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1.
J Pharm Biomed Anal ; 246: 116212, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735209

RESUMO

Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.

2.
Environ Sci Technol ; 58(10): 4558-4570, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38408313

RESUMO

Calcium is a highly demanded metal, and its transport across the intestine of Daphnia magna remains a significant unresolved question. Due to technical constraints, the visualization of the kinetic process of Ca passage through D. magna has been challenging. Here, we developed the second near-infrared Ca sensor (NIR-II Ca) and conducted real-time in vivo imaging of Ca in daphnids with a high signal-to-noise ratio, deep tissue penetration, and minimal damage. Through the utilization of the NIR-II Ca sensor, we for the first time visualized and quantified the kinetic process of Ca passage in the intestine in real time. The results revealed that trophically available Ca passed through the intestines in 24 h, whereas waterborne Ca required only 35 min. This rapid "flushing through" mechanism established waterborne Ca as the primary source of Ca absorption. However, environmental stressors such as water acidification and cadmium significantly delayed the Ca passage and absorption. The development of NIR imaging and sensors allows for real-time dynamic visualization of contaminants/nutrients in organisms and holds great potential as a powerful tool for future studies into material kinetic processes in living animals.


Assuntos
Cádmio , Poluentes Químicos da Água , Animais , Cálcio , Daphnia magna , Daphnia , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
3.
Hypertension ; 80(12): 2674-2686, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37846580

RESUMO

BACKGROUND: Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling. However, the specific role of CHMP4C in the progression of cardiac hypertrophy remains largely unknown. METHODS: Mouse models with CHMP4C knockout or cardiadc-specific overexpression were subjected to transverse aortic constriction surgery for 4 weeks. Cardiac morphology and function were assessed through histological staining and echocardiography. Confocal imaging and coimmunoprecipitation assays were performed to identify the direct target of CHMP4C. An EGFR (epidermal growth factor receptor) inhibitor was administrated to determine whether effects of CHMP4C on cardiac hypertrophy were EGFR dependent. RESULTS: CHMP4C was significantly upregulated in both pressure-overloaded mice and spontaneously hypertensive rats. Compared with wild-type mice, CHMP4C deficiency exacerbated transverse aortic constriction-induced cardiac hypertrophy, whereas CHMP4C overexpression in cardiomyocytes attenuated cardiac dysfunction. Mechanistically, the effect of CHMP4C on cardiac hypertrophy relied on the EGFR signaling pathway. Fluorescent staining and coimmunoprecipitation assays confirmed that CHMP4C interacts directly with EGFR and promotes lysosome-mediated degradation of activated EGFR, thus attenuating cardiac hypertrophy. Notably, an EGFR inhibitor canertinib counteracted the exacerbation of cardiac hypertrophy induced by CHMP4C knockdown in vitro and in vivo. CONCLUSIONS: CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte , Insuficiência Cardíaca , Ratos , Camundongos , Animais , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Cardiomegalia/metabolismo , Insuficiência Cardíaca/metabolismo , Receptores ErbB , Miócitos Cardíacos/metabolismo , Lisossomos/metabolismo , Lisossomos/patologia , Camundongos Knockout , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
4.
Langmuir ; 39(32): 11304-11316, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37535432

RESUMO

Silane is known as an effective coating for enhancing the resistance of concrete to harmful acids and radicals that are usually produced by the metabolism of microorganisms. However, the mechanism of silane protection is still unclear due to its nanoscale attributes. Here, the protective behavior of silane on the calcium silicate hydrate (C-S-H) surface is examined under the attack environment of nitrate/sulfate ions using molecular dynamics simulations. The findings revealed that silane coating improved the resistance of C-S-H to nitrate/sulfate ions. This resistance is considered the origin of silane protection against harmful ion attacks. Further research on the details of molecular structures suggests that the interaction between the oxygen in the silane molecule and the calcium in C-S-H, which can prevent the coordination of sulfate and nitrate to calcium on the C-S-H surface, is the cause of the silane molecules' strong adsorption. These results are also proved in terms of free energy, which found that the adsorption free energy on the C-S-H surface followed the order silane > sulfate > nitrate. This research confirms the excellent protection performance of silane on the nanoscale. The revealed mechanism can be further used to help the development of high-performance composite coatings.

5.
Adv Sci (Weinh) ; 10(19): e2301104, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37088786

RESUMO

Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR-absorbing small molecule named TBT-2(TP-DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE-PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR-responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Nanomedicina Teranóstica/métodos
6.
ACS Nano ; 17(5): 4591-4600, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36857475

RESUMO

Fluorescence-guided phototherapy, including photodynamic and photothermal therapy, is considered an emerging noninvasive strategy for cancer treatments. Organic molecules are promising theranostic agents because of their facile construction, simple modification, and good biocompatibility. Organic systems that integrated multifunctionalities in a single component and achieved high efficiency in both imaging and therapies are rarely reported as the inherently competitive energy relaxation pathways are hard to modulate, and fluorescence quenching occurs upon molecular aggregation. Herein, a versatile theranostic platform with near-infrared emission, high fluorescence quantum yield, robust reactive oxygen species production, and excellent photothermal conversion efficiency was developed based on an aggregation-induced emission luminogen, namely, TPA-TBT. In vivo studies revealed that the TPA-TBT nanoaggregates exhibit outstanding photodynamic and photothermal therapy efficacy to ablate tumors inoculated in a mouse model. This work offers a design strategy to develop one-for-all cancer theranostic agents by modulating and utilizing the relaxation energy of excitons in full.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Medicina de Precisão , Nanopartículas/uso terapêutico , Nanomedicina Teranóstica/métodos , Fototerapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
7.
Angew Chem Int Ed Engl ; 62(17): e202215206, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527254

RESUMO

Introducing chirality into the metal-halide hybrids has enabled many emerging properties including chiroptical activity, spin-dependent transport, and ferroelectricity. However, most of the chiral metal-halide hybrids to date are non-emissive, and the underlying mechanism remains elusive. Here, we show a new strategy to turn on the circularly polarized luminescence (CPL) in chiral metal-halide hybrids. We demonstrate that alloying Sb3+ into chiral indium-chloride hybrids dramatically increases the photoluminescence quantum yield in two new series of chiral indium-antimony chlorides. These materials exhibit strong CPL signals with tunable energy and a high dissymmetry factor up to 1.5×10-2 . Mechanistic studies reveal that the emission originates from the self-trapped excitons centered in 5s2 Sb3+ . Moreover, near-ultraviolet pumped white light is demonstrated with a polarization up to 6.0 %. Our work demonstrates new strategies towards highly luminescent chiral metal-halide hybrids.

8.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 51-61, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38279482

RESUMO

Cells associated with cancer (CAFs) contribute significantly to the stroma of a tumor microenvironment (TME), which is related to the occurrence, treatment, and prognosis of lung adenocarcinoma (LUAD). Therefore, this study investigated the function of CAF-associated genes in the microenvironment of LUAD. The Cancer Genome Atlas (TCGA) database was used to download RNA-seq data from the TCGA Lung Adenocarcinoma cohort (TCGA-LUAD). The GSE68465 dataset, as the external validation set, was from the Gene Expression Omnibus (GEO) database. Besides, CAF-associated genes were sourced from the GeneCards and Molecular Signatures Database (MsigDB). For LUAD, differentially expressed CAF-related genes were selected from overlapping CAF and LUAD patient and control samples. Next, LASSO and Univariate Cox analyses were used to construct the risk model. Additionally, an analysis of Cox regression was used to construct a nomogram. Next, the immune infiltration in malignant tumour tissues was compared between high- and low-risk groups using Estimation of STromal and Immune cells in MAlignant Tumours (ESTIMATE) tissues and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The sensitivity differences of immunotherapy between the two risk groups were estimated by Tumor Immune Dysfunction and Exclusion (TIDE), and compared by rank-sum test. Finally, the model genes were detected by fluorescent real-time quantitative polymerase chain reaction (qRT-PCR). A total of 57 DE-CAFGs were acquired, and 9 of them (SHCBP1, CCNA2, AKAP12, CCNB1, GALNT3, SCGB1A1, CPS1, CDC6, and CXCL13) were selected as prognostic biomarkers. The Cox independent prognosis revealed the RiskScore and Stage were the two LUAD independent prognosis factors Moreover, 11 types of immune cells (memory B cells, resting natural killer cells (NK cells), Eosinophils, Macrophages M0, CD4 memory resting T cells, CD4 memory activated T cells, resting Mast cells, naive B cells, T cells regulatory (Tregs), neutrophils, and plasma cell), and 18 human leukocyte antigen (HLA) genes were different with the two risk groups. Lastly, the TIDE analysis showed differences between the two risk groups for TIDE, T cell dysfunction, and T cell exclusion, PD-L1 treatment scores. Lastly, Both LUAD and normal samples expressed the 9 model genes differently. A CAF-related prognostic model was constructed, which may have potential immunotherapy guiding significance for LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Fibroblastos Associados a Câncer , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Imunoterapia , Linfócitos T CD4-Positivos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Microambiente Tumoral/genética , Proteínas Adaptadoras da Sinalização Shc
9.
J Biochem Mol Toxicol ; 36(11): e23196, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35979984

RESUMO

Doxorubicin (DOX) is a potent chemotherapeutic agent used for cancer treatment, however, DOX-induced cardiotoxicity is a serious clinical problem because it causes acute and chronic heart dysfunction. Many studies have indicated that the α1-adrenergic receptor protects the heart from pathologic stress through activation survival signaling, however, the mechanism remains largely unknown. Previous studies have detected that the phenylephrine-induced complex-1 (PEX1) transcription factor, also known as zinc-finger protein 260 (Zfp260), is an effector of α1-adrenergic signaling in cardiac hypertrophy. Our present study aimed to investigate the role and underlying mechanism of PEX1 in cardiomyocyte survival during DOX-induced cardiotoxicity. Mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. We found that PEX1 expression was downregulated in DOX-treated murine hearts. PEX1 deficiency resulted in increased apoptosis, and conversely, PEX1 overexpression alleviated apoptosis induced by DOX in primary cardiomyocytes, as well as upregulated antiapoptotic genes such as BCL-2 and BCL-XL. Mechanistically, we identified that PEX1 might exert its antiapoptosis effect by playing a pivotal role in the action of α1-adrenergic signaling activation, which depends on the presence of GATA-4. Based on these findings, we supposed that PEX1 may be a novel transcription factor involved in cardiac cell survival and a promising candidate target for DOX-induced cardiotoxicity.


Assuntos
Adrenérgicos , Cardiotoxicidade , Camundongos , Animais , Cardiotoxicidade/metabolismo , Adrenérgicos/metabolismo , Adrenérgicos/farmacologia , Doxorrubicina/toxicidade , Miócitos Cardíacos/metabolismo , Apoptose , Fatores de Transcrição/metabolismo , Estresse Oxidativo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/farmacologia
10.
Food Chem X ; 13: 100265, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35498983

RESUMO

Effects of acidic electrolyzed water (AEW) treatment (pH = 2.5, ACC = 80 mg L-1, 10 min) on pulp firmness, amounts of CWM and CWP, activities and expression of relevant genes of CWDEs in pulp of Fuyan longan during storage at 25 °C were evaluated. Compared to control samples, during storage, AEW-treated fruit retained a higher pulp firmness, prevented WSP formation, reduced the degradation of CSP, cellulose and hemicellulose, and lowered CWDEs activities and their corresponding gene expression. When stored for 5 d, pulp firmness (113.6 g mm-1), CWM (13.9 g kg-1), and CSP (1.4 g kg-1) in AEW-treated fruit displayed the clearly higher contents than those in control samples. These data suggest that AEW treatment can slow down the pulp softening and retain higher pulp CWP levels in postharvest fresh longans, which was because AEW lowered activities of CWDEs and its gene expression levels, and maintained the cell wall structure's integrity.

11.
Small ; 18(8): e2106906, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35199486

RESUMO

Resistive pressure sensors have been widely studied for application in flexible wearable devices due to their outstanding pressure-sensitive characteristics. In addition to the outstanding electrical performance, environmental friendliness, breathability, and wearable comfortability also deserve more attention. Here, a biodegradable, breathable multilayer pressure sensor based piezoresistive effect is presented. This pressure sensor is designed with all biodegradable materials, which show excellent biodegradability and breathability with a three-dimensional porous hierarchical structure. Moreover, due to the multilayer structure, the contact area of the pressure sensitive layers is greatly increased and the loading pressure can be distributed to each layer, so the pressure sensor shows excellent pressure-sensitive characteristics over a wide pressure sensing range (0.03-11.60 kPa) with a high sensitivity (6.33 kPa-1 ). Furthermore, the sensor is used as a human health monitoring equipment to monitor the human physiological signals and main joint movements, as well as be developed to detect different levels of pressure and further integrated into arrays for pressure imaging and a flexible musical keyboard. Considering the simple manufacturing process, the low cost, and the excellent performance, leaf vein-based pressure sensors provide a good concept for environmentally friendly wearable devices.


Assuntos
Dispositivos Eletrônicos Vestíveis , Humanos , Monitorização Fisiológica , Porosidade , Tato
13.
Commun Chem ; 5(1): 174, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36697742

RESUMO

Creating conjugated macrocycles has attracted extensive research interest because their unique chemical and physical properties, such as conformational flexibility, intrinsic inner cavities and aromaticity/antiaromaticity, make these systems appealing building blocks for functional supramolecular materials. Here, we report the synthesis of four-, six- and eight-membered tetraphenylethylene (TPE)-based macrocycles on Ag(111) via on-surface Ullmann coupling reactions. The as-synthesized macrocycles are spontaneously segregated on the surface and self-assemble as large-area two-dimensional mono-component supramolecular crystals, as characterized by scanning tunneling microscopy (STM). We propose that the synthesis benefits from the conformational flexibility of the TPE backbone in distinctive multi-step reaction pathways. This study opens up opportunities for exploring the photophysical properties of TPE-based macrocycles.

14.
Front Cardiovasc Med ; 8: 758500, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34859073

RESUMO

Background: Cardiac pacing in patients with bradyarrhythmia may employ variable pacing sites, which may have different effects on cardiac function. Left bundle branch pacing (LBBP) is a new physiological pacing modality, and the acute outcomes on cardiac mechanical synchrony during LBBP remain uncertain. We evaluated the acute effects of four pacing sites on cardiac synchrony and contraction using speckle-tracking echocardiography, and comparisons among four different pacing sites were rare. Methods: We enrolled 21 patients with atrioventricular block or sick sinus syndrome who each sequentially underwent acute pacing protocols, including right ventricular apical pacing (RVAP), right ventricular outflow tract pacing (RVOP), His bundle pacing (HBP), and left bundle branch pacing (LBBP). Electrocardiograms and echocardiograms were recorded at baseline and during pacing. The interventricular mechanical delay (IVMD), the standard deviation of the times to longitudinal peak strain during 17 segments (PSD), and the Yu index were used to evaluate ventricular mechanical synchrony. Layer-specific strain was computed using two-dimensional speckle tracking technique to provide in-depth details about ventricular synchrony and function. Results: Left ventricular ejection fraction (LVEF) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased during RVAP and RVOP but were not significantly different during HBP and LBBP compared with baseline. RVAP and RVOP significantly prolonged QRS duration, whereas HBP and LBBP showed non-significant effects. IVMD and PSD were significantly increased during RVAP but were not significantly different during RVOP, HBP, or LBBP. LBBP resulted in a significant improvement in the IVMD and Yu index compared with RVAP. No significant differences in mechanical synchrony were found between HBP and LBBP. Conclusion: Among these pacing modalities, RVAP has a negative acute impact on cardiac synchrony and contraction. HBP and LBBP best preserve physiological cardiac synchrony and function.

15.
Adv Mater ; 33(48): e2105113, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34605067

RESUMO

Microscopic control of macroscopic phenomena is one of the core subjects in materials science. Particularly, the spatio-temporal control of material behaviors through a non-contact way is of fundamental importance but is difficult to accomplish. Herein, a strategy to realize remote spatio-temporal control of luminescence behaviors is reported. A multi-arm salicylaldehyde benzoylhydrazone-based aggregation-induced emission luminogen (AIEgen)/metal-ion system, of which the fluorescence can be gated by the UV irradiation with time dependency, is developed. By changing the metal-ion species, the fluorescence emission and the intensity can also be tuned. The mechanism of the UV-mediated fluorescence change is investigated, and it is revealed that a phototriggered aggregation-induced emission (PTAIE) process contributes to the behaviors. The AIEgen is further covalently integrated into a polymeric network and the formed gel/metal-ion system can achieve laser-mediated mask-free writing enabled by the PTAIE process. Moreover, by further taking advantage of the time-dependent self-healing property of hydrazone-based dynamic covalent bond, transformable 4D soft patterns are generated. The findings and the strategy increase the ways to manipulate molecules on the supramolecule or aggregate level. They also show opportunities for the development of controllable smart materials and expand the scope of the materials in advanced optoelectronic applications.

16.
Adv Mater ; 33(33): e2100021, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216407

RESUMO

Chromophores that exhibit aggregation-induced emission (i.e., aggregation-induced emission luminogens [AIEgens]) emit intense fluorescence in their aggregated states, but show negligible emission as discrete molecular species in solution due to the changes in restriction and freedom of intramolecular motions. As solvent-swollen quasi-solids with both a compact phase and a free space, gels enable manipulation of intramolecular motions. Thus, AIE-active gels have attracted significant interest owing to their various distinctive properties and promising application potential. Herein, a comprehensive overview of AIE-active gels is provided. The fabrication strategies employed are detailed, and the applications of AIEgens are summarized. In addition, the gel functions arising from the AIE moieties are revealed, along with their structure-property relationships. Furthermore, the applications of AIE-active gels in diverse areas are illustrated. Finally, ongoing challenges and potential means to address them are discussed, along with future perspectives on AIE-active gels, with the overall aim of inspiring research on novel materials and ideas.

17.
Cell Death Dis ; 12(4): 393, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846290

RESUMO

Cardiac septum malformations account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the vascular development and angiogenesis. It is unclear whether Sox7 also contributes to cardiac septation development. We identified a de novo 8p23.1 deletion with Sox7 haploinsufficiency in an atrioventricular septal defect (AVSD) patient using whole exome sequencing in 100 AVSD patients. Then, multiple Sox7 conditional loss-of-function mice models were generated to explore the role of Sox7 in atrioventricular cushion development. Sox7 deficiency mice embryos exhibited partial AVSD and impaired endothelial to mesenchymal transition (EndMT). Transcriptome analysis revealed BMP signaling pathway was significantly downregulated in Sox7 deficiency atrioventricular cushions. Mechanistically, Sox7 deficiency reduced the expressions of Bmp2 in atrioventricular canal myocardium and Wnt4 in endocardium, and Sox7 binds to Wnt4 and Bmp2 directly. Furthermore, WNT4 or BMP2 protein could partially rescue the impaired EndMT process caused by Sox7 deficiency, and inhibition of BMP2 by Noggin could attenuate the effect of WNT4 protein. In summary, our findings identify Sox7 as a novel AVSD pathogenic candidate gene, and it can regulate the EndMT involved in atrioventricular cushion morphogenesis through Wnt4-Bmp2 signaling. This study contributes new strategies to the diagnosis and treatment of congenital heart defects.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Defeitos dos Septos Cardíacos/metabolismo , Fatores de Transcrição SOXF/metabolismo , Proteína Wnt4/metabolismo , Animais , Estudos de Casos e Controles , Pré-Escolar , Endocárdio/embriologia , Endocárdio/crescimento & desenvolvimento , Endocárdio/metabolismo , Feminino , Defeitos dos Septos Cardíacos/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Fatores de Transcrição SOXF/deficiência , Fatores de Transcrição SOXF/genética , Transdução de Sinais
18.
J Mol Med (Berl) ; 98(7): 1035-1048, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32572506

RESUMO

Conotruncal heart defects (CTDs) are closely related to defective outflow tract (OFT) development, in which cardiac neural crest cells (CNCCs) play an indispensable role. However, the genetic etiology of CTDs remains unclear. Mesoderm posterior 2 (MESP2) is an important transcription factor regulating early cardiogenesis. Nevertheless, MESP2 variants have not been reported in congenital heart defect (CHD) patients. We first identified four MESP2 variants in 601 sporadic nonsyndromic CTD patients that were not detected in 400 healthy controls using targeted sequencing. Reverse transcription-quantitative PCR (RT-qPCR), immunohistochemistry, and immunofluorescence assays revealed MESP2 expression in the OFT of Carnegie stage (CS) 11, CS13, and CS15 human embryos and embryonic day (E) 8.5, E10, and E11.5 mouse embryos. Functional analyses in HEK 293T cells, HL-1 cells, JoMa1 cells, and primary mouse CNCCs revealed that MESP2 directly regulates the transcriptional activities of downstream CTD-related genes and promotes CNCC proliferation by regulating cell cycle factors. Three MESP2 variants, c.346G>C (p.G116R), c.921C>G (p.Y307X), and c.59A>T (p.Q20L), altered the transcriptional activities of MYOCD, GATA4, NKX2.5, and CFC1 and inhibited CNCC proliferation by upregulating p21cip1 or downregulating Cdk4. Based on our findings, MESP2 variants disrupted MESP2 function by interfering with CNCC proliferation during OFT development, which may contribute to CTDs. KEY MESSAGES: This study first analyzed MESP2 variants identified in sporadic nonsyndromic CTD patients. MESP2 is expressed in the OFT of different stages of human and mouse embryos. MESP2 regulates the transcriptional activities of downstream CTD-related genes and promotes CNCC proliferation by regulating cell cycle factor p21cip1 or Cdk4.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proliferação de Células/genética , Variação Genética/genética , Cardiopatias Congênitas/genética , Coração/fisiopatologia , Crista Neural/patologia , Animais , Ciclo Celular/genética , Linhagem Celular , Regulação para Baixo/genética , Embrião de Mamíferos/patologia , Regulação da Expressão Gênica/genética , Células HEK293 , Cardiopatias Congênitas/patologia , Humanos , Camundongos , Miocárdio/patologia , Organogênese/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética , Transcrição Gênica/genética , Regulação para Cima/genética
19.
Comput Struct Biotechnol J ; 18: 381-392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32128068

RESUMO

Pulmonary atresia (PA) is a rare congenital heart defect (CHD) with complex manifestations and a high mortality rate. Since the genetic determinants in the pathogenesis of PA remain elusive, a thorough identification of the genetic factors through whole exome sequencing (WES) will provide novel insights into underlying mechanisms of PA. We performed WES data from PA/VSD (n = 60), PA/IVS (n = 20), TOF/PA (n = 20) and 100 healthy controls. Rare variants and novel genes were identified using variant-based association and gene-based burden analysis. Then we explored the expression pattern of our candidate genes in endothelium cell lines, pulmonary artery tissues, and embryonic hearts. 56 rare damage variants of 7 novel candidate genes (DNAH10, DST, FAT1, HMCN1, HNRNPC, TEP1, and TYK2) were certified to have function in PA pathogenesis for the first time. In our research, the genetic pattern among PA/VSD, PA/IVS and TOF/PA were different to some degree. Taken together, our findings contribute new insights into the molecular basis of this rare congenital birth defect.

20.
Food Chem ; 320: 126641, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32213424

RESUMO

The aim of this study was to use acidic electrolyzed water (AEW) to treat longan fruit and evaluate the effects of AEW treatment on storability, quality attributes and nutritive properties of longans during storage. The data indicated that, as compared to the control samples, AEW treatment could effectively reduce the respiration rate and pericarp cell membrane permeability, retard the occurrences of pericarp browning, pulp breakdown and fruit disease, keep a higher rate of commercially acceptable fruit. Additionally, AEW treatment could suppress the decrease of chromaticity values of L*, a* and b* of the fruit surface, keep higher amounts of pericarp carotenoid, chlorophyll, flavonoid and anthocyanin, maintain higher amounts of pulp total soluble solid (TSS), total soluble sugars, sucrose and vitamin C. These results demonstrated that AEW treatment at pH of 2.5, ACC of 80 mg/L could maintain higher quality attributes and nutritive properties, and display better storability of harvested longans.


Assuntos
Sapindaceae/química , Ácidos/química , Antocianinas/química , Eletrólitos , Frutas/química , Água/química
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