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2.
Risk Manag Healthc Policy ; 17: 1165-1176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737417

RESUMO

Objective: This study aimed to evaluate the impact of twin pregnancies with antiphospholipid antibody (aPL) positivity, a rare and complex clinical condition that remains a huge challenge for management. Methods: This study enrolled twin-pregnant women at our hospital between January 2018 and August 2023. Women with and without aPL positivity were selected using propensity score matching (PSM). Clinical features and pregnancy outcomes were compared between the two groups in the PSM cohort. To analyze the effect of aPL positivity on pregnancy outcomes, multivariate logistic models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Among the 773 women with twin pregnancies, aPL positivity was found in 26 women (3.36%). In the PSM cohort, there were 24 twin-pregnant women with positive aPL, and 48 women without aPL were selected as controls. Twin-pregnant women with aPL positivity had a higher proportion of abortion (8.33% vs 0, P = 0.043), preterm birth < 34 weeks (33.33% vs 8.33%, P = 0.007) and very low birthweight (<1500 g) (20.83% vs 4.17%, P = 0.016) than the control group. In addition, stillbirth of one fetus was observed in one twin-pregnant woman with positive aPL. Multivariate logistic regression analysis revealed that twin pregnancy with aPL positivity was associated with preterm birth < 34 weeks (aOR = 2.76, 95% CI: 0.83-4.70, P = 0.005), very low birthweight (<1500 g) (OR = 2.40, 95% CI: 0.18-4.67, P = 0.034) and small for gestational age (SGA) (aOR = 1.66, 95% CI: 0.22-3.10, P =0.024). Conclusion: Twin pregnancies with aPL positivity were correlated with obstetric complications, including abortion, preterm birth < 34 weeks and very low birthweight (<1500 g). The detection of aPL may be of clinical significance for women with twin pregnancies and should be considered in future studies.

3.
Mol Reprod Dev ; 91(4): e23742, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644727

RESUMO

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4-PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4-PBA restored hypoxia-induced trophoblast viability, inhibited HIF-1α protein expression, inflammation, and PERK/ATF-4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4-PBA decreased hypoxia-induced apoptosis in trophoblasts. The results of the JC-1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4-PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin-1, LC3II, and decreased p62 were seen in hypoxia-stimulated cells. These changes were reversed by 4-PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4-PBA on the viability, apoptosis, and autophagosome number of hypoxia-induced trophoblasts. In summary, 4-PBA reduces autophagy and apoptosis via the PERK/ATF-4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4-PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.


Assuntos
Fator 4 Ativador da Transcrição , Apoptose , Autofagia , Hipóxia Celular , Fenilbutiratos , Pré-Eclâmpsia , Fator de Transcrição CHOP , Trofoblastos , eIF-2 Quinase , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Trofoblastos/patologia , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/patologia , Autofagia/efeitos dos fármacos , Fator de Transcrição CHOP/metabolismo , Apoptose/efeitos dos fármacos , Gravidez , Fenilbutiratos/farmacologia , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Hipóxia Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Linhagem Celular
4.
Artigo em Inglês | MEDLINE | ID: mdl-38677471

RESUMO

PURPOSE: This study aims to elucidate the longitudinal alterations in frailty and health-related quality of life experienced by elderly patients undergoing surgical treatment for esophageal cancer. Additionally, it seeks to ascertain the impact of preoperative frailty on postoperative health-related quality of life over time. METHODS: 131 patients were included in the prospective study. Patients' frailty and health-related quality of life were assessed utilizing the Tilburg and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) at preoperative, 1 week, 1-month, and 3 months postoperatively. Statistical analyses were performed using generalized estimating equations (GEE), repeated-measures analysis of variance (ANOVA), and linear mixed models (LMMs). RESULTS: Out of 131 patients, 28.2% had frailty before surgery, and the prevalence of frailty consistently higher after surgery compared to baseline (67.9%, 51.9%, 39.7%). There was no significant change in frailty scores in preoperative frail patients within 3 months following surgery (P= .496, P< .999, P< .999); whereas in preoperative non-frail patients, the frailty scores increased at 1 week (P< .001) and then decreased at 1-month (P= .014), followed by no change at 3 months. In addition, preoperative frail patients had significantly worse global quality of life (QL) (ß=-4.24(-8.31; -.18), P= .041), physical functioning (ß=-9.87(-14.59; -5.16), P< .001), role functioning (ß=-10.04(-15.76; -4.33), P= .001) and social functioning (ß=-8.58(-15.49; -1.68), P= .015), compared to non-frail patients. CONCLUSIONS: A significant proportion of participants exhibited a high prevalence of preoperative frailty. These patients, who were preoperatively frail, exhibited a marked reduction in health-related quality of life, a more gradual recovery across various functional domains, and an increased symptom burden during the follow-up period. Therefore, it is crucial to meticulously identify and closely monitor patients with preoperative frailty for any changes in their postoperative physiology, role, and social functioning.

5.
Cell Signal ; 119: 111192, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685522

RESUMO

IRAK1 has been implicated in promoting development of various types of cancers and mediating radioresistance. However, its role in cervical cancer tumorigenesis and radioresistance, as well as the potential underlying mechanisms, remain poorly defined. In this study, we evaluated IRAK1 expression in radiotherapy-treated cervical cancer tissues and found that IRAK1 expression is negatively associated with the efficacy of radiotherapy. Consistently, ionizing radiation (IR)-treated HeLa and SiHa cervical cancer cells express a lower level of IRAK1 than control cells. Depletion of IRAK1 resulted in reduced activation of the NF-κB pathway, decreased cell viability, downregulated colony formation efficiency, cell cycle arrest, increased apoptosis, and impaired migration and invasion in IR-treated cervical cancer cells. Conversely, overexpressing IRAK1 mitigated the anti-cancer effects of IR in cervical cancer cells. Notably, treatment of IRAK1-overexpressing IR-treated HeLa and SiHa cells with the NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) partially counteracted the effects of excessive IRAK1. Furthermore, our study demonstrated that IRAK1 deficiency enhanced the anti-proliferative role of IR treatment in a xenograft mouse model. These collective observations highlight IRAK1's role in mitigating the anti-cancer effects of radiotherapy, partly through the activation of the NF-κB pathway. SUMMARY: IRAK1 enhances cervical cancer resistance to radiotherapy, with IR treatment reducing IRAK1 expression and increasing cancer cell vulnerability and apoptosis.


Assuntos
Apoptose , Quinases Associadas a Receptores de Interleucina-1 , NF-kappa B , Neoplasias do Colo do Útero , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Humanos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Feminino , Animais , NF-kappa B/metabolismo , Apoptose/efeitos da radiação , Camundongos , Células HeLa , Proliferação de Células , Camundongos Nus , Linhagem Celular Tumoral , Transdução de Sinais , Movimento Celular , Tolerância a Radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos da radiação , Radiação Ionizante
6.
Jpn J Clin Oncol ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521965

RESUMO

Tumor-infiltrating lymphocytes are a general term for lymphocytes or immune cells infiltrating the tumor microenvironment. Numerous studies have demonstrated tumor-infiltrating lymphocytes to be robust prognostic and predictive biomarkers in breast cancer. Recently, immune checkpoint inhibitors, which directly target tumor-infiltrating lymphocytes, have become part of standard of care treatment for triple-negative breast cancer. Surprisingly, tumor-infiltrating lymphocytes quantified by conventional methods do not predict response to immune checkpoint inhibitors, which highlights the heterogeneity of tumor-infiltrating lymphocytes and the complexity of the immune network in the tumor microenvironment. Tumor-infiltrating lymphocytes are composed of diverse immune cell populations, including cytotoxic CD8-positive T lymphocytes, B cells and myeloid cells. Traditionally, tumor-infiltrating lymphocytes in tumor stroma have been evaluated by histology. However, the standardization of this approach is limited, necessitating the use of various novel technologies to elucidate the heterogeneity in the tumor microenvironment. This review outlines the evaluation methods for tumor-infiltrating lymphocytes from conventional pathological approaches that evaluate intratumoral and stromal tumor-infiltrating lymphocytes such as immunohistochemistry, to the more recent advancements in computer tissue imaging using artificial intelligence, flow cytometry sorting and multi-omics analyses using high-throughput assays to estimate tumor-infiltrating lymphocytes from bulk tumor using immune signatures or deconvolution tools. We also discuss higher resolution technologies that enable the analysis of tumor-infiltrating lymphocytes heterogeneity such as single-cell analysis and spatial transcriptomics. As we approach the era of personalized medicine, it is important for clinicians to understand these technologies.

7.
Int J Surg ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498357

RESUMO

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has emerged as a pivotal surgical intervention for the treatment of prostate cancer. However, the complexity of clinical cases, heterogeneity of prostate cancer, and limitations in physician expertise pose challenges to rational decision-making in RARP. To address these challenges, we aimed to organize the knowledge of previously complex cohorts and establish an online platform named the RARP Knowledge Base (RARPKB) to provide reference evidence for personalized treatment plans. MATERIALS AND METHODS: PubMed searches over the past two decades were conducted to identify publications describing RARP. We collected, classified, and structured surgical details, patient information, surgical data, and various statistical results from the literature. A knowledge-guided decision-support tool was established using MySQL, DataTable, ECharts, and JavaScript. ChatGPT-4 and two assessment scales were used to validate and compare the platform. RESULTS: The platform comprised 583 studies, 1589 cohorts, 1 911 968 patients, and 11 986 records, resulting in 54 834 data entries. The knowledge-guided decision support tool provide personalized surgical plan recommendations and potential complications on the basis of patients' baseline and surgical information. Compared with ChatGPT-4, RARPKB outperformed in authenticity (100% versus [vs.] 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), matching of patients (100% vs. 0%), and personalized recommendations for complications (100% vs. 20%). Post-use, the average System Usability Scale score was 88.88±15.03, and the Net Promoter Score of RARPKB was 85. The knowledge base is available at http://rarpkb.bioinf.org.cn. CONCLUSIONS: We introduced the pioneering RARPKB, the first knowledge base for robot-assisted surgery, with an emphasis on prostate cancer. RARPKB can assist in personalized and complex surgical planning for prostate cancer to improve its efficacy. RARPKB provides a reference for the future applications of artificial intelligence in clinical practice.

8.
Plant Physiol Biochem ; 209: 108525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518396

RESUMO

Members of the CEP (C-terminally Encoded Peptide) gene family have been shown to be involved in various developmental processes and stress responses in plants. In order to understand the roles of CEP peptides in stress response, a comprehensive bioinformatics approach was employed to identify NtCEP genes in tobacco (Nicotiana tabacum L.) and to analyze their potential roles in stress responses. Totally 21 NtCEP proteins were identified and categorized into two subgroups based on their CEP domains. Expression changes of the NtCEP genes in response to various abiotic stresses were analyzed via qRT-PCR and the results showed that a number of NtCEPs were significant up-regulated under drought, salinity, or temperature stress conditions. Furthermore, application of synthesized peptides derived from NtCEP5, NtCEP13, NtCEP14, and NtCEP17 enhanced plant tolerance to different salt stress treatments. NtCEP5, NtCEP9 and NtCEP14, and NtCEP17 peptides were able to promote osmotic tolerance of tobacco plants. The results from this study suggest that NtCEP peptides may serve as important signaling molecules in tobacco's response to abiotic stresses.


Assuntos
Nicotiana , Proteínas de Plantas , Nicotiana/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Estresse Salino , Peptídeos/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Filogenia
9.
Am J Cancer Res ; 14(1): 227-242, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323277

RESUMO

Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) is regulated by the mTOR (mammalian target of rapamycin) signaling pathway. Phosphorylated EIF4EBP1 protein leads to pathway activation and correlates with aggressive breast cancer features. However, the clinical relevance of EIF4EBP1 gene expression as a prognostic biomarker in bulk breast tumors is not understood. In this study, EIF4EBP1 expression was analyzed in over 5000 breast cancers from three large independent cohorts, TCGA, METABRIC, and SCAN-B (GSE96058), and expression was dichotomized into low and high groups by the median. We also performed gene set enrichment analysis (GSEA) and cell cybersorting via the xCell algorithm to investigate EIF4EBP1 biology and expression patterns within the tumor microenvironment (TME). We additionally confirmed EIF4EBP1 expression location in the TME via single cell RNA sequencing. EIF4EBP1 expression was highest in both triple negative and high-grade tumors (both P<0.001), and tumor mutational burden scores were highest in the high EIF4EBP1-expression groups (all P<0.001). High EIF4EBP1 expression significantly correlated to worse overall survival in all three cohorts (hazard ratios (HR) 1.4-1.9), and worse distant relapse-free survival in patients treated with neoadjuvant taxane-anthracycline chemotherapy (HR 2.4). GSEA demonstrated enriched mTOR and cell proliferation-related gene sets, including, MYC, G2M checkpoint, and E2F targets across all three bulk tumor and single cell RNA sequencing cohorts. Phenotypically, these pathways were reflected by increased Ki67 gene expression and signaling via pharmacologically-activated mTOR gene sets in EIF4EBP1 high-expressing tumors (all P<0.001). EIF4EBP1 expression was increased in whole breast tumors compared to normal breast tissue (P<0.001), and was expressed predominantly in cancer epithelial cells, particularly in basal epithelial cell subclasses. EIF4EBP1 expression did not correlate to a consistent immune system phenotype across all three cohorts. Overall, these findings support that high EIF4EBP1 gene expression in bulk breast tumors could represent a poor prognostic marker via mTOR signaling pathways activation and upregulation of cell cycling, ultimately leading to increased tumorigenesis.

10.
BMC Med Educ ; 24(1): 143, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355517

RESUMO

BACKGROUND: Large language models like ChatGPT have revolutionized the field of natural language processing with their capability to comprehend and generate textual content, showing great potential to play a role in medical education. This study aimed to quantitatively evaluate and comprehensively analysis the performance of ChatGPT on three types of national medical examinations in China, including National Medical Licensing Examination (NMLE), National Pharmacist Licensing Examination (NPLE), and National Nurse Licensing Examination (NNLE). METHODS: We collected questions from Chinese NMLE, NPLE and NNLE from year 2017 to 2021. In NMLE and NPLE, each exam consists of 4 units, while in NNLE, each exam consists of 2 units. The questions with figures, tables or chemical structure were manually identified and excluded by clinician. We applied direct instruction strategy via multiple prompts to force ChatGPT to generate the clear answer with the capability to distinguish between single-choice and multiple-choice questions. RESULTS: ChatGPT failed to pass the accuracy threshold of 0.6 in any of the three types of examinations over the five years. Specifically, in the NMLE, the highest recorded accuracy was 0.5467, which was attained in both 2018 and 2021. In the NPLE, the highest accuracy was 0.5599 in 2017. In the NNLE, the most impressive result was shown in 2017, with an accuracy of 0.5897, which is also the highest accuracy in our entire evaluation. ChatGPT's performance showed no significant difference in different units, but significant difference in different question types. ChatGPT performed well in a range of subject areas, including clinical epidemiology, human parasitology, and dermatology, as well as in various medical topics such as molecules, health management and prevention, diagnosis and screening. CONCLUSIONS: These results indicate ChatGPT failed the NMLE, NPLE and NNLE in China, spanning from year 2017 to 2021. but show great potential of large language models in medical education. In the future high-quality medical data will be required to improve the performance.


Assuntos
Inteligência Artificial , Avaliação Educacional , Licenciamento , China , Confiabilidade dos Dados , Educação em Enfermagem , Educação em Farmácia , Educação Médica
11.
J Surg Res ; 296: 106-114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38271794

RESUMO

INTRODUCTION: The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. METHODS: Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. RESULTS: A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. CONCLUSIONS: NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfócitos T CD4-Positivos , Microambiente Tumoral , Prognóstico
12.
Aging (Albany NY) ; 16(2): 1663-1684, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38265972

RESUMO

BACKGROUND: Usenamine A (C18H17NO6) is a newly developed, natural anticancer drug that reportedly exerts low toxicity. The therapeutic efficacy and underlying mechanisms of usenamine A in lung adenocarcinoma (LUAD) remain poorly understood. We aimed to explore the therapeutic effects and molecular mechanisms through which usenamine A inhibits LUAD tumorigenesis. METHODS: We used LUAD cell lines H1299 and A549 in the present study. CCK-8 and colony formation assays were performed to analyze cell proliferation. Cell migration, invasion, and apoptosis were evaluated using wound-healing, transwell, and flow cytometric assays, respectively. Levels of reactive oxygen species were measured using a DCFH-DA probe. Inflammatory factors (lactate dehydrogenase, interleukin [IL]-1ß, and IL-18) were detected using enzyme-linked immunosorbent assays. Western blotting was performed to determine the expression of NOD-like receptor pyrin 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway-related proteins. Pyroptosis was detected using transmission electron microscopy. The interaction and co-localization of DDX3X and sequestosome 1 (SQSTM1) were identified using co-immunoprecipitation and immunofluorescence assays, respectively. For in vivo assessment, we established a xenograft model to validate the usenamine A-mediated effects and mechanisms of action in LUAD. RESULTS: Usenamine A inhibited the proliferation, migration, and invasion of LUAD cells. Furthermore, usenamine A induced NLRP3/caspase-1/GSDMD-mediated pyroptosis in LUAD cells. Usenamine A upregulated DDX3X expression to trigger pyroptosis. DDX3X interacted with SQSTM1, which is responsible for inducing pyroptosis. In vivo, usenamine A suppressed LUAD tumorigenesis by triggering NLRP3/caspase-1/GSDMD-mediated pyroptosis via the upregulation of the DDX3X/SQSTM1 axis. CONCLUSIONS: Usenamine A was found to induce NLRP3/caspase-1/GSDMD-mediated pyroptosis in LUAD by upregulating the DDX3X/SQSTM1 axis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Carcinogênese , Caspase 1 , Transformação Celular Neoplásica , RNA Helicases DEAD-box/genética , Gasderminas , Neoplasias Pulmonares/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas de Ligação a Fosfato , Pirina , Piroptose , Proteína Sequestossoma-1 , Animais
13.
Int J Mol Sci ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279327

RESUMO

As the final stage of leaf development, leaf senescence is affected by a variety of internal and external signals including age and environmental stresses. Although significant progress has been made in elucidating the mechanisms of age-dependent leaf senescence, it is not clear how stress conditions induce a similar process. Here, we report the roles of a stress-responsive and senescence-induced gene, ERD7 (EARLY RESPONSIVE TO DEHYDRATION 7), in regulating both age-dependent and stress-induced leaf senescence in Arabidopsis. The results showed that the leaves of erd7 mutant exhibited a significant delay in both age-dependent and stress-induced senescence, while transgenic plants overexpressing the gene exhibited an obvious accelerated leaf senescence. Furthermore, based on the results of LC-MS/MS and PRM quantitative analyses, we selected two phosphorylation sites, Thr-225 and Ser-262, which have a higher abundance during senescence, and demonstrated that they play a key role in the function of ERD7 in regulating senescence. Transgenic plants overexpressing the phospho-mimetic mutant of the activation segment residues ERD7T225D and ERD7T262D exhibited a significantly early senescence, while the inactivation segment ERD7T225A and ERD7T262A displayed a delayed senescence. Moreover, we found that ERD7 regulates ROS accumulation by enhancing the expression of AtrbohD and AtrbohF, which is dependent on the critical residues, i.e., Thr-225 and Ser-262. Our findings suggest that ERD7 is a positive regulator of senescence, which might function as a crosstalk hub between age-dependent and stress-induced leaf senescence.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Peróxido de Hidrogênio , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Cromatografia Líquida , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Fosforilação , Folhas de Planta/metabolismo , Senescência Vegetal , Plantas Geneticamente Modificadas/metabolismo , Espectrometria de Massas em Tandem
14.
Plant Cell ; 36(3): 709-726, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38000892

RESUMO

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.


Assuntos
Celulase , Solanum lycopersicum , Frutas/metabolismo , Solanum lycopersicum/genética , Celulase/genética , Celulase/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pectinas/metabolismo , Parede Celular/metabolismo
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123709, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38043293

RESUMO

Using p-aminophenol and dithioacetamide as precursors, green luminescent nitrogen (N) and sulfur (S) co-doped carbon dots (N, S-CDs) are prepared by hydrothermal method with the quantum yield (QY) of 7.1 %. Superior properties of the N, S-CDs including high photostability, outstanding biocompatibility, and desirable biological penetration were found, which could realize the monitor of 4-nitrophenol (4-NP) and pH. The N, S-CDs can be designed as a fluorescent probe for sensitive detection of 4-NP in water samples with linear ranges of 0-85 µM and a detection limit of 0.037 µM. Moreover, the fluorescence intensity of N, S-CDs is sensitive to pH and shows a linear relationship with pH values ranging from 3.50 to 7.25 and 7.25-12.00, accompanied with a significant color variation of the N, S-CDs solution from colorless to brown. Finally, the proposed N, S-CDs have also been applied to monitor the 4-NP in oocysts due to its low cytotoxicity, providing a great capacity for various targets molecules detection.


Assuntos
Carbono , Pontos Quânticos , Carbono/química , Pontos Quânticos/química , Diagnóstico por Imagem , Luminescência , Concentração de Íons de Hidrogênio , Nitrogênio/química , Corantes Fluorescentes/química
16.
Front Cardiovasc Med ; 10: 1250340, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965091

RESUMO

Myocardial infarction (MI) is a prevalent cardiovascular disease characterized by myocardial necrosis resulting from coronary artery ischemia and hypoxia, which can lead to severe complications such as arrhythmia, cardiac rupture, heart failure, and sudden death. Despite being a research hotspot, the etiological mechanism of MI remains unclear. The emergence and widespread use of omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and other omics, have provided new opportunities for exploring the molecular mechanism of MI and identifying a large number of disease biomarkers. However, a single-omics approach has limitations in understanding the complex biological pathways of diseases. The multi-omics approach can reveal the interaction network among molecules at various levels and overcome the limitations of the single-omics approaches. This review focuses on the omics studies of MI, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and other omics. The exploration extended into the domain of multi-omics integrative analysis, accompanied by a compilation of diverse online resources, databases, and tools conducive to these investigations. Additionally, we discussed the role and prospects of multi-omics approaches in personalized medicine, highlighting the potential for improving diagnosis, treatment, and prognosis of MI.

17.
Sci Rep ; 13(1): 19409, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938596

RESUMO

This study aimed to assess the feasibility of using magnetic resonance imaging (MRI)-based Delta radiomics characteristics extrapolated from the Ax LAVA + C series to identify intermediary- and high-risk factors in patients with cervical cancer undergoing surgery following neoadjuvant chemoradiotherapy. A total of 157 patients were divided into two groups: those without any intermediary- or high-risk factors and those with one intermediary-risk factor (negative group; n = 75). Those with any high-risk factor or more than one intermediary-risk factor (positive group; n = 82). Radiomics characteristics were extracted using Ax-LAVA + C MRI sequences. The data was divided into training (n = 126) and test (n = 31) sets in an 8:2 ratio. The training set data features were selected using the Mann-Whitney U test and the Least Absolute Shrinkage and Selection Operator (LASSO) test. The best radiomics features were then analyzed to build a preoperative predictive radiomics model for predicting intermediary- and high-risk factors in cervical cancer. Three models-the clinical model, the radiomics model, and the combined clinic and radiomics model-were developed in this study utilizing the random forest Algorithm. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity were used to assess the predictive efficacy and clinical benefits of each model. Three models were developed in this study to predict intermediary- and high-risk variables associated with postoperative pathology for patients who underwent surgery after receiving neoadjuvant radiation. In the training and test sets, the AUC values assessed using the clinical model, radiomics model, and combined clinical and radiomics models were 0.76 and 0.70, 0.88 and 0.86, and 0.91 and 0.89, respectively. The use of machine learning algorithms to analyze Delta Ax LAVA + C MRI radiomics features can aid in the prediction of intermediary- and high-risk factors in patients with cervical cancer receiving neoadjuvant therapy.


Assuntos
Terapia Neoadjuvante , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Algoritmos , Instituições de Assistência Ambulatorial , Fatores de Risco
18.
Molecules ; 28(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37894624

RESUMO

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.


Assuntos
Ampelopsis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Ampelopsis/química , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Flavonoides/química , Glucose , Compostos Fitoquímicos/farmacologia , Etnofarmacologia , Extratos Vegetais/química
19.
World J Clin Cases ; 11(28): 6792-6796, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37901013

RESUMO

BACKGROUND: Pulmonary artery (PA) aneurysms are usually diagnosed radiographically and present as small or large lesions resembling inflammation or a neoplasm on chest radiography. It has rarely been reported as an endobronchial mass. CASE SUMMARY: We report the case of a 64-year-old man who presented with recurrent hemoptysis. Bronchoscopy revealed a tumorous protrusion blocking the right middle lobe bronchus, which was confirmed to be a PA aneurysm using endobronchial ultrasound bronchoscopy and computed tomography angiography. CONCLUSION: Although endobronchial PA aneurysms are rare, bronchoscopists need to add this lesion to the list of endobronchial masses for which a biopsy is to be assiduously avoided.

20.
World J Oncol ; 14(5): 406-422, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37869243

RESUMO

Background: Determining the prognosis of hormone receptor positive (HR+) breast cancer (BC), which accounts for 80% of all BCs, is critical in improving survival outcomes. Stratifying individuals at high risk of BC-related mortality and improving prognosis has been the focus of research for over a decade. However, these tools are not universal as they are limited to clinical factors. We hypothesized that a new framework for predicting prognosis in HR+ BC patients can develop using artificial intelligence. Methods: A total of 2,338 HR+ human epidermal growth factor receptor 2 negative (HER2-) BC cases were analyzed from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) cohorts. Groups were then divided into high- and low-risk categories utilizing a recurrence prediction model (RPM). An RPM was created by extracting nine prognosis-related genes from over 18,000 genes using a logistic progression model. Results: Risk classification by RPM was significantly stratified in both the discovery cohort and validation cohort. In the time-dependent area under the curve analysis, there was some variation depending on the cohort, but accuracy was found to decline significantly after about 10 years. Cell cycle related gene sets, MYC, and PI3K-AKT-mTOR signaling were enriched in high-risk tumors by the Gene Set Enrichment Analysis. High-risk tumors were associated with high levels of immune cells from the lymphoid and myeloid lineage and immune cytolytic activity, as well as low levels of stem cells and stromal cells. High-risk tumors were also associated with poor therapeutic effects of chemotherapy and endocrine therapy. Conclusions: This model was able to stratify prognosis in multiple cohorts. This is because the model reflects major BC therapeutic target pathways and tumor immune microenvironment and, further is supported by the therapeutic effect of chemotherapy and endocrine therapy.

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