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1.
Artigo em Inglês | MEDLINE | ID: mdl-38995710

RESUMO

Contrastive unsupervised representation learning (CURL) is a technique that seeks to learn feature sets from unlabeled data. It has found widespread and successful application in unsupervised feature learning, with the design of positive and negative pairs serving as the type of data samples. While CURL has seen empirical successes in recent years, there is still room for improvement in terms of the pair data generation process. This includes tasks such as combining and re-filtering samples, or implementing transformations among positive/negative pairs. We refer to this as the sample selection process. In this article, we introduce an optimized pair-data sample selection method for CURL. This method efficiently ensures that the two types of sampled data (similar pair and dissimilar pair) do not belong to the same class. We provide a theoretical analysis to demonstrate why our proposed method enhances learning performance by analyzing its error probability. Furthermore, we extend our proof into PAC-Bayes generalization to illustrate how our method tightens the bounds provided in previous literature. Our numerical experiments on text/image datasets show that our method achieves competitive accuracy with good generalization bounds.

2.
bioRxiv ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38746204

RESUMO

Dopamine in the nucleus accumbens ramps up as animals approach desired goals. These ramps have received intense scrutiny because they seem to violate long-held hypotheses on dopamine function. Furthermore, it has been proposed that they are driven by local acetylcholine release, i.e., that they are mechanistically separate from dopamine signals related to reward prediction errors. Here, we tested this hypothesis by simultaneously recording accumbal dopamine and acetylcholine signals in rats executing a task involving motivated approach. Contrary to recent reports, we found that dopamine ramps were not coincidental with changes in acetylcholine. Instead, we found that acetylcholine could be positively, negatively, or uncorrelated with dopamine depending on whether the task phase was determined by a salient cue, reward prediction error, or active approach, respectively. Our results suggest that accumbal dopamine and acetylcholine are largely independent but may combine to engage different postsynaptic mechanisms depending on the behavioral task states.

3.
Front Artif Intell ; 7: 1331853, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487743

RESUMO

The application of artificial intelligence technology in the medical field has become increasingly prevalent, yet there remains significant room for exploration in its deep implementation. Within the field of orthopedics, which integrates closely with AI due to its extensive data requirements, rotator cuff injuries are a commonly encountered condition in joint motion. One of the most severe complications following rotator cuff repair surgery is the recurrence of tears, which has a significant impact on both patients and healthcare professionals. To address this issue, we utilized the innovative EV-GCN algorithm to train a predictive model. We collected medical records of 1,631 patients who underwent rotator cuff repair surgery at a single center over a span of 5 years. In the end, our model successfully predicted postoperative re-tear before the surgery using 62 preoperative variables with an accuracy of 96.93%, and achieved an accuracy of 79.55% on an independent external dataset of 518 cases from other centers. This model outperforms human doctors in predicting outcomes with high accuracy. Through this methodology and research, our aim is to utilize preoperative prediction models to assist in making informed medical decisions during and after surgery, leading to improved treatment effectiveness. This research method and strategy can be applied to other medical fields, and the research findings can assist in making healthcare decisions.

4.
Ecotoxicol Environ Saf ; 275: 116252, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38547731

RESUMO

BACKGROUND: Phthalates are widely used plasticizers, which were identified as risk factors in the development of many human diseases. However, the effects of phthalates in the periodontitis are unknown. We aimed to investigated the relationship of periodontitis and phthalate exposure as well as the underlying mechanisms. MATERIALS AND METHODS: Univariate and multivariate logistic regressions were employed to evaluate the association between phthalate metabolites and periodontitis. The generalized additive model and piecewise logistic regression were conducted to investigate the dose-response relationship. Cell and animal models were used to explore the role and mechanism of DEHP in the development of periodontitis. Transcriptome sequencing, bioinformatics analysis, western blot, immunofluorescence and mice model of periodontitis were also employed. RESULTS: MEHP (OR 1.14, 95% CI 1.05-1.24), MCPP (OR 1.08, 95% CI 1.00-1.17), MEHHP (OR 1.18, 95% CI 1.08-1.29), MEOHP (OR 1.18, 95% CI 1.07-1.29), MiBP (OR 1.15, 95% CI 1.04-1.28), and MECPP (OR 1.20, 95% CI 1.09-1.32) were independent risk factors. And MEHHP, the metabolite of DEHP, showed the relative most important effects on periodontitis with the highest weight (0.34) among all risk factors assessed. And the increase of inflammation and the activation of NFκB pathway in the periodontitis model mice and cells were observed. CONCLUSION: Exposure to multiple phthalates was positively associated with periodontitis in US adults between 30 and 80 years old. And DEHP aggravated inflammation in periodontitis by activating NFκB pathway.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Periodontite , Ácidos Ftálicos , Adulto , Humanos , Animais , Camundongos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/análise , Dietilexilftalato/metabolismo , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/metabolismo , Periodontite/induzido quimicamente , Inflamação , Poluentes Ambientais/análise
5.
Int J Nanomedicine ; 19: 1055-1076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322754

RESUMO

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Colesterol/metabolismo , Carcinogênese , Transformação Celular Neoplásica , Proliferação de Células , Microambiente Tumoral
6.
J Proteome Res ; 23(1): 3-15, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38018860

RESUMO

The purpose of this study was to determine potential metabolic biomarkers and therapeutic drugs in the gingival tissue of individuals with periodontitis. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the gingival tissue samples from 20 patients with severe periodontitis and 20 healthy controls. Differential metabolites were identified using variable important in projection (VIP) values from the orthogonal partial least squares discrimination analysis (OPLS-DA) model and then verified for significance between groups using a two-tailed Student's t test. In total, 65 metabolites were enriched in 33 metabolic pathways, with 40 showing a significant increase and 25 expressing a significant decrease. In addition, it was found that patients with severe periodontitis have abnormalities in metabolic pathways, such as glucose metabolism, purine metabolism, amino acid metabolism, and so on. Furthermore, based on a multidimensional analysis, 12 different metabolites may be the potential biomarkers of severe periodontitis. The experiment's raw data have been uploaded to the MetaboLights database, and the project number is MTBLS8357. Moreover, osteogenesis differentiation characteristics were detected in the selected metabolites. The findings may provide a basis for the study of diagnostic biomarkers and therapeutic metabolites in severe periodontitis.


Assuntos
Metabolômica , Periodontite , Humanos , Metabolômica/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Biomarcadores
7.
Int Immunopharmacol ; 127: 111423, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38141410

RESUMO

AIM: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. METHODS: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. RESULTS: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. CONCLUSIONS: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.


Assuntos
Ferroptose , Periodontite , Camundongos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ligamento Periodontal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Simulação de Acoplamento Molecular , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/farmacologia , Osteogênese , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Periodontite/tratamento farmacológico , Periodontite/metabolismo , Células-Tronco/metabolismo , Ubiquitinas/metabolismo , Ubiquitinas/farmacologia
8.
J Alzheimers Dis ; 97(2): 909-926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38160355

RESUMO

BACKGROUND: Structural magnetic resonance imaging (sMRI) is vital for early Alzheimer's disease (AD) diagnosis, though confirming specific biomarkers remains challenging. Our proposed Multi-Scale Self-Attention Network (MUSAN) enhances classification of cognitively normal (CN) and AD individuals, distinguishing stable (sMCI) from progressive mild cognitive impairment (pMCI). OBJECTIVE: This study leverages AD structural atrophy properties to achieve precise AD classification, combining different scales of brain region features. The ultimate goal is an interpretable algorithm for this method. METHODS: The MUSAN takes whole-brain sMRI as input, enabling automatic extraction of brain region features and modeling of correlations between different scales of brain regions, and achieves personalized disease interpretation of brain regions. Furthermore, we also employed an occlusion sensitivity algorithm to localize and visualize brain regions sensitive to disease. RESULTS: Our method is applied to ADNI-1, ADNI-2, and ADNI-3, and achieves high performance on the classification of CN from AD with accuracy (0.93), specificity (0.82), sensitivity (0.96), and area under curve (AUC) (0.95), as well as notable performance on the distinguish of sMCI from pMCI with accuracy (0.85), specificity (0.84), sensitivity (0.74), and AUC (0.86). Our sensitivity masking algorithm identified key regions in distinguishing CN from AD: hippocampus, amygdala, and vermis. Moreover, cingulum, pallidum, and inferior frontal gyrus are crucial for sMCI and pMCI discrimination. These discoveries align with existing literature, confirming the dependability of our model in AD research. CONCLUSION: Our method provides an effective AD diagnostic and conversion prediction method. The occlusion sensitivity algorithm enhances deep learning interpretability, bolstering AD research reliability.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/patologia , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Algoritmos , Disfunção Cognitiva/diagnóstico
9.
J Proteome Res ; 23(1): 344-355, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38113133

RESUMO

Diabetes mellitus hinders the process of bone regeneration by inhibiting the function of mesenchymal stem cells (MSCs) through elevated glucose levels, thereby impeding osteointegration. The stem cell niche (SCN) plays a crucial role in determining the fate of stem cells by integrating various signals. However, the precise mechanism by which high glucose levels affect the SCN and subsequently influence the function of MSCs remains unclear. In this study, we employed proteomic analysis to identify proteins with altered expression in the extracellular matrix (ECM), aiming to elucidate the underlying mechanism. Three cell supernatants were collected from bone marrow mesenchymal stem cells (BMSCs) or BMSCs stimulated with high glucose (BMSCs+Hg). A total of 590 differentially expressed proteins were identified, which were found to be associated with the ECM, including aging, autophagy, and osteogenic differentiation. The findings of our study indicate that elevated glucose levels exert an influence on the molecular aspects of the SCN, potentially contributing to a better comprehension of the underlying mechanism.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Osteogênese/genética , Proteômica , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Células da Medula Óssea , Células Cultivadas
10.
Vet Sci ; 10(12)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38133240

RESUMO

Porcine circovirus type 3 (PCV3) is commonly associated with clinical symptoms such as porcine dermatitis and nephropathy syndrome (PDNS)-like lesions, respiratory signs, and reproductive disorders. This study aimed to investigate the epidemiology of PCV3 in a boar stud. The objectives were to detect PCV3 in semen, as well as matched serum, oral fluid, and preputial fluid samples from adult boars using quantitative polymerase chain reaction (qPCR), analyze PCV3-IgG antibody data, and genetically characterize a positive sample. A total of 112 samples from 28 boars were collected from a large-scale pig farm in Guangxi, China. The qPCR results showed that the PCV3 DNA was not detected in semen, with a positive rate of 0% (0/28), while it was detected in serum (3.57%-1/28), oral fluid (64.28%-18/28), and preputial fluid (46.4%-13/28). The seropositivity rate of PCV3-IgG in serum was 82.14% (23/28) according to the indirect enzyme-linked immunosorbent serologic assay (ELISA) results. Phylogenetic analysis revealed that one of the PCV3 isolates belonged to the PCV3c clades. This is the first report of PCV3 detection in preputial fluid from boars. The results suggest that PCV3 is transmitted among boars on pig farms and exhibits epidemic characteristics.

11.
Eur J Med Res ; 28(1): 481, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925501

RESUMO

BACKGROUND: Most sarcomatoid differentiated renal cell carcinoma was differentiated from Chromophobe renal cell carcinoma (KICH) and related to a bad prognosis. Thus, finding biomarkers is important for the therapy of KICH. METHODS: The UCSC was used for determining the expression of mRNA and miRNA and clinical data in KICH and normal samples. KEGG and GO were used for predicting potential function of differently expressed genes (DEGs). Optimal prognostic markers were determined by Lasso regression. Kaplan-Meier survival, ROC, and cox regression were used for assessing prognosis value. GSEA was used for predicting potential function of markers. The relations between markers and immune cell infiltration were determined by Pearson method. The upstream miRNA of markers was predicted in TargetScan and DIANA. RESULTS: The 6162 upregulated and 13,903 downregulated DEGs were identified in KICH. Further CENPE and LDHA were screened out as optimal prognostic risk signatures. CENPE was highly expressed while LDHA was lowly expressed in KICH samples, and the high expressions of 2 genes contributed to bad prognosis. The functions of CENPE and LDHA were mainly enriched in proliferation related pathways such as cell cycle and DNA replication. In addition, the correlation of 2 genes with immune infiltrates in KICH was also observed. Finally, we found that has-miR-577 was the common upstream of 2 genes and the binding sites can be predicted. CONCLUSION: CENPE and LDHA were identified as the important prognostic biomarkers in KICH, and they might be involved in the proliferation of cancer cell.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Ciclo Celular , Neoplasias Renais/genética , MicroRNAs/genética , Prognóstico
12.
J Mater Chem B ; 11(40): 9666-9675, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37779509

RESUMO

Non-specific adsorption of bioprobes based on surface-enhanced Raman spectroscopy (SERS) technology inevitably endows white blood cells (WBC) in the peripheral blood with Raman signals, which greatly interfere the identification accuracy of circulating tumor cells (CTCs). In this study, an innovative strategy was proposed to effectively identify CTCs by using SERS technology assisted by a receiver operating characteristic (ROC) curve. Firstly, a magnetic Fe3O4-Au complex SERS bioprobe was developed, which could effectively capture the triple negative breast cancer (TNBC) cells and endow the tumor cells with distinct SERS signals. Then, the ROC curve obtained based on the comparison of SERS intensity of TNBC cells and WBC was used to construct a tumor cell identification model. The merit of the model was that the detection sensitivity and specificity could be intelligently switched according to different identification purposes such as accurate diagnosis or preliminary screening of tumor cells. Finally, the difunctional recognition ability of the model for accurate diagnosis and preliminary screening of tumor cells was further validated by using the healthy human blood added with TNBC cells and blood samples of real tumor patients. This novel difunctional identification strategy provides a new perspective for identification of CTCs based on the SERS technology.


Assuntos
Técnicas Biossensoriais , Células Neoplásicas Circulantes , Neoplasias de Mama Triplo Negativas , Humanos , Células Neoplásicas Circulantes/patologia , Neoplasias de Mama Triplo Negativas/diagnóstico , Análise Espectral Raman/métodos , Prata/química
13.
bioRxiv ; 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37781610

RESUMO

The orbitofrontal cortex (OFC) and hippocampus (HC) are both implicated in forming the cognitive or task maps that support flexible behavior. Previously, we used the dopamine neurons as a sensor or tool to measure the functional effects of OFC lesions (Takahashi et al., 2011). We recorded midbrain dopamine neurons as rats performed an odor-based choice task, in which errors in the prediction of reward were induced by manipulating the number or timing of the expected rewards across blocks of trials. We found that OFC lesions ipsilateral to the recording electrodes caused prediction errors to be degraded consistent with a loss in the resolution of the task states, particularly under conditions where hidden information was critical to sharpening the predictions. Here we have repeated this experiment, along with computational modeling of the results, in rats with ipsilateral HC lesions. The results show HC also shapes the map of our task, however unlike OFC, which provides information local to the trial, the HC appears to be necessary for estimating the upper-level hidden states based on the information that is discontinuous or separated by longer timescales. The results contrast the respective roles of the OFC and HC in cognitive mapping and add to evidence that the dopamine neurons access a rich information set from distributed regions regarding the predictive structure of the environment, potentially enabling this powerful teaching signal to support complex learning and behavior.

14.
Hum Reprod ; 38(12): 2382-2390, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37801294

RESUMO

STUDY QUESTION: Can blastocyst aneuploidy be predicted for patients with previous aneuploid pregnancy loss (PAPL) and receiving preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: Multivariable logistic regression models were established to predict high risk of blastocyst aneuploidy using four identified factors, presenting good predictive performance. WHAT IS KNOWN ALREADY: Aneuploidy is the most common embryonic chromosomal abnormality leading to pregnancy loss. Several studies have demonstrated a higher embryo aneuploidy rate in patients with PAPL, which has suggested that PGT-A should have benefits in PAPL patients intending to improve their pregnancy outcomes. However, recent studies have failed to demonstrate the efficacy of PGT-A for PAPL patients. One possible way to improve the efficacy is to predict the risk of blastocyst aneuploidy risk in order to identify the specific PAPL population who may benefit from PGT-A. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter retrospective cohort study based on data analysis of 1119 patients receiving PGT-A in three reproductive medical centers of university affiliated teaching hospitals during January 2014 to June 2020. A cohort of 550 patients who had one to three PAPL(s) were included in the PAPL group. In addition, 569 patients with monogenic diseases without pregnancy loss were taken as the non-PAPL group. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGT-A was conducted using single nucleotide polymorphism microarrays and next-generation sequencing. Aneuploidy rates in Day 5 blastocysts of each patient were calculated and high-risk aneuploidy was defined as a rate of ≥50%. Candidate risk factors for high-risk aneuploidy were selected using the Akaike information criterion and were subsequently included in multivariable logistic regression models. Overall predictive accuracy was assessed using the confusion matrix, discrimination by area under the receiver operating characteristic curve (AUC), and calibration by plotting the predicted probabilities versus the observed probabilities. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst aneuploidy rates were 30 ± 25% and 21 ± 19% for PAPL and non-PAPL groups, respectively. Maternal age (odds ratio (OR) = 1.31, 95% CI 1.24-1.39, P < 0.001), number of PAPLs (OR = 1.40, 95% CI 1.05-1.86, P = 0.02), estradiol level on the ovulation trigger day (OR = 0.47, 95% CI 0.30-0.73, P < 0.001), and blastocyst formation rate (OR = 0.13, 95% CI 0.03-0.50, P = 0.003) were associated with high-risk of blastocyst aneuploidy. The predictive model based on the above four variables yielded AUCs of 0.80 using the training dataset and 0.83 using the test dataset, with average and maximal discrepancies of 2.89% and 12.76% for the training dataset, and 0.98% and 5.49% for the test dataset, respectively. LIMITATIONS, REASONS FOR CAUTION: Our conclusions might not be compatible with those having fewer than four biopsied blastocysts and diminished ovarian reserves, since all of the included patients had four or more biopsied blastocysts and had exhibited good ovarian reserves. WIDER IMPLICATIONS OF THE FINDINGS: The developed predictive model is critical for counseling PAPL patients before PGT-A by considering maternal age, number of PAPLs, estradiol levels on the ovulation trigger day, and the blastocyst formation rate. This prediction model achieves good risk stratification and so may be useful for identifying PAPL patients who may have higher risk of blastocyst aneuploidy and can therefore acquire better pregnancy outcomes by PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China under Grant (81871159). No competing interest existed in the study. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aborto Espontâneo , Diagnóstico Pré-Implantação , Gravidez , Humanos , Feminino , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Blastocisto/patologia , Testes Genéticos/métodos , Resultado da Gravidez , Aborto Espontâneo/genética , Aborto Espontâneo/patologia , Aneuploidia , Estradiol
15.
ACS Appl Mater Interfaces ; 15(38): 44773-44785, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37721368

RESUMO

Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol-disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo. These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Dissulfetos/química , Nanopartículas/química , Antineoplásicos/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Imageamento por Ressonância Magnética , Glutationa , Meios de Contraste/uso terapêutico
16.
Mol Clin Oncol ; 19(3): 74, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37614370

RESUMO

A 60-year-old male patient underwent laparoscopic radical cystectomy with bilateral pelvic lymph node dissection and urinary diversion as a treatment for muscle-invasive bladder cancer and was discharged two weeks later. One month later, the patient was readmitted with septic and haemorrhagic shock, and was diagnosed with right external iliac artery disruption. The patient underwent an exploratory operation and a vessel split of the right external iliac artery was found. The artery split was covered by a vascular stent. Klebsiella pneumoniae subsp. Pneumoniae was isolated in blood culture and the patient then received adequate antibiotics based on the drug sensitivity test. The patient eventually had a good recovery and was discharged five weeks later. In summary, although iliac artery injury after successful pelvic surgery is a rare event, this life-threatening complication should be taken into full consideration, particularly in patients with high-risk factors such as diabetes mellitus.

17.
Dose Response ; 21(3): 15593258231187348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424703

RESUMO

Objectives: To investigate the potential mechanisms of 125I seed implantation therapeutic treatment on inactivating the VEGFR2/PI3K/AKT pathway in cholangiocarcinoma. Methods: The human cholangiocarcinoma cell lines HCCC-9810 and HuCCT1 were purchased for in vitro studies. The BALB/c nude mice were obtained for in vivo studies. The proliferation of cells was detected by CCK-8, colony formation, and BrdU staining. The migration and invasion of cells were determined by wound healing assay and Transwell assay, respectively. Hematoxylin and eosin staining was utilized for histological evaluation. Protein expression was determined by western blotting and immunohistochemistry. Results: Compared with the control group, .6 mCi group and .8 mCi group inhibited cholangiocarcinoma cells proliferation, invasion, migration, and promoted apoptosis, the protein expression of p-VEGFR2, VEGFR2, PI3K, p-AKT/AKT, cyclin B1, cyclin A, CDK1, and Bcl-2 was decreased. Similar results were obtained from in vitro experiments. However, when VEGF is overexpressed, the inhibitory effect of .8 mCi was partially significantly reversed on cholangiocarcinoma cells. The in vivo studies further confirmed the inhibitory effects of .6 mCi group and .8 mCi group on cholangiocarcinoma. Conclusion: 125I seed irradiation could inhibit cholangiocarcinoma cells proliferation, migration, and invasion and promote apoptosis through inactivation of the VEGFR2/PI3K/AKT signaling pathway.

18.
ACS Biomater Sci Eng ; 9(8): 4720-4734, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37491189

RESUMO

Hyperglycemia in patients with diabetes affect osteoblast function, leading to abnormal bone metabolism and implant failure. Adequate bone volume surrounding an implant is essential for osseointegration, which can be improved by implant surface modifications. In this study, titanium surfaces were hydrothermally treated with a mixture of phytic acid (PA) and calcium hydroxide to produce a calcium-decorated surface. The control group comprised pure titanium with a sandblasted/acid-etched (SLA) surface. The elemental composition, hydrophilicity, surface roughness, and morphology of the titanium surfaces were examined. Evaluation of in vitro osteogenic differentiation ability in a high-glucose environment using alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence staining revealed that Ca-PA-modified SLA titanium surfaces can promote osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Evaluation of oxidative stress and aging using reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and ß-galactosidase staining revealed that Ca-PA-modified SLA titanium surfaces can reduce ROS production and ameliorate oxidative stress damage in hBMSCs. In vivo assessment of osteogenesis in a diabetic rat model revealed that Ca-PA coating promotes peri-implant osseointegration. Ca-PA-modified SLA titanium surface is a candidate for improving implant osseointegration in patients with diabetes.


Assuntos
Diabetes Mellitus , Osteogênese , Humanos , Ratos , Animais , Espécies Reativas de Oxigênio , Ácido Fítico/farmacologia , Titânio/farmacologia , Proliferação de Células , Senescência Celular , Osseointegração , Glucose
19.
World J Psychiatry ; 13(5): 191-202, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37303933

RESUMO

BACKGROUND: The teaching mode of fitness exercise prescriptions for college students in physical education conforms to the scientific principles and rules of fitness, which can adapt to the characteristics of students' individual physiological functions and stimulate their interest in learning. AIM: To analyze the effect of prescribed exercise teaching on the sports quality and mental health of college students. METHODS: The participants of the study were 240 students in our class of 2021, of which 142 were men and 98 were women. The 240 students were randomly divided into an experimental group using the exercise prescription teaching model and a control group using the conventional teaching model. The experimental and control groups were divided into four classes of 30 students each. The teaching activities of the two teaching mode groups were strictly controlled, and the same tests were used before and after the experiment to test the subjects' exercise quality (in-cluding standing long jump, 50 m race, 800 m race, sit-ups, sit-and-reach), physical form (including height, weight, Ketorolai index), cardiopulmonary function (including heart rate, blood pressure, spirometry, 12-min running distance, maximum oxygen intake) and mental health (SCL-90, including somatization, obsessive-compulsive, interpersonal, depression, anxiety, hostility, phobia, paranoia, psychotic symptoms) to understand the effects of the exercise prescription teaching mode on students' physical and mental health status. RESULTS: There were differences in the exercise scores of standing long jump, 50 m, 800 m/1000 m running, sit-ups, and sit-and-reach in the experimental group after the experiment compared with those before the experiment, and the above indices of the experimental group were different from those of the control group after the experiment (P < 0.05). There were differences in body weight and Ketorolai index in the experimental group after the experiment compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment (P < 0.05). After the experiment, there were differences in spirometry, 12-min running distance, and maximum oxygen intake in the experimental group compared to those before the experiment, and the indices of the experimental group were also different from those of the control group after the experiment (P < 0.05). After the experiment, the indicators of somatization, interpersonal sensitivity, depression, anxiety, and hostility in the experimental group were different from those in the pre-experimental group, and the indexes of the experimental group were also different from those of the control group after the experiment (P < 0.05). CONCLUSION: Exercise prescription teaching can mobilize college students' consciousness, enthusiasm, and initiative; expand personalities; enhance physical fitness and improve their mental health more than the conventional fitness exercise prescription teaching method.

20.
J Orthop Translat ; 40: 27-36, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37274179

RESUMO

Background: Pure magnesium-based ortho-implants have a number of advantages. However, vital parameters like degradation rate and biocompatibility still call for significant improvement. Methods: In this study, poly (1,3-trimethylene carbonate) (PTMC) and polydopamine (PDA) bilayer and micro arc oxidation composite coatings were prepared successively on magnesium surface by immersion method and microarc oxidation. Its corrosion resistance and biocompatibility were evaluated by in vitro corrosion tests, cellular compatibility experiments, and in vivo animal experiments. Results: In vitro experiments demonstrated that the composite coating provides excellent corrosion protection and biocompatibility. Animal studies demonstrated that the composite coating slowed the degradation of the implant and was not toxic to animal viscera. Conclusion: In conclusion, the inorganic-organic composite coating proposed in this study provided good corrosion resistance and enhanced biocompatibility for pure magnesium implants. The translational potential of this article: The translational potential of this article is to develop an anti-corrosion composite coating on a pure magnesium surface and to verify the viability of its use in animal models. It is hoped to open up a new approach to the design of new degradable orthopedic magnesium-based implants.

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