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1.
BMC Psychiatry ; 24(1): 357, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745124

RESUMO

BACKGROUND: Social anxiety among postoperative breast cancer patients is a prevalent concern, with its intensity fluctuating throughout the course of treatment. The study aims to describe the trajectory of social anxiety in postoperative breast cancer patients, explore the influencing factors, and provide theoretical support for the construction of future intervention programs. METHODS: This study was conducted from June 2022 to January 2023, encompassing 213 breast cancer patients from three first-class hospitals in China. Data collection occurred at four distinct time points. A growth mixture model was employed to identify latent categories representing the trajectories of social anxiety changes among patients. A multiple regression analysis was utilized to explore predictive factors associated with different latent trajectory categories. RESULTS: The trajectory of social anxiety changes in postoperative breast cancer patients includes five potential categories: maintaining mild social anxiety group, changing from mild to moderate social anxiety group, maintaining moderate social anxiety group, changing from moderate to severe social anxiety group, and maintaining severe social anxiety group. Cluster analysis results indicated three types: positive, negative, and low. Logistic regression analysis revealed that younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination were factors that influenced patients' social anxiety (P < 0.05). CONCLUSION: The trajectory of social anxiety in postoperative breast cancer patients comprises five potential categories. In clinical practice, it is essential to strengthen the management of high-risk populations susceptible to experiencing social anxiety emotions, including younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination.


Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Adulto , Mastectomia/psicologia , Período Pós-Operatório , China , Ansiedade/psicologia , Idoso
2.
J Sci Food Agric ; 104(11): 6809-6820, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38572795

RESUMO

BACKGROUND: The present study aimed to investigate the effects of tremella polysaccharides on the gel properties and antioxidant activity of yak skin gelatin with a view to improving the quality of collagen jellies. The preparation of composite gels were performed by yak skin gelatin (66.7 mg mL-1) and tremella polysaccharides with different concentrations (0, 2, 4, 6, 8 mg mL-1), and finally the collagen jelly was prepared by composite gel (yak skin gelatin: 66.7 mg mL-1; tremella polysaccharides:6 mg mL-1) with the best performance. RESULTS: Tremella polysaccharides not only improved the hardness, springiness, gel strength, water holding capacity and melting temperature of yak skin gelatin, but also enhanced the composite gel's scavenging activity against ABTS radicals, DPPH radicals, O2 and OH radicals. The filling of tremella polysaccharides into the gelatin network increased the number of crosslinking sites inside the gel, which resulted in the gel network structure becoming dense and orderly. The gel particles became finer and more uniform, and the thermal stability was improved. Furthermore, the sensory score of commercially available gelatin jelly decreased more rapidly during storage compared to the composite gel jelly. CONCLUSION: The gel properties and antioxidant activity of yak skin gelatin were improved by adding tremella polysaccharides, and then the quality and storage properties of the jelly were improved, which also provided technical reference for the development of functional gel food. © 2024 Society of Chemical Industry.


Assuntos
Antioxidantes , Colágeno , Gelatina , Géis , Polissacarídeos , Pele , Gelatina/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Bovinos , Géis/química , Pele/química , Pele/efeitos dos fármacos , Colágeno/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Basidiomycota/química , Humanos
3.
Adv Mater ; 36(9): e2308344, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37921116

RESUMO

Nanoscale vesicles such as synaptic vesicles play a pivotal role in efficient interneuronal communications in vivo. However, the coexistence of single vesicle and vesicle clusters in living cells increases the heterogeneity of vesicle populations, which largely complicates the quantitative analysis of the vesicles. The high spatiotemporal monitoring of vesicle assemblies is currently incompletely resolved. Here, this work uses synthetic vesicles and DNA nanorulers to reconstruct in vitro the vesicle assemblies that mimic vesicle clusters in living cells. DNA nanorulers program the lateral distance of vesicle assemblies from 3 to 10 nm. This work uses the carbon fiber nanoelectrode (CFNE) to amperometric monitor artificial vesicle assemblies with sub-10 nm interspaces, and obtain a larger proportion of complex events. This work resolves the heterogeneity of individual vesicle release kinetics in PC12 cells with the temporal resolution down to ≈0.1 ms. This work further analyzes the aggregation state of intracellular vesicles and the exocytosis of living cells with electrochemical vesicle cytometry. The results indicate that the exocytosis of vesicle clusters is critically dependent on the size of clusters. This technology has the potential as a tool to shed light on the heterogeneity analysis of vesicle populations.


Assuntos
Comunicação , DNA , Animais , Ratos , Cinética , Células PC12
4.
Cancer Imaging ; 23(1): 82, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667393

RESUMO

PURPOSE: This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients. METHOD: This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong's test. RESULTS: In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83-0.93), 0.90 (95% CI 0.85-0.94), and 0.88 (95% CI 0.83-0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P < 0.01). CONCLUSION: All three scorings had favorite diagnostic accuracy. While in conjunction with age and PSAD the prediction power was significantly improved, and the Model 2 that based on Scoring 2 yielded the highest performance.


Assuntos
Nomogramas , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética
5.
Medicine (Baltimore) ; 102(38): e34896, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37746946

RESUMO

BACKGROUND: To critically evaluate the effects of different nursing measures based on the concept of fast-track surgery (FTS) on the negative emotions of patients with breast cancer. METHODS: A systematic search of 8 databases, namely PubMed, Cochrane Library, Embase, Psycho info, China national knowledge infrastructure, Wanfang, China science and technology journal database, and China biomedical literature database, was performed to find randomized controlled trials from inception to April 2023. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. All analyses were performed with Review Manager 5.3. RESULTS: Ten studies were included in the systematic review, with a total of 830 patients (FTS group: 415; control group: 415). The results showed that different nursing measures based on the concept of FTS could significantly reduce anxiety (MD = -1.74, 95% confidence intervals [-2.41, -1.08], P < .00001) and depression (MD = -1.98, 95% confidence intervals [-2.44, -1.51], P < .00001) in patients after modified breast cancer surgery compared with the control group. CONCLUSIONS: Based on the concept of FTS, the nursing measures such as reducing preoperative fasting time, posture management, preventive analgesia, and early functional exercise can effectively reduce the anxiety and depression of patients during the perioperative period.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Emoções , Ansiedade/etiologia , Ansiedade/prevenção & controle , Exercício Físico , Transtornos de Ansiedade
6.
J Magn Reson Imaging ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37602942

RESUMO

BACKGROUND: Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence. PURPOSE: To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI). STUDY TYPE: Retrospective. POPULATION: Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution). FIELD STRENGTH/SEQUENCES: T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T. ASSESSMENT: The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter. STATISTICAL TESTS: Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant. RESULTS: The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752]). DATA CONCLUSION: TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 4.

7.
Medicine (Baltimore) ; 102(27): e33939, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37417622

RESUMO

BACKGROUND: To critically evaluate the effects of massage therapy on cancer pain. METHODS: Nine Chinese and English databases (PubMed, Cochrane Library, Embase, SCOPUS, Web of Science core, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, and VIP) were systematically searched from the inception of databases to November 2022 for randomized controlled trials. According to Cochrane Collaboration, 2 reviewers independently assessed the risk of bias and extracted data from the included studies. All analyses were performed with Review Manager 5.4. RESULTS: Thirteen randomized controlled trials were included in the meta-analysis, containing 1000 patients (498 in the massage therapy group and 502 in the control group). Massage therapy could significantly relieve cancer pain in patients (standardized mean difference = -1.16, 95% confidence interval [-1.39, -0.93], P < .00001), especially those in the perioperative period and those with hematological malignancies. Foot reflexology and hand acupressure had a moderate effect on cancer pain relief, with hand acupressure being more effective. Massage duration of 10 to 30 minutes and a program length of ≥1 week had a better effect and could significantly relieve pain. The occurrence of adverse events was reported in 4 of the 13 studies, all of which were no adverse events. CONCLUSIONS: Massage therapy can be used as a complementary alternative therapy to relieve cancer pain in patients with hematological malignancies, breast cancer, and cancers of the digestive system. It is suggested that chemotherapy patients use foot reflexology, and perioperative period patients use hand acupressure. A massage duration of 10 to 30 minutes and a program length of ≥1 week is recommended to achieve better effects.


Assuntos
Neoplasias da Mama , Dor do Câncer , Terapias Complementares , Neoplasias Hematológicas , Humanos , Feminino , Dor do Câncer/terapia , Massagem
8.
J Orthop Sports Phys Ther ; 53(6): 343­352, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36947532

RESUMO

OBJECTIVE: To determine the most effective exercise modalities for managing cancer-related fatigue during and after cancer treatment. DESIGN: Network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: Seven electronic databases were systematically searched from inception to January 2022. STUDY SELECTION CRITERIA: Randomized controlled trials testing the effects of exercise on relieving cancer-related fatigue in adult patients with cancer. DATA SYNTHESIS: An NMA of 56 studies was conducted, and the PRISMA-NMA guidelines were followed when reporting results. To determine the most effective interventions, the surface under the cumulative ranking curve (SUCRA) value was calculated for each exercise modality. RESULTS: Combined aerobic and resistance exercise (standardized mean difference [SMD], 1.57; credible interval [CrI], 1.03-2.10), yoga (SMD, 1.02; CrI: 0.44, 1.60), and regular physical activity (SMD, 1.07; CrI: 0.21, 1.92) could significantly alleviate cancer-related fatigue compared to control groups (usual care, wait-list, and regular physical activity). Combined aerobic and resistance exercise (SUCRA, 97.2%) had the highest probability of efficacy, followed by yoga (SUCRA, 75.5%) and regular physical activity (SUCRA, 74.1%). During cancer treatment, combined aerobic and resistance exercise (SUCRA, 94.5%) ranked first in efficacy, followed by regular physical activity (SUCRA, 82.1%) and yoga (SUCRA, 73.8%). After cancer treatment, only combined aerobic and resistance exercise (SMD, 0.99; CrI: 0.13, 1.84) had a significant effect on cancer-related fatigue. CONCLUSION: Combined aerobic and resistance exercise, yoga, and regular physical activity were the most effective exercise modalities for alleviating cancer-related fatigue. Combined aerobic and resistance exercise is recommended during and after cancer treatment. J Orthop Sports Phys Ther 2023;53(6):1-10. Epub: 23 March 2023. doi:10.2519/jospt.2023.11251.


Assuntos
Neoplasias , Yoga , Adulto , Humanos , Metanálise em Rede , Exercício Físico , Neoplasias/complicações , Neoplasias/terapia , Fadiga/etiologia , Fadiga/terapia
9.
Medicine (Baltimore) ; 102(12): e33239, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36961181

RESUMO

This literature on financial toxicity (FT) of breast cancer aimed to identify the leading countries, institutions, key researchers, influential references, top journals, research hotspots, and frontiers in the field. Published articles on FT in breast cancer patients were systematically retrieved and screened from the Web of Science databases from inception to March 28, 2022. The CiteSpace software was used to generate knowledge maps to analyze bibliometric characteristics in FT research on breast cancer patients. A total of 615 publications were included, with a year-on-year increase in the number of publications. A total of 591 authors conducted research on the FT in breast cancer patients, with Yabroff KR being the most prolific author. The US was the absolute leader in this field, with almost all major research institutions and authors located in the US. Supportive Care in Cancer was the most productive journal, and the Journal of Clinical Oncology was the most co-cited journal. The keywords representing the research hotspots were "quality of life," "care," "cost," etc. Keywords burst detection indicated that "financial toxicity," "survivors," "impact," "burden," "income," and "experience" have become the new research frontiers in the last 5 years. There is an overall upward trend in the research on FT of breast cancer over the last 30 years, which has important and ongoing research value. There is still a paucity of relevant research and more collaboration between authors, institutions, and countries is needed in the future to identify future research directions.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Bibliometria , Estresse Financeiro , Qualidade de Vida
10.
Toxicol Appl Pharmacol ; 467: 116479, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36963520

RESUMO

Drug-induced organ injury is one of the key factors causing organ failure and death in the global public. Triptolide (TP) is the main immunosuppressive component of Tripterygium wilfordii Hook. f. (Leigongteng, LGT) for the first-line management of autoimmune conditions, but it can cause serious multi-organ injury. Lysimachia christinae (Jinqiancao, JQC) is a detoxifying Chinese medicine and could suppress LGT's toxicity. It contains many immune enhancement and organ protection components including chlorogenic acid (CA), rutin (Rut), and quercetin (Que). This study aimed to explore the protection of combined treatments of these organ-protective ingredients of JQC on TP-induced liver, kidney, and heart injury and initially explore the mechanisms. Molecular docking showed that CA, Rut, and Que bounded protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-related molecules intimately and might competitively antagonize TP. Corresponding in vivo results showed that the combination activated TP-inhibited protein of AKT/mTOR pathway, and reversed TP-induced excessive ferroptosis (excessive Fe 2+ and lipid peroxidation malondialdehyde accumulation, decreased levels of antioxidant enzymes catalase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and superoxide dismutase, and down-regulated P62/nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway), and apoptosis (activated apoptotic factor Fas and Bax and inhibited Bcl-2) in the organ of mice to varying degrees. In conclusion, the combined treatments of CA, Rut, and Que from JQC inhibited TP-induced multi-organ injury in vivo, and the mechanism may largely involve immunomodulation and activation of the AKT/mTOR pathway-mediated cell death reduction including ferroptosis and apoptosis inhibition.


Assuntos
Diterpenos , Ferroptose , Fenantrenos , Camundongos , Animais , Quercetina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Clorogênico , Lysimachia , Rutina/farmacologia , Simulação de Acoplamento Molecular , Estresse Oxidativo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Diterpenos/toxicidade , Fenantrenos/toxicidade , Apoptose , Compostos de Epóxi/toxicidade
11.
Front Oncol ; 13: 1123141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824129

RESUMO

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

12.
Int J Med Sci ; 20(1): 114-124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619221

RESUMO

Background: Interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) promotes peritoneal angiogenesis by stimulating SP4-mediated vascular endothelial growth factor (VEGF) production in peritoneal dialysis (PD). Moreover, histone methyltransferase enhancer of zeste homologue 2 (EZH2) is involved in IL-6/sIL-6R signalling via the acceleration of vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanism underlying how EZH2 epigenetically activates VFGF expression in IL-6/sIL-6R signalling during PD is still unclear. Methods and Results: In this study, we measured the expression of EZH2, DNMT3B and SP4 in human peritoneal mesothelial cells (HPMCs) treated with IL-6/sIL-6R stimulation and/or EZH2 overexpression, silencing or inhibition. Methylation of the CpG site in the SP4 promoter region and VEGF production were measured under these treatments in HPMCs. Moreover, tube formation in human umbilical vein endothelial cells (HUVECs) was detected following treatment with conditioned media from these stimulated HPMCs. The 5/6 nephrectomy (5/6Nx) rat model was established, and the rats were injected with peritoneal dialysate. EZH2, DNMT3B and SP4 expression and microvessels were analysed in 5/6Nx + PD rats treated with IL-6/sIL-6R and EZH2 overexpression. The results showed that IL-6/sIL-6R and EZH2 overexpression enhanced the expression of EZH2, DNMT3B and SP4, but EZH2 silencing/inhibition reduced these expression levels. The results for VEGF production and tube formation in vitro followed the same trend. IL-6/sIL-6R and EZH2 overexpression increased the methylation percentage of the -170 bp CpG site in the SP4 promoter region in HPMCs. Moreover, IL-6/sIL-6R and EZH2 overexpression stimulated EZH2, DNMT3B and SP4 expression and promoted angiogenesis in 5/6Nx + PD rats. Conclusions: Thus, this study indicated that EZH2 is involved in IL-6/sIL-6R signalling and epigenetically regulates SP4 expression, thereby stimulating VEGF production and angiogenesis in PD. Targeting EZH2 is expected to be a novel therapeutic approach for end-stage renal disease (ESRD) patients with PD treatment.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Interleucina-6 , Diálise Peritoneal , Receptores de Interleucina-6 , Fator de Transcrição Sp4 , Animais , Humanos , Ratos , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células Endoteliais da Veia Umbilical Humana , Interleucina-6/metabolismo , Diálise Peritoneal/efeitos adversos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptores de Interleucina-6/metabolismo , Fator de Transcrição Sp4/metabolismo , Epigênese Genética
13.
Adv Sci (Weinh) ; 10(8): e2204866, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36683178

RESUMO

Acute myeloid leukemia (AML) is the most refractory hematologic malignancy characterized by acute onset, rapid progression, and high recurrence rate. Here, codelivery of BCL2 (ABT199) and MCL1 (TW37) inhibitors using phenylboronic acid-functionalized polypeptide nanovehicles to achieve synergetic and potent treatment of AML is adopted. Leveraging the dynamic boronic ester bonds, BN coordination, and π-π stacking, the nanovehicles reveal remarkably efficient and robust drug coencapsulation. ABT199 can induce a series of pro-apoptotic reactions by promoting the dissociation of the pro-apoptotic protein Bim from BCL2, while the released Bim is often captured by MCL1 protein overexpressed in AML. TW37 has a strong inhibitory ability to MCL1, thereby can restrain the depletion of Bim protein. Dual inhibitor-loaded nanoparticles (NPAT) reveal excellent stability, acid/enzyme/H2 O2 -triggered drug release, and significant cytotoxicity toward MOLM-13-Luc and MV-411 AML cells with low half maximal inhibitory concentrations of 1.15 and 7.45 ng mL-1 , respectively. In mice bearing MOLM-13-Luc or MV-411 AML cancer, NPAT reveal significant inhibition of tumor cell infiltration in bone marrow and main organs, potent suppression of tumor growth, and remarkably elevated mouse survival. With facile construction, varying drug combination, superior safety, synergetic efficacy, the phenylboronic acid-functionalized smart nanodrugs hold remarkable potential for AML treatment.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Camundongos , Animais , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Leucemia Mieloide Aguda/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico
14.
Adv Mater ; 35(10): e2209603, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36524741

RESUMO

Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.


Assuntos
Albuminas , Glutationa , Imageamento por Ressonância Magnética , Nanopartículas Metálicas , Sondas Moleculares , Neoplasias , Glutationa/administração & dosagem , Glutationa/farmacocinética , Glutationa/farmacologia , Sondas Moleculares/administração & dosagem , Sondas Moleculares/farmacocinética , Sondas Moleculares/farmacologia , Albuminas/administração & dosagem , Albuminas/farmacocinética , Albuminas/farmacologia , Imageamento por Ressonância Magnética/métodos , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Aumento da Imagem/métodos , Holografia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Nanopartículas Metálicas/administração & dosagem , Transferrina/administração & dosagem , Transferrina/farmacocinética , Transferrina/farmacologia , Distribuição Tecidual , Células A549 , Humanos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Cisplatino/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia
15.
Eur J Nucl Med Mol Imaging ; 50(3): 727-741, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36409317

RESUMO

PURPOSE: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI). METHODS: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS. RESULTS: In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05). CONCLUSION: Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.


Assuntos
Aprendizado Profundo , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Próstata/patologia
16.
J Nanobiotechnology ; 20(1): 532, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517801

RESUMO

The increasing prevalence of antibiotic resistance by Pseudomonas aeruginosa (PA) raises an urgent need for an effective vaccine. The outer membrane proteins of PA, especially those that are upregulated during infection, are ideal vaccine targets. However, the strong hydrophobicity of these proteins hinders their application for this purpose. In this study, we selected eight outer membrane proteins from PA with the most significantly upregulated expression. Their extracellular loops were analyzed and screened by using sera from patients who had recovered from PA infection. As a result, a novel immunogenic epitope (Ep167-193) from PilY1 (PA4554) was found. Moreover, we constructed a macrophage membrane-coated PLGA (poly lactic-co-glycolic acid) nanoparticle vaccine carrying PilY1 Ep167-193 (PNPs@M-Ep167-193) that elicits a Th2 immune response and confers adequate protection in mice. Our data furnished the promising vaccine candidate PNPs@M-Ep167-193 while providing additional evidence for structure-based epitope identification and vaccine design.


Assuntos
Nanopartículas , Infecções por Pseudomonas , Camundongos , Animais , Pseudomonas aeruginosa , Epitopos , Infecções por Pseudomonas/prevenção & controle , Macrófagos , Proteínas de Membrana
17.
Food Technol Biotechnol ; 60(3): 321-329, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36320354

RESUMO

Research background: Anthocyanins possess valuable health-promoting activities with significant health benefits for humans. However, their instability is a limiting factor for their usage in functional foods and beverages. Experimental approach: In this work, a new method to enhance the stability of anthocyanins from mulberry fruit through acylation by using succinic acid as a selected acyl donor was explored. The Box-Behnken design of response surface methodology was applied to determine the optimized conditions for the acylation process. Results and conclusions: The highest acylation conversion rate was 79.04% at anthocyanins to succinic acid mass ratio 1:8.96, acylation duration 3 h and temperature 50 °C. Structural analysis of acylated anthocyanins revealed that succinic acid introduces a C-O-C bond and a hydroxyl group. The thermostability and light stability of mulberry anthocyanins were significantly improved after acylation, and the antioxidant activity expressed as total reducing power and Fe2+-chelating capacity of the acylated anthocyanins was also enhanced. Novelty and scientific contribution: Succinic acid acylation provides a novel method for stabilizing mulberry anthocyanins, as evidenced by the increased stability and antioxidant ability of anthocyanins, and thus facilitates its use in the food and nutraceutical industries.

18.
Gen Hosp Psychiatry ; 79: 135-145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36375342

RESUMO

PURPOSE: This meta-analysis was to critically evaluate the effects of Internet-based cognitive behavioral therapy (ICBT) on the symptoms of anxiety and depression in cancer patients. METHODS: Eight Chinese and English databases (CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed, Embase, and PsycINFO) were systematically searched from the inception of databases to May 2022 for relevant randomized controlled trials (RCTs). According to the Cochrane Collaboration criteria, two reviewers independently assessed the risk of bias and extract data from included studies. All analyses were performed with Review Manager 5.4. RESULTS: Thirteen qualified studies were included in the meta-analysis, twelve of which reported the effect of ICBT on anxiety in 2079 cancer patients; thirteen of the studies reported the effect of ICBT on depression in 2179 patients. The meta-analysis indicated that ICBT was effective in improving anxiety [SMD = -0.37, 95%CI (-0.62, -0.12), P < 0.01, I2 = 86%] and depression [SMD = -0.27, 95%CI (-0.44, -0.09), P < 0.01, I2 = 72%] symptoms in cancer patients, especially those undergoing anti-cancer treatment. Therapist-guided ICBT was more effective than self-directed ICBT. ICBT lasting for ≤12 weeks could relieve anxiety and depressive symptoms of cancer patients. ICBT with number of modules ≥5 had a small effect on anxiety and depression relief while ICBT with number of modules <5 was found to be ineffective. CONCLUSIONS: ICBT lasting for ≤12 weeks, especially therapist-directed, helps relieve the anxiety and depressive symptoms of cancer patients. The ideal number of modules for ICBT and its long-term efficacy need to be validated by more studies of higher-quality.


Assuntos
Terapia Cognitivo-Comportamental , Neoplasias , Humanos , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Depressão/terapia , Depressão/psicologia , Internet , Neoplasias/complicações , Neoplasias/terapia , Resultado do Tratamento
19.
Front Med (Lausanne) ; 9: 949108, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186800

RESUMO

Aim: Nutrition is an important part of the care of patients with chronic kidney disease (CKD). However, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We carried out this study to find out whether a low-protein diet supplemented with ketoacids (LPD + KA) could improve muscle wasting in patients with CKD. Methods: Patients were enrolled in this non-blind, parallel-group, randomized trial assessing the nutritional status of CKD, randomly assigned to either the LPD + KA group or conventional LPD group. Blood samples such as Hemoglobin, Cystatin C, Creatinine, BUN, Albumin, Pre- Albumin, Glycerin Trilaurate, and Cholesterol were measured at baseline and every 3 months. The parameters of skeletal muscle and other body composition were assessed before and after dietary intervention for 12 months. Results: A total of 58 patients with CKD completed the study and were available for further analysis. The hemoglobin and albumin were observed to be markedly improved in the LPD + KA group during the follow-up as compared to baseline. Body mass index and total body water index of both groups were increased upon follow-up but the increase in the LPD + KA group was comparatively higher. Moreover, an increase in body fat%, skeletal muscle mass index, and appendicular skeletal muscle mass index was observed in both groups between baseline and follow-up, but it was statistically insignificant. Conclusion: This study did not find a significant improvement of KAs on muscle wasting, and a long time or more indices study may need to find the effects of the LPD + KA diets. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT02568020].

20.
Front Pediatr ; 10: 869415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911835

RESUMO

Background: Malnutrition is common in complex congenital heart disease (CCHD). The purpose of this study was to compare the safety and efficacy of early initiation of high-energy enteral nutrition (EN) with regular energy EN in infants after surgery for CCHD. Methods: This is a subgroup analysis of a randomized controlled trial (RCT) which was conducted in the cardiac intensive care unit (CICU) of the largest pediatric heart center in China. Eighty children with CCHD after surgery were from two groups, the intervention group (n = 40) was given high-energy EN and the control group (n = 40) was given regular energy EN. We analyzed the effects of the two interventions on outcomes such as caloric attainment rate, gastrointestinal intolerance, duration of mechanical ventilation, and anthropometry at discharge. Results: There was no difference in the daily milk intake between the two groups, but the calorie intake (50.2 vs. 33.4, P < 0.001), protein intake (1.1 vs. 0.9, P < 0.001) and caloric attainment rate were higher in the intervention group (77.5 vs. 45.0%, P = 0.003). In addition, the incidence of pneumonia (P = 0.003) and duration of mechanical ventilation (P = 0.008) were less in the intervention group, and biceps circumference and triceps skinfold thickness at hospital discharge were greater than those in the control group (P < 0.001). We have not found statistical differences in gastrointestinal intolerance, glycemic fluctuations, incidence of pressure ulcers, length of CICU stay and postoperative hospital days between the two groups. Conclusions: Early initiation of high-energy EN may be safe and effective in infants after complex cardiac surgery. Low doses high-energy EN did not increase gastrointestinal intolerance or glycemic fluctuations and also improved post-operative nutrition by increasing caloric and protein intake without increasing fluid intake.

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