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1.
Artigo em Inglês | MEDLINE | ID: mdl-38180325

RESUMO

A novel ligninase-producing and cellulose-degrading actinobacterium, designated strain NEAU-A12T, was isolated from a soil sample collected from Aohan banner, Chifeng City, Inner Mongolia Autonomous Region, PR China. A polyphasic taxonomic study was used to establish the status of strain NEAU-A12T. 16S rRNA gene sequence analysis revealed that strain NEAU-A12T belonged to the genus Actinoplanes and showed the highest similarity (98.3 %) to Actinoplanes palleronii DSM 43940T, while showing less than 98.3 % similarity to other members of the genus Actinoplanes. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and glycosylphosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be arabinose, glucose and xylose. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The major fatty acids were C15 : 0, C16 : 0, C16 : 1 ω7c and C17 : 0. Meanwhile, genomic analysis revealed a genome size of 10 192 524 bp and a DNA G+C content of 70.6 mol%, and indicated that strain NEAU-A12T had the potential to degrade lignin and cellulose, as well as produce bioactive compounds. In addition, the average nucleotide identity values between strain NEAU-A12T and its reference strains A. palleronii DSM 43940T, Actinoplanes regularis DSM 43151T, Actinoplanes philippinensis DSM 43019T, Actinoplanes xinjiangensis DSM 45184T and Actinoplanes italicus DSM 43146T were 80.3, 80.3, 84.1, 84.3 and 84.0 %, respectively. The levels of digital DNA-DNA hybridization between them were found to be 23.6 % (21.3-26.1 %), 23.8 % (21.5-26.3 %), 28.3 % (25.9-30.8 %), 28.6 % (26.0-30.9 %) and 28.4 % (26.2-31.1 %), respectively. Based on phenotypic, chemotaxonomic and genotypic data, strain NEAU-A12T is considered to represent a novel species of the genus Actinoplanes, for which the name Actinoplanes sandaracinus sp. nov. is proposed, with NEAU-A12T (=CCTCC AA 2020039T=DSM 112043T) as the type strain.


Assuntos
Actinoplanes , Celulose , Solo , RNA Ribossômico 16S/genética , Composição de Bases , Ácidos Graxos/química , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
2.
Molecules ; 28(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37298829

RESUMO

Due to the presence of physiological barriers, it is difficult to achieve the desired therapeutic efficacy of drugs; thus, it is necessary to develop an efficient drug delivery system that enables advanced functions such as self-monitoring. Curcumin (CUR) is a naturally functional polyphenol whose effectiveness is limited by poor solubility and low bioavailability, and its natural fluorescent properties are often overlooked. Therefore, we aimed to improve the antitumor activity and drug uptake monitoring by simultaneously delivering CUR and 5-Fluorouracil (5-FU) in the form of liposomes. In this study, dual drug-loaded liposomes (FC-DP-Lip) encapsulating CUR and 5-FU were prepared by the thin-film hydration method; their physicochemical properties were characterized; and their biosafety, drug uptake distribution in vivo, and tumor cell toxicity were evaluated. The results showed that the nanoliposome FC-DP-Lip showed good morphology, stability, and drug encapsulation efficiency. It showed good biocompatibility, with no side effects on zebrafish embryonic development. In vivo uptake in zebrafish showed that FC-DP-Lip has a long circulation time and presents gastrointestinal accumulation. In addition, FC-DP-Lip was cytotoxic against a variety of cancer cells. This work showed that FC-DP-Lip nanoliposomes can enhance the toxicity of 5-FU to cancer cells, demonstrating safety and efficiency, and enabling real-time self-monitoring functions.


Assuntos
Antineoplásicos , Curcumina , Nanopartículas , Animais , Curcumina/farmacologia , Curcumina/química , Lipossomos/química , Fluoruracila/farmacologia , Peixe-Zebra , Antineoplásicos/farmacologia , Antineoplásicos/química , Tamanho da Partícula , Nanopartículas/química
3.
Int J Syst Evol Microbiol ; 72(10)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36268867

RESUMO

A novel cellulose-degrading actinobacterium, designated strain NEAU-S10T, was isolated from soil collected from Chifeng, Inner Mongolia Autonomous Region, PR China, and characterized using a polyphasic approach. Pairwise similarity of the 16S rRNA gene sequence showed that strain NEAU-S10T was a representative of Saccharothrix and was closely related to Saccharothrix carnea NEAU-yn17T (99.2 %), Saccharothrix saharensis SA152T (99.0 %), Saccharothrix texasensis DSM 44231T (98.5 %) and Saccharothrix xinjiangensis NBRC 101911T (98.5 %). Physiological and chemotaxonomic characteristics of the strain further supported its affiliation to the genus Saccharothrix. The whole-cell sugars contained galactose, ribose and mannose. The polar lipids contained diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The predominant menaquinones were MK-9(H0), MK-9(H2), MK-9(H4) and MK-10(H4). The major fatty acids were iso-C16 : 0, C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C17 : 0. The genomic DNA G+C content was 71.8 mol%. The levels of digital DNA-DNA hybridization between isolate and S. carnea NEAU-yn17T, S. saharensis SA152T and S. texasensis DSM 44231T were 40.1 % (37.6-42.6 %), 38.soap8 % (36.3-41.3 %) and 44.8 % (42.2-47.3 %) and the ANI values between them were determined to be 90.2, 89.8 and 91.7 %, the results indicated that strain NEAU-S10T could be distinguished from its reference strains. The assembled genome sequence of strain NEAU-S10T was found to be 10 305 394 bp long. The NCBI Prokaryotic Genome Annotation Pipeline (PGAP) revealed 8 994 protein-coding genes. Genomic analysis and Congo red staining test indicated that strain NEAU-S10T had the potential to degrade cellulose. The genomic and phenotypic results indicate that strain NEAU-S10T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix luteola sp. nov. is proposed, with NEAU-S10T (=CCTCC AA 2020037T=JCM 34800T) as the type strain.


Assuntos
Fosfatidiletanolaminas , Solo , RNA Ribossômico 16S/genética , Microbiologia do Solo , Vitamina K 2 , Celulose , Cardiolipinas , Vermelho Congo , Galactose , Manose , Ribose , Composição de Bases , Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Análise de Sequência de DNA , Fosfatidilinositóis , Fosfolipídeos
4.
Inorg Chem ; 61(29): 11293-11305, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35820030

RESUMO

Lu2(1-x)Eu2xO3 nanoscintillators (x = 0.005, 0.01, 0.03, 0.05, 0.07, and 0.10) with red emission were synthesized by a coprecipitation method. It is found that their photo- and radioluminescence intensities increase with increasing Eu3+ concentration until x = 0.05. According to their concentration-dependent luminescence intensity ratios (I610(C2)/I582(S6)), the existing energy transfer from Eu3+(S6) (occupying S6 sites) to Eu3+(C2) (occupying C2 sites) can be confirmed. Based on the spectral data and density functional theory (DFT) calculations, the origin of Lu2O3:Eu3+ persistent luminescence at low concentration might be related to the tunneling processes between Eu3+ (occupying C2 and S6 sites) and oxygen interstitials (Oi×). After dispersing afterglow-suppressed Lu2O3:Eu3+ nanoscintillators into polymethyl methacrylate (PMMA) polymer-acetone solution, flexible PMMA-Lu2O3:Eu3+ composite films with high thermal stability and radiation resistance were fabricated by a doctor blade method. As the flexible composite film was used as an imaging plate, static X-ray images with high spatial resolution (5.5 lp/mm) under an extremely low dose of ∼1.1 µGyair can be acquired. When a watch with a moving second hand was used as an object, the dynamic X-ray imaging can be realized under a dose rate of 55 µGyair·s-1. Our results demonstrate that Lu2O3:Eu3+ nanoscintillators can be regarded as candidate materials for dynamic digital radiographic imaging.


Assuntos
Európio , Polimetil Metacrilato , Transferência de Energia , Luminescência , Raios X
5.
Int J Mol Sci ; 23(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743311

RESUMO

(1) Background: Curcumin (CUR) and tetrandrine (TET) are natural compounds with various bioactivities, but have problems with low solubility, stability, and absorption rate, resulting in low bioavailability, and limited applications in food, medicine, and other fields. It is very important to improve the solubility while maintaining the high activity of drugs. Liposomes are micro-vesicles synthesized from cholesterol and lecithin. With high biocompatibility and biodegradability, liposomes can significantly improve drug solubility, efficacy, and bioavailability. (2) Methods: In this work, CUR and TET were encapsulated with nano-liposomes and g DSPE-MPEG 2000 (DP)was added as a stabilizer to achieve better physicochemical properties, biosafety, and anti-tumor effects. (3) Results: The nano-liposome (CT-DP-Lip) showed stable particle size (under 100 nm) under different conditions, high solubility, drug encapsulation efficiency (EE), loading capacity (LC), release rate in vitro, and stability. In addition, in vivo studies demonstrated CT-DP-Lip had no significant toxicity on zebrafish. Tumor cytotoxicity test showed that CT-DP-Lip had a strong inhibitory effect on a variety of cancer cells. (4) Conclusions: This work showed that nano-liposomes can significantly improve the physical and chemical properties of CUR and TET and make them safer and more efficient.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Curcumina , Neoplasias , Animais , Benzilisoquinolinas , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Lipossomos/química , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Peixe-Zebra
6.
Antonie Van Leeuwenhoek ; 114(5): 581-590, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33649883

RESUMO

An aerobic, non-motile, Gram-stain positive, cellulose-degrading actinobacterium, designated strain NEAU-GS84T, was isolated from a forest soil sample collected from Linchun Ridge Forest Park in Sanya, Hainan Province, China, and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics indicated that strain NEAU-GS84T could belong to the genus Herbidospora. The 16S rRNA gene sequence analysis indeed confirmed that strain NEAU-GS84T belonged to the genus Herbidospora and was most closely related to Herbidospora yilanensis JCM 18062T (99.2% 16S rRNA gene sequence similarity) and Herbidospora galbida NEAU-GS14T (99.0%). The cell wall of strain NEAU-GS84T contained meso-diaminopimelic acid as the major diamino acid and the whole-cell hydrolysates mainly contained glucose, madurose and ribose. The major polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxyphosphatidylethanolamin, phosphoglycolipids, two phosphatidylinositol mannosides and one unidentified phospholipid. The predominant menaquinone was MK-10(H4). Major fatty acids were 10-methly C17:0, C17:0 and iso-C16:0. These chemotaxonomic data substantiated the affiliation of strain NEAU-GS84T to the genus Herbidospora. The DNA G+C content was 70.7 mol%. The genome size of strain NEAU-GS84T is about 8.37 Mb and contained 41 cellulose-binding domain synthesis genes, 13 ß-glucosidase synthesis genes, 6 endoglucanase synthesis genes and 9 xylanase synthesis genes. Based on digital DNA-DNA hybridization and average nucleotide identity values, the new strain NEAU-GS84T could be differentiated from its closest relatives. Therefore, the strain represents a novel species of the genus Herbidospora, for which the name Herbidospora solisilvae sp. nov. is proposed. The type strain is NEAU-GS84T (= CCTCC AA 2018041T = JCM 33460T).


Assuntos
Celulose , Solo , Actinobacteria , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos , Florestas , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo , Vitamina K 2
7.
Cell Tissue Res ; 382(3): 487-498, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32743695

RESUMO

Accumulating research continues to highlight the notable role of microRNAs (miRs) and long non-coding RNAs (lncRNAs) as important regulators in the process of human dental pulp stem cell (hDPSCs) differentiation. The current study aimed to investigate the novel regulatory circuitry of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-140-5p/G protein-coupled receptor (GPCR)-kinase 2 interacting protein 2 (GIT2) on the odontogenic differentiation of hDPSCs. In hDPSCs, miR-140-5p was downregulated during the odontogenic differentiation, which was verified to directly target GIT2. RNA crosstalk determined by dual-luciferase reporter and RNA pull-down assays revealed that MALAT1 could bind to miR-140-5p to upregulate the expression of GIT2. After that, the levels of MALAT1, miR-140-5p, and GIT2 in hDPSCs were up- or downregulated by exogenous transfection or lentivirus infection in order to investigate their effects on the differentiation of hDPSCs. It was observed that elevation of miR-140-5p or knockdown of GIT2 resulted in inhibited alkaline phosphatase (ALP) activity, expression of dentin sialophosphoprotein (DSPP), dentin matrix-protein-1 (DMP-1), and distal-less homeobox 3 (DLX3) as well as positive expression of desmoplakin (DSP) protein. The promotive effects of MALAT1 on odontogenic differentiation were diminished by restoration of miR-140-5p or inhibition of GIT2. Taken together, this study provides valuable evidence suggesting MALAT1 as a potential contributor to the odontogenic differentiation of hDPSCs.


Assuntos
Polpa Dentária/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , MicroRNAs/metabolismo , Odontogênese/fisiologia , RNA Longo não Codificante/metabolismo , Diferenciação Celular/fisiologia , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Regulação para Baixo , Proteínas Ativadoras de GTPase/genética , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Transfecção
8.
Mol Pharm ; 17(11): 4089-4100, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32845647

RESUMO

The highly rigid and planar scaffolds with π-conjugated systems have been widely considered to be indispensable for ß-amyloid (Aß) binding ligands. In this study, a library of diphenoxy compounds with different types of more flexible linkers as Aß ligands were synthesized and evaluated. Most of them displayed good affinity (Ki < 100 nM) for Aß1-42 aggregates, and some ligands even showed values of Ki less than 10 nM. Structure-activity relationship analysis revealed that modification on the linkers or substituents tolerated great flexibility, which challenged the long-held belief that rigid and planar structures are exclusively favored for Aß binding. Three ligands were labeled by iodine-125, and they exhibited good properties in vitro and in vivo, which further supported that this flexible scaffold was potential and promising for the development of Aß imaging agents.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fenóis/química , Fenóis/metabolismo , Piperazina/química , Placa Amiloide/metabolismo , Polietilenoglicóis/química , Propano/química , Animais , Autorradiografia/métodos , Encéfalo/metabolismo , Humanos , Radioisótopos do Iodo/química , Ligantes , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Fenóis/síntese química , Compostos Radiofarmacêuticos/metabolismo , Relação Estrutura-Atividade , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos
9.
Anesth Analg ; 131(6): 1830-1839, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32739962

RESUMO

BACKGROUND: In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. METHODS: Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. RESULTS: Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). CONCLUSIONS: TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).


Assuntos
Músculos Abdominais/inervação , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Cesárea/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Cesárea/tendências , Método Duplo-Cego , Feminino , Humanos , Lipossomos , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Gravidez
10.
Nanomedicine ; 27: 102196, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272233

RESUMO

Bone-targeted therapies have been the choice of treatments for cancer metastases in bone to minimize skeletal morbidity and preserve patients' quality of life. Rhein is of particular interest due to its high bone affinity. Here we reported a novel Rhein- polyethylene glycol (PEG)-nano hydroxyapatite (nHA) conjugate to deliver doxorubicin (DOX) and Phosphorus-32 (32P) simultaneously for enhanced cancer chemo-radiotherapy. The synthetic Rhein-PEG-nHA conjugates were sphere in shape with an average diameter of ~120 nm. Their morphology, drug release and bone affinity were confirmed in vitro. The release profiles of DOX depend on pH condition, but 32P exhibited good stability. Rhein-PEG-nHA also showed high bone affinity in vivo, and the tumor volume decreased after the DOX@Rhein-PEG-nHA and 32P@Rhein-PEG-nHA treatments. Most importantly, the DOX/32P@Rhein-PEG-nHA showed the strongest inhibition on the growth of bone metastases of breast cancer. We revealed the potential of Rhein-PEG-nHA in combined chemo-radiation treatment for bone metastases of breast cancer.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Sistemas de Liberação de Medicamentos , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Durapatita/química , Durapatita/farmacologia , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Camundongos , Metástase Neoplásica , Radioisótopos de Fósforo/química , Radioisótopos de Fósforo/farmacologia , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Mater Sci Mater Med ; 31(3): 28, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125534

RESUMO

Keratins derived from human hair have been suggested to be particularly effective in general surgical wound healing. However, the healing of a combined radiation-wound injury is a multifaceted regenerative process. Here, hydrogels fabricated with human hair keratins were used to test the wound healing effects on rats suffering from combined radiation-wound injuries. Briefly, the keratin extracts were verified by dodecyl sulfate polyacrylamide gel electrophoresis analysis and amino acid analysis, and the keratin hydrogels were then characterized by morphological observation, Fourier transform infrared spectroscopy analysis and rheology analyses. The results of the cell viability assay indicated that the keratin hydrogels could enhance cell growth after radiation exposure. Furthermore, keratin hydrogels could accelerate wound repair and improve the survival rate in vivo. The results demonstrate that keratin hydrogels possess a strong ability to accelerate the repair of a combined radiation-wound injury, which opens up new tissue regeneration applications for keratins.


Assuntos
Queratinas Específicas do Cabelo/química , Queratinas Específicas do Cabelo/uso terapêutico , Lesões por Radiação/terapia , Cicatrização/efeitos dos fármacos , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Citocinas/metabolismo , Células HaCaT , Cabelo/química , Humanos , Hidrogéis/química , Inflamação , Contagem de Leucócitos , Microscopia Eletrônica de Varredura , Ratos , Regeneração , Reologia , Dodecilsulfato de Sódio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 918-921, 2019 Sep 10.
Artigo em Zh | MEDLINE | ID: mdl-31515790

RESUMO

OBJECTIVE: To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy. METHODS: Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband. RESULTS: The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene. CONCLUSION: The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Glomerulosclerose Segmentar e Focal/genética , Proteínas dos Microfilamentos/genética , Doença de Charcot-Marie-Tooth/complicações , Criança , Feminino , Forminas , Glomerulosclerose Segmentar e Focal/complicações , Heterozigoto , Humanos , Masculino , Mutação , Linhagem
13.
Molecules ; 23(8)2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087276

RESUMO

A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 µM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.


Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Cumarínicos/síntese química , Cumarínicos/farmacologia , Cianoacrilatos/síntese química , Cianoacrilatos/farmacologia , Desenho de Fármacos , Transdução de Sinais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Cumarínicos/química , Cianoacrilatos/química , Ativação Enzimática/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
14.
BMC Microbiol ; 17(1): 38, 2017 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212613

RESUMO

BACKGROUND: Porphyromonas gingivalis is strongly associated with the development, progression, severity and recurrence of periodontitis. Periodontal ligament stem cells (PDLSCs) play an important role in the maintenance of periodontal tissue self-renewal and repair. The purpose of this study was to investigate the ability of P. gingivalis to infect PDLSCs using an in vitro monolayer model. METHODS: We separated and cultured primary PDLSCs using the tissue block with limiting dilution method. The efficiency of P. gingivalis (ATCC 33277) infection of PDLSCs was measured using agar plate culture and quantitative polymerase chain reaction (q-PCR) methods. PDLSCs infected with P. gingivalis were also observed by transmission electron microscopy. RESULTS: We assessed stem cell properties including cell morphology, clone formation, growth activity, cell surface antigens and multiple differentiation capacity. The infection rates of P. gingivalis in PDLSC at MOIs of 50, 100, 200, and 500 were 5.83%, 8.12%, 7.77% and 7.53% according to the agar plate culture method. By q-PCR, the efficiencies of P. gingivalis infection of PDLSCs at MOIs of 50, 100, 200, and 500 were 6.74%, 10.56%, 10.36% and 9.78%, respectively. Overall, the infection efficiency based on q-PCR was higher than that according to agar plate culture. Using transmission electron microscopy, we verified that P. gingivalis (ATCC 33277) could infect and invade PDLSCs after 2 h of incubation, and endocytic vacuoles were not found surrounding the internalized bacteria. CONCLUSIONS: In conclusion, our data demonstrate that P. gingivalis can invade PDLSCs.


Assuntos
Ligamento Periodontal/microbiologia , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Células-Tronco , Adolescente , Adulto , Antígenos de Superfície , Infecções por Bacteroidaceae/microbiologia , Ciclo Celular , Diferenciação Celular , Células Cultivadas , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Ligamento Periodontal/crescimento & desenvolvimento , Ligamento Periodontal/patologia , Periodontite/patologia , Porphyromonas gingivalis/genética , Células-Tronco/patologia , Adulto Jovem
15.
Bioorg Med Chem Lett ; 27(20): 4682-4686, 2017 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28919340

RESUMO

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5µM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2µM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.


Assuntos
Antineoplásicos/síntese química , Cianoacrilatos/química , Desenho de Fármacos , NF-kappa B/metabolismo , Pregnenolona/química , Células A549 , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Células MCF-7 , NF-kappa B/antagonistas & inibidores , Relação Estrutura-Atividade
16.
Int J Pharm ; 649: 123657, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38040398

RESUMO

Reactive oxygen species (ROS) can not only induce cellular oxidative stress, but also trigger antitumor immune response. However, single ROS generated therapy is usually not enough to induce efficient antitumor immune response. Furthermore, the adaptive antioxidant mechanisms coupled with overexpressed ROS can also decrease the antitumor capacity of ROS therapy. To circumvent this problem, we designed a synergistic strategy for inducing robust ROS based ICD effect by constructing a coloaded liposomes (PPA, Pyropheophorbide-alpha and SHK, shikonin) with Fe3+ gradient to simultaneously enhance ROS mediated oxidative stress and glutathione depletion. Interestingly, the coloaded liposome possesses an acid/GSH dual triggered release profile. More importantly, with the help of depleting GSH, LipoPS (coloaded liposome of SHK and PPA) can excite robust ROS and demonstrate synergistic antitumor efficacy with amplified ICD effect. Summarized, the established coloaded liposome LipoPS exhibits good therapeutic security and synergistic antitumor effect with strong antitumor immune activation, providing potential for further development.


Assuntos
Morte Celular Imunogênica , Lipossomos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo
17.
Adv Sci (Weinh) ; 11(13): e2305756, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38189598

RESUMO

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability- in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti-inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro-assembly under pre-programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS-containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS-containing porous layer delivers dual bio-signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.


Assuntos
Periodontite , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Porosidade , Osteogênese , Colágeno/química , Periodontite/tratamento farmacológico
18.
J Clin Anesth ; 94: 111402, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38340677

RESUMO

STUDY OBJECTIVE: To investigate the efficacy, safety, pharmacodynamics, and pharmacokinetics of liposomal bupivacaine (LB) administered via ultrasound-guided sciatic nerve block in the popliteal fossa in participants undergoing bunionectomy. DESIGN: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). SETTING: Operating room, postanesthesia care unit, and health care facility (6 sites). PATIENTS: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy. INTERVENTIONS: Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI. MEASUREMENTS: The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints. MAIN RESULTS: Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 h after surgery (LSM, 17.7 [95% confidence interval (CI), 13.7, 22.8] morphine milligram equivalents [MMEs] vs 45.3 [95% CI, 35.1, 58.5] MMEs; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups. CONCLUSIONS: LB 133 mg administered via sciatic nerve block in the popliteal fossa after bunionectomy demonstrated superior and long-lasting postsurgical pain control versus BUPI. The clinical relevance of these findings is supported by concurrent reductions in pain and opioid consumption over 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.


Assuntos
Anestésicos Locais , Dor Pós-Operatória , Adulto , Humanos , Analgésicos Opioides , Bupivacaína , Lipossomos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Nervo Isquiático
19.
Plant Commun ; 5(1): 100681, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37660253

RESUMO

Bananas (Musa spp.) are monocotyledonous plants with high genetic diversity in the Musaceae family that are cultivated mainly in tropical and subtropical countries. The fruits are a popular food, and the plants themselves have diverse uses. Four genetic groups (genomes) are thought to have contributed to current banana cultivars: Musa acuminata (A genome), Musa balbisiana (B genome), Musa schizocarpa (S genome), and species of the Australimusa section (T genome). However, the T genome has not been effectively explored. Here, we present the high-quality TT genomes of two representative accessions, Abaca (Musa textilis), with high-quality natural fiber, and Utafun (Musa troglodytarum, Fe'i group), with abundant ß-carotene. Both the Abaca and Utafun assemblies comprise 10 pseudochromosomes, and their total genome sizes are 613 Mb and 619 Mb, respectively. Comparative genome analysis revealed that the larger size of the T genome is likely attributable to rapid expansion and slow removal of transposons. Compared with those of Musa AA or BB accessions or sisal (Agava sisalana), Abaca fibers exhibit superior mechanical properties, mainly because of their thicker cell walls with a higher content of cellulose, lignin, and hemicellulose. Expression of MusaCesA cellulose synthesis genes peaks earlier in Abaca than in AA or BB accessions during plant development, potentially leading to earlier cellulose accumulation during secondary cell wall formation. The Abaca-specific expressed gene MusaMYB26, which is directly regulated by MusaMYB61, may be an important regulator that promotes precocious expression of secondary cell wall MusaCesAs. Furthermore, MusaWRKY2 and MusaNAC68, which appear to be involved in regulating expression of MusaLAC and MusaCAD, may at least partially explain the high accumulation of lignin in Abaca. This work contributes to a better understanding of banana domestication and the diverse genetic resources in the Musaceae family, thus providing resources for Musa genetic improvement.


Assuntos
Musa , Musa/genética , Genoma de Planta , Lignina
20.
JACC Cardiovasc Interv ; 17(13): 1519-1528, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38842991

RESUMO

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).


Assuntos
Angioplastia Coronária com Balão , Cateteres Cardíacos , Fármacos Cardiovasculares , Materiais Revestidos Biocompatíveis , Angiografia Coronária , Doença da Artéria Coronariana , Valor Preditivo dos Testes , Ultrassonografia de Intervenção , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Estudos Prospectivos , Fatores de Risco , China
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