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1.
PLoS One ; 19(8): e0309001, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39172904

RESUMEN

To analyze English discourse more accurately and provide more detailed feedback information, this study applies Rasch measurement and Conditional Random Field (CRF) models to English discourse analysis. The Rasch measurement model is widely used to evaluate and quantify the potential traits of individuals, and it has remarkable advantages in measurement and evaluation. By combining the CRF model, the Rasch model is employed to model the structural and semantic information in the discourse and use this model to carry out sequence labeling, to enhance the ability to capture the internal relations of the discourse. Finally, this study conducts comparative experiments on integrating the Rasch measurement and CRF models, comparing the outcomes against traditional scoring methods and the standalone CRF model. The research findings indicate that: (1) The discourse component syntactic analysis model on the Penn Treebank (PTB) database obtained Unlabeled Attachment Score (UAS) values of 94.07, 95.76, 95.67, and 95.43, and Labeled Attachment Score (LAS) values of 92.47, 92.33, 92.49, and 92.46 for the LOC, CRF, CRF2O, and MFVI models, respectively. After adding the Rasch measurement model, the UAS values of the four models on the PTB database are 96.85, 96.77, 96.92, and 96.78 for the LOC, CRF, CRF2O, and MFVI models, respectively, with LAS values of 95.33, 95.34, 95.39, and 95.32, all showing significant improvement. (2) By combining contextual information with CRF models, students can better understand their discourse expression, capture the connections between English discourse sentences, and analyze English discourse more comprehensively. This study provides new ideas and methods for researchers in English language education and linguistics.


Asunto(s)
Lenguaje , Humanos , Semántica , Modelos Teóricos
2.
Biomater Sci ; 12(17): 4440-4451, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39044564

RESUMEN

Sonodynamic therapy (SDT) is a promising strategy to treat deep-seated bacterial infections with good tissue penetration and spatiotemporal controllability. However, the low ROS generation efficiency of current sonosensitizers limits the development of SDT. Herein, we report a porphyrin derivative, TAPyPP-2, the sonodynamic activity of which is enhanced with less oxygen dependence by tuning its molecular assembly behavior. TAPyPP-2 can spontaneously form an ultra-small nano-assembly with a diameter of 6 nm in water by conjugation with primary amine salt-decorated pyridinium via π-π staking. The ultra-small assembly behavior can lower the energy gap between singlet and triplet states to 0.01 eV and promote the separation of holes and electrons, which facilitates ROS generation under ultrasound irradiation, in particular type I ROS. The unique hydrophilic ratio and positive charges endow TAPyPP-2 with superior abilities to interact with Staphylococcus aureus, resulting in extremely high sonodynamic antibacterial activity. Therefore, TAPyPP-2 successfully kills Staphylococcus aureus bacteria in the enclosed cavity of synovial joint and achieves effective SDT of septic arthritis. This work is anticipated to motivate enormous interest in the development of efficient SDT.


Asunto(s)
Antibacterianos , Porfirinas , Staphylococcus aureus , Porfirinas/química , Porfirinas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Animales , Terapia por Ultrasonido , Ratones , Especies Reactivas de Oxígeno/metabolismo , Ondas Ultrasónicas , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/terapia
3.
Angew Chem Int Ed Engl ; : e202407757, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978264

RESUMEN

On the basis of a novel ynol-diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17-nor-cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)-3-deoxyfortalpinoid F, (+)-harringtonolide, (-)-fortalpinoids M/N/P, and analog (-)-20-deoxocephinoid P have been achieved in 14-17 linear longest steps starting from commercially available materials.

4.
iScience ; 27(7): 110224, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39040058

RESUMEN

Cancer-associated fibroblasts (CAFs) play a significant role in tumor development and treatment failure, yet the precise mechanisms underlying their contribution to renal cell carcinoma (RCC) remains underexplored. This study explored the interaction between CAFs and tumor cells, and related mechanisms. CAFs isolated from tumor tissues promoted the tumor progression and drugs resistance both in vivo and in vitro. Mechanistically, chemokine (C-X-C motif) ligand (CXCL) 3 secreted from CAFs mediated its effects. CXCL3 activated its receptor CXCR2 to active the downstream ERK1/2 signaling pathway, subsequently promoting epithelial-mesenchymal transition and cell stemness. Blocking the crosstalk between CAFs and tumor cells by CXCR2 inhibitor SB225002 attenuated the functions of CAFs. Furthermore, Renca cells facilitated the transformation of normal interstitial fibroblasts (NFs) into CAFs and the expression of CXCL3 through TGF-ß-Smad2/3 signaling pathway. In turn, transformed NFs promoted the tumor progression and drug resistance of RCC. These findings may constitute potential therapeutic strategies for RCC treatment.

5.
J Dermatol ; 51(8): 1060-1067, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38895831

RESUMEN

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).


Asunto(s)
Melanocitos , Pigmentación de la Piel , Trasplante Autólogo , Vitíligo , Humanos , Vitíligo/terapia , Estudios Retrospectivos , Femenino , Masculino , Adulto , Melanocitos/trasplante , Adulto Joven , Adolescente , Persona de Mediana Edad , Resultado del Tratamiento , Niño , Estudios de Seguimiento , Células Cultivadas , Preescolar
6.
Artículo en Inglés | MEDLINE | ID: mdl-38705909

RESUMEN

Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.

7.
Exp Cell Res ; 439(1): 114094, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38750718

RESUMEN

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolization (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.


Asunto(s)
Apoptosis , Proteínas Relacionadas con la Autofagia , Autofagia , Berberina , Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas , Ratones Desnudos , Berberina/farmacología , Berberina/análogos & derivados , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Autofagia/efectos de los fármacos , Animales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Ratones , Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/análogos & derivados , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Transducción de Señal/efectos de los fármacos , Cisteína Endopeptidasas
8.
J Diabetes ; 16(6): e13565, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38751373

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored. METHODS: Streptozotocin (STZ)-induced DN mouse models and high glucose (HG)-treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG-treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh-SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24-h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice. RESULTS: SNHG14 expression was elevated in the kidneys of DN mice and HG-treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG-stimulated MCs. SNHG14 bound to miR-30e-5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG-treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice. CONCLUSIONS: SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG-stimulated MCs via the miR-30e-5p/SOX4 axis.


Asunto(s)
Diabetes Mellitus Experimental , Nefropatías Diabéticas , Progresión de la Enfermedad , MicroARNs , ARN Largo no Codificante , Factores de Transcripción SOXC , Animales , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , ARN Largo no Codificante/genética , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Ratones , MicroARNs/genética , Humanos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Masculino , Silenciador del Gen , Fibrosis , Proliferación Celular , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones Endogámicos C57BL
9.
J Nanobiotechnology ; 22(1): 145, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566211

RESUMEN

Resistance to androgen receptor (AR) inhibitors, including enzalutamide (Enz), as well as bone metastasis, are major challenges for castration-resistant prostate cancer (CRPC) treatment. In this study, we identified that miR26a can restore Enz sensitivity and inhibit bone metastatic CRPC. To achieve the highest combination effect of miR26a and Enz, we developed a cancer-targeted nano-system (Bm@PT/Enz-miR26a) using bone marrow mesenchymal stem cell (BMSC) membrane and T140 peptide to co-deliver Enz and miR26a. The in vitro/in vivo results demonstrated that miR26a can reverse Enz resistance and synergistically shrink tumor growth, invasion, and metastasis (especially secondary metastasis) in both subcutaneous and bone metastatic CRPC mouse models. We also found that the EZH2/SFRP1/WNT5A axis may be involved in this role. These findings open new avenues for treating bone metastatic and Enz-resistant CRPC.


Asunto(s)
Benzamidas , Feniltiohidantoína , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Animales , Ratones , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Resistencia a Antineoplásicos , Proliferación Celular , Línea Celular Tumoral , Nitrilos/farmacología
10.
Front Oncol ; 14: 1357145, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38567148

RESUMEN

Objective: To investigate the value of predicting axillary lymph node (ALN) metastasis based on intratumoral and peritumoral dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinico-radiological characteristics in breast cancer. Methods: A total of 473 breast cancer patients who underwent preoperative DCE-MRI from Jan 2017 to Dec 2020 were enrolled. These patients were randomly divided into training (n=378) and testing sets (n=95) at 8:2 ratio. Intratumoral regions (ITRs) of interest were manually delineated, and peritumoral regions of 3 mm (3 mmPTRs) were automatically obtained by morphologically dilating the ITR. Radiomics features were extracted, and ALN metastasis-related radiomics features were selected by the Mann-Whitney U test, Z score normalization, variance thresholding, K-best algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. Clinico-radiological risk factors were selected by logistic regression and were also used to construct predictive models combined with radiomics features. Then, 5 models were constructed, including ITR, 3 mmPTR, ITR+3 mmPTR, clinico-radiological and combined (ITR+3 mmPTR+ clinico-radiological) models. The performance of models was assessed by sensitivity, specificity, accuracy, F1 score and area under the curve (AUC) of receiver operating characteristic (ROC), calibration curves and decision curve analysis (DCA). Results: A total of 2264 radiomics features were extracted from each region of interest (ROI), 3 and 10 radiomics features were selected for the ITR and 3 mmPTR, respectively. 5 clinico-radiological risk factors were selected, including lesion size, human epidermal growth factor receptor 2 (HER2) expression, vascular cancer thrombus status, MR-reported ALN status, and time-signal intensity curve (TIC) type. In the testing set, the combined model showed the highest AUC (0.839), specificity (74.2%), accuracy (75.8%) and F1 Score (69.3%) among the 5 models. DCA showed that it had the greatest net clinical benefit compared to the other models. Conclusion: The intra- and peritumoral radiomics models based on DCE-MRI could be used to predict ALN metastasis in breast cancer, especially for the combined model with clinico-radiological characteristics showing promising clinical application value.

11.
Opt Express ; 32(6): 9995-10004, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571222

RESUMEN

We present a design of middle-infrared modulation absorbers based on vanadium dioxide (VO2). By using the electron beam evaporation technique, the Ag/SiO2/VO2/Ag/VO2 multilayer structure can achieve double band strong absorption in the mid-infrared, and dynamically adjust the absorption performance through VO2. The simulation results demonstrate a remarkable absorption rate of 91.8% and 98.9% at 9.09 µm and 10.25 µm, respectively. The high absorption is elucidated by analyzing the field strength distribution in each layer. Meanwhile, based on the phase change characteristics of VO2, the absorber has exceptional thermal regulation, with a remarkable 78% heat regulation range in the mid-infrared band. The size altering of the absorbing layer is effective in enhancing and optimizing the structure's absorption performance. The structure is used to characterize probe molecules of CV and R6 G by mid-infrared spectroscopy, which illustrates an impressive limit of detection (LOD) of 10-7 M for both substances. These results provide valuable insights for designing future high-performance tunable optical devices.

12.
Heliyon ; 10(7): e28722, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38623231

RESUMEN

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat-saturated T2-weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648-0.778), 0.706 (95% CI, 0.637-0.768), and 0.719 (95% CI, 0.651-0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686-0.810), 0.754 (95% CI, 0.688-0.812) and 0.725 (95% CI, 0.657-0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733-0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

13.
Micromachines (Basel) ; 15(3)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38542538

RESUMEN

We introduced a new, highly efficient, and uncomplicated mixing device for centrifugal microfluidic platforms, called the gravity mixer. The gravity mixer featured a slope channel that can precisely and sequentially control micro-volume liquids using centrifugal, capillary, and gravitational forces to achieve the desired mixing effect. By adjusting the angular velocity, micro-volumes of liquids in the slope channel of the gravity mixer could be precisely controlled across a wide range. We evaluated the change in mixing efficiency by varying the slope geometry, including the slope angle and the number of mixing cycles. Our study of gravity mixers with different slope angles revealed that the 80° angle gravity mixer achieved the best mixing efficiency, with a standard deviation of 2.39. Additionally, the mixing process in the gravity mixer is highly repeatable, achieving the desired mixing efficiency after only three cycles of operation. Our gravity mixer design and implementation can facilitate the development of more complex 3D-printed lab-on-chip devices.

14.
PLoS One ; 19(3): e0299425, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38517859

RESUMEN

To help non-native English speakers quickly master English vocabulary, and improve reading, writing, listening and speaking skills, and communication skills, this study designs, constructs, and improves an English vocabulary learning model that integrates Spiking Neural Network (SNN) and Convolutional Long Short-Term Memory (Conv LSTM) algorithms. The fusion of SNN and Conv LSTM algorithm can fully utilize the advantages of SNN in processing temporal information and Conv LSTM in sequence data modeling, and implement a fusion model that performs well in English vocabulary learning. By adding information transfer and interaction modules, the feature learning and the timing information processing are optimized to improve the vocabulary learning ability of the model in different text contents. The training set used in this study is an open data set from the WordNet and Oxford English Corpus data corpora. The model is presented as a computer program and applied to an English learning application program, an online vocabulary learning platform, or a language education software. The experiment will use the open data set to generate a test set with text volume ranging from 100 to 4000. The performance indicators of the proposed fusion model are compared with those of five traditional models and applied to the latest vocabulary exercises. From the perspective of learners, 10 kinds of model accuracy, loss, polysemy processing accuracy, training time, syntactic structure capturing accuracy, vocabulary coverage, F1-score, context understanding accuracy, word sense disambiguation accuracy, and word order relation processing accuracy are considered. The experimental results reveal that the performance of the fusion model is better under different text sizes. In the range of 100-400 text volume, the accuracy is 0.75-0.77, the loss is less than 0.45, the F1-score is greater than 0.75, the training time is within 300s, and the other performance indicators are more than 65%; In the range of 500-1000 text volume, the accuracy is 0.81-0.83, the loss is not more than 0.40, the F1-score is not less than 0.78, the training time is within 400s, and the other performance indicators are above 70%; In the range of 1500-3000 text volume, the accuracy is 0.82-0.84, the loss is less than 0.28, the F1-score is not less than 0.78, the training time is within 600s, and the remaining performance indicators are higher than 70%. The fusion model can adapt to various types of questions in practical application. After the evaluation of professional teachers, the average scores of the choice, filling-in-the-blank, spelling, matching, exercises, and synonyms are 85.72, 89.45, 80.31, 92.15, 87.62, and 78.94, which are much higher than other traditional models. This shows that as text volume increases, the performance of the fusion model is gradually improved, indicating higher accuracy and lower loss. At the same time, in practical application, the fusion model proposed in this study has a good effect on English learning tasks and offers greater benefits for people unfamiliar with English vocabulary structure, grammar, and question types. This study aims to provide efficient and accurate natural language processing tools to help non-native English speakers understand and apply language more easily, and improve English vocabulary learning and comprehension.


Asunto(s)
Memoria a Corto Plazo , Vocabulario , Humanos , Lenguaje , Redes Neurales de la Computación , Algoritmos
15.
Acta Cardiol Sin ; 40(2): 214-224, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38532816

RESUMEN

Background: Sirtuin 2 (SIRT2) and galectin-3 have been shown to protect the heart against fibrosis. However, their impacts on radiation-induced myocardial fibrosis (RIMF) remain to be elucidated. To deepen this understanding, the current study sought to explore the effects of SIRT2 and galectin-3 on RIMF and the underlying mechanisms. Methods: Galectin-3 knockout mice were obtained, and a radiation-induced heart damage (RIHD) mouse model was induced by local radiation exposure to the heart. Lentivirus transfection was then performed, and heart function, fibrosis of heart tissues, and levels of SIRT2, galectin-3, and fibrosis-related markers collagen type-I/-III and matrix metalloproteinase (MMP)2/MMP9 were respectively assessed by echocardiography, hematoxylin-eosin and Masson staining, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunofluorescence staining. Additionally, Western blot and chromatin immunoprecipitation were used to test H3K27 acetylation levels and the binding of H3K27ac to galectin-3, respectively. Results: After radiation exposure, heart tissues from the galectin-3 knockout mice had a smaller fibrotic area compared to normal mice, with reduced expression levels of collagen type-I/-III and MMP2/MMP9. SIRT2 was down-regulated and galectin-3 was up-regulated after RIHD treatment. The histone deacetylase inhibitor sirtinol promoted galectin-3 expression and H3K27 acetylation in a time-dependent manner, and increased H3K27ac enrichment in the galectin-3 promoter. Overexpression of SIRT2 down-regulated H3K27ac, collagen type-I/-III, and MMP2/MMP9 expression levels, and reduced the fibrotic area in mouse heart tissues. However, these effects were reversed by the additional overexpression of galectin-3. Conclusions: SIRT2 facilitates deacetylation of H3K27 to inhibit galectin-3 transcription, thus ameliorating RIMF in mice.

16.
BMJ Open Respir Res ; 11(1)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38479820

RESUMEN

BACKGROUND: No studies have investigated whether high-sensitivity C reactive protein (hsCRP) can be used to predict the forced expiratory volume in 1 s (FEV1)/estimated value of FEV1 (FEV1%pred). This study aimed to assess the association between hsCRP and FEV1%pred in middle-aged and elderly individuals without underlying lung disease. METHODS: The data for this study were obtained from a prospective cohort study that included 1047 middle-aged and elderly citizens from Beijing aged 40-75 years without any evidence of underlying lung diseases with FEV1 >70% after receiving inhalational bronchodilators. The baseline analysis of the participants was performed from 30 May 2018 to 31 October 2018. Restricted cubic spline regression and multivariate linear regression models were used to assess the non-linear association and linear association between hsCRP and FEV1/FEV in 6 s (FEV6) and FEV1%pred, respectively. RESULTS: The hsCRP values of 851 participants were recorded; the values were normal in 713 (83.8%) participants. The remaining 196 participants (18.7%) had missing data. A non-linear association was observed between normal hsCRP values and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a 2.4% lower in FEV1%pred. Significantly higher FEV1/FEV6 differences were observed in the female subgroup than those in the male subgroup (p=0.011 for interaction). CONCLUSIONS: hsCRP had a non-linear association with FEV1/FEV6 and a linear negative association with FEV1%pred in individuals with normal hsCRP values. hsCRP can be used to predict FEV1%pred, which can be used to predict the development of chronic obstructive pulmonary disease. hsCRP has a stronger association with lung function in women than that in men. TRIAL REGISTRATION NUMBER: NCT03532893.


Asunto(s)
Enfermedades Pulmonares , Pulmón , Anciano , Persona de Mediana Edad , Humanos , Masculino , Femenino , Volumen Espiratorio Forzado , Beijing/epidemiología , Estudios Prospectivos , Proteína C-Reactiva
18.
J Comput Chem ; 45(17): 1456-1469, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38471809

RESUMEN

B 6 O 7 OH 6 2 - is a highly polymerized borate anion of three six-membered rings. Limited research on the B 6 O 7 OH 6 2 - hydrolysis mechanism under neutral solution conditions exists. Calculations based on density functional theory show that B 6 O 7 OH 6 2 - undergoes five steps of hydrolysis to form H3BO3 and B OH 4 - . At the same time, there are a small number of borate ions with different degrees of polymerization during the hydrolysis process, such as triborate, tetraborate, and pentaborate anions. The structure of the borate anion and the coordination environment of the bridging oxygen atoms control the hydrolysis process. Finally, this work explains that in existing experimental studies, the reason for the low B 6 O 7 OH 6 2 - content in solution environments with low total boron concentrations is that it depolymerizes into other types of borate ions and clarifies the borate species. The conversion relationship provides a basis for identifying the possibility of various borate ions existing in the solution. This work also provides a certain degree of theoretical support for the cause of the "dilution to salt" phenomenon.

19.
Chem Commun (Camb) ; 60(23): 3202-3204, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38415740

RESUMEN

N-nitro type reagents have been demonstrated as mild nitration tools in recent years. This work presents an exploration of direct nitration of aryl alkenes mediated by DNDMH, a novel N-nitro type reagent developed in our previous study. It exhibits herein a new property of DNDMH as an effective direct nitration reagent for aryl alkenes, through probably the delivery of nitro radicals with the aid of TEMPO and Cu(OAc)2.

20.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167059, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38336104

RESUMEN

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i was observed after treatment with nifedipine. In our study, ANO1 acted primarily as an activator or amplifier in [Ca2+]i and contraction of tubal smooth muscle cells. We found that tubal SRC was markedly attenuated in patients with ectopic pregnancy. Then, our study was designed to determine whether chloride channel Ano1-mediated smooth muscle motility is associated with tubal SRC. Our findings reveal a new mechanism for the regulation of tubal motility that may be associated with abnormal pregnancies such as ectopic pregnancies.


Asunto(s)
Calcio , Músculo Liso , Animales , Femenino , Humanos , Ratones , Embarazo , Calcio/metabolismo , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Músculo Liso/metabolismo , Miocitos del Músculo Liso/metabolismo , Oviductos/metabolismo
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