Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.749
Filtrar
2.
Ann Surg Oncol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044106

RESUMEN

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

3.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3002-3011, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041160

RESUMEN

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.


Asunto(s)
Envejecimiento , Medicamentos Herbarios Chinos , Riñón , Metabolómica , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Ratas , Riñón/efectos de los fármacos , Riñón/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos
4.
J Phys Chem Lett ; 15(28): 7191-7198, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38968446

RESUMEN

We investigate the electronic structure and linear and nonlinear [second-harmonic generation (SHG)] spectra of the NbOCl2 monolayer, bilayer, and bulk by using a real-time first-principles approach based on many-body theory. First, the interlayer couplings between NbOCl2 layers are very weak, due to the relatively large interlayer distance, saturation of the p orbital of Cl atoms, and high degree of localization of charge density around the Nb atom for both the lowest conduction band and the highest valence band. Second, the quasiparticle gaps and exciton binding energy for the three systems show layer-dependent features and decrease with an increase in layer thickness. Most importantly, the linear and SHG spectra of the NbOCl2 monolayer, bilayer, and bulk are dominated by strong excitonic resonances and exhibit layer-independent features due to the weak interlayer couplings. Our findings demonstrate that excitonic effects should be included in studying the optical properties of not only two-dimensional materials but also layered bulk materials with weak interlayer couplings.

5.
Int J Biol Sci ; 20(9): 3269-3284, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993552

RESUMEN

Background: Lenvatinib is the most common multitarget receptor tyrosine kinase inhibitor for the treatment of advanced hepatocellular carcinoma (HCC). Acquired resistance to lenvatinib is one of the major factors leading to the failure of HCC treatment, but the underlying mechanism has not been fully characterized. Methods: We established lenvatinib-resistant cell lines, cell-derived xenografts (CDXs) and patient-derived xenografts (PDXs) and obtained lenvatinib-resistant HCC tumor tissues for further study. Results: We found that ubiquitin-specific protease 14 (USP14) was significantly increased in lenvatinib-resistant HCC cells and tumors. Silencing USP14 significantly attenuated lenvatinib resistance in vitro and in vivo. Mechanistically, USP14 directly interacts with and stabilizes calcium- and integrin-binding protein 1 (CIB1) by reversing K48-linked proteolytic ubiquitination at K24, thus facilitating the P21-activated kinase 1 (PAK1)-ERK1/2 signaling axis. Moreover, in vivo adeno-associated virus 9 mediated transduction of CIB1 promoted lenvatinib resistance in PDXs, whereas CIB1 knockdown resensitized the response of PDXs to lenvatinib. Conclusions: These findings provide new insights into the role of CIB1/PAK1-ERK1/2 signaling in lenvatinib resistance in HCC. Targeting CIB1 and its pathways may be a novel pharmaceutical intervention for the treatment of lenvatinib-resistant HCC.


Asunto(s)
Carcinoma Hepatocelular , Resistencia a Antineoplásicos , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Ubiquitina Tiolesterasa , Quinasas p21 Activadas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Quinolinas/farmacología , Quinolinas/uso terapéutico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Animales , Quinasas p21 Activadas/metabolismo , Quinasas p21 Activadas/genética , Ratones , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas , Ratones Desnudos , Ubiquitinación
6.
Cell Rep ; 43(8): 114520, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39024099

RESUMEN

We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens it. These three mutations, alongside D339H, alter key epitopes in spike, likely explaining the reduced sensitivity of these subvariants to neutralization. Our findings highlight the increased neutralization resistance of JN.1 subvariants and suggest that future vaccine formulations should consider the JN.1 spike as an immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.

7.
BMJ ; 385: e077890, 2024 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-38897625

RESUMEN

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.


Asunto(s)
Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la Neoplasia
9.
Ecotoxicol Environ Saf ; 280: 116545, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38850709

RESUMEN

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.


Asunto(s)
Aluminio , Monoterpenos Bicíclicos , Citrus , Limoneno , Fotosíntesis , Hojas de la Planta , Terpenos , Aluminio/toxicidad , Terpenos/metabolismo , Citrus/metabolismo , Citrus/efectos de los fármacos , Limoneno/metabolismo , Fotosíntesis/efectos de los fármacos , Monoterpenos Bicíclicos/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacos , Monoterpenos/metabolismo , Hemiterpenos/metabolismo , Ciclohexenos/metabolismo , Fosfatos de Azúcar/metabolismo , Butadienos/metabolismo , Eritritol/análogos & derivados , Eritritol/metabolismo , Ácido Mevalónico/metabolismo , Monoterpenos Ciclohexánicos , Citrus sinensis/metabolismo , Citrus sinensis/efectos de los fármacos , Citrus sinensis/genética , Clorofila/metabolismo , Transferasas Alquil y Aril/metabolismo , Transferasas Alquil y Aril/genética , Volatilización
10.
Sci Rep ; 14(1): 14079, 2024 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890341

RESUMEN

While cryogenic electron microscopy (cryo-EM) is fruitfully used for harvesting high-resolution structures of sizable macromolecules, its application to small or flexible proteins composed of small domains like immunoglobulin (IgG) remain challenging. Here, we applied single particle cryo-EM to Rituximab, a therapeutic IgG mediating anti-tumor toxicity, to explore its solution conformations. We found Rituximab molecules exhibited aggregates in cryo-EM specimens contrary to its solution behavior, and utilized a non-ionic detergent to successfully disperse them as isolated particles amenable to single particle analysis. As the detergent adversely reduced the protein-to-solvent contrast, we employed phase plate contrast to mitigate the impaired protein visibility. Assisted by phase plate imaging, we obtained a canonical three-arm IgG structure with other structures displaying variable arm densities co-existing in solution, affirming high flexibility of arm-connecting linkers. Furthermore, we showed phase plate imaging enables reliable structure determination of Fab to sub-nanometer resolution from ab initio, yielding a characteristic two-lobe structure that could be unambiguously docked with crystal structure. Our findings revealed conformation diversity of IgG and demonstrated phase plate was viable for cryo-EM analysis of small proteins without symmetry. This work helps extend cryo-EM boundaries, providing a valuable imaging and structural analysis framework for macromolecules with similar challenging features.


Asunto(s)
Microscopía por Crioelectrón , Fragmentos Fab de Inmunoglobulinas , Inmunoglobulina G , Conformación Proteica , Microscopía por Crioelectrón/métodos , Fragmentos Fab de Inmunoglobulinas/química , Fragmentos Fab de Inmunoglobulinas/ultraestructura , Inmunoglobulina G/química , Rituximab/química , Humanos , Modelos Moleculares
11.
Opt Express ; 32(8): 13657-13671, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859330

RESUMEN

We systematically studied the relation between the conditional auto-correlation function (CACF) and cross-correlation function (CCF) of biphotons or pairs of single photons. The biphotons were generated from a heated atomic vapor via the spontaneous four-wave mixing (SFWM) process. In practical usage, one single photon of a pair is utilized as the heralding photon, and another is employed as the heralded photon. Motivated by the data of CACF of the heralded photons versus CCF, we proposed a universal formula to predict the CACF. The derived formula was based on general theory and is also valid for the biphoton generation process of spontaneous parametric down-conversion (SPDC). With the formula, we utilized the experimentally determined parameters to predict CACFs, which can well agree with the measured CACFs. The proposed formula enables one to quantitatively know the CACF of heralded single photons without the measurement of Hanbury-Brown-Twiss-type three-fold coincidence count. This study provides a better understanding of biphoton generation using the SFWM or SPDC process. Our work demonstrates a valuable tool for analyzing a vital property of how the heralded photons are close to Fock-state single photons.

12.
Mil Med Res ; 11(1): 36, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38863031

RESUMEN

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.


Asunto(s)
Elementos de Facilitación Genéticos , Neoplasias , Sitios de Carácter Cuantitativo , Humanos , Elementos de Facilitación Genéticos/genética , Neoplasias/genética , Variación Genética/genética , Estudio de Asociación del Genoma Completo/métodos , Neoplasias Colorrectales/genética , Estudios de Casos y Controles , ARN/genética , China , ARN Potenciadores
13.
Hepatol Int ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878111

RESUMEN

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

14.
Cureus ; 16(5): e60477, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38883031

RESUMEN

Immune-mediated necrotizing myopathy (IMNM) represents a rare category of inflammatory myopathies characterized by more severe and rapid progression of symmetrical proximal muscle weakness. It is also marked by notably elevated serum muscle enzyme levels and distinct histological features, setting it apart from other types of myositis. Moreover, acute chronic lung respiratory dysfunction is a major comorbidity of great concern. We herein present two cases of IMNM associated with anti-signal recognition particle antibodies complicated by acute respiratory distress syndrome.

15.
Int J Biol Macromol ; 274(Pt 1): 133177, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38885855

RESUMEN

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.

16.
Biomed Environ Sci ; 37(5): 457-470, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38843919

RESUMEN

Objective: This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2 (HER2)-low early breast cancer (BC) and HER2-IHC0 BC. Methods: Patients diagnosed with HER2-negative BC ( N = 999) at our institution between January 2011 and December 2015 formed our study population. Clinicopathological characteristics, association between estrogen receptor (ER) expression and HER2-low, and evolution of HER2 immunohistochemical (IHC) score were assessed. Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes (5-year follow-up) between the HER2-IHC0 and HER2-low groups. Results: HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor (PgR) positivity than HER2-IHC0 BC group ( P < 0.001). The rate of HER2-low status increased with increasing ER expression levels (Mantel-Haenszel χ 2 test, P < 0.001, Pearson's R = 0.159, P < 0.001). Survival analysis revealed a significantly longer overall survival (OS) in HER2-low BC group than in HER2-IHC0 group ( P = 0.007) in the whole cohort and the hormone receptor (HR)-negative group. There were no significant differences between the two groups in terms of disease-free survival (DFS). The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion: HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.


Asunto(s)
Neoplasias de la Mama , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/genética , Femenino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Persona de Mediana Edad , Pronóstico , Adulto , China/epidemiología , Anciano , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pueblos del Este de Asia
17.
bioRxiv ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38826376

RESUMEN

SARS-CoV-2 variants derived from the immune evasive JN.1 are on the rise worldwide. Here, we investigated JN.1-derived subvariants SLip, FLiRT, and KP.2 for their ability to be neutralized by antibodies in bivalent-vaccinated human sera, XBB.1.5 monovalent-vaccinated hamster sera, sera from people infected during the BA.2.86/JN.1 wave, and class III monoclonal antibody (Mab) S309. We found that compared to parental JN.1, SLip and KP.2, and especially FLiRT, exhibit increased resistance to COVID-19 bivalent-vaccinated human sera and BA.2.86/JN.1-wave convalescent sera. Interestingly, antibodies in XBB.1.5 monovalent vaccinated hamster sera robustly neutralized FLiRT and KP.2 but had reduced efficiency for SLip. These JN.1 subvariants were resistant to neutralization by Mab S309. In addition, we investigated aspects of spike protein biology including infectivity, cell-cell fusion and processing, and found that these subvariants, especially SLip, had a decreased infectivity and membrane fusion relative to JN.1, correlating with decreased spike processing. Homology modeling revealed that L455S and F456L mutations in SLip reduced local hydrophobicity in the spike and hence its binding to ACE2. In contrast, the additional R346T mutation in FLiRT and KP.2 strengthened conformational support of the receptor-binding motif, thus counteracting the effects of L455S and F456L. These three mutations, alongside D339H, which is present in all JN.1 sublineages, alter the epitopes targeted by therapeutic Mabs, including class I and class III S309, explaining their reduced sensitivity to neutralization by sera and S309. Together, our findings provide insight into neutralization resistance of newly emerged JN.1 subvariants and suggest that future vaccine formulations should consider JN.1 spike as immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.

18.
Dis Esophagus ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38881278

RESUMEN

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

19.
Front Pharmacol ; 15: 1383831, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863976

RESUMEN

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

20.
Br J Cancer ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918556

RESUMEN

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...