Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 190
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Small ; : e2401397, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898735

RESUMO

Pyroptosis, an inflammatory cell death, plays a pivotal role in activating inflammatory response, reversing immunosuppression and enhancing anti-tumor immunity. However, challenges remain regarding how to induce pyroptosis efficiently and precisely in tumor cells to amplify anti-tumor immunotherapy. Herein, a pH-responsive polydopamine (PDA) nanocluster, perfluorocarbon (PFC)@octo-arginine (R8)-1-Hexadecylamine (He)-porphyrin (Por)@PDA-gambogic acid (GA)-cRGD (R-P@PDA-GC), is rationally design to augment phototherapy-induced pyroptosis and boost anti-tumor immunity through a two-input programmed cascade therapy. Briefly, oxygen doner PFC is encapsulated within R8 linked photosensitizer Por and He micelles as the core, followed by incorporation of GA and cRGD peptides modified PDA shell, yielding the ultimate R-P@PDA-GC nanoplatforms (NPs). The pH-responsive NPs effectively alleviate hypoxia by delivering oxygen via PFC and mitigate heat resistance in tumor cells through GA. Upon two-input programmed irradiation, R-P@PDA-GC NPs significantly enhance reactive oxygen species production within tumor cells, triggering pyroptosis via the Caspase-1/GSDMD pathway and releasing numerous inflammatory factors into the TME. This leads to the maturation of dendritic cells, robust infiltration of cytotoxic CD8+ T and NK cells, and diminution of immune suppressor Treg cells, thereby amplifying anti-tumor immunity.

2.
J Nanobiotechnology ; 22(1): 180, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622591

RESUMO

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia/métodos , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Oxigênio , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
3.
J Liposome Res ; : 1-13, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712581

RESUMO

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

4.
Chem Biodivers ; 21(6): e202400511, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538539

RESUMO

Two undescribed germacrane-type sesquiterpenoids, salcasins A (1) and B (2), together with three known compounds (3-5) were isolated and identified from the whole plant of Salvia cavaleriei var. simplicifolia Stib. The structures of the undescribed compounds were elucidated on the basis of spectroscopic methods, such as HR-ESI-MS, 1D and 2D NMR data. The relative configurations of 1 and 2 were established by analyzing their NOESY spectra as well as by 13C NMR calculations with DP4+ probability analyses. The absolute configurations of 1 and 2 were determined by comparing experimental and calculated ECD spectra. Furthermore, the in vivo anti-Alzheimer's disease activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. Among all isolated compounds, salcasin A (1) significantly delayed AD-like symptoms of worm paralysis, which may be a potential anti-AD candidate agent.


Assuntos
Doença de Alzheimer , Caenorhabditis elegans , Salvia , Sesquiterpenos de Germacrano , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Salvia/química , Caenorhabditis elegans/efeitos dos fármacos , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Estrutura Molecular , Conformação Molecular , Modelos Animais de Doenças
5.
Environ Sci Technol ; 57(30): 10919-10928, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37475130

RESUMO

Artificial sweeteners have been frequently detected in the feedstocks of anaerobic digestion. As these sweeteners can lead to the shift of anaerobic microbiota in the gut similar to that caused by antibiotics, we hypothesize that they may have an antibiotic-like impact on antibiotic resistance genes (ARGs) in anaerobic digestion. However, current understanding on this topic is scarce. This investigation aimed to examine the potential impact of acesulfame, a typical artificial sweetener, on ARGs in anaerobic digestion by using metagenomics sequencing and qPCR. It was found that acesulfame increased the number of detected ARG classes and the abundance of ARGs during anaerobic digestion. The abundance of typical mobile genetic elements (MGEs) and the number of potential hosts of ARGs also increased under acesulfame exposure, suggesting the enhanced potential of horizontal gene transfer of ARGs, which was further confirmed by the correlation analysis between absolute abundances of the targeted ARGs and MGEs. The increased horizontal dissemination of ARGs may be associated with the SOS response induced by the increased ROS production, and the increased cellular membrane permeability. These findings indicate that artificial sweeteners may accelerate ARG spread through digestate disposal, thus corresponding strategies should be considered to prevent potential risks in practice.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Edulcorantes , Edulcorantes/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistência Microbiana a Medicamentos/genética , Anaerobiose/efeitos dos fármacos , Genes Bacterianos , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/farmacologia
6.
Radiographics ; 43(6): e220125, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37141138

RESUMO

Radiology is among the medical specialties that have made the fewest gains in closing the gap in underrepresented minorities and women. Diversity, equity, and inclusion (DEI) initiatives are important for promoting healthy learning environments for trainees, health equity for patients, and equitable career development opportunities for employees, all of which contribute to innovation in today's competitive health care environment. DEI committees can self-organize or form from institutional directives. These committees can implement impactful projects in multiple domains in education, recruitment and retention, department culture, and health equity research. This article describes the formation of a grassroots DEI committee, key initiatives and strategies, and structures for accountability. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.


Assuntos
Diversidade, Equidade, Inclusão , Radiologia , Humanos , Feminino , Grupos Minoritários , Aprendizagem
7.
Bioorg Chem ; 139: 106714, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37454496

RESUMO

The pathogenesis of Alzheimer's disease (AD), a multifactorial progressive neurodegenerative disease associated with aging, is unclear. Ethyl caffeate is a plant polyphenol that has been reported to have neuroprotective effects, but the mechanisms by which it acts are unclear. In this study, for the first time, we investigated the molecular mechanism of its anti-AD properties using the Caernorhabditis elegans model. The results of our experiments showed that ethyl caffeate delayed the paralysis symptoms of CL4176 to a different extent and reduced the exogenous 5-hydroxytryptophan-induced paralysis phenotype. Further studies revealed that ethyl caffeate lowered Aß plaques and depressed the expression of Aß monomers and oligomers, but did not influence the mRNA levels of Aß. Moreover, it was able to bring paraquat-induced ROS levels down to near-standard conditions. Real-time quantitative PCR experiment showed a significant upregulation of the transcript abundance of daf-16, skn-1 and hsf-1, key factors associated with the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway (IIS), and their downstream genes sod-3, gst-4 and hsp-16.2. It was further shown that ethyl caffeate activated the translocation of DAF-16 and SKN-1 from the cytoplasm to the nucleus and enhanced the expression of sod-3::GFP, gst-4::GFP and hsp-16.2::GFP in transgenic nematodes. This meant that the protection against Aß toxicity by ethyl caffeate may be partly through the IIS signaling pathway. In addition, ethyl caffeate suppressed the aggregation of polyglutamine proteins in AM141, which indicated a potential protective effect against neurodegenerative diseases based on abnormal folding and aggregation of amyloid proteins. Taken together, ethyl caffeate is expected to develop as a potential drug for the management of AD.

8.
J Prosthet Dent ; 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38061938

RESUMO

STATEMENT OF PROBLEM: The use of intraoral scanners (IOSs) correlates with clinical outcome and patient satisfaction. While the accuracy of IOSs has been well evaluated, studies on the effect of scanning duration on data accuracy are limited. PURPOSE: The purpose of this in vitro study was to investigate the relationship between different scanning durations and the accuracy of the scanned data. MATERIAL AND METHODS: Two experienced operators used the same intraoral scanner (TRIOS 3; 3Shape A/S) to scan a gypsum cast, but with 5 different scanning durations (30 seconds, 60 seconds, 90 seconds, 120 seconds, and 180 seconds), and the trueness of the scanned data was assessed. Ten scans for each duration group were performed, and all the acquired data were evaluated for precision analysis. In addition, each scanned complete arch cast was divided into anterior and posterior regions at the canine teeth, and the 3-way ANOVA test was used to assess the scanning trueness and precision of the scanned anterior and posterior dental arch. RESULTS: The intraoral scanning results between the 2 operators were highly consistent. The data of the 30-second group showed the lowest trueness and precision (P<.001), whereas no significant difference was found among the other groups (P>.05). The trueness and precision of the scanning data in the posterior region was inferior to that in the anterior region (P<.001). CONCLUSIONS: The duration time of the intraoral scanning (ranging from 60 seconds to 180 seconds) did not influence the accuracy of the acquired data, while excessively rapid scanning adversely affected accuracy.

9.
Int J Mol Sci ; 23(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743309

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aß-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aß-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aß monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.


Assuntos
Doença de Alzheimer , Proteínas de Caenorhabditis elegans , Diterpenos , Doenças Neurodegenerativas , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Diterpenos/farmacologia , Fatores de Transcrição Forkhead/genética , Paralisia/induzido quimicamente , RNA Mensageiro/metabolismo
10.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077432

RESUMO

Alzheimer's disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aß1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aß monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.


Assuntos
Doença de Alzheimer , Proteínas de Caenorhabditis elegans , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Estresse Oxidativo , Fenantrenos , Espécies Reativas de Oxigênio/metabolismo
11.
Reprod Fertil Dev ; 33(12): 700-712, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34399087

RESUMO

This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.


Assuntos
Dexametasona/farmacologia , Placenta/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Glucocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 46(21): 5600-5605, 2021 Nov.
Artigo em Zh | MEDLINE | ID: mdl-34951212

RESUMO

Scutellariae Radix is a commonly used Chinese medicinal first recorded in the Shennong's Classic of Materia Medica. In the ancient books of traditional Chinese medicine(TCM), Scutellariae Radix is used in two specifications, solid one(Ziqin) and hollow one(Kuqin). In the current rules and regulations of Chinese medicine, Scutellariae Radix is used without the specific requirements for the specifications applied. To clarify the evolution of Scutellariae Radix specifications and analyze the current specifications of Scutellariae Radix pieces, the present study reviews the Scutellariae Radix from ancient literature, modern rules and regulations, and differences between Ziqin and Kuqin in composition, efficacy, and transformation mechanism. According to the research on ancient books, Kuqin is effective in clearing the fire of the upper energizer, and Ziqin in purging the heat of the lower energizer. Modern studies have revealed that Kuqin and Ziqin are significantly different in chemical components, and Ziqin and Kuqin target the colon and lung, respectively, which are consistent with the relevant records in ancient books. The review study suggests that the two specifications of Scutellariae Radix are reasonable since they can facilitate the precise treatment of Scutellariae Radix.


Assuntos
Medicamentos de Ervas Chinesas , Literatura Moderna , Materia Medica , Medicina Tradicional Chinesa , Scutellaria baicalensis
13.
Parasitol Res ; 119(10): 3339-3345, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827102

RESUMO

Genetic variations in the 18S ribosomal DNA (18S), 28S ribosomal DNA (28S), second internal transcribed spacer of ribosomal DNA (ITS2), and mitochondrial cytochrome c oxidase subunit 1 (cox1) of Neoschoengastia gallinarum collected from subtropical China were examined. First, a portion of the 18S (p18S), a portion of the 28S (p28S), and the complete ITS2 were separately amplified from individual mites and sequenced. The lengths of the sequences of p18S, p28S, and ITS2 were found to be 1379 bp, 3465~3468 bp, and 200 bp, respectively. The intraspecific sequence variation was 0~0.1% for p28S and 0~1.6% for ITS2, though no variation was observed for p18S, suggesting conservation of rDNA sequences. Second, a portion of the mitochondrial cox1 gene (pcox1) of N. gallinarum was analyzed. The length of the pcox1 sequence is 460 bp, and two distinct groups were observed in N. gallinarum. All pcox1 sequences in group I were identical, and there was only one nucleotide transition observed in group II; however, 7.0~7.2% variations between the two groups were observed, suggesting that two genotypes of N. gallinarum: genotype I and genotype II. Phylogenetic analyses based on pcox1 sequences indicated that N. gallinarum isolates (genotype I or genotype II) clustered into one branch; according to cox1 sequence analysis of Trombiculidae, Walchia hayashii is the closest species. The present study shows that ITS2 rDNA sequence can act as marker for the identification of N. gallinarum samples. Furthermore, analysis of the mitochondrial pcox1 sequence suggests the existence of two genotypes, which has implications for further studies of the ecology and population genetic structures of N. gallinarum.


Assuntos
Ciclo-Oxigenase 1/genética , DNA Ribossômico/genética , Trombiculidae/genética , Animais , China , DNA Mitocondrial/genética , Variação Genética , Genótipo , Filogenia , Análise de Sequência de DNA , Trombiculidae/classificação
14.
Chem Biodivers ; 17(5): e2000067, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32154990

RESUMO

One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1ß-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Curcuma/química , Sesquiterpenos Monocíclicos/farmacologia , Fenóis/farmacologia , Rizoma/química , Animais , Caenorhabditis elegans , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estrutura Molecular , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Relação Estrutura-Atividade
15.
Molecules ; 25(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178320

RESUMO

The mixed-ligand copper(II) iminodiacetates [Cu(ida)(2-mim)(H2O)2]·H2O (1), [Cu(ida)(2-mim)2]·2H2O (2), [Cu(ida)(2-mim)(H2O)]n·4.5nH2O (3), and [Cu2(ida)2(2-mim)2]n·nH2O (4) (H2ida = iminodiacetic acid, 2-mim = 2-methylimidazole) were obtained from neutral or alkaline solutions at different temperatures. The novel complex 4 contains very small holes with diameters of 2.9 Å, which can adsorb O2 selectively and reversibly between 1.89 to 29.90 bars, compared with the different gases of N2, H2, CO2, and CH4. This complex is stable up to 150 °C based on thermal analyses and XRD patterns. The four complexes show catalytic activities that facilitate the conversion of cyclohexane to cyclohexanol and cyclohexanone with hydrogen peroxide in a solution. The total conversion is 31% for 4.


Assuntos
Complexos de Coordenação/química , Cicloexanos/química , Imidazóis/química , Iminoácidos/química , Adsorção , Catálise , Cobre/química , Cristalografia por Raios X , Ligantes , Oxirredução/efeitos dos fármacos , Oxigênio/química
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1217-1221, 2020 Nov 10.
Artigo em Zh | MEDLINE | ID: mdl-33179224

RESUMO

OBJECTIVE: To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development. METHODS: Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed. RESULTS: For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes. CONCLUSION: For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.


Assuntos
Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Feminino , Feto/diagnóstico por imagem , Testes Genéticos , Humanos , Cariotipagem , Gravidez , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
17.
J Cell Physiol ; 234(8): 13832-13842, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30637734

RESUMO

Wearing titanium particle-induced osteoclastogenesis, accompanied by peri-implant osteolysis, is the main cause of long-term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri-implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti-inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle-induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL-induced osteoclastogenesis, fusion of F-actin rings, bone resorption, and expression of osteoclast marker genes in a dose-dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL-induced osteoclastogenesis via the inhibition of NF-κB and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c-Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle-induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri-implant osteolysis.


Assuntos
Flavonoides/farmacologia , Glicosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Osteólise/induzido quimicamente , Osteólise/patologia , Ligante RANK/farmacologia , Titânio/efeitos adversos , Animais , Biomarcadores/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Durapatita/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , Crânio/patologia
18.
Mol Cancer ; 18(1): 15, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670025

RESUMO

BACKGROUND: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC). METHODS: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo. RESULTS: In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Animais , Apoptose/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Camundongos , Camundongos Nus , Prognóstico
19.
Org Biomol Chem ; 18(1): 76-80, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31773124

RESUMO

Eupulcherol A (1), a novel triterpenoid with an unprecedented carbon skeleton, was isolated from Euphorbia pulcherrima. Its structure was determined by comprehensive analysis of spectroscopic data, including HRESIMS and 1D and 2D NMR, and the absolute configuration was defined by single crystal X-ray diffraction analysis. Biological studies showed that compound 1 possessed anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A plausible biogenetic pathway for eupulcherol A (1) was also proposed.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antiprotozoários/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Euphorbia/química , Triterpenos/farmacologia , Doença de Alzheimer/parasitologia , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação
20.
Environ Sci Technol ; 53(7): 3579-3588, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30829479

RESUMO

In the environment, microplastics are subjected to multiple aging processes; however, information regarding the impact of aging on the environmental behavior of microplastics is still lacking. This study investigated the alteration properties of polystyrene and high-density polyethylene microplastics by heat-activated K2S2O8 and Fenton treatments to improve the understanding of their long-term natural aging in aquatic environments. Our results indicated that the O/C ratio was an alternative parameter to the carbonyl index (CI) to quantitatively describe the surface alteration properties of microplastics. The correlation model of the O/C ratio or CI versus alteration time was developed and compared by natural alteration of microplastics in freshwater samples. Moreover, the regression equation of the equilibrium adsorption capacity of altered microplastics versus the O/C ratio and average size was proposed. This study is the first effort in differentiating the relationships between the alteration properties and alteration time/adsorption capacity of microplastics, which would be helpful for predicting the weathering degree and accumulation of hydrophilic antibiotics onto aged microplastics in aquatic environments. This research develops promising strategies to accelerate the aging reactions using advanced oxidation processes, which would provide further information to assess the microplastic pollution in actual environments.


Assuntos
Plásticos , Poluentes Químicos da Água , Adsorção , Água Doce , Polietileno
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA