RESUMO
Large scale human genome projects have created tremendous human genome databases for some well-studied populations. Vietnam has about 95 million people (the 14th largest country by population in the world) of which more than 86% are Kinh people. To date, genetic studies for Vietnamese people mostly rely on genetic information from other populations. Building a Vietnamese human genetic variation database is a must for properly interpreting Vietnamese genetic variants. To this end, we sequenced 105 whole genomes and 200 whole exomes of 305 unrelated Kinh Vietnamese (KHV) people. We also included 101 other previously published KHV genomes to build a Vietnamese human genetic variation database of 406 KHV people. The KHV database contains 24.81 million variants (22.47 million single nucleotide polymorphisms (SNPs) and 2.34 million indels) of which 0.71 million variants are novel. It includes more than 99.3% of variants with a frequency of >1% in the KHV population. Noticeably, the KHV database revealed 107 variants reported in the human genome mutation database as pathological mutations with a frequency above 1% in the KHV population. The KHV database (available at https://genomes.vn) would be beneficial for genetic studies and medical applications not only for the Vietnamese population but also for other closely related populations.
Assuntos
Povo Asiático/genética , Bases de Dados Genéticas , Variação Genética , Genoma Humano , Biologia Computacional/métodos , Genética Populacional , Humanos , Anotação de Sequência Molecular , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Vietnã , Sequenciamento do Exoma , Sequenciamento Completo do GenomaRESUMO
Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells that can be isolated from bone marrow, adipose tissue, the umbilical cord, dental pulp, etc. These cells have unique properties that give them excellent therapeutic potential, including immunoregulation, immunomodulation, and tissue regeneration functions. MSC-based products are considered advanced therapy medicinal products (ATMPs) under European regulations (1394/2007); thus, they must be manufactured under good manufacturing practices and via effective manufacturing methods. The former can be achieved via a proper laboratory design and compliance with manufacturing protocols, whereas the latter requires an approach that ensures that the quality of the products is consistent regardless of the manufacturing procedure. To meet these daunting requirements, this study proposes an exchangeable approach that combines optimized and equivalent manufacturing processes under the Quality by Design (QbD) principle, allowing investigators to convert from small laboratory-scale to large-scale manufacturing of MSC-based products for clinical applications without altering the quality and quantity of the cell-based products.
RESUMO
Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.
Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Medula Óssea , Células da Medula Óssea , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Obesidade/metabolismoRESUMO
OBJECTIVES: In order to improve the short-comings of glass ionomers such as polishability and esthetics while preserving their excellent clinical bonding effectiveness, nanofiller technology has been introduced in a paste-paste resin-modified glass ionomer (nano-filled RMGI, Ketac Nano, KN, 3M ESPE). One objective of this study was to investigate if the introduction of nanotechnology had any significant effect on the setting reaction of the nanoionomer compared to a control RMGI, Vitremer (VM, 3M ESPE). Another objective was to determine the mechanism of bonding of KN in combination with its primer (KNP) to the tooth. METHODS: Fourier-Transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses were performed on KN and VM during the setting of the GIs. FTIR and XPS were also used to study the reaction of the primer of KN (KNP) with hydroxyapatite (HAP). Shear adhesion to dentin and enamel was measured with KN and compared with several RMGIs and one conventional glass ionomers (CGI). The interfaces were examined with scanning electron microscopy (SEM). RESULTS: FTIR data show that KN undergoes both acid-base and methacrylate setting reactions of classical RMGIs. XPS and FTIR studies of the interaction KNP with HAP shows the formation of calcium-polycarboxylate bond. Shear adhesion and failure mode of KN to enamel and dentin were similar to the other RMGIs and CGI. SEM images of KN with tooth structure showed a tight interface with a thin but distinct layer of 2-3 microns attributed to the primer. This was also observed for VM but not for the other three materials. CONCLUSIONS: KN showed two setting reactions expected in true RMGIs. The adhesion with dentin and enamel was similar to other glass-ionomers. The formation of calcium-polycarboxylate was also evident. This chemical bonding is a significant factor in the excellent long-term adhesion of these materials.
Assuntos
Cimentos de Ionômeros de Vidro , Nanotecnologia , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: To evaluate, in vitro, dentin caries inhibition ability of a composite restoration with glass-ionomer liners in an open-sandwich configuration. METHOD AND MATERIALS: Rectangular dentin cavities (n = 5) were restored with a composite and glass-ionomer liner in an open-sandwich configuration where the liner was applied up to the cavity margin. Liners used were 3 resin-modified glass-ionomers (Vitrebond, 3M ESPE; Vitrebond Plus, 3M ESPE; Fuji Lining LC Paste Pak, GC) and a conventional glass-ionomer (Ketac Bond, 3M ESPE). The control group was a composite restoration (Filtek Z250, 3M ESPE) without a liner. Specimens were immersed in lactic acid gel for 3 weeks to create a demineralized lesion before being subjected to microradiographic analysis. The width of the area where the demineralization was completely inhibited at the restoration interface was measured. The total mineral loss (DeltaZ) was determined at 0.25 and 1.0 mm from the cavity margin. RESULTS: An inhibition zone was observed at the interface of all open-sandwich restorations but not in Filtek Z250. DeltaZ at 0.25 mm of all the open-sandwich restorations was significantly less than that of Filtek Z250 (analysis of variance, Scheffe's S, P < .05). At 1.0 mm, only the open-sandwich restorations in Vitrebond and Vitrebond Plus groups had significantly less DeltaZ than Filtek Z250. CONCLUSION: Under an in vitro demineralization challenge, glass-ionomer liners in an open-sandwich restoration exhibited pronounced inhibition zones at the dentin margin and lowered the amount of mineral loss in the vicinity of 0.25 mm from the restoration interface.
Assuntos
Cariostáticos/administração & dosagem , Forramento da Cavidade Dentária , Restauração Dentária Permanente/métodos , Fluoretos/administração & dosagem , Cimentos de Ionômeros de Vidro/uso terapêutico , Desmineralização do Dente/prevenção & controle , Animais , Bovinos , Resinas Compostas , Colagem Dentária/métodos , Dentina , Cimentos de Ionômeros de Vidro/química , MicrorradiografiaRESUMO
OBJECTIVES: The contribution of chemical bonding of the polycarboxylic acid in classical powder/liquid conventional glass ionomers (GI) and resin-modified glass-ionomers (RMGI) has been attributed to the excellent long-term bond strengths and clinical retention. RMGIs have been recently introduced as paste/liquid systems for convenience of clinical usage. The objective of this study was to investigate the long-term bond strengths and mechanism of adhesion of paste-liquid RMGI in order to ascertain whether similar characteristics are retained. METHODS: Long-term shear adhesion to dentin and enamel was measured on two paste-liquid RMGIs and one powder/liquid RMGI. Scanning electron microscopy (SEM), Fourier-transformed infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses were carried out on the paste-liquid RMGI Vitrebond Plus (VBP) and compared with the classical powder/liquid RMGI Vitrebond (VB). RESULTS: VBP maintains adhesion to dentin and enamel over long times; its long-term adhesive performance is equivalent to VB. FTIR data confirm that VBP exhibits the carboxylate crosslinking reaction of a true glass ionomer. SEM images show evidence of micromechanical bonding at the interface between VBP and the tooth. XPS and FTIR data show that the methacrylated copolyalkenoic acid component present in VB and VBP chemically bonds to the calcium in HAP. SIGNIFICANCE: The new paste-liquid RMGI liner, VBP, shows equivalent adhesion to its powder-liquid predecessor, VB. The adhesion mechanism was attributed to micromechanical and chemical bonding. This chemical bond is a significant factor in the excellent long-term adhesion of these materials.