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1.
BMC Psychiatry ; 24(1): 268, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594713

RESUMO

BACKGROUND: Access to high-quality mental healthcare remains challenging for people with psychosis globally, including China. Smartphone-based symptom monitoring has the potential to support scalable mental healthcare. However, no such tool, until now, has been developed and evaluated for people with psychosis in China. This study investigated the acceptability and the experience of using a symptom self-monitoring smartphone app (YouXin) specifically developed for people with psychosis in China. METHODS: Semi-structured interviews were conducted with 10 participants with psychosis to explore the acceptability of YouXin. Participants were recruited from the non-randomised feasibility study that tested the validity, feasibility, acceptability and safety of the YouXin app. Data analysis was guided by the theoretical framework of acceptability. RESULTS: Most participants felt the app was acceptable and easy to use, and no unbearable burdens or opportunity costs were reported. Participants found completing the self-monitoring app rewarding and experienced a sense of achievement. Privacy and data security were not major concerns for participants, largely due to trust in their treating hospital around data protection. Participants found the app easy to use and attributed this to the training provided at the beginning of the study. A few participants said they had built some form of relationship with the app and would miss the app when the study finished. CONCLUSIONS: The YouXin app is acceptable for symptom self-monitoring in people with experience of psychosis in China. Participants gained greater insights about their symptoms by using the YouXin app. As we only collected retrospective acceptability in this study, future studies are warranted to assess hypothetical acceptability before the commencement of study to provide a more comprehensive understanding of implementation.


Assuntos
Aplicativos Móveis , Transtornos Psicóticos , Humanos , Smartphone , Estudos Retrospectivos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/terapia , Pesquisa Qualitativa
2.
Signal Transduct Target Ther ; 9(1): 83, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570490

RESUMO

Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/patologia , Relevância Clínica , Inteligência Artificial , Perfilação da Expressão Gênica , Microambiente Tumoral/genética
3.
Front Public Health ; 12: 1148705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327578

RESUMO

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.


Assuntos
COVID-19 , Hanseníase , Humanos , Mycobacterium leprae/genética , Pandemias , DNA Bacteriano/genética , COVID-19/epidemiologia , Hanseníase/epidemiologia , Hanseníase/microbiologia , China/epidemiologia
5.
Digit Health ; 10: 20552076231222097, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188856

RESUMO

Background: Psychosis causes a significant burden globally, including in China, where limited mental health resources hinder access to care. Smartphone-based remote monitoring offers a promising solution. This study aimed to assess the validity, feasibility, acceptability, and safety of a symptom self-monitoring smartphone app, YouXin, for people with psychosis in China. Methods: A pre-registered non-randomised validity and feasibility study with a mixed-methods design. Participants with psychosis were recruited from a major tertiary psychiatric hospital in Beijing, China. Participants utilised the YouXin app to self-monitor psychosis and mood symptoms for four weeks. Feasibility outcomes were recruitment, retention and outcome measures completeness. Active symptom monitoring (ASM) validity was tested against corresponding clinical assessments (PANSS and CDS) using Spearman correlation. Ten participants completed qualitative interviews at study end to explore acceptability of the app and trial procedures. Results: Feasibility parameters were met. The target recruitment sample of 40 participants was met, with 82.5% completing outcome measures, 60% achieving acceptable ASM engagement (completing >33% of all prompts), and 33% recording sufficient passive monitoring data to extract mobility indicators. Five ASM domains (hallucinations, suspiciousness, guilt feelings, delusions, grandiosity) achieved moderate correlation with clinical assessment. Both quantitative and qualitative evaluation showed high acceptability of YouXin. Clinical measurements indicated no symptom and functional deterioration. No adverse events were reported, suggesting YouXin is safe to use in this clinical population. Conclusions: The trial feasibility, acceptability and safety parameters were met and a powered efficacy study is indicated. However, refinements are needed to improve ASM validity and increase passive monitoring data completeness.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38192142

RESUMO

BACKGROUND: Efficient targeted molecular therapeutics are needed for the treatment of triple-negative breast cancer (TNBC), a highly invasive and difficult-to-treat form of breast cancer associated with a poor prognosis. OBJECTIVES: This study aims to evaluate the potential of selective CDK4/6 inhibitors as a therapeutic option for TNBC by impairing the cell cycle G1 phase through the inhibition of retinoblastoma protein (Rb) phosphorylation. METHODS: In this study, we synthesized a compound called JHD205, derived from the chemical structure of Abemaciclib, and examined its inhibitory effects on the malignant characteristics of TNBC cells. RESULTS: Our results demonstrated that JHD205 exhibited superior tumor growth inhibition compared to Abemaciclib in breast cancer xenograft chicken embryo models. Western blot analysis revealed that JHD205 could dosedependently degrade CDK4 and CDK6 while also causing abnormal changes in other proteins associated with CDK4/6, such as p-Rb, Rb, and E2F1. Moreover, JHD205 induced apoptosis and DNA damage and inhibited DNA repair by upregulating Caspase3 and p-H2AX protein levels. CONCLUSION: Collectively, our findings suggest that JHD205 holds promise as a potential treatment for breast carcinoma.

7.
Food Chem ; 433: 137365, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37683462

RESUMO

This study aimed to investigate the effect of phosphorylation modification of collagen peptide on its calcium-binding capacity and pro-mineralization activity. In this study, collagen peptide (Leu-Thr-Phe, LTF) and phosphorylated LTF (P-LTF) were synthesized and further chelated with calcium ions. The results showed that phosphorylation of LTF significantly enhanced its calcium-binding capacity. Spectra analysis revealed that the calcium-binding sites of P-LTF were mainly carbonyl, carboxyl, and phosphate groups. Molecular docking further demonstrated that the phosphate group introduced by phosphorylation enhanced the calcium-binding capacity of LTF by ionic bonds and coordination bonds. The stability analysis results suggested that intestinal fluid could repair the peptide-calcium complex destroyed by gastric fluid. The cell experiment displayed that P-LTF-Ca significantly improved the mineralization activity of MC3T3-E1 cells, and the order of effective influence was P-LTF-Ca > LTF-Ca > P-LTF > LTF. This study provided the theoretical basis for the potential application of phosphorylation modification in improving bone health.


Assuntos
Cálcio , Osteoblastos , Animais , Bovinos , Cálcio/metabolismo , Fosforilação , Simulação de Acoplamento Molecular , Colágeno/química , Peptídeos/química , Cálcio da Dieta , Fosfatos/farmacologia
8.
ACS Omega ; 8(48): 46292-46299, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38075784

RESUMO

Due to their high toxicity and ongoing bioaccumulation, mercury ions (Hg2+) can cause significant harm to both the environment and human health. Therefore, rapid, accurate, and selective methods for Hg2+ detection are highly desirable. Herein, we present a simple method for depositing platinum nanoparticles (PtNPs) on graphene oxide (GO) to obtain graphene oxide-PtNPs (GO-PtNPs). The fabricated GO-PtNPs exhibit excellent peroxidase-like activity and high stability. Further, the GO-PtNPs nanozymes preferentially reduced Hg2+, thereby inhibiting the catalytic activity. By monitoring the color change in the chromogenic substrate, Hg2+ can be detected within 15 min. With a detection limit of 88.3 pM, the GO-PtNPs system may be employed to detect Hg2+ in a linear range of 0.1 nM to 10 µM. The simplicity and low cost of the proposed approach as well as its applicability to complicated samples demonstrate its capacity for mercury sensing in environmental samples.

9.
ACS Omega ; 8(49): 46346-46361, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38107919

RESUMO

A colorimetric sensor detects an analyte by utilizing the optical properties of the sensor unit, such as absorption or reflection, to generate a structural color that serves as the output signal to detect an analyte. Detecting the refractive index of an analyte by recording the color change of the sensor structure on its surface has several advantages, including simple operation, low cost, suitability for onsite analysis, and real-time detection. Colorimetric sensors have drawn much attention owing to their rapidity, simplicity, high sensitivity and selectivity. This Review discusses the use of colorimetric sensors in the food industry, including their applications for detecting food contaminants. The Review also provides insight into the scope of future research in this area.

10.
BMC Psychiatry ; 23(1): 820, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940908

RESUMO

BACKGROUND: There is a lack of epidemiological data on depressive morbidity in children and adolescents in rural China. This study determines the frequency and correlates of depression among children and adolescents to offer useful insights for family education and government policy-making in rural China. METHODS: A cross-sectional online survey was conducted between April 20 to May 10, 2022. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and the correlative factors of depression were analyzed. RESULTS: In this study, 23,180 children and adolescents were enrolled (median (range) age: 12 (9-18) years); of them, 8,261 (35.6%) suffered from depression with a CES-D score of > 15. The onset of depression was significantly related to age, grade, gender, parental absence, attending key schools or classes, presence of moderate or severe internet addiction (IA), school record, social relationships, parental occupation, and education status. Furthermore, female gender (OR = 1.175; 95% CI: 1.108-1.247; p < 0.001), junior middle school (OR = 1.487; 95% CI: 1.380-1.601; p < 0.001), parental absence (OR = 1.272; 95% CI: 1.183-1.367; p < 0.001), attending key schools (OR = 1.221; 95% CI: 1.120-1.332; p < 0.001), attending key classes (OR = 1.099; 95% CI: 1.001-1.207; p = 0.048), and presence of moderate or above IA (OR = 13.593; 95% CI: 12.028-15.361; p < 0.001) were the most prominent independent factors for depression. CONCLUSION: Depression is very common among Chinese children and adolescents living in poor areas of Weining County. Older age, higher school grade, female gender, parental absence, attending key schools or classes, and the presence of moderate to severe IA are some important factors that may dictate the occurrence of depression in these children and adolescents.


Assuntos
Depressão , População do Leste Asiático , Humanos , Criança , Feminino , Adolescente , Depressão/epidemiologia , Estudos Transversais , Inquéritos e Questionários , Pobreza , Instituições Acadêmicas
11.
RNA Biol ; 20(1): 859-874, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37882644

RESUMO

Circular RNAs (circRNAs) are novel noncoding RNAs with covalently closed-loop structures that can regulate eukaryotic gene expression. Due to their stable structure, circRNAs are widely distributed in the cytoplasm and have important biological functions, including as microRNA sponges, RNA-binding protein conjugates, transcription regulators, and translation templates. Breast cancer is among the most common malignant cancers diagnosed in women worldwide. Despite the development of comprehensive treatments, breast cancer still has high mortality rates. Recent studies have unmasked critical roles for circRNAs in breast cancer as regulators of tumour initiation, progression, and metastasis. Further, research has revealed that some circRNAs have the potential for use as diagnostic and prognostic biomarkers in clinical practice. Herein, we review the biogenesis and biological functions of circRNAs, as well as their roles in different breast cancer subtypes. Moreover, we provide a comprehensive summary of the clinical significance of circRNAs in breast cancer. CircRNAs are believed to be a hot focus in basic and clinical research of breast cancer, and innovative future research directions of circRNAs could be used as biomarkers, therapeutic targets, or novel drugs.Abbreviations: CeRNA: Competitive endogenous RNA; ciRNA: Circular intronic RNA; circRNA: Circular RNA; EIciRNA: Exon-intron circRNA; EMT: Epithelial-mesenchymal transition; IRES: Internal ribosome entry site; lncRNA: Long non-coding RNA; miRNA: MicroRNA; MRE: MiRNA response element; ncRNA: Non-coding RNA; RBP: RNA-binding protein; RNA-seq: RNA sequencing; RT-PCR: Reverse transcription-polymerase chain reaction.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , RNA Circular , Neoplasias da Mama/genética , Relevância Clínica , MicroRNAs/genética , Biomarcadores , Proteínas de Ligação a RNA/genética , Biologia
12.
Cancers (Basel) ; 15(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37835407

RESUMO

The transcriptional co-activator with PDZ binding motif (TAZ) is a key effector of the Hippo signaling pathway. We and others previously reported that high expression levels of TAZ are positively associated with decreased survival rates and shorter times to relapse in basal-like breast cancer (BLBC) patients. The oncogenic activity of TAZ involves the regulation of diverse signal transduction pathways that direct processes such as cell proliferation, migration, and resistance to apoptosis, albeit through poorly characterized gene expression programs. Here, using a tet-inducible system in mammary epithelial MCF10A cells, we have characterized the TAZ-regulated transcription program using RNA sequencing in a temporal and spatial manner. We further identified global TAZ binding sites at different TAZ activation time points by chromatin immunoprecipitation (ChIP) sequencing analysis. We found that the vast majority of TAZ was rapidly localized in enhancer regions at the early TAZ activation time point and then gradually spread to promoter regions. TAZ bound to enhancer regions following a switch in potential TEAD and FOSL2 transcription factor motifs. Furthermore, the ATAC sequencing analysis indicated that TAZ activation led to chromatin structural alterations. Together, our results have revealed the landscape of genome-wide TAZ binding sites and may lead to improvements in the current understanding of how TAZ regulates the gene expression program that contributes to the development of breast cancer.

13.
Int Immunopharmacol ; 122: 110564, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37451019

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological hyperactivation-related disease with a high mortality rate. The purpose of this study was to examine the relationship between complete blood count parameters and the occurrence of acute kidney injury (AKI) and mortality in patients with HLH. METHODS: We included 585 adult patients with HLH. Logistic regression models for AKI and 28-day mortality were developed. RESULTS: Multivariate logistic regression models revealed that hemoglobin (HB) ≤ 7.3 g/dl (adjusted OR, 1.651; 95% CI, 1.044-2.612), hemoglobin-to-red blood cell distribution width ratio (HRR) < 0.49 (adjusted OR, 1.692), neutrophil-to-lymphocyte ratio (NLR) ≥ 3.15 (adjusted OR, 1.697), and neutrophil-to-lymphocyte-platelet ratio (NLPR) ≥ 11.0 (adjusted OR, 1.608) were independent risk factors for the development of AKI. Moreover, lower platelet levels (31 × 109/L < platelets < 84 × 109/L, adjusted OR, 2.133; platelets ≤ 31 × 109/L, adjusted OR, 3.545) and higher red blood cell distribution width-to-platelet ratio (RPR) levels (0.20 < RPR < 0.54, adjusted OR, 2.595; RPR ≥ 0.54, adjusted OR, 4.307), lymphocytes ≤ 0.34 × 109/L (adjusted OR, 1.793), NLPR ≥ 11.0 (adjusted OR, 2.898), and the aggregate index of systemic inflammation (AISI) ≤ 7 (adjusted OR,1.778) were also independent risk factors for 28-day mortality. Furthermore, patients with AKI had a worse prognosis than those without AKI (P < 0.05). CONCLUSION: In patients with HLH, hematological parameters are of great value for the early identification of patients at high risk of AKI and 28-day mortality.


Assuntos
Injúria Renal Aguda , Linfo-Histiocitose Hemofagocítica , Humanos , Adulto , Estudos Retrospectivos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Plaquetas , Linfócitos , Prognóstico , Injúria Renal Aguda/etiologia
14.
Front Oncol ; 13: 1187495, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333808

RESUMO

Background: Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a new subtype listed by the 2016 World Health Organization (WHO) classification, which occurred in end-stage renal disease (ESRD) patients. This study will present the imaging characteristics of the four cases diagnosed with ACD-RCC. Ultrasound is expected to help detect abnormalities early in the follow-up of patients on regular dialysis, allowing patients to receive early treatment. Case presentation: We searched the pathology database of our hospital for all inpatients diagnosed with ACD-RCC between January 2016 and May 2022. Pathology, ultrasound, and radiology readings are performed by experienced physicians with the title of attending physician or higher. Four cases were included in this study, all of whom were male, aged from 17 to 59. Two cases suffered from ACD-RCC in both kidneys, and kidney nephrectomies were performed. One case underwent renal transplantation, whose creatinine was back to normal, and the rest were on hemodialysis. On the pathological images, heteromorphic cells and oxalate crystals can be seen. Both ultrasound and enhanced CT showed an enhancement of the solid component of the occupancy. We followed up with outpatient and telephone visits. Conclusion: In clinical work, ACD-RCC should be considered when the mass appears in the background of multiple cysts in the kidney in patients with ESRD. A timely diagnosis will help with treatment and prognosis.

15.
BMJ Open ; 13(6): e070130, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37263682

RESUMO

OBJECTIVE: To evaluate the current state of family doctor contract services (FDCS) in Beijing, identify the roles of family doctors who have worked with disabled older adults and investigate the barriers and facilitators faced by family doctors in providing care for them. DESIGN: A convergent mixed methods study was carried out from October 2020 to January 2021 to collect and analyse both quantitative and qualitative data. The integration strategies in this study were connecting the results of the quantitative phase to data collection of the qualitative phase. SETTING: A multi-stage sampling strategy was used to select 15 community health centres (CHCs) in four districts of Beijing. Of the four districts, two were from urban areas and two were from rural areas. PARTICIPANTS: The inclusion criteria for participants were (1) family doctors, (2) contracted with disabled older adults, (3) engaged in related work for disabled older adults more than 6 months. METHODS: A cluster sampling of 283 family doctors was used in the questionnaire. A purposive sample of 30 family doctors from the same CHCs was selected during the same period. Frequency and rank, rank-sum test, Kruskal-Wallis test were conducted in qualitative data analysis, the views of the interviewees were analysed through the thematic framework method. RESULTS: Currently, family doctors provided various services to satisfy the health needs of disabled older adults, while the usage of FDCS for disabled older adults is affected by many factors. The differences of the importance of family doctors' role (p<0.001) and service satisfaction (p=0.004) were significant among four districts. Compared with contracted health senior citizens, this study has identified five unique roles of family doctors, including 'psychological consultant', 'rehabilitation physiotherapist', 'health educator', 'health manager' and 'family health guardian'. Moreover, family doctors are confronted with a myriad of barriers (including high risks in the process of home visits, a lack of supervisory and incentive mechanisms, insufficiency of time and energy, etc) and facilitators (including establishing a doctor-patient trust relationship, developing humanistic care services, etc) in the FDCS for disabled older adults. CONCLUSIONS: Family doctors play a pivotal role in the FDCS for disabled older adults, while the effect and quality of FDCS in China needs to be improved. It is suggested that further research needs to focus on solving existing barriers of FDCS to optimise the health of disabled older adults and improve the quality of their lives.


Assuntos
Serviços Contratados , Médicos de Família , Humanos , Idoso , Pequim , China , Inquéritos e Questionários
16.
Food Chem ; 425: 136445, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37270885

RESUMO

Ochratoxin A (OTA) is a powerful mycotoxin present in a variety of food products, and its detection is important for human health. Here, a fluorescent aptasensor is reported for sensitive OTA determination. Specifically, the surface of bio-inspired passion fruit-like dendritic mesoporous silica nanospheres-enriched quantum dots (MSNQs-apt) was first modified with the OTA aptamer as the recognition unit and fluorescence emitter, while the aptamer-complementary DNA (MNPs-cDNA) was linked with the magnetic nanoparticles (MNPs) as the separation element. In the range of 2.56 pg/mL to 8 ng/mL, the proposed aptasensor exhibited satisfactory linearity and a detection limit of 1.402 pg/mL. The developed aptasensor achieved recoveries of 90.98-103.20% and 94.33-107.57 % in red wine and wheat flour samples, respectively. By simply replacing the aptamer, this aptasensor can be easily extended to detection of other analytes, suggesting its potential as a universal detection platform for mycotoxins in food products.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Micotoxinas , Nanosferas , Ocratoxinas , Passiflora , Pontos Quânticos , Humanos , Dióxido de Silício , Farinha , Triticum , Ocratoxinas/análise , Limite de Detecção
17.
Biochem Biophys Res Commun ; 667: 186-193, 2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37229827

RESUMO

The deubiquitinating enzyme USP14 has been established as a crucial regulator in various diseases, including tumors, neurodegenerative diseases, and metabolic diseases, through its ability to stabilize its substrate proteins. Our group has utilized proteomic techniques to identify new potential substrate proteins for USP14, however, the underlying signaling pathways regulated by USP14 remain largely unknown. Here, we demonstrate the key role of USP14 in both heme metabolism and tumor invasion by stabilizing the protein BACH1. The cellular oxidative stress response factor NRF2 regulates antioxidant protein expression through binding to the antioxidant response element (ARE). BACH1 can compete with NRF2 for ARE binding, leading to the inhibition of the expression of antioxidant genes, including HMOX-1. Activated NRF2 also inhibits the degradation of BACH1, promoting cancer cell invasion and metastasis. Our findings showed a positive correlation between USP14 expression and NRF2 expression in various cancer tissues from the TCGA database and normal tissues from the GTEx database. Furthermore, activated NRF2 was found to increase USP14 expression in ovarian cancer (OV) cells. The overexpression of USP14 was observed to inhibit HMOX1 expression, while USP14 knockdown had the opposite effect, suggesting a role for USP14 in regulating heme metabolism. The depletion of BACH1 or inhibition of heme oxygenase 1 (coded by HMOX-1) was also found to significantly impair USP14-dependent OV cell invasion. In conclusion, our results highlight the importance of the NRF2-USP14-BACH1 axis in regulating OV cell invasion and heme metabolism, providing evidence for its potential as a therapeutic target in related diseases.


Assuntos
Fator 2 Relacionado a NF-E2 , Neoplasias Ovarianas , Humanos , Feminino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Antioxidantes , Proteômica , Neoplasias Ovarianas/genética , Heme , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Ubiquitina Tiolesterase/genética
18.
J Cancer Res Clin Oncol ; 149(12): 9979-9990, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37256383

RESUMO

PURPOSE: Postmastectomy radiotherapy (PMRT) in patients with T1-2N1 breast cancer is still controversial. This study was to evaluate the survival prognosis of T1-2N1 patients with or without PMRT. PATIENTS AND METHODS: From January 2006 to May 2017, 2606 female breast cancer patients underwent mastectomy in our medical center, among whom 402 patients of T1-2N1 stage with or without PMRT were finally analyzed. The median follow-up duration was 59.5 months. The primary endpoint was overall survival (OS). The secondary endpoint was disease-free survival (DFS). RESULTS: In the study of our center, no statistically significant difference was observed between the T1-2N1 PMRT and non-PMRT subgroups for the 5-year OS (94.4% vs 95.4%, p = 0.667) and DFS (90.1% vs. 91.1%, p = 0.798). By the date of the last follow-up, 8.96% (n = 36) of the patients experienced any recurrence. Univariate analysis revealed that PMRT was not a prognostic factor for either OS (p = 0.667) or DFS (p = 0.798) in T1-2N1 patients. We then did a meta-analysis on the current treatment patterns, in which 2606 PMRT and 4281 non-PMRT T1-2N1 breast cancer patients with mastectomy were included. The meta-analysis showed that PMRT didn't improve the OS of the patients (HR = 0.85, p = 0.11), but patients with PMRT had better DFS than those in the non-PMRT group (HR = 0.62, p < 0.001). CONCLUSION: PMRT did not affect the survival of T1-2N1 breast cancer patients who underwent mastectomy, suggesting that radiotherapy may be safely omitted for them.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia
19.
J Agric Food Chem ; 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37017929

RESUMO

A novel milk-clotting enzyme isolated from Penicillium sp. ACCC 39790 (PsMCE) was prepared by heterologous expression. The recombinant PsMCE had an apparent molecular mass of 45 kDa and exhibited maximum casein hydrolysis activity at pH 4.0 and 50 °C. The PsMCE activity was enhanced by calcium ions and strongly inhibited by pepstatin A. Through hydrolysis pattern and cleavage site analyses, the milk-clotting activity of PsMCE was related to its specific hydrolysis between Phe105 and Met106 in the κ-casein proteins. The structural basis of PsMCE was characterized using homology modeling, molecular docking, and interactional analysis. The P1' region of PsMCE is critical for its selective binding to the hydrolytic site in κ-casein, and the hydrophobic forces play a decisive role in the specific cleavage of Phe105 and Met106. These interactional analyses between PsMCE and the ligand peptide clarified the fundamentals of its high milk-clotting index (MCI). PsMCE could be applied in cheese making due to its thermolability and high MCI value as a potential milk-clotting enzyme.

20.
Foods ; 12(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36900527

RESUMO

Selenium-enriched peptide (SP, selenopeptide) is an excellent organic selenium supplement that has attracted increasing attention due to its superior physiological effects. In this study, dextran-whey protein isolation-SP (DX-WPI-SP) microcapsules were fabricated via high-voltage electrospraying technology. The results of preparation process optimization showed that the optimized preparation process parameters were 6% DX (w/v), feeding rate Q = 1 mL/h, voltage U = 15 kV, and receiving distance H = 15 cm. When the content of WPI (w/v) was 4-8%, the average diameter of the as-prepared microcapsules was no more than 45 µm, and the loading rate for SP ranged from ~46% to ~37%. The DX-WPI-SP microcapsules displayed excellent antioxidant capacity. The thermal stability of the microencapsulated SP was improved, which was attributed to the protective effects of the wall materials for SP. The release performance was investigated to disclose the sustained-release capacity of the carrier under different pH values and an in-vitro-simulated digestion environment. The digested microcapsule solution showed negligible influence on the cellular cytotoxicity of Caco-2 cells. Overall, our work provides a facile strategy of electrospraying microcapsules for the functional encapsulation of SP and witnesses a broad prospect that the DX-WPI-SP microcapsules can exhibit great potential in the food processing field.

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