Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 509
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Mol Cell ; 84(8): 1406-1421.e8, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38490199

RESUMEN

Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. In the formative state, genes important for pluripotency exit establish contacts with emerging enhancers within these multiway hubs, suggesting that the structural changes we have observed may play an important role in modulating transcription and establishing new cell identities.


Asunto(s)
Células Madre Embrionarias de Ratones , Secuencias Reguladoras de Ácidos Nucleicos , Ratones , Animales , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cromatina/genética , Cromatina/metabolismo , Elementos de Facilitación Genéticos
2.
Mol Cell ; 82(4): 833-851.e11, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-35180428

RESUMEN

HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) driven by MLL rearrangements or NPM1 mutations to mediate HOXA topologically associated domain (TAD) formation and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CCCTC-binding factor (CTCF) chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly interacts with and regulates a fraction of CTCF-binding sites (CBSs) in the AML genome by recruiting CTCF/cohesin complex and R-loop-associated regulators to form R-loops. HOTTIP-mediated R-loops reinforce the CTCF boundary and facilitate formation of TADs to drive gene transcription. Either deleting CBS or targeting RNase H to eliminate R-loops in the boundary CBS of ß-catenin TAD impaired CTCF boundary activity, inhibited promoter/enhancer interactions, reduced ß-catenin target expression, and mitigated leukemogenesis in xenograft mouse models with aberrant HOTTIP expression. Thus, HOTTIP-mediated R-loop formation directly reinforces CTCF chromatin boundary activity and TAD integrity to drive oncogene transcription and leukemia development.


Asunto(s)
Factor de Unión a CCCTC/metabolismo , Cromatina/metabolismo , Leucemia Mieloide Aguda/metabolismo , Estructuras R-Loop , ARN Largo no Codificante/metabolismo , beta Catenina/metabolismo , Animales , Factor de Unión a CCCTC/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Cromatina/genética , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Regulación Leucémica de la Expresión Génica , Células HEK293 , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Ratones Transgénicos , ARN Largo no Codificante/genética , Relación Estructura-Actividad , Transcripción Genética , Activación Transcripcional , beta Catenina/genética , Cohesinas
3.
Nature ; 606(7915): 797-803, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35705814

RESUMEN

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy ( NCT02231775 , n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.021). The findings were validated in several additional cohorts2-4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P = 0.0006 and P = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P = 0.018 and P = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P = 0.021 and P < 0.0001). Together, these results have important implications for therapy.


Asunto(s)
Antagonistas de Receptores Androgénicos , Melanoma , Quinasas de Proteína Quinasa Activadas por Mitógenos , Terapia Molecular Dirigida , Proteínas Proto-Oncogénicas B-raf , Receptores Androgénicos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Receptores Androgénicos/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Análisis de Supervivencia
4.
Med Res Rev ; 44(4): 1545-1565, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38279970

RESUMEN

Overexpression of the epidermal growth factor receptor (EGFR, erbB1) has been observed in a wide range of solid tumors and has frequently been associated with poor prognosis. As a result, EGFR inhibition has become an attractive anticancer drug design strategy, and a large number of small molecular inhibitors have been developed. Despite the widespread clinical use of EGFR tyrosine kinase inhibitors (TKIs), their drug resistance, inadequate accumulation in tumors, and severe side effects have spurred the search for better antitumor drugs. Metal complexes have attracted much attention because of their different mechanisms compared with EGFR-TKIs. Therefore, the combination of metals and inhibitors is a promising anticancer strategy. For example, Ru and Pt centers are introduced to design complexes with double or multiple targets, while Au complexes are combined with inhibitors to overcome drug resistance. Co complexes are designed as prodrugs with weak side effects and enhanced targeting by the hypoxia activation strategy, and other metals such as Rh and Fe enhance the anticancer effect of the complexes. In addition, the introduction of Ga center is beneficial to the development of nuclear imaging tracers. In this paper, metal EGFR-TKI complexes in the last 15 years are reviewed, their mechanisms are briefly introduced, and their advantages are summarized.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Receptores ErbB , Inhibidores de Proteínas Quinasas , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Ligandos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo
5.
Biol Reprod ; 111(1): 92-109, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38412119

RESUMEN

In bovine follicular development, the proliferation of bovine granulosa cells affects follicular selection, atresia, and cystic follicle formation. When cystic follicles appear on the ovaries, granulosa cells stop proliferating, resulting in the reduction of granulosa cells layer. In our previous study, the whole transcriptome sequencing revealed that Bone morphogenetic protein receptor 2 (BMPR2) was differentially expressed between cystic and normal follicular granulosa cells. We speculated that long noncoding RNA may act as competing endogenous RNA targeting microRNAs and then regulating the expression of BMPR2 and the function of granulosa cells, thereby affecting follicular development and cyst formation. In this study, the results elucidated that long noncoding RNA S100PBP (NONBTAT011846.2) directly bound miR-2285bc, which targeted in the BMPR2 3'-UTR. miR-2285bc suppresses granulosa cells proliferation by downregulating BMPR2 expression. Furthermore, long noncoding RNA S100PBP was silenced by small interfering RNA, and long noncoding RNA S100PBP regulated BMPR2 expression by sponging miR-2285bc investigated through cross-verification. When small interfering RNA of long noncoding RNA S100PBP was transfected into granulosa cells, the results revealed similar molecular changes as those transfected with miR-2285bc mimics. Silencing long noncoding RNA S100PBP or overexpressing miR-2285bc altered the expressions of some follicular development-related genes, which could be related to follicular cyst occurrence. In conclusion, our findings support that long noncoding RNA S100PBP regulates the expression of BMPR2 through sponge miR-2285bc, promotes the proliferation of granulosa cells, inhibits their apoptosis, and increases the synthesis and secretion of follicular steroid hormones, thus promoting the development of bovine follicles.


Asunto(s)
Receptores de Proteínas Morfogenéticas Óseas de Tipo II , Proliferación Celular , Células de la Granulosa , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Células de la Granulosa/metabolismo , Bovinos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Regulación de la Expresión Génica
6.
J Viral Hepat ; 31(9): 557-564, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38771314

RESUMEN

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.


Asunto(s)
Antígeno CTLA-4 , Carcinoma Hepatocelular , Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Antígeno CTLA-4/metabolismo , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/complicaciones , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/fisiología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/virología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/virología , Linfocitos T Reguladores/inmunología , Cirrosis Hepática/inmunología , Cirrosis Hepática/virología
7.
Biotechnol Bioeng ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138638

RESUMEN

Engineered bacteria-based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria-mediated photodynamic therapy (PDT)-immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria-based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT-immunotherapy. The biosynthetic pathway of 5-aminolevulinic acid (5-ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light-controllable releasement of anti-programmed cell death-ligand 1 nanobodies (anti-PD-L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria-based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT-immunotherapy.

8.
Liver Int ; 44(3): 865-875, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38263792

RESUMEN

BACKGROUND AND AIMS: The relationship between moderate alcohol intake and health outcomes among individuals with metabolic dysfunction-associated fatty liver disease (MAFLD) is complex. Our aim was to investigate the association of minimal alcohol consumption with all-cause and cause-specific mortality among MAFLD individuals of different genders. METHODS: Our study included 2630 MAFLD individuals from the Third National Health and Nutrition Examination Survey. Cox regression analysis was performed to assess the association between alcohol use measures and all-cause and cause-specific mortality. Restricted cubic spline curves were used to evaluate the relationship between alcohol consumption per week and all-cause mortality. RESULTS: In the entire MAFLD cohort, we observed significant disparities in clinical characteristics between male and female individuals with MAFLD. Higher weekly alcohol consumption was significantly associated with all-cause and cause-specific mortality (male, hazard ratios [HRs]: 1.009, 95% CIs: 1.004-1.014; female, HRs: 1.032, 95% CIs: 1.022-1.042). In males with MAFLD, a linear association with all-cause mortality was observed for weekly alcohol consumption (p for non-linearity = .21). Conversely, in females with MAFLD, the risk of all-cause mortality remained relatively stable until 2 drinks per week, after which it rapidly increased with each additional drink consumed, and the increase in mortality risk was higher than that observed in males (p for non-linearity < .05). CONCLUSIONS: Our findings indicate that any increase in weekly alcohol consumption was associated with increased all-cause mortality in men with MAFLD. Conversely, consuming less than 2 drinks per week had minimal impact on the risk of mortality among female.


Asunto(s)
Consumo de Bebidas Alcohólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Masculino , Encuestas Nutricionales , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Conductas Relacionadas con la Salud
9.
Cell Biol Toxicol ; 40(1): 24, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38653919

RESUMEN

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.


Asunto(s)
Neoplasias de la Mama , Proliferación Celular , Elonguina , Ubiquitinación , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Femenino , Elonguina/metabolismo , Elonguina/genética , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Ratones Desnudos , Ratones , Regulación Neoplásica de la Expresión Génica , Transducción de Señal , Ratones Endogámicos BALB C , Células MCF-7 , Factores de Transcripción/metabolismo , Factores de Transcripción/genética
10.
BMC Cardiovasc Disord ; 24(1): 367, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014301

RESUMEN

OBJECTIVE: To investigate the accuracy and consistency of MDCT and TEE in the preoperative assessment of aortic root surgery. METHODS: From January 2021 to September 2022, 118 patients who underwent aortic root surgery were included in this study. All patients underwent high-quality preoperative MDCT and TEE examinations, and the examination results were independently measured and assessed by two senior radiologists or ultrasound specialists. Bland-Altman analysis and Pearson correlation testing were employed to assess the correlation and consistency between MDCT and TEE. These analyses were then compared with actual intraoperative measurement data. RESULTS: Among all the patients, 73 (61.86%) had tricuspid aortic valve (TAV), and 45 (38.14%) had bicuspid aortic valve (BAV). A comparison between the TEE and MDCT measurements showed that for the annulus diameter, the area-derived diameter had the best correlation and agreement. For the sinus of Valsalva diameter, the circumference-derived diameter was optimal. However, for the STJ diameter, the minimum cross-sectional diameter showed the best agreement with TEE. In contrast, measurements of geometric height showed a weaker correlation and agreement. CONCLUSION: Contrast-enhanced MDCT can be a valuable tool for perioperative evaluation in aortic root surgery, with good correlation, consistency, and feasibility when compared to TEE. The choice of MDCT measurement methodology, specifically area-derived and circumference-derived diameter, proved to be more accurate than other methods. Further research is required to enhance the understanding of aortic valve repair and associated imaging techniques.


Asunto(s)
Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Ecocardiografía Transesofágica , Tomografía Computarizada Multidetector , Valor Predictivo de las Pruebas , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Válvula Aórtica/anomalías , Masculino , Femenino , Persona de Mediana Edad , Anciano , Reproducibilidad de los Resultados , Enfermedad de la Válvula Aórtica Bicúspide/cirugía , Enfermedad de la Válvula Aórtica Bicúspide/diagnóstico por imagen , Adulto , Estudios Retrospectivos , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/cirugía , Cuidados Preoperatorios
12.
Arch Insect Biochem Physiol ; 115(1): e22073, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38288485

RESUMEN

Although neonicotinoids are widely used and important insecticide, there are growing concerns about their effect on nontarget insects and other organisms. Moreover, the effects of nitenpyram (NIT), a second generation of neonicotinoid insecticides, on Chrysopa pallens are still unclear. Therefore, this study purposed to investigate the acute toxicity of NIT to C. pallens using the spotting method. To examine the potential effects of a sublethal dose of NIT (LD30 , 1.85 ng of active ingredient per insect) on C. pallens, we constructed the life tables and analyzed the transcriptome data. The life table results showed that the period of second instar larvae, adult pre-oviposition period and total pre-oviposition period were significantly prolonged after exposure to sublethal dose of NIT, but had no significant effects on the other instars, longevity, oviposition days, and fecundity. The population parameters, including the preadult survival rate, gross reproduction rate, net reproductive rate, the intrinsic rate of increase, and finite rate of increase, were not significantly affected, and only the mean generation time was significantly prolonged by NIT. Transcriptome analysis showed that there were 68 differentially expressed genes (DEGs), including 50 upregulated genes and 18 downregulated genes. Moreover, 13 DEGs related to heat shock protein, nose resistant to fluoxetine protein 6, and prophenoloxidas were upregulated. This study showed the potential effects of sublethal doses of NIT on C. pallens and provided a theoretical reference for the comprehensive application of chemical and biological control in integrated pest management.


Asunto(s)
Insecticidas , Femenino , Animales , Neonicotinoides , Insecticidas/toxicidad , Insectos/genética , Reproducción
13.
J Chem Phys ; 160(19)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38752535

RESUMEN

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

14.
Cryobiology ; : 104957, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39179195

RESUMEN

Establishment of a new method for improved shoot tip cryopreservation is crucial to facilitate the long-term preservation of plant germplasm as well as the use of cryotherapy for pathogen eradication. The present study reported a vitrification (V) cryo-foil method for shoot tip cryopreservation and virus eradication in apple. Shoot tip regrowth levels after cryopreservation were comparable among V cryo-foil (53%), V cryo-plate (46%) and conventional droplet vitrification (Dr-vi, 48%). The V cryo-foil is more efficient to perform than Dr-vi as more shoot tips can be cryopreserved by one person. In the histological study applying an image-overlaying strategy, shoot tips cryopreserved by V cryo-foil showed a higher survival chance in the youngest leaf primordia than in the apical dome. When V cryo-foil was tested for virus eradication, fifty-five percent (55%) of cryo-derived shoots were free of the apple stem pitting virus (ASPV), while none and less than 10% were free of the apple stem grooving virus (ASGV) and the apple chlorotic leaf spot virus (ACLSV), respectively. Thus, these two viruses were efficiently preserved by V cryo-foil cryopreservation. Noticeably, although the shoot regrowth level was reduced to 27%, a higher frequency (81%) of ASPV eradication was achieved when a reduced duration of cryoprotectant exposure was applied in V cryo-foil, supporting the use of insufficient cryoprotection for improved virus eradication.

15.
BMC Public Health ; 24(1): 700, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443845

RESUMEN

BACKGROUND: Chronic low back pain (LBP) related to flight is a prevalent health issue in military aviation, impacting pilots. The objective of this investigation was to ascertain if the application of core muscle training in conjunction with interferential current (IFC) therapy results in a reduction in pain severity and associated disability, consequently enhancing core muscle functionality in Chinese Air Force high-performance fighter pilots experiencing chronic LBP. METHODS: Fifty-three fighter pilots with chronic LBP were randomized into 3 groups: a core muscle exercise combined with IFC group (CG, n = 19), a core muscle exercise group (EG, n = 19), and an IFC group (IG, n = 15). The three groups underwent therapeutic intervention 5 times a week for 12 weeks. The primary outcomes were pain intensity, Oswestry Disability Index (ODI) score and SF-12 health-related quality of life (PCS and MCS) score. Secondary outcomes included evaluations of trunk muscle strength, endurance, and range of motion (ROM) during medial/lateral rotation to assess muscle functionality. Measurements were obtained both before and after the implementation of the intervention therapy. RESULTS: After 12 weeks of intervention therapy, all the health condition parameters significantly improved among the three groups. However, the CG had a significant improvement in pain intensity compared to the EG (MD = - 0.84 scores; 95% CI = - 1.54 to - 0.15; p = 0.013) and the IG (MD = - 1.22 scores; 95% CI = - 1.96 to - 0.48; p = 0.000). Additionally, the CG led to greater conservation of ODI and improved SF-12 PCS scores than did the IG (p < 0.05). Finally, compared with those at baseline, the core muscle function parameters in the CG and EG improved significantly at the end of the study, but no statistically significant differences were observed between the two groups (p > 0.05). CONCLUSION: Among participants with chronic LBP, three intervention therapies appear effective in reducing pain, diminishing disability, and enhancing quality of life. Also, combined therapy significantly improved pain and disability compared to the other two monotherapies; moreover, combined therapy and core muscle exercise provided similar benefits in terms of core muscle function after 12 weeks of intervention therapy.


Asunto(s)
Dolor de la Región Lumbar , Pilotos , Humanos , Dolor de la Región Lumbar/terapia , Calidad de Vida , Músculos , Manejo del Dolor
16.
Biotechnol Lett ; 46(3): 399-407, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38416308

RESUMEN

OBJECTIVE: A convenient strategy was developed to recycle selectable markers using Cre/loxP system for constructing Komagataella phaffii strains co-expressing multiple proteins. RESULTS: A plasmid in this strategy was generated from pPICZαA with integration of lox71-Sh ble-lox66. Firstly, the plasmid was inserted with one target protein gene and then transformed into K. phaffii KM71. Secondly, the auxiliary plasmid pPICZαA/cre/his4 containing CRE recombinase gene was further chromosomally inserted to Sh ble gene therein. Finally, methanol induction was conducted to produce CRE for Cre/loxP-mediated recombination, and consequently, the sequence between lox71 and lox66 was deleted, leading to recycling of ZeoR and His- markers. Then the resulted strain expressing the one target protein was used as the host to which another target protein gene could be inserted by the same procedures. CONCLUSIONS: With easy manipulation, the method was effective in recycling of the selectable markers, and consequently two protein genes were sequential integrated chromosomally and successfully co-expressed in the yeast.


Asunto(s)
Integrasas , Plásmidos , Saccharomycetales , Integrasas/genética , Saccharomycetales/genética , Saccharomycetales/metabolismo , Plásmidos/genética , Recombinación Genética/genética , Marcadores Genéticos/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
17.
Ren Fail ; 46(2): 2392849, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39165231

RESUMEN

AIMS: To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization. METHODS: We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-ß1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells. RESULTS: LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro, LCZ696 also significantly alleviated the EMT of TGF-ß1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-ß1 increased the expression of TGFßRI, p-Smad3, p-PDGFRß and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-ß/Smad3, PDGFRß and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-ß1 secretion from M2 macrophages. CONCLUSION: Our study demonstrated that LCZ696 improves PF and ameliorates TGF-ß1-induced EMT of HPMCs by blocking TGF-ß/Smad3, PDGFRß and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Transición Epitelial-Mesenquimal , Macrófagos , Fibrosis Peritoneal , Tetrazoles , Valsartán , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones , Animales , Valsartán/farmacología , Compuestos de Bifenilo/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/prevención & control , Humanos , Tetrazoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Aminobutiratos/farmacología , Células RAW 264.7 , Modelos Animales de Enfermedad , Combinación de Medicamentos , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Masculino , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Transcripción STAT6/metabolismo , Peritoneo/patología , Peritoneo/citología , Peritoneo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL
18.
J Clin Nurs ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757751

RESUMEN

AIMS AND OBJECTIVES: To investigate knowledge, attitudes, and practices regarding the application of the Injury Severity Score (ISS) among emergency department nurses in China and the factors influencing these variables. BACKGROUND: ISS is the first trauma scoring method to be developed and the most widely used in clinical practice. The correct application of the ISS by emergency department nurses plays an important role in assisting in the diagnosis and treatment of trauma patients, and it is crucial to understand nurses' knowledge, attitudes and practices. DESIGN: A cross-sectional multicentre study. METHODS: Nurses from the emergency departments of 25 grade II and grade III hospitals in Gansu Province, China participated in this study. Data was collected online using a self-administered questionnaire. Student's t-test or analysis of variance was performed to compare the differences between the groups. Multiple logistic regression analysis identified factors influencing nurses' knowledge, attitudes and practices regarding applying ISS. A STROBE checklist was used to report findings. RESULTS: Among 459 nurses, a good level of attitude and passing levels of knowledge and practice regarding applying the ISS were revealed. Nurses in higher hospital grades, who had been exposed to ISS and received training had higher levels of knowledge and practices. Previous exposure to the ISS and training related to it were factors that influenced nurses' attitudes. CONCLUSIONS: Chinese emergency department nurses' knowledge, attitudes and practices of applying the ISS still need to be improved. Hospitals and nursing managers should provide training opportunities for nurses about ISS knowledge and practices, while grade II hospitals should pay more attention to training and continuing education in this area. RELEVANCE TO CLINICAL PRACTICE: In hospitals, nursing managers may benefit from enhancing related education and training to promote the emergency department nurses' knowledge and practice of the ISS, by developing specific curricula and providing continuing education and training opportunities, while grade II hospitals should pay more attention to training and continuing education in this area. NO PATIENT OR PUBLIC CONTRIBUTIONS: This study focused on emergency department nurses' knowledge, attitudes, and practices regarding the application of the ISS. The research questions and design were derived from clinical nursing practice, literature review, and expert panel review, and patients or the public are temporarily not involved.

19.
Nano Lett ; 23(23): 11043-11050, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38032845

RESUMEN

Layered MXene nanofluidic membranes still face the problems of low mechanical property, poor ion selectivity, and low output power density. In this work, we successfully constructed heterostructured membranes with the combination of the layered channels of the MXene layer on the top and the nanoscale poly(p-phenylene-benzodioxazole) nanofiber (PBONF) layer on the bottom through a stepwise filtration method. The as-prepared MXene/PBONF-50 heterogeneous membrane exhibits high mechanical properties (strength of 221.6 MPa, strain of 3.2%), high ion selectivity of 0.87, and an excellent output power density of 15.7 W/m2 at 50-fold concentration gradient. Excitingly, the heterogeneous membrane presents a high power density of 6.8 W/m2 at a larger testing area of 0.79 mm2 and long-term stability. This heterogeneous membrane construction provides a viable strategy for the enhancement of mechanical properties and osmotic energy conversion of 2D materials.

20.
Wei Sheng Yan Jiu ; 53(4): 576-583, 2024 Jul.
Artículo en Zh | MEDLINE | ID: mdl-39155225

RESUMEN

OBJECTIVE: To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. METHODS: From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. RESULTS: The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P<0.05), and the differences were statistically significant(all P<0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P<0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P<0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. CONCLUSION: Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.


Asunto(s)
Glucemia , Fibronectinas , Metabolismo de los Lípidos , Humanos , Adolescente , Fibronectinas/sangre , Masculino , Femenino , China , Niño , Glucemia/análisis , LDL-Colesterol/sangre , Triglicéridos/sangre , HDL-Colesterol/sangre , Lípidos/sangre
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA