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1.
Dev Biol ; 508: 93-106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286185

RESUMO

Despite extensive studies on endogenous heart regeneration within the past 20 years, the players involved in initiating early regeneration events are far from clear. Here, we assessed the function of neutrophils, the first-responder cells to tissue damage, during zebrafish heart regeneration. We detected rapid neutrophil mobilization to the injury site after ventricular amputation, peaking at 1-day post-amputation (dpa) and resolving by 3 dpa. Further analyses indicated neutrophil mobilization coincides with peak epicardial cell proliferation, and recruited neutrophils associated with activated, expanding epicardial cells at 1 dpa. Neutrophil depletion inhibited myocardial regeneration and significantly reduced epicardial cell expansion, proliferation, and activation. To explore the molecular mechanism of neutrophils on the epicardial regenerative response, we performed scRNA-seq analysis of 1 dpa neutrophils and identified enrichment of the FGF and MAPK/ERK signaling pathways. Pharmacological inhibition of FGF signaling indicated its' requirement for epicardial expansion, while neutrophil depletion blocked MAPK/ERK signaling activation in epicardial cells. Ligand-receptor analysis indicated the EGF ligand, hbegfa, is released from neutrophils and synergizes with other FGF and MAPK/ERK factors for induction of epicardial regeneration. Altogether, our studies revealed that neutrophils quickly motivate epicardial cells, which later accumulate at the injury site and contribute to heart regeneration.


Assuntos
Traumatismos Cardíacos , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Neutrófilos , Pericárdio/fisiologia , Ligantes , Coração/fisiologia , Proliferação de Células
2.
J Am Chem Soc ; 146(7): 4842-4850, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38295276

RESUMO

Although polylactic acid (PLA) represents a pivotal biodegradable polymer, its biodegradability has inadvertently overshadowed the development of effective recycling techniques, leading to the potential wastage of carbon resources. The photoreforming-recycling approach for PLA exhibits significant potential in terms of concepts and methods. However, the reaction faces enormous challenges due to the limited selectivity of organic oxidation products as well as the increased costs and challenging separation of organic products associated with alkali-solution-assisted prehydrolysis. Herein, we report an alkali-free direct-photoreforming pathway for real-world PLA plastics utilizing the Pd-CdS photocatalyst under visible-light illumination, obviating the need for chemical pretreatment of PLA. The devised pathway successfully produces H2 at a rate of 49.8 µmol gcat.-1 h-1, sustained over 100 h, and exhibits remarkable selectivity toward pyruvic acid (95.9% in liquid products). Additionally, experimental findings elucidate that Pd sites not only function as a typical cocatalyst for enhancing the photocatalytic evolution of H2 but also suppress competitive side reactions (e.g., lactic acid coupling or decarboxylation), consequently augmenting the yield and selectivity of pyruvic acid and H2. This investigation provides a straightforward and sustainable direct-photoreforming route capable of simultaneously mitigating and repurposing plastic waste into valuable chemicals, thus offering a promising solution to the current environmental challenges.

3.
Molecules ; 29(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38398498

RESUMO

Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.


Assuntos
Antineoplásicos , Neoplasias , Pró-Fármacos , Humanos , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Platina/química , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
4.
J Environ Sci (China) ; 141: 40-50, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38408833

RESUMO

The Tibetan Plateau, known as the "Third Pole", is currently in a state of perturbation caused by intensified human activity. In this study, 56 samples were obtained at the five sampling sites in typical area of Lhasa city and their physical and chemical properties were investigated by TEM/EDS, STXM, and NEXAFS spectroscopy. After careful examination of 3387 single particles, the results showed that Fe should be one of the most frequent metal elements. The Fe-containing single particles in irregular shape and micrometer size was about 7.8% and might be mainly from local sources. Meanwhile, the Fe was located on the subsurface of single particles and might be existed in the form of iron oxide. Interestingly, the core-shell structure of iron-containing particles were about 38.8% and might be present as single-, dual- or triple-core shell structure and multi-core shell structure with the Fe/Si ratios of 17.5, 10.5, 2.9 and 1.2, respectively. Meanwhile, iron and manganese were found to coexist with identical distributions in the single particles, which might induce a synergistic effect between iron and manganese in catalytic oxidation. Finally, the solid spherical structure of Fe-containing particles without an external layer were about 53.4%. The elements of Fe and Mn were co-existed, and might be presented as iron oxide-manganese oxide-silica composite. Moreover, the ferrous and ferric forms of iron might be co-existed. Such information can be valuable in expanding our understanding of Fe-containing particles in the Tibetan Plateau atmosphere.


Assuntos
Compostos Férricos , Ferro , Manganês , Humanos , Ferro/química , Tibet , Microscopia Eletrônica de Transmissão
5.
Dev Biol ; 487: 57-66, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35490764

RESUMO

Over the past 20 years, various zebrafish injury models demonstrated efficient heart regeneration after cardiac tissue loss. However, no established coronary vessel injury methods exist in the zebrafish model, despite coronary endothelial dysfunction occurring in most patients with acute coronary syndrome. This is due to difficulties performing surgery on small coronary vessels and a lack of genetic tools to precisely manipulate coronary cells in zebrafish. We determined that the Notch ligand gene deltaC regulatory sequences drive gene expression in zebrafish coronary endothelial cells, enabling us to overcome these obstacles. We created a deltaC fluorescent reporter line and visualized robust coronary growth during heart development and regeneration. Importantly, this reporter facilitated the visualization of coronary growth without an endocardial background. Moreover, we visualized robust coronary growth on the surface of juvenile hearts and regrowth in the wounded area of adult hearts ex vivo. With this approach, we observed growth inhibition by reported vascular growth antagonists of the VEGF, EGF and Notch signaling pathways. Furthermore, we established a coronary genetic ablation system and observed that severe coronary endothelial cell loss resulted in fish death, whereas fish survived mild coronary cell loss. Coronary cell depletion triggered regenerative responses, which resulted in the restoration of damaged cardiac tissues within several weeks. Overall, our work demonstrated the efficacy of using deltaC regulatory elements for high-resolution visualization of the coronary endothelium; screening small molecules for coronary growth effects; and revealed complete recovery in adult zebrafish after coronary-induced heart damage.


Assuntos
Traumatismos Cardíacos , Peixe-Zebra , Animais , Proliferação de Células , Células Endoteliais/metabolismo , Coração/fisiologia , Traumatismos Cardíacos/metabolismo , Humanos , Miócitos Cardíacos/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
6.
Circulation ; 146(1): 48-63, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35652354

RESUMO

BACKGROUND: Certain nonmammalian species such as zebrafish have an elevated capacity for innate heart regeneration. Understanding how heart regeneration occurs in these contexts can help illuminate cellular and molecular events that can be targets for heart failure prevention or treatment. The epicardium, a mesothelial tissue layer that encompasses the heart, is a dynamic structure that is essential for cardiac regeneration in zebrafish. The extent to which different cell subpopulations or states facilitate heart regeneration requires research attention. METHODS: To dissect epicardial cell states and associated proregenerative functions, we performed single-cell RNA sequencing and identified 7 epicardial cell clusters in adult zebrafish, 3 of which displayed enhanced cell numbers during regeneration. We identified paralogs of hapln1 as factors associated with the extracellular matrix and largely expressed in cluster 1. We assessed HAPLN1 expression in published single-cell RNA sequencing data sets from different stages and injury states of murine and human hearts, and we performed molecular genetics to determine the requirements for hapln1-expressing cells and functions of each hapln1 paralog. RESULTS: A particular cluster of epicardial cells had the strongest association with regeneration and was marked by expression of hapln1a and hapln1b. The hapln1 paralogs are expressed in epicardial cells that enclose dedifferentiated and proliferating cardiomyocytes during regeneration. Induced genetic depletion of hapln1-expressing cells or genetic inactivation of hapln1b altered deposition of the key extracellular matrix component hyaluronic acid, disrupted cardiomyocyte proliferation, and inhibited heart regeneration. We also found that hapln1-expressing epicardial cells first emerge at the juvenile stage, when they associate with and are required for focused cardiomyocyte expansion events that direct maturation of the ventricular wall. CONCLUSIONS: Our findings identify a subset of epicardial cells that emerge in postembryonic zebrafish and sponsor regions of active cardiomyogenesis during cardiac growth and regeneration. We provide evidence that, as the heart achieves its mature structure, these cells facilitate hyaluronic acid deposition to support formation of the compact muscle layer of the ventricle. They are also required, along with the function of hapln1b paralog, in the production and organization of hyaluronic acid-containing matrix in cardiac injury sites, enabling normal cardiomyocyte proliferation and muscle regeneration.


Assuntos
Proteínas da Matriz Extracelular , Coração , Miócitos Cardíacos , Proteoglicanas , Animais , Proliferação de Células , Proteínas da Matriz Extracelular/metabolismo , Coração/fisiologia , Humanos , Ácido Hialurônico/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Organogênese , Proteoglicanas/metabolismo , Regeneração/fisiologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
7.
Small ; 19(43): e2300673, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37376842

RESUMO

Urea oxidation reaction (UOR) is one of the promising alternative anodic reactions to water oxidation that has attracted extensive attention in green hydrogen production. The application of specifically designed electrocatalysts capable of declining energy consumption and environmental consequences is one of the major challenges in this field. Therefore, the goal is to achieve a resistant, low-cost, and environmentally friendly electrocatalyst. Herein, a water-stable fluorinated Cu(II) metalorganic framework (MOF) {[Cu2 (L)(H2 O)2 ]·(5DMF)(4H2 O)}n (Cu-FMOF-NH2 ; H4 L = 3,5-bis(2,4-dicarboxylic acid)-4-(trifluoromethyl)aniline) is developed utilizing an angular tetracarboxylic acid ligand that incorporates both trifluoromethyl (-CF3 ) and amine (-NH2 ) groups. The tailored structure of Cu-FMOF-NH2 where linkers are connected by fluoride bridges and surrounded by dicopper nodes reveals a 4,24T1 topology. When employed as electrocatalyst, Cu-FMOF-NH2 requires only 1.31 V versus reversible hydrogen electrode (RHE) to deliver 10 mA cm-2 current density in 1.0 m KOH with 0.33 m urea electrolyte and delivered an even higher current density (50 mA cm-2 ) at 1.47 V versus RHE. This performance is superior to several reported catalysts including commercial RuO2 catalyst with overpotential of 1.52 V versus RHE. This investigation opens new opportunities to develop and utilize pristine MOFs as a potential electrocatalyst for various catalytic reactions.

8.
Phys Chem Chem Phys ; 25(37): 25353-25360, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37703044

RESUMO

Photocatalytic oxidation is an efficient and promising technology for reducing indoor pollution levels of formaldehyde (HCHO). However, developing efficient and low-cost photocatalysts for the removal of HCHO remains challenging due to the time-consuming and expensive nature of traditional "trial and error" and "directed research" approaches. To achieve this goal, first-principles density functional theory (DFT) calculations were conducted to high-throughput screen candidate TM-C3N6 photocatalysts for high-performance degradation of HCHO. The results revealed that Zr-C3N6 and Hf-C3N6 in functionalizing C3N6 with 28 transition metals showed excellent adsorption energy of HCHO, boosting the highly effective capture of HCHO. Meanwhile, an excellent adsorption performance mechanism was further elicited by the electric structure-property relationship. In addition, reaction mechanisms for HCHO degradation and three potential reaction pathways for HCHO degradation were systematically evaluated. Our findings indicated that hydroxyl-assisted dehydrogenation and oxygen-assisted dehydrogenation are the most favorable pathways, with rate-limiting steps involving the formation of ˙OH and ˙O radicals. Overall, this study may provide new insights into a high-throughput screening of novel photocatalysts that are both high-performing and low-cost for the removal of formaldehyde. This, in turn, can accelerate the experimental development process and reduce the associated costs and time consumption.

9.
Rapid Commun Mass Spectrom ; 36(13): e9315, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35411976

RESUMO

RATIONALE: For disulfide-containing peptides, mass spectrometric analyses are rarely comparably studied between their dithiol and disulfide forms. Persulfide ions afforded from peptides with a disulfide ring are from either an unusual N-Cα bond cleavage or a canonical peptide bond cleavage; their isomeric structures are, however, not identified just from peaks of mass spectra. METHODS: Isomeric structures of [C3 P4 X5 |C6 M ], [C3 MA P4 X5 |C6 MB ] and [P4 X5 C6 |C3 M ] were identified from a series of the X5 substituted dicysteine octapeptides using electrospray ionization tandem mass spectrometry for both their dithiol and disulfide forms. Formation mechanisms of different persulfide ions were investigated systematically by theoretical methods. Moreover, electrostatic potential-mapped molecular van der Waals surfaces were used to determine the stabilities of the intermediates, which gave a further evaluation of favored bond cleavage. RESULTS: Mass spectral analyses indicated that the fragmented ions changed largely when an intramolecular disulfide bond was formed. New types of disulfide-containing fragmented ions [C3 P4 X5 |C6 M ] or [C3 MA P4 X5 |C6 MB ] were thus proposed. Energy analysis showed that the N-Cα cleavage was not competitive energetically with that of the amide bond for Y5 and its phosphorylated analogue. However, the N-Cα cleavage products dominated for the S5 - and T5 -containing peptides. Stabilities of the intermediates were found to be related with the electrostatic potential-mapped molecular van der Waals surfaces. CONCLUSIONS: Persulfide ions containing more residues than previously found were proposed not only from b7 ions but also from y6 ions. In addition, a new kind of phosphorylated analogue, [C3 P4 p Y5 |C6 M ], is reported in this work. Our study provides convincing results for separating isomeric structures in the cases of N-Cα cleavages, which greatly assists in the structural identification of disulfide-containing peptides.


Assuntos
Dissulfetos , Peptídeos , Amidas , Dissulfetos/química , Íons/química , Peptídeos/química , Espectrometria de Massas por Ionização por Electrospray/métodos
10.
Phys Chem Chem Phys ; 24(43): 26776-26784, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36314447

RESUMO

To rapidly design nitrogen reduction reaction (NRR) electrocatalysts with superior activity and selectivity is a great challenge. Herein, we propose a simple mixture strategy including three screening steps and a descriptor to predict NRR electrocatalysts with outstanding activity and selectivity based on density functional theory (DFT). Twenty-eight candidate transition-metal dimers anchored on nitrogen-doped graphene were systematically investigated through our mixture strategy. The results show that VRu-NC exhibits a high NRR activity and suppression of the competitive hydrogen evolution reaction (HER) following the mixed mechanism with a favorable limiting potential (UL) of -0.21 V. Finally, the mechanism of the catalytic reaction pathway was investigated according to the profile of atomic orbitals and electronic properties. This work proposes a feasible strategy for rapid screening of the high-performance of double atomic electrocatalysts with excellent activity and selectivity for the NRR.

11.
Support Care Cancer ; 30(11): 9221-9232, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36056273

RESUMO

PURPOSE: Regular physical activity (PA) is essential for childhood cancer survivors (CCS), yet most CCS have difficulty participating in it. The level of PA participation among CCS in China is lower than those of western countries, leading to a worse long-term survival of CCS in China. Here, the study aims to explore the associated factors on the PA performance among CCS. METHODS: From September to December 2020, the study used purposive sampling to recruit 35 families (88.9%) as sampling units among two hospitals in Hangzhou City, China. The data collection conducted two designs on semi-structured interviews with different roles under family structure - children (n = 35) and parents (n = 35) - respectively. The design of predetermined questions relied on the health belief model (HBM) as a thematic framework. The qualitative analysis applied codebook thematic analysis and used the deductive approach to finalize the main findings. RESULTS: The study only presented preliminary conclusions from interviews with CCS, which resulted in four themes (changes in PA performance; perceptions on participating PA; cognitions of PA; impacts from others) with eight sub-themes. In particular, CCS replied diversity changes in PA, but most of them mentioned the inactive PA after diagnosis, especially the decline of moderate-to-vigorous PA (MVPA). As for the "perceptions of PA," almost all CCS had substantial perceived benefits about PA, specifically on their physical well-being. All children also expressed perceived barriers to PA, including the side effects of disease and treatment, fatigue, academic burden, changes in psychological status, and lack of companions. On the cognitions of PA, the CCS had limited realizations of regular PA and low self-efficacy on MVPA. Furthermore, CCS expressed their need for support from their parents, school teachers, and healthcare providers. But in reality, they recieved less support on PA from these important people. CONCLUSION: The changes in PA after illness among CCS are apparent and unavoidable because of the interaction impacts from internal factors (e.g., personal characters, cognization, perceptions of PA) and external factors (e.g., disease effects, interpersonal supports). The findings explained the main elements under HBM but also provided explored views as the evidence on developing theories and guiding motivations and practices on PA among CCS. IMPLICATIONS FOR CANCER SURVIVORS: In this exploratory study of 35 CCS, we identified the current situation of PA among CCS in China and explored the associated factors. As the first qualitative study on the CCS in mainland China, the study considered particular effects on social culture and living environment.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Criança , Neoplasias/psicologia , Exercício Físico/psicologia , Pesquisa Qualitativa , Modelo de Crenças de Saúde
12.
Molecules ; 27(11)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35684580

RESUMO

The authors of this paper conducted a comparative metabolomic analysis of Ophiocordyceps sinensis (OS), providing the metabolic profiles of the stroma (OSBSz) and sclerotia (OSBSh) of OS by widely targeted metabolomics and untargeted metabolomics. The results showed that 778 and 1449 metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. The metabolites in OSBSz and OSBSh are significantly differentiated; 71 and 96 differentially expressed metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. This suggests that these 71 metabolites (riboflavine, tripdiolide, bromocriptine, lumichrome, tetrahymanol, citrostadienol, etc.) and 96 metabolites (sancycline, vignatic acid B, pirbuterol, rubrophen, epalrestat, etc.) are potential biomarkers. 4-Hydroxybenzaldehyde, arginine, and lumichrome were common differentially expressed metabolites. Using the widely targeted metabolomics approach, the key pathways identified that are involved in creating the differentiation between OSBSz and OSBSh may be nicotinate and nicotinamide metabolism, thiamine metabolism, riboflavin metabolism, glycine, serine, and threonine metabolism, and arginine biosynthesis. The differentially expressed metabolites identified using the untargeted metabolomics approach were mainly involved in arginine biosynthesis, terpenoid backbone biosynthesis, porphyrin and chlorophyll metabolism, and cysteine and methionine metabolism. The purpose of this research was to provide support for the assessment of the differences between the stroma and sclerotia, to furnish a material basis for the evaluation of the physical effects of OS, and to provide a reference for the selection of detection methods for the metabolomics of OS.


Assuntos
Arginina/metabolismo , Cordyceps , Arginina/química , Biomarcadores , Metaboloma , Metabolômica/métodos
13.
J Med Virol ; 93(2): 1057-1069, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32761898

RESUMO

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.


Assuntos
COVID-19/fisiopatologia , Adolescente , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Criança , Pré-Escolar , Tosse/virologia , Feminino , Febre/virologia , Humanos , Lactente , Recém-Nascido , Masculino
14.
Pharmacol Res ; 169: 105616, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33872809

RESUMO

Targeted therapy has become increasingly important and indispensable in cancer therapy. Cullin3-RING ligases (CRL3) serve as essential executors for regulating protein homeostasis in cancer development, highlighting that CRL3 might be promising targets in various cancer treatment. However, how to design new targeted therapies by disrupting the function of CRL3 is poorly understood. Here, we focus on the substrate adaptors of CRL3, and carry out a systematical research on the function of Kelch-like (KLHL) family proteins. We have identified twenty-four KLHL proteins with function of tumor promotion and thirteen KLHL proteins with high clinical significance on cancer therapy. Furthermore, we have clarified the novel biological function of KLHL13 as a vital factor that contributes to malignant progression in lung cancer. Taken together, our findings reveal multiple potential therapeutical targets and provide evidence for targeting CRL3 via KLHL substrate adaptors for cancer therapy.


Assuntos
Proteínas Culina/metabolismo , Repetição Kelch , Terapia de Alvo Molecular/métodos , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo
15.
Gastric Cancer ; 24(6): 1293-1306, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34251544

RESUMO

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Vírus Oncolíticos , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Masculino , Microdomínios da Membrana/metabolismo , Camundongos , Camundongos Nus , Esfingomielina Fosfodiesterase/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
16.
Nature ; 522(7555): 226-230, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-25938716

RESUMO

In response to cardiac damage, a mesothelial tissue layer enveloping the heart called the epicardium is activated to proliferate and accumulate at the injury site. Recent studies have implicated the epicardium in multiple aspects of cardiac repair: as a source of paracrine signals for cardiomyocyte survival or proliferation; a supply of perivascular cells and possibly other cell types such as cardiomyocytes; and as a mediator of inflammation. However, the biology and dynamism of the adult epicardium is poorly understood. To investigate this, we created a transgenic line to ablate the epicardial cell population in adult zebrafish. Here we find that genetic depletion of the epicardium after myocardial loss inhibits cardiomyocyte proliferation and delays muscle regeneration. The epicardium vigorously regenerates after its ablation, through proliferation and migration of spared epicardial cells as a sheet to cover the exposed ventricular surface in a wave from the chamber base towards its apex. By reconstituting epicardial regeneration ex vivo, we show that extirpation of the bulbous arteriosus-a distinct, smooth-muscle-rich tissue structure that distributes outflow from the ventricle-prevents epicardial regeneration. Conversely, experimental repositioning of the bulbous arteriosus by tissue recombination initiates epicardial regeneration and can govern its direction. Hedgehog (Hh) ligand is expressed in the bulbous arteriosus, and treatment with a Hh signalling antagonist arrests epicardial regeneration and blunts the epicardial response to muscle injury. Transplantation of Sonic hedgehog (Shh)-soaked beads at the ventricular base stimulates epicardial regeneration after bulbous arteriosus removal, indicating that Hh signalling can substitute for the influence of the outflow tract. Thus, the ventricular epicardium has pronounced regenerative capacity, regulated by the neighbouring cardiac outflow tract and Hh signalling. These findings extend our understanding of tissue interactions during regeneration and have implications for mobilizing epicardial cells for therapeutic heart repair.


Assuntos
Traumatismos Cardíacos/metabolismo , Proteínas Hedgehog/metabolismo , Pericárdio/fisiologia , Regeneração/fisiologia , Transdução de Sinais , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados , Proliferação de Células/genética , Feminino , Proteínas Hedgehog/genética , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Pericárdio/citologia , Regeneração/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
17.
J Clin Lab Anal ; 35(5): e23769, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33942367

RESUMO

OBJECTIVE: Denys-Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision-making. METHODS: We present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. "Next-generation" sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay. RESULTS: We found the first case of Denys-Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted "disease-causing" by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild-type WT1. CONCLUSIONS: The uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.


Assuntos
Povo Asiático/genética , Síndrome de Denys-Drash/genética , Proteínas WT1/genética , Tumor de Wilms/genética , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Tumoral , China , Simulação por Computador , Feminino , Seguimentos , Humanos , Lactente , Laparoscopia , Mutação , Linhagem , Tomografia Computadorizada por Raios X , Proteínas WT1/química , Tumor de Wilms/diagnóstico , Tumor de Wilms/diagnóstico por imagem
18.
Sensors (Basel) ; 21(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34577381

RESUMO

Atmospheric oxygen anions play an important role in medical health, clinical medicine, environmental health, and the ecological environment. Therefore, the concentration of atmospheric anions is an important index for measuring air quality. This paper proposes a monitoring system for atmospheric oxygen anions based on Beidou positioning and unmanned vehicles. This approach combines Beidou positioning technology, 4G pass-through, the unmanned capacitance suction method, electromagnetic field theory, and atmospheric detection technology. The proposed instrument can monitor the overall negative oxygen ion concentration, temperature, and humidity in a certain region over time and provide data visualization for the concentration of negative oxygen ions.


Assuntos
Poluição do Ar , Ânions/análise , Umidade , Íons , Temperatura
19.
J Med Virol ; 92(7): 909-914, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32222992

RESUMO

Coronavirus Disease 2019 (COVID-19) is a newly emerging infectious disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After its first occurrence in Wuhan of China from December 2019, COVID-19 rapidly spread around the world. According to the World Health Organization statement on 13 March 2020, there had been over 132 500 confirmed cases globally. Nevertheless, the case reports of children are rare, which results in the lack of evidence for preventing and controlling of children's infection. Here, we report three cases of SARS-CoV-2 infected children diagnosed from 3 February to 17 February 2020 in Tianjin, China. All of these three cases experienced mild illness and recovered soon after the treatment, with the nucleic acid of throat swab turning negative within 14, 11, and 7 days after diagnosis, respectively. However, after been discharged, all three cases were tested SARS-CoV-2 positive in the stool samples within 10 days, in spite of their remained negative nucleic acid in throat swab specimens. Therefore, it is necessary to be aware of the possibility of fecal-oral transmission of SARS-CoV-2 infection, especially for children cases.


Assuntos
Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Convalescença , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , RNA Viral/sangue , Ácido Ascórbico/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Biomarcadores/sangue , COVID-19 , Teste para COVID-19 , Ceftriaxona/uso terapêutico , Criança , China , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fezes/virologia , Humanos , Interferons/uso terapêutico , Masculino , Pandemias , Alta do Paciente , Faringe/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribavirina/uso terapêutico , SARS-CoV-2 , Tomografia Computadorizada por Raios X
20.
Pediatr Hematol Oncol ; 37(7): 620-629, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32529889

RESUMO

Since the emergence of patients with COVID-19 in December 2019, the virus has rapidly spread worldwide. Children with malignant tumors are more prone to be infected and develop severe infections. Prevention and control of the pandemic and ensuring the progress of the cancer diagnosis and treatment is a significant problem in the current scenario. This article proposes a scientific management system for patients with solid tumors to guarantee emergency surgery, rationally arrange limited-term surgery, appropriately defer elective surgery, and guarantee regular chemotherapy, while protecting children from SARS-CoV-2 infection and ensuring the continuity of comprehensive diagnosis and treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Neoplasias , Pandemias , Pneumonia Viral , Adolescente , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Lactente , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , SARS-CoV-2
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