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1.
ACS Appl Mater Interfaces ; 13(36): 42473-42485, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474563

RESUMO

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for in vivo CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. In vivo CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, in vivo treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4+ and CD8+ T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.

2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(8): 919-921, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34590556

RESUMO

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, of which the pathogenesis is complex and the mortality rate is high. However, current basic research is facing the dilemma of high heterogeneity and difficult translation to clinical practice. In-depth basic research is one of the most important ways to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. The purpose of this review is to analyze the current progress and challenges in the field of basic research on sepsis, and look forward to the potential research directions in the future. Cell function, energy metabolism, microbiota, epigenetics and recovery period of sepsis may be the research priorities.


Assuntos
Microbiota , Sepse , Humanos , Pesquisa , Sepse/terapia
3.
J Hazard Mater ; 424(Pt A): 127283, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34564045

RESUMO

Microplastics (MPs) pollution is increasingly appreciated as a significant environmental issue, however, the large-scale pattern of MPs in farmland soils and its associated environmental impacts are unknown. This study investigated a national-scale distribution of micro(meso)plastics (MMPs) in the soil of 30 farmlands across China. The abundance of MMPs in soils was 25.56-2067.78 items kg-1, with a mean of 358.37 items kg-1, i.e. 6.79 mg kg-1 or 0.0007% after mass conversion. MPs accounted for 93.1% of MMPs, the abundance varied greatly among different regions, high in arid or semi-arid north but relatively low in mild southwest regions. Major MPs included polypropylene, polyethylene, and polyester, tending to decrease in abundance from surface to deeper soil layers. Further, meta-analysis revealed that MPs exposure influenced bulk density, soil enzymes including fluorescein diacetate hydrolase (FDAse) and urease, and crop biomass, and minimum effective concentrations (MEC) were in the range of 0.0040-10%. We found that actual abundance in the national-scale soils was lower than MEC, but partly overlapped or close, which implies various degrees of environmental impacts. These findings disclose the national-scale pollution pattern of MPs in farmlands and its latent risks to soil environments and crop growth.

4.
Sci Total Environ ; 802: 149838, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34454156

RESUMO

Microplastics (MPs) have been widely detected in aquatic environments, and become emerging contaminants of growing concern. It is urgently needed to explore how to effectively remove MPs from water. This study first established an alternative method of removing MPs by magnetic nano-Fe3O4. Results showed that 1.3 g·L-1 nano-Fe3O4 and 150 min treatments caused optimal magnetization of MPs via surface absorption. Then, magnetized MPs in water can be conveniently removed by suction of the magnet. The average removal rate of four common types of MPs including polyethylene, polypropylene, polystyrene and polyethylene terephthalate in size of approximately 200-900 µm was 86.87 ± 6.92%, 85.05 ± 4.70%, 86.11 ± 6.21%, and 62.83 ± 8.34%, respectively. The removal rate varied among polymer- and size-different MPs, and was positively related to the density of nano-Fe3O4 absorbed on MP surfaces. In addition, the removal rate of MPs in artificial seawater was relatively high in comparison to pure water. Furthermore, the established approach was effectively applied to remove MPs in environmental water bodies including river water, domestic sewage, and natural seawater, with the removal rate of higher than 80%. Altogether, this study provided a novel and simple removal approach to remove MPs in water, which has a certain application prospect.

5.
BMJ Open ; 11(8): e048803, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426465

RESUMO

INTRODUCTION: Techniques using local anaesthetics provide high-quality analgesia, while the anti-inflammatory properties of these drugs may represent an additional advantage. Perioperative intravenous lidocaine has shown positive effects not only on postoperative pain but also on bowel function and duration of hospital stay, due to its analgesic, anti-inflammatory and opioid-sparing effects. However, these potential benefits are not well established in patients undergoing resection with colorectal cancer. This research aims to determine the effect of perioperative intravenous lidocaine on postoperative outcomes in patients undergoing resection of colorectal cancer. METHODS AND ANALYSIS: PubMed, Embase, Web of Science, CNKI, SinoMed and WanFang Data databases were electronically retrieved to include the randomised controlled trials comparing perioperative intravenous lidocaine with placebo infusion in patients undergoing resection of colorectal cancer before August 2021. Registers of clinical trials, potential grey literature and abstracts from conferences will also be searched. Two reviewers will screen literature, extract data and assess risk of bias of studies included independently. The primary outcome variable will be long-term survival outcome, tumour recurrence and metastasis rate, and restoration of intestinal function. The secondary outcome variables will consist of the severity of postoperative pain at 4, 12, 24 and 48 hours after surgery, the incidence of postoperative nausea and vomiting, and the length of hospital stay. A meta-analysis will be performed using RevMan V.5.4 software provided by the Cochrane Collaboration and Stata V.12.0. subgroup and sensitivity analyses will be conducted. ETHICS AND DISSEMINATION: Because the data used for this systematic review will be exclusively extracted from published studies, ethical approval and informed consent of patients will not be required. The systematic review will be published in a peer-reviewed journal, presented at conferences and shared on social media platforms. PROSPERO REGISTRATION NUMBER: CRD42020216232.


Assuntos
Neoplasias Colorretais , Lidocaína , Anestésicos Locais/uso terapêutico , Neoplasias Colorretais/cirurgia , Humanos , Lidocaína/uso terapêutico , Metanálise como Assunto , Revisões Sistemáticas como Assunto
6.
Nat Commun ; 12(1): 4778, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362929

RESUMO

N6,2'-O-dimethyladenosine (m6Am), a terminal modification adjacent to the mRNA cap, is a newly discovered reversible RNA modification. Yet, a specific and sensitive tool to directly map transcriptome-wide m6Am is lacking. Here, we report m6Am-seq, based on selective in vitro demethylation and RNA immunoprecipitation. m6Am-seq directly distinguishes m6Am and 5'-UTR N6-methyladenosine (m6A) and enables the identification of m6Am at single-base resolution and 5'-UTR m6A in the human transcriptome. Using m6Am-seq, we also find that m6Am and 5'-UTR m6A respond dynamically to stimuli, and identify key functional methylation sites that may facilitate cellular stress response. Collectively, m6Am-seq reveals the high-confidence m6Am and 5'-UTR m6A methylome and provides a robust tool for functional studies of the two epitranscriptomic marks.


Assuntos
Adenosina/análogos & derivados , Adenosina/metabolismo , Transcriptoma , Regiões 5' não Traduzidas , Fatores Ativadores da Transcrição , Adenosina/genética , Sequência de Bases , Células HEK293 , Humanos , Imunoprecipitação , Metilação , RNA Mensageiro/metabolismo
7.
Eur J Pharmacol ; 907: 174265, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174266

RESUMO

Natural small molecules have become attractive in osteoarthritis (OA) treatment. This study aims to investigate the effect of asiatic acid (AA) on OA development in vitro and in vivo. Chondrocytes were pretreated with AA at optimized concentrations and subsequently treated with interleukin-1 beta (IL-1ß). Inflammatory mediator nitric oxide (NO) was measured by Griess method. The mRNA expression level of inflammatory markers nitric oxide synthase (iNOS) and cyclooxygenase 2 (Cox2), as well as chondrogenic or hypertrophic markers including SRY-box transcription factor 9 (Sox9), Aggrecan, Collagen 2a1 (Col II), and Matrix metalloproteinase-13 (Mmp13) were measured by using real-time PCR analysis. The nuclear factor-kappa B (NF-κB) signaling activity was determined by dual luciferase assay and Western blot analysis. Surgery-induced OA animal model was constructed, and AA was administrated to study its effect on OA pathogenesis. AA induced a dose-dependent inhibitory effect up to -67.4% on NO production. AA could repress iNOS and Cox2 protein expression levels (-77.2% and -73.4%, respectively) in IL-1ß induced chondrocytes. AA increased the formation of cartilage extracellular matrix components including glycosaminoglycans (GAGs) and collagen type II. AA also mRNA expression of chondrogenesis marker including Aggrecan, Sox9, Col II and Fibronectin (402.87%, 151.04%, 314.15% and 187.76%, respectively) as well as hypertrophic marker Mmp13 (-67.8%). AA repressed the chondrocyte inflammation by directly inhibiting NF-κB signaling activity, which was revealed by the inhibition effect of AA on IκBα phosphorylation (-105.4%) and NF-κB/p65 translocation (-60.9%) induced by IL-1ß. Furthermore, In vivo OA study indicated the protective effect of AA on OA progression by preventing articular cartilage from degeneration and destruction. AA treatment could significantly reduce OA score (16.125 vs 5.25) and repress mRNA expression level of Mmp13 and Col X (23.5, vs 2.375 and 18.125 vs 94.5). Taken together, our findings suggest that AA could effectively rescue IL-1ß induced chondrocytes and protected cartilage in OA progression, which shed light on a potential novel therapeutic strategy of OA treatment.

8.
Artigo em Italiano | MEDLINE | ID: mdl-34152110

RESUMO

BACKGROUND: Family integrated care (FICare) is a model that integrates families as partners in the modern neonatal intensive care unit (NICU) care and which can improve the health outcomes of preterm infants. Our study aimed to explore the effect of FICare on extremely preterm infants. METHODS: 182 preterm infants with complete data were collecte from June 2017 to June 2018 in the Chongqing Health Center for Women and Children. 66 of 182 infants were enrolled into the FICare group, and another 66 matched subjects were in the control group. SPSS 20.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. The correlation between each factor and weight gain was analyzed by linear regression. RESULTS: The rate of weight gain during hospitalization (t=4.32), oxygen exposure time (Z=1.967), hospitalization expenses (t=3.03) and the incidence of retinopathy of prematurity (ROP) (χ²=4.805) were higher in the FICare group (P<0.05). Elevated birth weight was associated with a decrease of the weight growth rate (P<0.001). The growth rate of small-for-gestational-age (SGA) infants was higher than normal gestational age infants, P=0.011. Every one year of increase in maternal age (P=0.016), each additional day for restoration days of birth weight (P=0.023), and each increment of δZ score (P<0.001) increased the weight growth rate. The irregular use of hormones reduced the weight growth rate (P=0.023). Compared with the control group, the weight growth rate of FICare group increased (P<0.001). CONCLUSIONS: FICare can significantly improve the weight gain in preterm infants ≤32 weeks during hospitalization.

10.
Chem Commun (Camb) ; 57(27): 3327-3330, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33870366

RESUMO

Since multicolor switch was involved in both Sr2+-related flame and precipitation reactions, these reactions can be thus utilized for constructing a complementary atomic flame/molecular colorimetry dual-mode sensing platform for a sensitive and wide-range analysis of cancer cells by virtue of the gas generation from platinum nanozyme-mediated hydrogen peroxide decomposition.


Assuntos
Colorimetria , Neoplasias/diagnóstico , Estrôncio/química , Humanos , Peróxido de Hidrogênio/química , Nanopartículas/química , Platina/química
11.
Cell Rep ; 34(10): 108822, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33691110

RESUMO

MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression. Further studies reveal critical roles for MED1 in epithelial-mesenchymal transition, cancer stem cell formation, and response to anti-HER2 therapy. Mechanistically, RNA sequencing (RNA-seq) transcriptome analyses and clinical sample correlation studies identify Jab1, a component of the COP9 signalosome complex, as the key direct target gene of MED1 contributing to these processes. Further studies reveal that Jab1 can also reciprocally regulate the stability and transcriptional activity of MED1. Together, our findings support a functional cooperation between these co-amplified genes in HER2+ mammary tumorigenesis and their potential usage as therapeutic targets for the treatment of HER2+ breast cancers.

12.
Inorg Chem ; 60(5): 3172-3180, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33599496

RESUMO

Abnormal bilirubin (BR) level is a sign of several fatal diseases, so it is of great significance and challenge to develop a facile and effective family routine strategy for BR sensing. Herein, novel water-stable Tb3+@MOF-808 has been synthesized using a coordinated postsynthetic modification strategy and designed as a convenient and efficient fluorescence probe. The fabricated fluorescent probe exhibits a remarkable fluorescence quenching effect with the successive addition of BR, which displays fascinating features, such as fast response time, high sensitivity, and excellent selectivity. The quenching mechanism between the fluorescent probe and BR was also illustrated in detail. Importantly, the devised fluorescent probe successfully achieved the determination of BR in serum and urine, which has also been successfully used in the design of portable BR test paper. The developed monitoring platform for BR levels in vivo provides promising application potential for the prevention and early diagnosis of fatal diseases. Additionally, a molecular logic gate device that performs intelligent fluorescent sensing of BR was constructed. More interestingly, Tb3+@MOF-808 is used for development of latent fingerprints on different guest surfaces. The lines of the fluorescent fingerprints are clear and coherent, the details are obvious, and even sweat pores can be observed by naked eyes, which provides new means for tracking the criminal clue and handling cases efficiently.


Assuntos
Bilirrubina/sangue , Bilirrubina/urina , Dermatoglifia , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Humanos , Limite de Detecção , Espectrometria de Fluorescência , Térbio/química
13.
Cytotherapy ; 23(7): 590-598, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33546925

RESUMO

BACKGROUND AIMS: Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration that requires a long time for bone healing. Bone marrow-derived mesenchymal stromal cells (MSCs) have been applied to accelerate bone formation in DO. Allogeneic MSCs are attractive, as they could be ready to use in clinics. Whether allogeneic MSCs would have an effect similar to autologous MSCs with regard to promoting bone formation in DO is still unknown. This study compares the effect of autologous MSCs versus allogeneic MSCs on bone formation in a rat DO model. METHODS: Rat bone marrow-derived MSCs were isolated, characterized and expanded in vitro. Adult rats were subjected to right tibia transverse osteotomy. On the third day of distraction, each rat received one injection of phosphate-buffered saline (PBS), autologous MSCs or allogeneic MSCs at the distraction site. Tibiae were harvested after 28 days of consolidation for micro-computed tomography examination, mechanical test and histological analysis. RESULTS: Results showed that treatment with both allogeneic and autologous MSCs promoted bone formation, with significantly higher bone mass, mechanical properties and mineral apposition rate as well as expression of angiogenic and bone formation markers at the regeneration sites compared with the PBS-treated group. No statistical difference in bone formation was found between the allogeneic and autologous MSC treatment groups. CONCLUSIONS: This study indicates that allogeneic and autologous MSCs have a similar effect on promoting bone consolidation in DO. MSCs from an allogeneic source could be used off-the-shelf with DO to achieve early bone healing.

14.
Sci Total Environ ; 772: 144952, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571765

RESUMO

Phosphate plays an important role in a wide range of chemical and biological processes, so the development of a new phosphate optical sensor with high sensitivity, specificity and visual recognition function has important practical significance. Herein, a ratiometric fluorescent (RF) probe and a smartphone-integrated colorimetric test paper sensing platform for assay phosphate was fabricated using hybrid fluorescent UiO-66-NH2 and Eu3+@MOF-808 metal-organic frameworks. After continuous addition of phosphate, the blue fluorescence emission of UiO-66-NH2 and the red emission of Eu3+@MOF-808 were regularly enhanced and quenched respectively, and the fluorescence response of the detection platform to phosphate exhibited a clear color change process (red â†’ pink â†’ blue). More importantly, the probe solution and test paper of the integrated smartphone are converted to digital values through RGB channels and successfully used to visualize semi-quantitative recognition of phosphate. In addition, an RF probe and a smartphone integrated fluorescent test paper were developed separately to devise logic gate devices for detecting phosphate. The multifunctional ratio sensing platform integrated by the smartphone furnishes a new strategy and broad prospects for the intelligent online identification of important targets in biological samples and environmental samples.

15.
Chemosphere ; 273: 129727, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33524747

RESUMO

Thiamethoxam (TMX) is one of the major compounds of neonicotinoids, the most widely used class of insecticides worldwide. Previously, TMX was considered a non-toxic neonicotinoid insecticide to mammals. However, the genotoxicity, cytotoxicity, and hepatotoxicity of TMX in mammals were recently reported. Thus far, the effects of TMX on the mouse liver and its detailed mechanism remain unclear. NNMT, strongly expressed in the liver, plays a critical role in body energy expenditure. To confirm the potential pathogenesis of liver dysfunction induced by TMX, ICR mice were exposed to TMX at a dose of 4 mg/kg and 20 mg/kg by gavage administration for 12 weeks. The data showed that chronic TMX exposure caused dyslipidemia and nonalcoholic fatty liver disease (NAFLD) in mice. Moreover, aggravated oxidative stress, dysfunction, and disorganized structure were also observed in TMX-treated mouse livers. In addition, increases of PPARγ, fatty acid synthase, and NNMT expression, as well as decreases of PPARα and GNMT expression, S-adenosylmethionine deficiency, and methionine metabolism disorder were also observed in TMX-treated mouse livers. These results suggest that chronic TMX exposure induces dyslipidemia and NAFLD in mice. Moreover, inhibition of NNMT in hepatocytes significantly reversed the effects of TMX. The molecular mechanism of TMX-induced NAFLD is mostly through NNMT-mediated methionine metabolism and methyl donor balance, which ultimately regulates PPARα signaling pathway. Inhibition of NNMT could be a potentially novel strategy for blocking the progression of NAFLD induced by TMX.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Fígado , Metionina , Camundongos , Camundongos Endogâmicos ICR , Nicotinamida N-Metiltransferase , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Tiametoxam
16.
Stem Cell Res Ther ; 12(1): 47, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419467

RESUMO

BACKGROUND: Paracrine signaling from endothelial progenitor cells (EPCs) is beneficial for angiogenesis and thus promotes tissue regeneration. Microgravity (MG) environment is found to facilitate the functional potentials of various stem or progenitor cells. The present study aimed to elucidate the effects of MG on pro-angiogenic properties and fracture repair capacities of conditioned media (CM) from EPCs. METHODS: Human peripheral blood-derived EPCs were cultured under MG or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free CM under MG (MG-CM) or NG (NG-CM) were collected, and their pro-angiogenic properties were examined in human umbilical vein endothelial cells (HUVECs). In order to investigate the effects of MG-CM on fracture healing, they were injected into the fracture gaps of rat models, and radiography, histology, and mechanical test were performed to evaluate neovascularization and fracture healing outcomes. RESULTS: MG upregulated the expression of hypoxia-induced factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and promoted NO release. Comparing to NG-CM, MG-CM significantly facilitated the proliferation, migration, and angiogenesis of HUVECs through NO-induced activation of FAK/Erk1/2-MAPK signaling pathway. In addition, MG-CM were verified to improve angiogenic activities in fracture area in a rat tibial fracture model, accelerate fracture healing, and well restore the biomechanical properties of fracture bone superior to NG-CM. CONCLUSION: These findings provided insight into the use of MG bioreactor to enhance the angiogenic properties of EPCs' paracrine signals via HIF-1α/eNOS/NO axis, and the administration of MG-CM favored bone fracture repair.


Assuntos
Células Progenitoras Endoteliais , Ausência de Peso , Animais , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Consolidação da Fratura , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Fisiológica , Ratos
17.
J Immunol ; 206(5): 1088-1101, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33495235

RESUMO

The skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent Ig in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, in this study, we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens, Flavobacterium columnare This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT- but not IgM- or IgD-specific titers against the bacteria. Moreover, we demonstrate the local proliferation and production of IgT+ B cells and specific IgT titers, respectively, within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection and that, because of the large surface of the skin, its SALT probably represents a prominent IgT-inductive site in fish.


Assuntos
Linfócitos B/imunologia , Infecções por Flavobacteriaceae/imunologia , Imunidade nas Mucosas/imunologia , Imunoglobulinas/imunologia , Membrana Mucosa/imunologia , Oncorhynchus mykiss/imunologia , Pele/imunologia , Animais , Proliferação de Células/fisiologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Flavobacteriaceae/microbiologia , Flavobacterium/imunologia , Imunidade Inata/imunologia , Isotipos de Imunoglobulinas/imunologia , Inflamação/imunologia , Inflamação/microbiologia , Tecido Linfoide/imunologia , Membrana Mucosa/microbiologia , Oncorhynchus mykiss/microbiologia , Pele/microbiologia
18.
Dev Cell ; 56(3): 341-355.e5, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33472043

RESUMO

Autophagy modulation is an emerging strategy for cancer therapy. By deleting an essential autophagy gene or disrupting its autophagy function, we determined a mechanism of HER2+ breast cancer tumorigenesis by directly regulating the oncogenic driver. Disruption of FIP200-mediated autophagy reduced HER2 expression on the tumor cell surface and abolished mammary tumorigenesis in MMTV-Neu mice. Decreased HER2 surface expression was due to trafficking from the Golgi to the endocytic pathways instead of the plasma membrane. Autophagy inhibition led to HER2 accumulation in early and late endosomes associated with intraluminal vesicles and released from tumor cells in small extracellular vesicles (sEVs). Increased HER2 release from sEVs correlated with reduced tumor cell surface levels. Blocking sEVs secretion rescued HER2 levels in tumor cells. Our results demonstrate a role for autophagy to promote tumorigenesis in HER2+ breast cancer. This suggests that blocking autophagy could supplement current anti-HER2 agents for treating the disease.


Assuntos
Autofagia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinogênese/metabolismo , Vesículas Extracelulares/metabolismo , Receptor ErbB-2/metabolismo , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Endossomos/metabolismo , Feminino , Complexo de Golgi/metabolismo , Humanos , Neoplasias Mamárias Animais/patologia , Camundongos , Complexo de Endopeptidases do Proteassoma/metabolismo , Transporte Proteico
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 251: 119464, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493933

RESUMO

Dyes detection remains a serious task because of their high toxicity. In present work, designed Eu3+ functionalized Zr-metal-organic framework (Eu3+@Zr-MOF-808) as fluorescent probe was constructed via post-synthetic modification (PSM) for rapid monitoring four most commonly used dyes (malachite green (MG), brilliant green (BG), alizarin red S (ARS), indigo red (IDR)). Systematic exploring on the sensing mechanism reveals that fluorescence resonance energy transfer (FRET) for BG, MG and IDR and inner filter effect (IFE) for ARS contribute to the realization of the fluorescence quenching process. It exhibits excellent sensing performances with low limit of detection (LOD) of 32, 58, 77 and 133 nM for BG, IDR, MG and ARS, respectively. The as-constructed Eu3+@Zr-MOF-808 was demonstrated to be a highly sensitive probe for screening of MG in fish pond and IDR in printing wastewater with satisfying results. Moreover, a portable test reagent bottle has been developed for visual on-site screening of sample containing dyes with naked eyes under UV light. This is the first attempt to construct the Eu3+@Zr-MOF-808 probe for sensingmultiple dyes in real samples and demonstrates promising applications in water quality monitoring.

20.
Biol Trace Elem Res ; 199(7): 2695-2706, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32984939

RESUMO

Boron is a trace element which plays important roles in immune response. The relationship between boron and splenic lymphocyte proliferation, apoptosis, secretion of cytokines, and genes potentially related to immune response in ostrich chicks were investigated in the present study. Different concentrations of boron (0, 0.01, 0.1, 0.5, 1, 5, 10, 25, 50, and 100 mmol/L) were applied to splenic lymphocytes of African ostrich, respectively. The effect of boron on lymphocyte proliferation was checked by the CCK-8 method. Flow cytometry was used to detect the effect of boron on apoptosis. The secretion levels of IL-6 and IFN-α were determined by ELISA. Splenic lymphocyte gene expression profiles of ostrich chicks treated with boron (0, 0.1, 100 mmol/L) were studied using RNA-seq technology. The results showed that cell proliferation increased with 0.01-10 mmol/L boron, when it was 25-100 mmol/L, the cell proliferation gradually decreased as the boron concentration increased. Apoptosis ratio in ostrich splenic lymphocytes was closely related to boron concentrations. 0.01- and 0.1-mmol/L boron inhibited apoptosis in splenic lymphocytes, whereas 1, 10, 50, and 100-mmol/L boron promoted apoptosis. As the concentration of boron increased, the secretion of IL-6 gradually decreased; IFN-α was initially increased and then decreased with boron concentrations increased, reaching the maximum level with 1 mmol/L boron. In terms of the RNA-Seq data, there was no differentially expressed gene between the 0- and 0.1-mmol/L boron-treated samples; 21 differentially expressed genes were found between the 0- and 100-mmol/L boron-treated samples; 43 differentially expressed genes were found between the 0.1- and 100-mmol/L boron-treated samples. Functional analysis of the differentially expressed genes by Gene Ontology verified multiple functions associated with immune response. Pathway analysis showed that systemic lupus erythematosus, alcoholism, viral carcinogenesis, and necroptosis pathway were the major enriched pathways, and BIRC2-3, FTH1, and IL-1ß genes showed differential expression in necroptosis pathway. These results demonstrated that low concentrations (0.01-0.1 mmol/L) of boron may promote the proliferation and the secretion of cytokines, inhibit cell apoptosis of ostrich splenic lymphocytes by enhancing the function of the cell membrane and the activity of intracellular catalytic enzymes, whereas high-concentration (25-100 mmol/L) boron had opposite effects on cells. The necroptosis pathway might play a pivotal role in regulating the immune response of boron-treated splenic lymphocytes in ostrich chicks.


Assuntos
Boro , Struthioniformes , Animais , Apoptose , Boro/farmacologia , Linfócitos , Baço
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