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1.
Cell Death Dis ; 15(4): 263, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615011

RESUMO

Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFß and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFß-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin-proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFß. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Complexo de Endopeptidases do Proteassoma , Infarto do Miocárdio/genética , Fator de Crescimento Transformador beta , Ubiquitinas
2.
Heliyon ; 10(7): e29082, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38617964

RESUMO

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007-2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 ß = -0.003, p = 0.005; TT4 ß = -0.035, p < 0.001). This negative correlation persisted when CDAI was categorized into quartiles (FT4, p for trend = 0.014; TT4, p for trend = 0.003). Conclusion: These findings suggest that a diet rich in antioxidants, as reflected by higher CDAI scores, is associated with significant decreases in levels of free and total T4. Further analyses will be necessary to better clarify the underlying mechanisms behind these observations.

3.
Braz J Otorhinolaryngol ; 90(4): 101429, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38636287

RESUMO

OBJECTIVE(S): Endoscopic thyroidectomy, such as axillary, areola and transoral approaches, offer the advantage of a good cosmetic outcome, but it requires a wider dissection field compared to open thyroidectomy. Recently, chest-collarbone approach thyroidectomy has been widely developed in China because of its shorter anatomical route compared to other endoscopic approaches. This study retrospectively evaluated endoscopic thyroidectomy via chest-collarbone approach in patients with thyroid nodules to determine its feasibility. METHODS: A total of 46 patients with thyroid disease who underwent endoscopic thyroidectomy between January 2022 and December 2022 were enrolled in the study and randomly matched to patients with thyroid disease who underwent open thyroidectomy at the same time based on nodule size and pathology. Postoperative bleeding, hoarseness situation, hospital stay, postoperative drainage volume, laryngeal nerve palsy, hypoparathyroidism and wound infection were assessed in both groups. RESULTS: Forty-four patients underwent endoscopic thyroidectomy successfully and two patients changed to open thyroidectomy. The amount of postoperative drainage for the endoscopic thyroidectomy group was 102.78 ±â€¯28.04 mL, and which was 71.91 ±â€¯19.20 for open thyroidectomy group (p < 0.001). The postoperative hospital stay for the endoscopic thyroidectomy group was 8.78 ±â€¯2.57 days, and which was 7.22 ±â€¯1.13 for open thyroidectomy group (p < 0.001). There was no significant difference in postoperative bleeding, hoarseness situation, and wound infection between the two groups. Laryngeal nerve palsy, supraclavicular nerve injury and hypoparathyroidism were not observed in any patient during this study. CONCLUSION: Chest-collarbone endoscopic thyroid surgery is acceptable. This treatment improves in a good cosmetic outcome in patients with thyroid disease. To assess patients with preoperative nodule size and nature of the case is the impact of the success rate, which is particularly important.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38643422

RESUMO

PURPOSE: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. METHODS: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). RESULTS: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). CONCLUSIONS: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

5.
Medicine (Baltimore) ; 103(10): e37350, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457537

RESUMO

Mean corpuscular volume (MCV) is an important indicator used to determine the etiology of anemia and is associated with a variety of diseases. However, the link between thyroid function and MCV has yet to be clarified. This study was thus developed to assess relationships between thyroid function and MCV in a population of adults in the US. Results from the National Health and Nutrition Examination Survey study performed from 2007 to 2012 were used to conduct a cross-sectional analysis. Key thyroid-related variables included in this analysis were thyroid-stimulating hormone, total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), antithyroglobulin, thyroglobulin, and antithyroid peroxidase levels. Generalized linear regression models were employed when estimating associations between MCV quartiles and thyroid parameters in 8104 adults 18 + years of age. In these participants, the weighted mean (SD) MCV was 89.36 (0.16) fL, with thyroid-stimulating hormone levels of 1.86 (0.03) mIU/mL, FT3 levels of 3.20 (0.01) pg/mL, FT4 levels of 0.80 (0.01) ng/dL, TT3 levels of 115.09 (0.64) ng/dL, and TT4 levels of 7.81 (0.04) µg/dL. When analyses were not adjusted, higher MCV values were related to reduced serum levels of FT3, TT3, or TT4. Following adjustment for possible confounding variables, this significant negative correlation between MCV and levels of FT3, TT3, and TT4 remained, and subgroup analysis revealed that this negative correlation was present in the male group and in the age group >50 years, but not in the female group and in the age group less than or equal to 50 years. These results suggest a significant negative correlation between MCV and FT3, TT3, and TT4, and this negative correlation originated more from the male population and those older than 50 years of age. The underlying mechanisms warrant additional investigation.


Assuntos
Glândula Tireoide , Tri-Iodotironina , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Tiroxina , Inquéritos Nutricionais , Estudos Transversais , Índices de Eritrócitos , Hormônios Tireóideos , Tireotropina
6.
Food Chem ; 445: 138732, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367558

RESUMO

In this study, a straightforward approach is presented for the first time to anchor Ir nanoparticles on the surface of uniform polyaniline (PANi) nanotubes (NTs), which can be used as an efficient peroxidase (POD)-like catalyst. The morphology and chemical structure of the PANi-Ir nanocomposite are characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffractometer (XRD), Raman and X-ray photoelectron spectroscopy (XPS) measurements. Owing to the strong interaction between Ir nanoparticles and PANi, a remarkable catalytic enhancement is achieved compared to the bare Ir black catalyst and individual PANi NTs, dominating withan electron transfer mechanism. Furthermore, an efficient colorimetric sensor for ascorbic acid (AA) is developed with a low detection limit of 1.0 µM (S/N = 3), and a total antioxidant capacity (TAC) sensing platform is also constructed for the rigorous detection and analysis of fruits and vegetables.


Assuntos
Compostos de Anilina , Nanopartículas , Nanotubos , Antioxidantes , Verduras , Irídio , Peroxidase , Frutas , Nanotubos/química , Nanopartículas/química , Peroxidases
7.
Int J Oral Sci ; 16(1): 19, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418457

RESUMO

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment. However, the sensitivity of existing detection techniques is not sufficient, and the criteria for evaluating optimal force have not been yet established. Here, by employing 3D finite element analysis methodology, we found that the apical distal region (A-D region) of mesial roots is particularly sensitive to orthodontic force in rats. Tartrate-resistant acidic phosphatase (TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams (g), leading to alveolar bone resorption and tooth movement. When the force reached 80 g, TRAP-positive osteoclasts started appearing on the root surface in the A-D region. Additionally, micro-computed tomography revealed a significant root resorption at 80 g. Notably, the A-D region was identified as a major contributor to whole root resorption. It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement, inclination, and hyalinization. These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model. Collectively, our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients' orthodontic treatment.


Assuntos
Perda do Osso Alveolar , Reabsorção da Raiz , Humanos , Ratos , Animais , Reabsorção da Raiz/diagnóstico por imagem , Osteoclastos , Microtomografia por Raio-X , Técnicas de Movimentação Dentária , Raiz Dentária/diagnóstico por imagem , Dente Molar/diagnóstico por imagem
8.
Clin Transl Immunology ; 13(2): e1489, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322490

RESUMO

Objectives: Tertiary lymphoid structures (TLSs) are lymphocyte aggregates that play an anti-tumor role in most solid tumors. However, the functions of TLS in gastric neuroendocrine neoplasms (GNENs) remain unknown. This study aimed to determine the characteristics and prognostic values of TLS in resected GNEN patients. Methods: Haematoxylin-eosin, immunohistochemistry (IHC) and multiple fluorescent IHC staining were used to assess TLS to investigate the correlation between TLSs and clinicopathological characteristics and its prognostic value. Results: Tertiary lymphoid structures were identified in 84.3% of patients with GNEN. They were located in the stromal area or outside the tumor tissue and mainly composed of B and T cells. A high density of TLSs promoted an anti-tumor immune response in GNEN. CD15+ TANs and FOXP3+ Tregs in TLSs inhibited the formation of TLSs. High TLS density was significantly associated with prolonged recurrence-free survival (RFS) and overall survival (OS) of GNENs. Univariate and multivariate Cox regression analyses revealed that TLS density, tumor size, tumor-node-metastasis (TNM) stage and World Health Organisation (WHO) classification were independent prognostic factors for OS, whereas TLS density, tumor size and TNM stage were independent prognostic factors for RFS. Finally, OS and RFS nomograms were developed and validated, which were superior to the WHO classification and the TNM stage. Conclusion: Tertiary lymphoid structures were mainly located in the stromal area or outside the tumor area, and high TLS density was significantly associated with the good prognosis of patients with GNEN. Incorporating TLS density into a nomogram may improve survival prediction in patients with resected GNEN.

9.
Eye (Lond) ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336992

RESUMO

OBJECTIVES: To investigate a comprehensive proteomic profile of the tear fluid in patients with diabetic retinopathy (DR) and further define non-invasive biomarkers. METHODS: A cross-sectional, multicentre study that includes 46 patients with DR, 28 patients with diabetes mellitus (DM), and 30 healthy controls (HC). Tear samples were collected with Schirmer strips. As for the discovery set, data-independent acquisition mass spectrometry was used to characterize the tear proteomic profile. Differentially expressed proteins between groups were identified, with gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further developed. Classifying performance of biomarkers for distinguishing DR from DM was compared by the combination of three machine-learning algorithms. The selected biomarker panel was tested in the validation cohort using parallel reaction monitoring mass spectrometry. RESULTS: Among 3364 proteins quantified, 235 and 88 differentially expressed proteins were identified for DR when compared to HC and DM, respectively, which were fundamentally related to retina homeostasis, inflammation and immunity, oxidative stress, angiogenesis and coagulation, metabolism, and cellular adhesion processes. The biomarker panel consisting of NAD-dependent protein deacetylase sirtuin-2 (SIR2), amine oxidase [flavin-containing] B (AOFB), and U8 snoRNA-decapping enzyme (NUD16) exhibited the best diagnostic performance in discriminating DR from DM, with AUCs of 0.933 and 0.881 in the discovery and validation set, respectively. CONCLUSIONS: Tear protein dysregulation is comprehensively revealed to be associated with DR onset. The combination of tear SIR2, AOFB, and NUD16 can be a novel potential approach for non-invasive detection or pre-screening of DR. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100054263. https://www.chictr.org.cn/showproj.html?proj=143177 . Date of registration: 2021/12/12.

10.
Mikrochim Acta ; 191(2): 90, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214747

RESUMO

A novel mosaic structure Silica@C/Co@ZIF-67 composite was synthesized by successfully embedding Co nanoparticles on the surface of silica spheres with the help of thermoplastic polyethyleneimine by carbon-reduction. The ZIF-67 half-shell layer structure was synthesized by the in-situ growth of ZIF-67 on the surface of silica spheres through the coordination of 2-methylimidazole with Co metal nodes. The composite was used as a magnetic solid-phase extraction adsorbent combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) for the extraction and determination of benzoylurea insecticides (BUs) in vegetables and tea. Based on the presence of π-π, hydrophobic and hydrogen bonding interactions between Silica@C/Co@ZIF-67 and BUs, the BUs were rapidly captured by the composites resulting in high adsorption performance. Under the optimal extraction parameters, the linear ranges were 0.3-200 µg L-1 for diflubenzuron, 0.6-200 µg L-1 for chlorbenzuron, and 1.0-200 µg L-1 for triflumuron, teflubenzuron, and flufenoxuron, with correlation coefficients (R2) greater than 0.9991. The limits of detection (LODs) of the method were 0.1-0.3 µg L-1, and the relative standard deviations (RSDs) were 1.2-3.0% for intra-day and 2.6-4.6% for inter-day. In the spiked recovery experiments of vegetables and tea, the recoveries of the five kinds of BUs ranged from 75.8 to 112.9%. In addition, after 10 repetitions using Silica@C/Co@ZIF-67, the recoveries of the five kinds of BUs were still as high as 78.4 to 83.9%.


Assuntos
Diflubenzuron , Inseticidas , Inseticidas/análise , Cromatografia Líquida de Alta Pressão/métodos , Chá/química , Dióxido de Silício
11.
Eur J Nucl Med Mol Imaging ; 51(6): 1530-1543, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38189910

RESUMO

PURPOSE: Noninvasive quantifying activated hepatic stellate cells (aHSCs) by molecular imaging is helpful for assessing disease progression and therapeutic responses of liver fibrosis. Our purpose is to develop platelet-derived growth factor receptor ß (PDGFRß)-targeted radioactive tracer for assessing liver fibrosis by positron emission tomography (PET) imaging of aHSCs. METHODS: Comparative transcriptomics, immunofluorescence staining and flow cytometry were used to evaluate PDGFRß as biomarker for human aHSCs and determine the correlation of PDGFRß with the severity of liver fibrosis. The high affinity affibody for PDGFRß (ZPDGFRß) was labeled with gallium-68 (68Ga) for PET imaging of mice with carbon tetrachloride (CCl4)-induced liver fibrosis. Binding of the [68Ga]Ga-labeled ZPDGFRß ([68Ga]Ga-DOTA-ZPDGFRß) for aHSCs in human liver tissues was measured by autoradiography. RESULTS: PDGFRß overexpressed in aHSCs was highly correlated with the severity of liver fibrosis in patients and CCl4-treated mice. The 68Ga-labeled ZPDGFRß affibody ([68Ga]Ga-DOTA-ZPDGFRß) showed PDGFRß-dependent binding to aHSCs. According to the PET imaging, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß increased with the accumulation of aHSCs and collagens in the fibrotic livers of mice. In contrast, hepatic uptake of [68Ga]Ga-DOTA-ZPDGFRß decreased with spontaneous recovery or treatment of liver fibrosis, indicating that the progression and therapeutic responses of liver fibrosis in mice could be visualized by PDGFRß-targeted PET imaging. [68Ga]Ga-DOTA-ZPDGFRß also bound human aHSCs and visualized fibrosis in patient-derived liver tissues. CONCLUSIONS: PDGFRß is a reliable biomarker for both human and mouse aHSCs. PDGFRß-targeted PET imaging could be used for noninvasive monitoring of liver fibrosis in mice and has great potential for clinical translation.


Assuntos
Radioisótopos de Gálio , Cirrose Hepática , Tomografia por Emissão de Pósitrons , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/metabolismo , Animais , Tomografia por Emissão de Pósitrons/métodos , Humanos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Camundongos , Masculino , Células Estreladas do Fígado/metabolismo , Compostos Heterocíclicos com 1 Anel/química
12.
Anal Chim Acta ; 1287: 342112, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38182348

RESUMO

BACKGROUND: Large accumulations of pesticide residues in the environment eventually enter the human body with food. Based on magnetic solid-phase extraction (MSPE) technology, it is possible to achieve efficient extraction of trace pesticide residues in foodstuffs, and the construction of MSPE adsorbents with excellent magnetic properties and many active sites is still one of the main research topics. Based on this, we developed a new strategy for the preparation of "MOF-on-MOF" composites, which were carbonized and used as adsorbents for the extraction of pesticide residues in cereals. RESULTS: A novel corn cob core-shell composite Fe2O3@C@ZIF-8 was created by embedding ZIF-8 onto the surface of Fe2O3@C derived from MIL-88A(Fe), and used for the extraction of benzoylurea insecticides(BUs) from cereals. The adsorption behaviour between Fe2O3@C@ZIF-8 and BUs was investigated by static and kinetic experiments and the adsorption mechanism was elaborated. For the trace analysis of BUs, a magnetic solid-phase extraction combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) approach was also developed. Under the optimized experimental conditions, the limits of detection and quantification were 0.015-0.03 µg L-1 and 0.05-0.1 µg L-1, and the relative standard deviations for the intra-day and inter-day ranges were 1.82%-2.13 % and 3.85%-4.59 %, respectively. The spiked recoveries of the four cereals ranged from 82.72% to 104.45 %. After 10 cycles of use of Fe2O3@C@ZIF-8, the recoveries of BUs ranged from 77.90% to 96.74 %. SIGNIFICANCE: The analytical method based on Fe2O3@C@ZIF-8 as adsorbent has a low limit of detection, a wide linear range and is highly applicable to the analysis of real samples. In addition, the strategy developed in this study for the preparation of thermoplastic polymer-assisted "MOF-on-MOF" composites has promising applications.


Assuntos
Resíduos de Praguicidas , Humanos , Zea mays , Adsorção , Carbono , Grão Comestível , Fenômenos Magnéticos
13.
Invest Ophthalmol Vis Sci ; 65(1): 38, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38252524

RESUMO

Purpose: Whether H1N1 infection-associated ocular manifestations result from direct viral infections or systemic complications remains unclear. This study aimed to comprehensively elucidate the underlying causes and mechanism. Method: TCID50 assays was performed at 24, 48, and 72 hours to verify the infection of H1N1 in human retinal microvascular endothelial cells (HRMECs). The changes in gene expression profiles of HRMECs at 24, 48, and 72 hours were characterized using RNA sequencing technology. Differentially expressed genes (DEGs) were validated using real-time quantitative polymerase chain reaction and Western blotting. CCK-8 assay and scratch assay were performed to evaluate whether there was a potential improvement of proliferation and migration in H1N1-infected cells after oseltamivir intervention. Results: H1N1 can infect and replicate within HRMECs, leading to cell rounding and detachment. After H1N1 infection of HRMECs, 2562 DEGs were identified, including 1748 upregulated ones and 814 downregulated ones. These DEGs primarily involved in processes such as inflammation and immune response, cytokine-cytokine receptor interaction, signal transduction regulation, and cell adhesion. The elevated expression levels of CXCL10, CXCL11, CCL5, TLR3, C3, IFNB1, IFNG, STAT1, HLA, and TNFSF10 after H1N1 infection were reduced by oseltamivir intervention, reaching levels comparable to those in the uninfected group. The impaired cell proliferation and migration after H1N1 infection was improved by oseltamivir intervention. Conclusions: This study confirmed that H1N1 can infect HRMECs, leading to the upregulation of chemokines, which may cause inflammation and destruction of the blood-retina barrier. Moreover, early oseltamivir administration may reduce retinal inflammation and hemorrhage in patients infected with H1N1.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Células Endoteliais , Influenza Humana/complicações , Oseltamivir , Retina , Inflamação
14.
Crit Rev Oncol Hematol ; 195: 104271, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272151

RESUMO

RNA-binding proteins (RBPs) refer to a class of proteins that participate in alternative splicing, RNA stability, polyadenylation, localization and translation of RNAs, thus regulating gene expression in post-transcriptional manner. Dysregulation of RNA-RBP interaction contributes to various diseases, including cancer. In breast cancer, disorders in RBP expression and function influence the biological characteristics of tumor cells. Targeting RBPs has fostered the development of innovative therapies for breast cancer. However, the RBP-related mechanisms in breast cancer are not completely clear. In this review, we summarize the regulatory mechanisms of RBPs and their signaling crosstalk in breast cancer. Specifically, we emphasize the potential of certain RBPs as prognostic factors due to their effects on proliferation, invasion, apoptosis, and therapy resistance of breast cancer cells. Most importantly, we present a comprehensive overview of the latest RBP-related therapeutic strategies and novel therapeutic targets that have proven to be useful in the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Proteínas de Ligação a RNA/genética
15.
Cancer Sci ; 115(2): 369-384, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050654

RESUMO

In gastric cancer (GC), the liver is a common organ for distant metastasis, and patients with gastric cancer with liver metastasis (GCLM) generally have poor prognosis. The mechanism of GCLM is unclear. Invadopodia are special membrane protrusions formed by tumor cells that can degrade the basement membrane and ECM. Herein, we investigated the role of invadopodia in GCLM. We found that the levels of invadopodia-associated proteins were significantly higher in liver metastasis than in the primary tumors of patients with GCLM. Furthermore, GC cells could activate hepatic stellate cells (HSCs) within the tumor microenvironment of liver metastases through the secretion of platelet-derived growth factor subunit B (PDGFB). Activated HSCs secreted hepatocyte growth factor (HGF), which activated the MET proto-oncogene, MET receptor of GC cells, thereby promoting invadopodia formation through the PI3K/AKT pathway and subsequently enhancing the invasion and metastasis of GC cells. Therefore, cross-talk between GC cells and HSCs by PDGFB/platelet derived growth factor receptor beta (PDGFRß) and the HGF/MET axis might represent potential therapeutic targets to treat GCLM.


Assuntos
Neoplasias Hepáticas , Podossomos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-sis/metabolismo , Células Estreladas do Fígado/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hepáticas/patologia , Transdução de Sinais , Microambiente Tumoral
16.
J Colloid Interface Sci ; 657: 83-90, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38035422

RESUMO

The development of non-precious metal electrocatalysts for oxygen evolution reaction (OER) is crucial for generating large-scale hydrogen through water electrolysis. In this work, bimetal phosphides embedded in electrospun carbon nanofibers (P-FeNi/CNFs) were fabricated through a reliable electrospinning-carbonization-phosphidation strategy. The incorporation of P-FeNi nanoparticles within CNFs prevented them from forming aggregation and further improved their electron transfer property. The bimetal phosphides helped to weaken the adsorption of O intermediate, promoting the OER activity, which was confirmed by the theoretical results. The as-prepared optimized P-Fe1Ni2/CNFs catalyst exhibited very high OER electrocatalytic performance, which required very low overpotentials of just 239 and 303 mV to reach 10 and 1000 mA cm-2, respectively. It is superior to the commercial RuO2 and many other related OER electrocatalysts reported so far. In addition, the constructed alkaline electrolyzer based on the P-Fe1Ni2/CNFs catalyst and Pt/C delivered a cell voltage of 1.52 V at 10 mA cm-2, surpassing the commercial RuO2||Pt/C (1.61 V) electrolyzer. It also offered excellent alkaline OER performance in simulated seawater electrolyte. This demonstrated its potential for practical applications across a broad range of environmental conditions. Our work provides new ideas for the ration design of highly efficient non-precious metal-based OER catalysts for water electrolysis.

17.
Small ; 20(1): e2304782, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649181

RESUMO

Rational designing electrocatalysts is of great significance for realizing high-efficiency H2 production in the water splitting process. Generally, reducing the usage of precious metals and developing low-potential nucleophiles oxidation reaction to replace anodic oxygen evolution reaction (OER) are efficient strategies to promote H2 generation. Here, NiS-coated nickel-carbon nanofibers (NiS@Ni-CNFs) are prepared for low-content Pt deposition (Pt-NiS@Ni-CNFs) to attain the alkaline HER catalyst. Due to the reconfiguration of NiS phase and synergistic effect between Pt and nickel sulfides, the Pt-NiS@Ni-CNFs catalyst shows a high mass activity of 2.74-fold of benchmark Pt/C sample. In addition, the NiS@Ni-CNFs catalyst performs a superior urea oxidation reaction (UOR) activity with the potential of 1.366 V versus reversible hydrogen electrode (RHE) at 10 mA cm-2 , which demonstrates the great potential in the replacement of OER. Thus, a urea-assisted water splitting electrolyzer of Pt-NiS@Ni-CNFs (cathode)||NiS@Ni-CNFs (anode) is constructed to exhibit small voltages of 1.44 and 1.65 V to reach 10 and 100 mA cm-2 , which is much lower than its overall water splitting process, and presents a 6.5-fold hydrogen production rate enhancement. This work offers great opportunity to design new catalysts toward urea-assisted water splitting with significantly promoted hydrogen productivity and reduced energy consumption.

18.
Adv Sci (Weinh) ; 11(7): e2307061, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072643

RESUMO

The realization of large-scale industrial application of alkaline water electrolysis for hydrogen generation is severely hampered by the cost of electricity. Therefore, it is currently necessary to synthesize highly efficient electrocatalysts with excellent stability and low overpotential under an industrial-level current density. Herein, Ir-incorporated in partially oxidized Ru aerogel has been designed and synthesized via a simple in situ reduction strategy and subsequent oxidation process. The electrochemical measurements demonstrate that the optimized Ru98 Ir2 -350 electrocatalyst exhibits outstanding hydrogen evolution reaction (HER) performance in an alkaline environment (1 M KOH). Especially, at the large current density of 1000 mA cm-2 , the overpotential is as low as 121 mV, far exceeding the benchmark Pt/C catalyst. Moreover, the Ru98 Ir2 -350 catalyst also displays excellent stability over 1500 h at 1000 mA cm-2 , denoting its industrial applicability. This work provides an efficient route for developing highly active and ultra-stable electrocatalysts for hydrogen generation under industrial-level current density.

19.
Life Sci Alliance ; 7(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38081642

RESUMO

tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5'tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.


Assuntos
Piruvato Carboxilase , Neoplasias da Glândula Tireoide , Humanos , Piruvato Carboxilase/metabolismo , Neoplasias da Glândula Tireoide/genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , Linhagem Celular
20.
J Clin Sleep Med ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38059337

RESUMO

STUDY OBJECTIVES: This study aimed to evaluate the safety and short-term effect of contemporaneous surgeries (Bariatric surgery plus uvulopalatopharyngoplasty (UPPP)) in the treatment of morbid obesity comorbid with severe obstructive sleep apnea(OSA). METHODS: A retrospective cohort study was performed to identify patients with obesity and severe OSA who underwent laparoscopic sleeve gastrectomy (LSG) with or without UPPP surgeries between December 2019 and December 2021 in our center. Patients were divided into two groups according to different surgical methods (contemporaneous group [LSG with UPPP] vs LSG only group). Data about surgical safety, OSA remission, and effectiveness of weight loss were collected and analyzed between the two groups before and 12 months after surgery. RESULTS: A total of 101 patients were included in this study (contemporaneous group [LSG with UPPP], n=42 vs LSG only group, n=59). There was no significant difference in surgical safety between the two groups, while both OSA and obesity were significantly improved after 12.5±2.1 months postoperative follow-up. The apnea-hypopnea index(AHI) decreased from 68.7±30.4/h to 10.2±7.0/h in the contemporaneous group (P <0.001) and from 64.7±26.2/h to 18.9±9.8/h in the LSG group (P <0.001). Moreover, the AHI decreased to below 5/h in 50% of patients (21/42) in the contemporaneous group while only in 13.5% in LSG group (P <0.001). In the LSG group 20 (34%) patients achieved a reduction in AHI <15 and resolution of daytime sleepiness. CONCLUSIONS: Contemporaneous surgery (concurrent bariatric and UPPP surgeries) is feasible and an effective option for patients with obesity and severe OSA. However, our finding suggests that approximately a third of patients undergoing LSG with UPPP may not derive significant benefit from the UPPP portion of the contemporaneous surgical approach.

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