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1.
Cancer Manag Res ; 16: 643-650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919874

RESUMO

Background & Aims: The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy. Methods: Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications. Results: Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group. Conclusion: The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.

2.
PLoS One ; 19(6): e0305863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38913666

RESUMO

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-ß, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.


Assuntos
Proteínas Quinases Ativadas por AMP , Remodelação das Vias Aéreas , Asma , Modelos Animais de Doenças , Rosuvastatina Cálcica , Transdução de Sinais , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Rosuvastatina Cálcica/farmacologia , Rosuvastatina Cálcica/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Remodelação das Vias Aéreas/efeitos dos fármacos , Camundongos , Ovalbumina , Feminino , Camundongos Endogâmicos BALB C , Líquido da Lavagem Broncoalveolar , Doença Crônica , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Imunoglobulina E/sangue
3.
Reprod Toxicol ; 126: 108604, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703919

RESUMO

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (TwHF). TG tablets are the representative TwHF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG.


Assuntos
Autofagia , Glicosídeos , Triterpenos Pentacíclicos , Espermatogônias , Testículo , Tripterygium , Triterpenos , Animais , Masculino , Tripterygium/química , Tripterygium/toxicidade , Autofagia/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia , Glicosídeos/toxicidade , Glicosídeos/farmacologia , Espermatogônias/efeitos dos fármacos , Camundongos , Triterpenos/farmacologia , Triterpenos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos
4.
Biomed Pharmacother ; 175: 116788, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772153

RESUMO

AIMS: Penicilazaphilone C (PAC) is hypothesized to potentially serve as a therapeutic treatment for allergic airway inflammation by inhibiting the NLRP3 inflammasome and reducing oxidative stress. METHODS: An allergic asthma model was induced in female BALB/c mice of the OVA, OVA+PAC, OVA+PAC+LPS, and OVA+Dex groups by sensitizing and subsequently challenging them with OVA. The OVA+PAC and Normal+PAC groups were treated with PAC, while the OVA+PAC+LPS group also received LPS. The OVA+Dex group was given dexamethasone (Dex). Samples of serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for histological and cytological analysis. RESULTS: Allergic mice treated with PAC or Dex showed inhibited inflammation and mucus production in the lungs. There was a decrease in the number of inflammatory cells in the BALF, lower levels of inflammatory cytokines in the serum and BALF, and a reduction in the protein expression of NLRP3, ASC, cleaved caspase-1, IL-1ß, activated gasdermin D, MPO, Ly6G, and ICAM-1. Additionally, oxidative stress was reduced, as shown by a decrease in MDA and DCF, but an increase in SOD and GSH. Treatment with PAC also resulted in a decrease in pulmonary memory CD4+ T cells and an increase in regulatory T cells. However, the positive effects seen in the PAC-treated mice were reversed when the NLRP3 inflammasome was activated by LPS, almost returning to the levels of the Sham-treated mice. SIGNIFICANCE: PAC acts in a similar way to anti-allergic inflammation as Dex, suggesting it may be a viable therapeutic option for managing allergic asthma inflammation.


Assuntos
Asma , Líquido da Lavagem Broncoalveolar , Inflamassomos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Feminino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/imunologia , Asma/induzido quimicamente , Camundongos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , Estresse Oxidativo/efeitos dos fármacos , Ovalbumina , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Modelos Animais de Doenças , Dexametasona/farmacologia , Anti-Inflamatórios/farmacologia
5.
Int Immunopharmacol ; 136: 112329, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38815351

RESUMO

PURPOSE: Our team identified a new cardiac glycoside, Toxicarioside H (ToxH), in a tropical plant. Previous research has indicated the potential of cardenolides in mitigating inflammation, particularly in the context of NETosis. Therefore, this study sought to examine the potential of ToxH in attenuating allergic airway inflammation by influencing the immune microenvironment. METHODS: An OVA-induced airway inflammation model was established in BALB/c mice. After the experiment was completed, serum, bronchoalveolar lavage fluid (BALF), and lung tissue samples were collected and further examined using H&E and PAS staining, flow cytometry, immunofluorescence observation, and Western blot analysis. RESULTS: Treatment with ToxH was found to be effective in reducing airway inflammation and mucus production. This was accompanied by an increase in Th1 cytokines (IFN-γ, IL-2, and TNF-ß), and the Th17 cytokine IL-17, while levels of Th2 cytokines (IL-4, IL-5, and IL-13) and Treg cytokines (IL-10 and TGF-ß1) were decreased in both the bronchoalveolar lavage fluid (BALF) and the CD45+ immune cells in the lungs. Additionally, ToxH inhibited the infiltration of inflammatory cells and decreased the number of pulmonary CD44+ memory T cells, while augmenting the numbers of Th17 and Treg cells. Furthermore, the neutrophil elastase inhibitor GW311616A was observed to suppress airway inflammation and mucus production, as well as alter the secretion of immune Th1, Th2, Th17, and Treg cytokines in the lung CD45+ immune cells. Moreover, our study also demonstrated that treatment with ToxH efficiently inhibited ROS generation, thereby rectifying the dysregulation of immune cells in the immune microenvironment in OVA-induced allergic asthma. CONCLUSIONS: Our findings indicate that ToxH could serve as a promising therapeutic intervention for allergic airway inflammation and various other inflammatory disorders. Modulating the balance of Th1/Th2 and Treg/Th17 cells within the pulmonary immune microenvironment may offer an effective strategy for controlling allergic airway inflammation.


Assuntos
Citocinas , Pulmão , Camundongos Endogâmicos BALB C , Ovalbumina , Animais , Ovalbumina/imunologia , Citocinas/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Camundongos , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Modelos Animais de Doenças , Asma/imunologia , Asma/tratamento farmacológico , Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Muco/metabolismo , Muco/imunologia , Alérgenos/imunologia
6.
Comput Methods Programs Biomed ; 247: 108097, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428250

RESUMO

BACKGROUND AND OBJECTIVE: Left ventricular hypertrophy (LVH) can impair ejection function and elevate the risk of heart failure. Therefore, early detection through screening is crucial. This study aimed to propose a novel method to enhance LVH detection using 12-lead electrocardiogram (ECG) waveforms with a two-dimensional (2D) convolutional neural network (CNN). METHODS: Utilizing 42,127 pairs of ECG-transthoracic echocardiogram data, we pre-processed raw data into single-shot images derived from each ECG lead and conducted lead selection to optimize LVH diagnosis. Our proposed one-shot screening method, implemented during pre-processing, enables the superimposition of waveform source data of any length onto a single-frame image, thereby addressing the limitations of the one-dimensional (1D) approach. We developed a deep learning model with a 2D-CNN structure and machine learning models for LVH detection. To assess our method, we also compared our results with conventional ECG criteria and those of a prior study that used a 1D-CNN approach, utilizing the same dataset from the University of Tokyo Hospital for LVH diagnosis. RESULTS: For LVH detection, the average area under the receiver operating characteristic curve (AUROC) was 0.916 for the 2D-CNN model, which was significantly higher than that obtained using logistic regression and random forest methods, as well as the two conventional ECG criteria (AUROC of 0.766, 0.790, 0.599, and 0.622, respectively). Incorporating additional metadata, such as ECG measurement data, further improved the average AUROC to 0.921. The model's performance remained stable across two different annotation criteria and demonstrated significant superiority over the performance of the 1D-CNN model used in a previous study (AUROC of 0.807). CONCLUSIONS: This study introduces a robust and computationally efficient method that outperforms 1D-CNN models utilized in previous studies for LVH detection. Our method can transform waveforms of any length into fixed-size images and leverage the selected lead of the ECG, ensuring adaptability in environments with limited computational resources. The proposed method holds promise for integration into clinical practice as a tool for early diagnosis, potentially enhancing patient outcomes by facilitating earlier treatment and management.


Assuntos
Eletrocardiografia , Hipertrofia Ventricular Esquerda , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Eletrocardiografia/métodos , Ecocardiografia , Redes Neurais de Computação , Programas de Rastreamento
7.
J Pharm Pharmacol ; 76(6): 724-735, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38517742

RESUMO

OBJECTIVES: Coptisine (Cop), an alkaloid isolated from Rhizoma Coptidis, has a protective effect against central nervous system diseases such as cerebral ischaemia-reperfusion (IR). Dysregulations in fatty acids metabolism are associated with neuroprotection and neuroinflammation. However, the effect of Cop on fatty acids metabolomics during anti-IR remains unclear. METHODS: Cerebral IR rats were established by middle cerebral artery occlusion, and the therapeutic effect of Cop was evaluated by 2, 3, 5-triphenytetrazolium chloride staining and neurological deficits scores. By liquid chromatography-tandem mass spectrometry (LC-MS/MS), fatty acids metabolomics analysis in ischaemic hemisphere and serum were investigated. RESULTS: We observed Cop (2 mg/kg/qd) was able to reduce cerebral infarct size and ameliorate the neurological function score. Meanwhile decrease in tumour necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) after Cop treatment. Compared with control, down-regulation of cyclopentenone PGs (e.g., PGA2, PGJ2, and 15-deoxy- delta-12,14-PGJ2) was observed in cerebral IR, but upregulation of them when followed by Cop treatment. Similarly, we found the ratios of 14,15-dihydroxyeicosatrienoic acid(14,15-DHET)/arachidonic acid and 11,12-DHET/arachidonic acid was lower in cerebral IR injury relative to control, while their ratios were increased after Cop treatment. CONCLUSION: Our results indicated that Cop protect against cerebral IR injury, and its mechanism might be closely associated with antiinflammation and the regulation of arachidonic acid metabolism.


Assuntos
Ácido Araquidônico , Berberina , Infarto da Artéria Cerebral Média , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Fator de Necrose Tumoral alfa , Animais , Berberina/farmacologia , Berberina/análogos & derivados , Ácido Araquidônico/metabolismo , Masculino , Ratos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Fármacos Neuroprotetores/farmacologia , Interleucina-1beta/metabolismo , Modelos Animais de Doenças , Espectrometria de Massas em Tandem , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/prevenção & controle , Metabolômica/métodos , Ácidos Graxos/metabolismo
8.
FEBS J ; 291(13): 2918-2936, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38525648

RESUMO

In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species, Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed in Escherichia coli and self-activated in vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolytic activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed in E. coli, but failed to activate itself. To resolve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via ion-exchange chromatography. After the noncovalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolytic activity and could efficiently catalyze inter-molecular protein ligation and intramolecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.


Assuntos
Cisteína Endopeptidases , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/química , Engenharia de Proteínas/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Ligases/genética , Ligases/metabolismo , Ligases/química , Bambusa/genética , Bambusa/enzimologia , Mutagênese Sítio-Dirigida , Folhas de Planta/enzimologia , Folhas de Planta/genética , Sequência de Aminoácidos
9.
Diabetes Res Clin Pract ; 209: 111564, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336218

RESUMO

AIMS: To evaluate sustainability of peer support (PS) benefits in diabetes management. METHODS: Supporting a Peer Leader program through Community Health Centers (CHCs) included trainings and consultations from baseline to 12 months. Evaluation at baseline, 12-month, and 18-month follow-up included primary outcome, HbA1c, and other outcomes of SBP, DBP, LDLc, PHQ-8, diabetes distress, and EQ-5D. RESULTS: 1284 participants with type 2 diabetes mellitus were recruited from 9 CHCs. Mean (SD) for age = 68.00 (7.55) years, 43.07 % male, mean (SD) for diabetes duration = 11.79 (7.34) years. Across 18-months, linear mixed model analyses controlling for confounders found the least square mean (SE) of HbA1c improved significantly from 7.62 % (0.06 %) to 7.53 % (0.06 %) for all, and from 9.25 % (0.09 %) to 8.52 % (0.11 %) among those ≥8 % at baseline. Parallel improvements were found among all for SBP, DBP, PHQ-8, diabetes distress, and, among those elevated at baseline for all outcomes. EQ-5D showed significant but modest increase from baseline to 18 months. No significant reversals between 12 and 18 months were found except for LDLc. Supporting robustness of findings, patterns were similar across age, diabetes duration, and gender. CONCLUSIONS: Relative to the fundamentally progressive nature of diabetes, it is striking that improvements associated with PS were generally sustained after program support ended.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Humanos , Masculino , Idoso , Feminino , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Comportamentos Relacionados com a Saúde , Grupo Associado , Autocuidado
10.
Sci Rep ; 14(1): 4430, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396057

RESUMO

The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P < 0.05). GO functional analysis of DEGs indicated that abnormal ciliary function played a role in the development of CPAM. Subsequently, analysis of these genes pathways showed the TGF-ß signaling pathway was significantly enriched. Finally, the results of immunohistochemical analysis of some DEGs showed that a significant reduction in the expression of SMAD6, a gene related to the TGF-ß signaling pathway, led to abnormal activation of the pathway. TGF-ß signaling pathway involved in the evolution of the disease obtained by DEGs enrichment pathway analysis. SMAD6, a gene involved in this pathway, might be a potential biomarker for the diagnosis and treatment of CPAM.


Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão , Criança , Humanos , Pulmão/metabolismo , Epitélio/metabolismo , Biomarcadores/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
11.
Nat Med ; 30(2): 584-594, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177850

RESUMO

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Cegueira
13.
Cell Rep Med ; 4(10): 101213, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37788667

RESUMO

The increasing prevalence of diabetes, high avoidable morbidity and mortality due to diabetes and diabetic complications, and related substantial economic burden make diabetes a significant health challenge worldwide. A shortage of diabetes specialists, uneven distribution of medical resources, low adherence to medications, and improper self-management contribute to poor glycemic control in patients with diabetes. Recent advancements in digital health technologies, especially artificial intelligence (AI), provide a significant opportunity to achieve better efficiency in diabetes care, which may diminish the increase in diabetes-related health-care expenditures. Here, we review the recent progress in the application of AI in the management of diabetes and then discuss the opportunities and challenges of AI application in clinical practice. Furthermore, we explore the possibility of combining and expanding upon existing digital health technologies to develop an AI-assisted digital health-care ecosystem that includes the prevention and management of diabetes.


Assuntos
Inteligência Artificial , Diabetes Mellitus , Humanos , Diabetes Mellitus/terapia
14.
Molecules ; 28(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687175

RESUMO

Coptisine (Cop) exerts a neuroprotective effect on central nervous system disease, particularly ischemic stroke. However, its protective mechanism is still unclear. This study aimed to investigate the protective effect of Cop on cerebral ischemia-reperfusion (IR) rats with a middle cerebral artery occlusion model by integrating a gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach with biochemical assessment. Our results showed that Cop could improve neurobehavioral function and decrease the ischemia size in IR rats. In addition, Cop was found to decrease inflammatory mediators (e.g., prostaglandin D2 (PGD2) and tumor necrosis factor-α (TNF-α) and attenuate oxidative stress response (e.g., increase the superoxide dismutase (SOD) expression and decrease 8-iso-PGF2α level). Furthermore, the GC-MS-based cerebrospinal fluid (CSF) metabolomics analysis indicated that Cop influenced the level of glycine, 2,3,4-trihydroxybutyric acid, oleic acid, glycerol, and ribose during IR injury. Cop exhibited a good neuroprotective effect against cerebral IR injury and metabolic alterations, which might be mediated through its antioxidant and anti-inflammatory properties.


Assuntos
Ataque Isquêmico Transitório , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Ratos , Antioxidantes/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Metabolômica , Anti-Inflamatórios/farmacologia
15.
Transl Oncol ; 38: 101770, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37716259

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

16.
J Chem Phys ; 159(5)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37526163

RESUMO

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features, such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, DP-range correction, DP long range, graphics processing unit support for customized operators, model compression, non-von Neumann molecular dynamics, and improved usability, including documentation, compiled binary packages, graphical user interfaces, and application programming interfaces. This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, this article presents a comprehensive procedure for conducting molecular dynamics as a representative application, benchmarks the accuracy and efficiency of different models, and discusses ongoing developments.

17.
CPT Pharmacometrics Syst Pharmacol ; 12(9): 1358-1370, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37470295

RESUMO

Tanezumab is a monoclonal antibody against nerve growth factor (NGF). We investigated tanezumab pharmacokinetic (PK)-NGF relationships and predicted the extent of systemic free NGF suppression with target-mediated drug disposition (TMDD) modeling using data from three pivotal phase III interventional studies (NCT02697773, NCT02709486, and NCT02528188) in patients with osteoarthritis. Patients received tanezumab 2.5 mg or 5 mg every 8 weeks (q8w) subcutaneously. A TMDD model using a previously established population PK model was used to describe plasma tanezumab and serum total NGF concentration data, and simulations were performed to predict "unobserved" free NGF versus time profiles and dose-response relationships for free NGF. A total of 2992 patients had available data for plasma tanezumab or serum total NGF concentrations and were included in the analysis; 706 of these had data for both tanezumab and total NGF concentrations. The model generally performed well to predict observed total NGF concentrations up to ~24 weeks after each dose. Simulations suggested free NGF concentration would be suppressed by ~75% (median) near the peak of tanezumab concentration and by less than 5% (median) around the trough tanezumab concentration with a tanezumab 2.5 mg q8w regimen. Free NGF concentration was predicted to return to baseline level at ~8 weeks (95% prediction interval: 5-16 weeks) after the last tanezumab dose. This model adequately described plasma tanezumab and serum total NGF concentrations following s.c. administration of tanezumab 2.5 or 5 mg q8w, allowed prediction of relative change in systemic free NGF following s.c. administration of tanezumab.


Assuntos
Anticorpos Monoclonais , Fator de Crescimento Neural , Humanos , Anticorpos Monoclonais Humanizados , Resultado do Tratamento
18.
Chemosphere ; 338: 139539, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37474028

RESUMO

In this study, oxygen-doped graphitic carbon nitride (g-C3N4), named O-g-C3N4, was successfully fabricated and characterized, and its performance in activating peroxymonosulfate (PMS, HSO5-) for the removal of phenol, 2,4-dichlorophenol (2,4-DCP), bisphenol A (BPA), rhodamine B (RhB), reactive brilliant blue (RBB) and acid orange 7 (AO7) was evaluated. The catalytic performance of O-g-C3N4 for AO7 removal increased by 14 times compared to g-C3N4. In the presence of 0.2 g L-1 O-g-C3N4, 3.5 mM PMS at natural pH 5.8, 96.4% of AO7 could be removed in 60 min, reduced toxicity of the treated AO7 solution was obtained, and the mineralization efficiency was 47.2% within 120 min. Density functional theory (DFT) calculations showed that the charge distribution changed after oxygen doping, and PMS was more readily adsorbed by O-g-C3N4 with the adsorption energy (Eads) of -0.855 kcal/mol than that of the pristine g-C3N4 (Eads: -0.305 kcal/mol). Mechanism investigation implied that AO7 was primarily removed by the sulfate radicals (SO4•-) and hydroxyl radicals (•OH) on the surface of O-g-C3N4, but the role of singlet oxygen (1O2) to AO7 elimination was negligible. The results of cyclic experiments and catalyst characterization after reaction confirmed the favorable catalytic activity and structural stability of O-g-C3N4 particles. Furthermore, the O-g-C3N4/PMS system was very resistant to most of the environmental impacts, and AO7 removal was still acceptable in natural water environment. This study may provide an efficient metal-free carbonaceous activator with low dosage for PMS activation to remove recalcitrant organic pollutants (ROPs).


Assuntos
Grafite , Grafite/química , Oxigênio , Peróxidos/química , Metais
19.
Transl Behav Med ; 13(8): 519-532, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37406180

RESUMO

Although there is broad evidence for the value of peer support (PS) in preventing and managing diabetes and other chronic diseases, identifying approaches to stage, scale, and adapt PS interventions is a challenge. Community organization may provide a process for such adaptation of standardized PS and diabetes management to individual communities. This community organization approach was used to develop PS in 12 communities in Shanghai, China. Through a convergent mixed methods design, project records, semi-structured interviews, and an implementation assessment characterized processes of adaptation of standardized materials, examined the extent to which the program was implemented, and identified key success factors and challenges. Findings from both interviews and the implementation assessment indicated that communities adapted standardized intervention components to meet the needs of their communities and assumed responsibility for implementation of different components of the program based on their community's available capacity. Additionally, community innovations occurring as part of the project were reported and standardized for dissemination in future iterations of the program. Key success factors identified included cooperation and collaboration among varied partners within and across communities. Two challenges illustrate the resilience of the community organization model in response to COVID-19 and the need for further adaptation in rural communities. Community organization provided a useful approach to standardization, adaptation, innovation, and reporting of PS interventions for diabetes management.


Assuntos
COVID-19 , Diabetes Mellitus , Humanos , China , Diabetes Mellitus/prevenção & controle , Comportamento Social , Padrões de Referência
20.
J Colloid Interface Sci ; 649: 547-558, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37356156

RESUMO

Solar energy-driven photocatalytic decomposition of water to produce H2 is of great significance for promoting the development of clean energy. To improve the efficiency of H2 production, a novel spherical Co2P/Cd0.9Zn0.1S (Co2P/CZS) composite with shell-core structure was successfully synthesized by electrostatic attraction. Under visible light irradiation, the optimal Co2P/CZS achieves an excellent H2 rate of 16.05 mmol h-1 g-1 in benzyl alcohol (PhCH2OH) solution, with a quantum efficiency of 34.3% at 450 nm. The Co2P thin layer coated on the CZS surface not only facilitates the photogenerated charge transfer from Co2P to CZS under visible light illumination, but reduces the energy barrier of PhCH2OH oxidation and H2 evolution. The present results show that shell-core Co2P/CZS composite may be one of promising catalyst to enhance the activity of H2 evolution, which provides an important reference basis for new catalyst design and wide prospects for further application of metal sulfides.

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