommendations, the system's error rate is also lower than that of endoscopists (1.5% vs. 16.6%; P<0.001). CONCLUSIONS: ENDOANGEL-CPS could potentially improve the accuracy of colorectal polyp size measurements and size-based surveillance intervals.
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Pólipos do Colo , Neoplasias Colorretais , Aprendizado Profundo , Humanos , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagemRESUMO
BACKGROUND: Double-balloon enteroscopy (DBE) is a standard method for diagnosing and treating small bowel disease. However, DBE may yield false-negative results due to oversight or inexperience. We aim to develop a computer-aided diagnostic (CAD) system for the automatic detection and classification of small bowel abnormalities in DBE. DESIGN AND METHODS: A total of 5201 images were collected from Renmin Hospital of Wuhan University to construct a detection model for localizing lesions during DBE, and 3021 images were collected to construct a classification model for classifying lesions into four classes, protruding lesion, diverticulum, erosion & ulcer and angioectasia. The performance of the two models was evaluated using 1318 normal images and 915 abnormal images and 65 videos from independent patients and then compared with that of 8 endoscopists. The standard answer was the expert consensus. RESULTS: For the image test set, the detection model achieved a sensitivity of 92% (843/915) and an area under the curve (AUC) of 0.947, and the classification model achieved an accuracy of 86%. For the video test set, the accuracy of the system was significantly better than that of the endoscopists (85% vs. 77 ± 6%, p < 0.01). For the video test set, the proposed system was superior to novices and comparable to experts. CONCLUSIONS: We established a real-time CAD system for detecting and classifying small bowel lesions in DBE with favourable performance. ENDOANGEL-DBE has the potential to help endoscopists, especially novices, in clinical practice and may reduce the miss rate of small bowel lesions.
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Aprendizado Profundo , Enteropatias , Humanos , Enteroscopia de Duplo Balão/métodos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Enteropatias/diagnóstico por imagem , Abdome/patologia , Endoscopia Gastrointestinal/métodos , Estudos RetrospectivosRESUMO
BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.
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Pólipos do Colo , Colonoscopia , Diagnóstico por Computador , Humanos , Colonoscopia/métodos , Pólipos do Colo/diagnóstico , Pólipos do Colo/diagnóstico por imagem , Diagnóstico por Computador/métodos , Reações Falso-Positivas , Masculino , Estudos Prospectivos , Inteligência Artificial , Feminino , Pessoa de Meia-Idade , Estudos Cross-Over , Adenoma/diagnóstico , Adenoma/diagnóstico por imagemRESUMO
BACKGROUND AND AIM: Early whitish gastric neoplasms can be easily misdiagnosed; differential diagnosis of gastric whitish lesions remains a challenge. We aim to build a deep learning (DL) model to diagnose whitish gastric neoplasms and explore the effect of adding domain knowledge in model construction. METHODS: We collected 4558 images from two institutions to train and test models. We first developed two sole DL models (1 and 2) using supervised and semi-supervised algorithms. Then we selected diagnosis-related features through literature research and developed feature-extraction models to determine features including boundary, surface, roundness, depression, and location. Then predictions of the five feature-extraction models and sole DL model were combined and inputted into seven machine-learning (ML) based fitting-diagnosis models. The optimal model was selected as ENDOANGEL-WD (whitish-diagnosis) and compared with endoscopists. RESULTS: Sole DL 2 had higher sensitivity (83.12% vs 68.67%, Bonferroni adjusted P = 0.024) than sole DL 1. Adding domain knowledge, the decision tree performed best among the seven ML models, achieving higher specificity than DL 1 (84.38% vs 72.27%, Bonferroni adjusted P < 0.05) and higher accuracy than DL 2 (80.47%, Bonferroni adjusted P < 0.001) and was selected as ENDOANGEL-WD. ENDOANGEL-WD showed better accuracy compared with 10 endoscopists (75.70%, P < 0.001). CONCLUSIONS: We developed a novel system ENDOANGEL-WD combining domain knowledge and traditional DL to detect gastric whitish neoplasms. Adding domain knowledge improved the performance of traditional DL, which provided a novel solution for establishing diagnostic models for other rare diseases potentially.
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Aprendizado Profundo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Estudos Retrospectivos , Diagnóstico Diferencial , Sensibilidade e Especificidade , AlgoritmosRESUMO
In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high-performance liquid chromatography chiral method was developed on polysaccharide-based Chiral MX (2) (4.6 × 250 mm, 5 µm) column. n-Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 µL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer in olodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase.
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Benzoxazinas , Termodinâmica , Estereoisomerismo , Benzoxazinas/química , Benzoxazinas/análise , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Limite de DetecçãoRESUMO
BACKGROUND AND AIMS: EGD is essential for GI disorders, and reports are pivotal to facilitating postprocedure diagnosis and treatment. Manual report generation lacks sufficient quality and is labor intensive. We reported and validated an artificial intelligence-based endoscopy automatic reporting system (AI-EARS). METHODS: The AI-EARS was designed for automatic report generation, including real-time image capturing, diagnosis, and textual description. It was developed using multicenter datasets from 8 hospitals in China, including 252,111 images for training, 62,706 images, and 950 videos for testing. Twelve endoscopists and 44 endoscopy procedures were consecutively enrolled to evaluate the effect of the AI-EARS in a multireader, multicase, crossover study. The precision and completeness of the reports were compared between endoscopists using the AI-EARS and conventional reporting systems. RESULTS: In video validation, the AI-EARS achieved completeness of 98.59% and 99.69% for esophageal and gastric abnormality records, respectively, accuracies of 87.99% and 88.85% for esophageal and gastric lesion location records, and 73.14% and 85.24% for diagnosis. Compared with the conventional reporting systems, the AI-EARS achieved greater completeness (79.03% vs 51.86%, P < .001) and accuracy (64.47% vs 42.81%, P < .001) of the textual description and completeness of the photo-documents of landmarks (92.23% vs 73.69%, P < .001). The mean reporting time for an individual lesion was significantly reduced (80.13 ± 16.12 seconds vs 46.47 ± 11.68 seconds, P < .001) after the AI-EARS assistance. CONCLUSIONS: The AI-EARS showed its efficacy in improving the accuracy and completeness of EGD reports. It might facilitate the generation of complete endoscopy reports and postendoscopy patient management. (Clinical trial registration number: NCT05479253.).
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Inteligência Artificial , Aprendizado Profundo , Humanos , Estudos Cross-Over , China , HospitaisRESUMO
BACKGROUND: White light (WL) and weak-magnifying (WM) endoscopy are both important methods for diagnosing gastric neoplasms. This study constructed a deep-learning system named ENDOANGEL-MM (multi-modal) aimed at real-time diagnosing gastric neoplasms using WL and WM data. METHODS: WL and WM images of a same lesion were combined into image-pairs. A total of 4201 images, 7436 image-pairs, and 162 videos were used for model construction and validation. Models 1-5 including two single-modal models (WL, WM) and three multi-modal models (data fusion on task-level, feature-level, and input-level) were constructed. The models were tested on three levels including images, videos, and prospective patients. The best model was selected for constructing ENDOANGEL-MM. We compared the performance between the models and endoscopists and conducted a diagnostic study to explore the ENDOANGEL-MM's assistance ability. RESULTS: Model 4 (ENDOANGEL-MM) showed the best performance among five models. Model 2 performed better in single-modal models. The accuracy of ENDOANGEL-MM was higher than that of Model 2 in still images, real-time videos, and prospective patients. (86.54 vs 78.85%, P = 0.134; 90.00 vs 85.00%, P = 0.179; 93.55 vs 70.97%, P < 0.001). Model 2 and ENDOANGEL-MM outperformed endoscopists on WM data (85.00 vs 71.67%, P = 0.002) and multi-modal data (90.00 vs 76.17%, P = 0.002), significantly. With the assistance of ENDOANGEL-MM, the accuracy of non-experts improved significantly (85.75 vs 70.75%, P = 0.020), and performed no significant difference from experts (85.75 vs 89.00%, P = 0.159). CONCLUSIONS: The multi-modal model constructed by feature-level fusion showed the best performance. ENDOANGEL-MM identified gastric neoplasms with good accuracy and has a potential role in real-clinic.
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Aprendizado Profundo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Prospectivos , Endoscopia GastrointestinalRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic reports are essential for the diagnosis and follow-up of gastrointestinal diseases. This study aimed to construct an intelligent system for automatic photo documentation during esophagogastroduodenoscopy (EGD) and test its utility in clinical practice. PATIENTS AND METHODS: Seven convolutional neural networks trained and tested using 210,198 images were integrated to construct the endoscopic automatic image reporting system (EAIRS). We tested its performance through man-machine comparison at three levels: internal, external, and prospective test. Between May 2021 and June 2021, patients undergoing EGD at Renmin Hospital of Wuhan University were recruited. The primary outcomes were accuracy for capturing anatomical landmarks, completeness for capturing anatomical landmarks, and detected lesions. RESULTS: The EAIRS outperformed endoscopists in retrospective internal and external test. A total of 161 consecutive patients were enrolled in the prospective test. The EAIRS achieved an accuracy of 95.2% in capturing anatomical landmarks in the prospective test. It also achieved higher completeness on capturing anatomical landmarks compared with endoscopists: (93.1% vs. 88.8%), and was comparable to endoscopists on capturing detected lesions: (99.0% vs. 98.0%). CONCLUSIONS: The EAIRS can generate qualified image reports and could be a powerful tool for generating endoscopic reports in clinical practice.
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Aprendizado Profundo , Endoscopia do Sistema Digestório , Endoscopia/métodos , Endoscopia do Sistema Digestório/métodos , Humanos , Estudos ProspectivosRESUMO
Protein covalent labeling is dramatically useful for studying protein function in living cells and organisms. In this field, the chemical tag technique combined with fluorogenic probes has emerged as a powerful tool. Herein, a series of TMP tag fluorogenic probes have been developed to span the green to full blue spectral range. These probes feature an acrylamide unit that acts as a linker group to conjugate the fluorophore and the ligand as well as a quencher and a covalent reaction group. After the probes bind to eDHFR:L28C, the acrylamide unit specifically reacts with the thiol group of the L28C residue beside the ligand binding pocket, achieving protein-specific labeling without any liberation of leaving groups. With these probes, multicolor and specific protein labeling with a fast reaction rate ( t1/2 = 33 s) and dramatic fluorescence enhancement (4000-fold) were obtained. Furthermore, no-wash protein labeling in both living cells and zebrafish was successfully achieved. We expect it may provide a general and highly effective chemical tool for the study of protein function in living cells and organisms.
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Acrilamida/química , Corantes Fluorescentes/química , Imagem Molecular/métodos , Razão Sinal-Ruído , Acrilamida/metabolismo , Animais , Núcleo Celular/metabolismo , Corantes Fluorescentes/metabolismo , Células HEK293 , Células HeLa , Humanos , Ligantes , Tetra-Hidrofolato Desidrogenase/genética , Peixe-ZebraRESUMO
Three new diarylethenes were synthesized from 1,2-bis(5-methyl-2-(4-substituted-phenyl)thiazol-4-yl)ethyne and benzyl azide through Ru(I)-catalyzed Huisgen cyclization reactions. The 4,5-bisthiazolyl-1,2,3-triazoles thus prepared, which belong to the terarylene family, showed thermally reversible photochromism. The absorption maximum wavelengths of the closed forms are longer than other terarylenes reported so far. The thermal back reactions are much faster when the substituents on the terminal phenyl groups are electron-withdrawing cyano groups than when they are electron-donating methoxy groups.
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BACKGROUND: NK cells are presented in tumor microenvironments and acts as an essential defense line against multiple malignancies. Recently, miRNAs are reported to involve in the development of natural killer (NK) cells via negatively regulating gene expression. Here, we aim to explore the function and mechanism underlying how miR-20a modulated the killing effect of NK cells to cervical cancer cells. METHODS: Abundances of miR-20a and runt-related transcription factor 1 (RUNX1) in NK cells from cervical cancer patients and healthy donors were detected by qRT-PCR and western blot. The releases of IFN-γ and TNF-α were determined by ELISA. The cytotoxicity of NK cells against cervical cancer cells was measured by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter, western blot, and RNA immunoprecipitation (RIP) assays were performed to assess the interaction between miR-20a and RUNX1. RESULT: miR-20a was upregulated while RUNX1 was downregulated in NK cells from cervical cancer patients compared to healthy donors. IL-2 stimulated the releases of IFN-γ and TNF-α, and the killing effect of NK cells to cervical cancer cells, which was overturned by miR-20a introduction. RUNX1 was identified to be a target of miR-20a. Restoration of RUNX1 abolished the inhibitory effects of miR-20a on the secretions of IFN-γ and TNF-α, as well as the killing effect of NK cells to colorectal cancer cells. CONCLUSION: miR-20a attenuated the killing effect of NK cells to cervical cancer cells by directly targeting RUNX1.
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Subunidade alfa 2 de Fator de Ligação ao Core/genética , Citotoxicidade Imunológica/genética , Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais/metabolismo , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Animais , Células Cultivadas , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Citotoxicidade Imunológica/imunologia , Regulação para Baixo , Feminino , Células HEK293 , Células HeLa , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Células Matadoras Naturais/imunologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante Heterólogo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismoRESUMO
During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.
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Cromatografia Líquida de Alta Pressão , Cromatografia Líquida de Alta Pressão/métodos , Rosuvastatina Cálcica , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , SolventesRESUMO
Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.
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Carvão Vegetal , Lignina , Óleo de Gergelim , Lignina/química , Carvão Vegetal/química , Adsorção , Óleo de Gergelim/química , Benzo(a)pireno/química , CinéticaRESUMO
The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.
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Aminas , Galinhas , Culinária , Proantocianidinas , Proantocianidinas/análise , Proantocianidinas/farmacologia , Animais , Aminas/química , Culinária/métodos , Compostos Heterocíclicos/química , Rosaceae/química , População do Leste AsiáticoRESUMO
Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.
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Coinfecção , Granuloma , Infecções por HIV , Pulmão , Macrófagos , Receptores de Interleucina-6 , Fator de Transcrição STAT3 , Humanos , Coinfecção/virologia , Coinfecção/imunologia , Coinfecção/microbiologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Macrófagos/imunologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Granuloma/imunologia , Pulmão/patologia , Pulmão/imunologia , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina-6/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Transdução de Sinais , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/complicações , Masculino , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/complicações , Feminino , Adulto , Interleucina-6/metabolismo , Interleucina-6/genética , Molécula CD68RESUMO
Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 µg/g, 297.74 ng/g, and 4.32 µg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.
Assuntos
Aminas , Produtos Finais de Glicação Avançada , Produtos da Carne , Produtos Finais de Glicação Avançada/metabolismo , Animais , Bovinos , Produtos da Carne/análise , Aminas/metabolismo , Água/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Temperatura Alta , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Culinária , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/farmacologiaRESUMO
Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi-omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population-specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon-stimulated genes (ISGs). Validation through multi-immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune-negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi-omics analysis integrating bulk transcriptomic, single-cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.
RESUMO
The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W-50 s, 50 W-100 s, 50 W-150 s, 100 W-50 s, 100 W-100 s, and 100 W-150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.