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1.
Molecules ; 29(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38611723

RESUMO

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents.


Assuntos
Mangifera , Animais , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Vietnã , Aves
2.
Molecules ; 29(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38930859

RESUMO

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.


Assuntos
Anti-Inflamatórios , Curcuma , Curcumina , Diabetes Mellitus Experimental , Hipoglicemiantes , Cicatrização , Animais , Curcuma/química , Cicatrização/efeitos dos fármacos , Camundongos , Ratos , Diabetes Mellitus Experimental/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Curcumina/farmacologia , Curcumina/análogos & derivados , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Carragenina , Inflamação/tratamento farmacológico , Inflamação/patologia , Diarileptanoides/farmacologia , Diarileptanoides/química
3.
Appl Microbiol Biotechnol ; 107(17): 5367-5378, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37436482

RESUMO

Fermentation technology using endophytes is considered a potential alternative approach for producing pharmaceutical compounds like podophyllotoxin (PTOX). In this study, fungus TQN5T (VCCM 44284) was selected from endophytic fungi isolated from Dysosma versipellis in Vietnam for PTOX production through TLC. The presence of PTOX in TQN5T was further confirmed by HPLC. Molecular identification indicated TQN5T as Fusarium proliferatum with 99.43% identity. This result was asserted by morphological characteristics such as white cottony, filamentous colony, layer and branched mycelium, and clear hyphae septa. Cytotoxic assay indicated both biomass extract and culture filtrate of TQN5T presented strong cytotoxicity on LU-1 and HepG2 with IC50 of 0.11, 0.20, 0.041, and 0071, respectively, implying anti-cancer compounds were accumulated in the mycelium and secreted into the medium. Further, the production of PTOX in TQN5T was investigated in the fermentation condition supplemented with 10 µg/ml of host plant extract or phenylalanine as elicitors. The results revealed a significantly higher amount of PTOX in the PDB + PE and PDB + PA at all studied time points in comparison with PDB (control). Especially, after 168 h of culture, PTOX content in the PDB with plant extract reached the peak with 314 µg/g DW which is 10% higher than the best yield of PTOX in previous studies, denoting F. proliferatum TQN5T as a promising PTOX producer. This is the first study on enhancing the PTOX production in endophytic fungi by supplementing phenylalanine-a precursor for PTOX biosynthesis in plants into fermented media, suggesting a common PTOX biosynthetic pathway between host plant and endophytes. KEY POINTS: • Fusarium proliferatum TQN5T was proven for PTOX production. • Both mycelia extract and spent broth extract of Fusarium proliferatum TQN5T presented strong cytotoxicity on cancer cell lines LU-1 and HepG2. • The supplementation of 10 µg/ml host plant extract and phenylalanine into fermentation media of F. proliferatum TQN5T improved the yield of PTOX.


Assuntos
Fusarium , Podofilotoxina , Podofilotoxina/metabolismo , Endófitos/metabolismo , Fusarium/metabolismo , Extratos Vegetais/metabolismo , Plantas/metabolismo
4.
Breed Sci ; 73(4): 365-372, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38106512

RESUMO

A large vascular bundle number (VBN) in the panicle neck in rice (Oryza sativa L.) is related to the ability to transport assimilates from stem and leaf to reproductive organs during seed maturation. Several quantitative trait loci (QTLs) for VBN have been identified by using segregating populations derived from a cross between indica and japonica rice cultivars. However, the detailed location, effect, and interaction of QTLs for VBN were not understood well. Here, to elucidate the genetic basis of VBN, we identified three stable QTLs for VBN-qVBN5, qVBN6 and qVBN11-by using 71 recombinant inbred lines derived from a cross between indica 'IR24' and japonica 'Asominori'. We confirmed their positions and characterized their effects by using chromosome segment substitution lines (CSSLs) with an 'IR24' genetic background. qVBN6 had the most substantial effect on VBN, followed by qVBN11 and qVBN5. We developed pyramided lines carrying two QTLs for VBN to estimate their interaction. The combination of qVBN6 and qVBN11 accumulated VBN negatively in the pyramided lines owing to the independent actions of each QTL. The QTLs detected for VBN will enhance our understanding of genetic mechanisms of VBN and can be used in rice breeding.

5.
Molecules ; 28(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37959661

RESUMO

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.


Assuntos
Infecções Bacterianas , Curcuma , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/farmacologia , Rizoma
6.
Anaerobe ; 74: 102550, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35331913

RESUMO

BACKGROUND: Clostridioides (Clostridium) difficile commonly causes hospital-acquired infection which can range from mild diarrhoea to life-threatening toxic megacolon and even death. Reports on C. difficile infection (CDI) in Vietnam are limited, so this study was designed to evaluate the prevalence, molecular epidemiology and antimicrobial susceptibility of C. difficile isolated from children with diarrhoea in Vietnam. Infants are often colonised with C. difficile and it was hypothesised that those colonising strains would represent strains of C. difficile circulating in the hospital/region at the time, however, this was not an attempt to determine if C. difficile was the cause of the diarrhoea. METHODS: Diarrhoeal stool samples collected at two children's hospitals in northern Vietnam from October 1, 2020 to February 28, 2021 were transported to Perth, Western Australia, for culture of C. difficile and further investigations on isolates; PCR ribotyping, toxin gene profiling and antimicrobial susceptibility testing. RESULTS: From these hospitals, 370 diarrhoeal stool samples were collected, most from children aged 1-15 months (71.9%; 266/370). The overall prevalence of C. difficile in stool samples from children aged ≤16 years was 37.8% (140/370) and the highest prevalence was in the 2-12 months age group (52.9%; 74/140). In total, 151 isolates of C. difficile were recovered; the proportion of toxigenic isolates was 16.6% (25/151). Of the 25 toxigenic C. difficile isolates, the toxin gene profiles A+B+CDT- and A-B+CDT- comprised 72% and 28%, respectively. The four most prevalent C. difficile ribotypes (RTs) were QX 011 (25/151), RT 010 (25/151), QX 107 (12/151) and RT 012 (11/151). All isolates were susceptible to vancomycin, metronidazole and fidaxomicin, while there was significant resistance to clindamycin (90.1%), and some to moxifloxacin (6.6%) and rifaximin (3.3%). CONCLUSION: The prevalence of C. difficile in children with diarrhoea was high (37.8%) although the proportion of toxigenic strains was comparatively low. The clinical significance of any isolate needs to be determined.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Clostridioides , Clostridioides difficile/genética , Clostridium/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Diarreia/tratamento farmacológico , Diarreia/epidemiologia , Humanos , Lactente , Testes de Sensibilidade Microbiana , Ribotipagem , Vietnã/epidemiologia
7.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362322

RESUMO

The incidence of diabetes mellitus (DM), one of the most common chronic metabolic disorders, has increased dramatically over the past decade and has resulted in higher rates of morbidity and mortality worldwide. The enzyme, α-Glucosidase (α-GLy), is considered a therapeutic target for the treatment of type 2 DM. Herein, we synthesized arylidene, heterocyclic, cyanoetoxy- and propargylated derivatives of quinopimaric acid (levopimaric acid diene adduct with p-benzoquinone) 1-50 and, first, evaluated their ability to inhibit α-GLy. Among the tested compounds, quinopimaric acid 1, 2,3-dihydroquinopimaric acid 8 and its amide and heterocyclic derivatives 9, 30, 33, 39, 44, with IC50 values of 35.57-65.98 µM, emerged as being good inhibitors of α-GLy. Arylidene 1ß-hydroxy and 1ß,13α-epoxy methyl dihydroquinopimarate derivatives 6, 7, 26-29, thiadiazole 32, 1a,4a-dehydroquinopimaric acid 40 and its indole, nitrile and propargyl hybrids 35-38, 42, 45, 48, and 50 showed excellent inhibitory activities. The most active compounds 38, 45, 48, and 50 displayed IC50 values of 0.15 to 0.68 µM, being 1206 to 266 more active than acarbose (IC50 of 181.02 µM). Kinetic analysis revealed the most active diterpene indole with an alkyne substituent 45 as a competitive inhibitor with Ki of 50.45 µM. Molecular modeling supported this finding and suggested that the indole core plays a key role in the binding. Compound 45 also has favorable pharmacokinetic and safety properties, according to the computational ADMET profiling. The results suggested that quinopimaric acid derivatives should be considered as potential candidates for novel alternative therapies in the treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Diterpenos , Humanos , alfa-Glucosidases/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cinética , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Indóis/uso terapêutico , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Estrutura Molecular
8.
Prep Biochem Biotechnol ; 52(1): 48-55, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34047684

RESUMO

Formalin-fixed paraffin-embedded (FFPE) tissues represent the biggest source of archival materials for molecular biology research and pathology investigations. Nevertheless, fixation by formalin may cause denaturation and modification of macromolecules constraining DNA quality and its downstream applications. In this study, we developed a fast, simple, and cost-effective phenol/chloroform-based protocol for the extraction of high-quality DNA from 101 FFPE colorectal cancer tissue blocks that can be used in multiple molecular studies. DNA samples extracted using this phenol/chloroform protocol and the QIAamp DNA FFPE Tissue kit were evaluated for the quantity, quality, and amplificability. Spectrophotometer analyses revealed significantly higher quality and quantity of DNA samples obtained with the phenol/chloroform protocol as compared to those of the QIAamp DNA FFPE Tissue kit. In addition, the amplificability of these samples as assessed by conventional and multiplex polymerase chain reaction (PCR), followed by sequencing and fragment analyses presented an absolute success rate. Additionally, it is able to amplify a DNA fragment of 725 base-pairs at an adequate amount for downstream applications. This fast, simple, and cost-effective method may facilitate the molecular analyses of a large number of FFPE specimens that best suits the needs of the overall study design in terms of the quality and quantity of the extracted DNA.


Assuntos
Neoplasias Colorretais/genética , DNA/genética , Neoplasias Colorretais/patologia , DNA/análise , Formaldeído , Genômica , Humanos , Inclusão em Parafina , Reação em Cadeia da Polimerase , Fixação de Tecidos
9.
High Educ (Dordr) ; : 1-19, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36187080

RESUMO

This study investigates the relationship between career development learning (CDL) and students' perceived employability (SPE) with the mediating role of human capital. Using a quantitative method based on structured questionnaires to collect data from 512 Vietnamese students before starting their internship at businesses and 322 of them after 4 months, the results of the partial least square Structural Equational Model analysis showed that CDL positively affects SPE over time. Besides, the study explored the mediating effect of human capital in the relationship between CDL and SPE. In particular, scholastic capital and cultural capital play mediating roles while social capital failed to be in the relationship between CDL and SPE. This study is expected to enrich current literature on students' employability and human capital theory. From practical aspects, the findings of this work can be of benefit to higher education institutions in supporting their students to enhance their employability in labour market.

10.
Trop Med Int Health ; 26(10): 1303-1313, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34370375

RESUMO

OBJECTIVES: The aim of this study was to assess acceptance of COVID-19 vaccination and the willingness to pay (WTP) for it, and investigate associated factors among pregnant women in Vietnam. METHODS: Cross-sectional survey of pregnant women in two obstetric hospitals in Hanoi and Ca Mau provinces, Vietnam. Data on acceptance and WTP for COVID-19, demographic characteristics, maternal characteristics, and risk perceptions toward COVID-19 were collected. Multivariate logistic and linear regression models were performed to identify factors associated with the acceptance and WTP for the vaccine. RESULTS: Of 651 pregnant women, 60.4% accepted to receive the vaccine, and 82.6% of the total pregnant women were willing to pay for a COVID-19 vaccine with the mean amount of WTP of USD 15.2 (SD ± 27.4). The most common reason for refusing vaccination was "Worry about the safety of the vaccine" (66.9%) in Hanoi and "The preventive effect of COVID-19 is low" (45.2%) in Ca Mau. A higher income, having children, self-perceived risk of COVID-19 infection, and perceived risk to friends were associated with a higher likelihood of acceptance and WTP for the vaccine. CONCLUSIONS: Implementing COVID-19 vaccination and resource mobilisation among pregnant women in Vietnam is feasible, although communication programmes to improve risk perception and awareness about vaccine should be developed for facilitating acceptance of the vaccine.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinação/estatística & dados numéricos , Adulto , Vacinas contra COVID-19/economia , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Análise Multivariada , Gravidez , Cuidado Pré-Natal , Vacinação/economia , Vietnã , Adulto Jovem
11.
Arch Virol ; 165(4): 823-834, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32008121

RESUMO

While conducting sentinel surveillance of hand, foot, and mouth disease (HFMD) in Vietnam, we found a sudden increase in the prevalence of coxsackievirus A10 (CV-A10) in 2016 and CV-A2 and CV-A4 in 2017, the emergence of which has been reported recently to be associated with various clinical manifestations in other countries. However, there have been only a limited number of molecular studies on those serotypes, with none being conducted in Vietnam. Therefore, we sequenced the entire VP1 genes of CV-A10, CV-A4, and CV-A2 strains associated with HFMD in Vietnam between 2012 and 2017. Phylogenetic analysis revealed a trend of endemic circulation of Vietnamese CV-A10, CV-A4, and CV-A2 strains and the emergence of thus-far undescribed HFMD-causing lineages of CV-A4 and CV-A2. The Vietnamese CV-A10 strains belonged to a genotype comprising isolates from patients with HFMD from several other countries; however, most of the Vietnamese strains were grouped into a local lineage. Recently, emerging CV-A4 strains in Vietnam were grouped into a unique lineage within a genotype comprising strains isolated from patients with acute flaccid paralysis from various countries. New substitutions were detected in the putative BC and HI loops in the Vietnamese CV-A4 strains. Except for one strain, Vietnamese CV-A2 isolates were grouped into a unique lineage of a genotype that includes strains from various countries that are associated with other clinical manifestations. Enhanced surveillance is required to monitor their spread and to specify their roles as etiological agents of HFMD or "HFMD-like" diseases, especially for CV-A4 and CV-A2. Further studies including whole-genome sequencing should be conducted to fully understand the evolutionary changes occurring in these newly emerging strains.


Assuntos
Proteínas do Capsídeo/genética , Enterovirus Humano A/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Surtos de Doenças , Enterovirus Humano A/classificação , Enterovirus Humano A/genética , Genoma Viral , Genótipo , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Filogenia , Vigilância de Evento Sentinela , Vietnã/epidemiologia
12.
Int J Mol Sci ; 21(19)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987737

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (ß-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/ß-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/ß-TCP transplanted group. For treatment studies, BMP-2/ß-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/ß-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/ß-TCP could become a suitable therapy for the management of MRONJ.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Proteína Morfogenética Óssea 2/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/uso terapêutico
13.
Int J Mol Sci ; 21(21)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143068

RESUMO

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated ß galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.


Assuntos
Envelhecimento/patologia , Reabsorção Óssea/patologia , Modelos Animais de Doenças , Imunomodulação , Células-Tronco Mesenquimais/patologia , Osteogênese , Periodontite/patologia , Animais , Apoptose , Reabsorção Óssea/etiologia , Diferenciação Celular , Proliferação de Células , Ligadura , Camundongos , Camundongos Endogâmicos C57BL , Periodontite/complicações , Periodontite/imunologia
14.
Cells Tissues Organs ; 207(3-4): 115-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574516

RESUMO

Stem cells have essential applications in in vitro tissue engineering or regenerative medicine. However, there is still a need to understand more deeply the mechanisms of stem cell differentiation and to optimize the methods to control stem cell function. In this study, we first investigated the activity of DNA methyltransferases (DNMTs) during chondrogenic differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (hBMSCs) and found that DNMT3A and DNMT3B were markedly upregulated during hBMSC chondrogenic differentiation. In an attempt to understand the effect of DNMT3A and DNMT3B on the chondrogenic differentiation of hBMSCs, we transiently transfected the cells with expression vectors for the two enzymes. Interestingly, DNMT3A overexpression strongly enhanced the chondrogenesis of hBMSCs, by increasing the gene expression of the mature chondrocyte marker, collagen type II, more than 200-fold. Analysis of the methylation condition in the cells revealed that DNMT3A and DNMT3B methylated the promoter sequence of early stem cell markers, NANOG and POU5F1(OCT-4). Conversely, the suppression of chondrogenic differentiation and the increase in stem cell markers of hBMSCs were obtained by chemical stimulation with the demethylating agent, 5-azacitidine. Loss-of-function assays with siRNAs targeting DNMT3A also significantly suppressed the chondrogenic differentiation of hBMSCs. Together, these results not only show the critical roles of DNMTs in regulating the chondrogenic differentiation of hBMSCs, but also suggest that manipulation of DNMT activity can be important tools to enhance the differentiation of hBMSCs towards chondrogenesis for potential application in cartilage tissue engineering or cartilage regeneration.


Assuntos
Condrogênese , Metilação de DNA , Células-Tronco Mesenquimais/citologia , Linhagem Celular , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Humanos , Células-Tronco Mesenquimais/metabolismo , Regulação para Cima , DNA Metiltransferase 3B
15.
Int J Mol Sci ; 20(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554264

RESUMO

Epithelial keratinization involves complex cellular modifications that provide protection against pathogens and chemical and mechanical injuries. In the oral cavity, keratinized mucosa is also crucial to maintain healthy periodontal or peri-implant tissues. In this study, we investigated the roles of type XVIII collagen, a collagen-glycosaminoglycan featuring an extracellular matrix component present in the basement membrane, in oral mucosal keratinization. Histological analysis of keratinized and non-keratinized oral mucosa showed that type XVIII collagen was highly expressed in keratinized mucosa. Additionally, a 3D culture system using human squamous carcinoma cells (TR146) was used to evaluate and correlate the changes in the expression of type XVIII collagen gene, COL18A1, and epithelial keratinization-related markers, e.g., keratin 1 (KRT1) and 10 (KRT10). The results showed that the increase in COL18A1 expression followed the increase in KRT1 and KRT10 mRNA levels. Additionally, loss-of-function analyses using silencing RNA targeting COL18A1 mRNA and a Col18-knockout (KO) mouse revealed that the absence of type XVIII collagen induces a dramatic decrease in KRT10 expression as well as in the number and size of keratohyalin granules. Together, the results of this study demonstrate the importance of type XVIII collagen in oral mucosal keratinization.


Assuntos
Colágeno Tipo XVIII/metabolismo , Grânulos Citoplasmáticos/metabolismo , Queratinas/metabolismo , Mucosa Bucal/metabolismo , Animais , Biomarcadores , Diferenciação Celular/genética , Colágeno Tipo VIII/genética , Colágeno Tipo VIII/metabolismo , Colágeno Tipo XVIII/genética , Imunofluorescência , Humanos , Camundongos , Camundongos Knockout
16.
J Cell Physiol ; 233(6): 4825-4840, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29150954

RESUMO

A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates.


Assuntos
Condrócitos/metabolismo , Condrogênese , Osteoblastos/metabolismo , Osteogênese , RNA Longo não Codificante/metabolismo , Células-Tronco/metabolismo , Animais , Desdiferenciação Celular , Linhagem Celular Tumoral , Senescência Celular , Condrogênese/genética , Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Humanos , Osteogênese/genética , Fenótipo , Primatas , RNA Longo não Codificante/genética , Transdução de Sinais
17.
Reproduction ; 156(5): R143-R153, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30325181

RESUMO

Human pluripotent stem cells have the capacity to self-renew indefinitely and the ability to differentiate into all cell types of a human body. These characteristics instill them with an enormous promise in regenerative medicine, where they could be used in cell, tissue and even organ-based replacement therapy. In this review, we discuss their potential clinical applications and the advantages and pitfalls for the different types of human pluripotent stem cells to transition from the bench to the bedside. We provide an overview of the current clinical trials, and the specific challenges we are still facing, including immune compatibility, suboptimal differentiation, risk of tumor formation and genome instability.


Assuntos
Células-Tronco Pluripotentes , Medicina Regenerativa/tendências , Humanos
18.
Health Econ ; 26(2): 263-272, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26676963

RESUMO

This paper evaluates the impact on cost and utilization of a shift from fee-for-service to capitation payment of district hospitals by Vietnam's social health insurance agency. Hospital fixed effects analysis suggests that capitation leads to reduced costs. Hospitals also increased service provision to the uninsured who continue to pay out-of-pocket on a fee-for-service basis. The study points to the need to anticipate unintended effects of payment reforms, especially in the context of a multiple purchaser system. Copyright © The World Bank Health Economics © 2015 John Wiley & Sons, Ltd.


Assuntos
Capitação/estatística & dados numéricos , Planos de Pagamento por Serviço Prestado , Hospitais/estatística & dados numéricos , Planos de Incentivos Médicos/economia , Gastos em Saúde , Humanos , Seguro Saúde/estatística & dados numéricos , Inquéritos e Questionários , Vietnã
19.
Hum Resour Health ; 15(1): 20, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28245877

RESUMO

BACKGROUND: Performance-based financing (PBF) has been implemented in a number of countries with the aim of transforming health systems and improving maternal and child health. This paper examines the effect of PBF on health workers' job satisfaction, motivation, and attrition in Zambia. It uses a randomized intervention/control design to evaluate before-after changes for three groups: intervention (PBF) group, control 1 (C1; enhanced financing) group, and control 2 (C2; pure control) group. METHODS: Mixed methods are employed. The quantitative portion comprises of a baseline and an endline survey. The survey and sampling scheme were designed to allow for a rigorous impact evaluation of PBF or C1 on several key performance indicators. The qualitative portion seeks to explain the pathways underlying the observed differences through interviews conducted at the beginning and at the three-year mark of the PBF program. RESULTS: Econometric analysis shows that PBF led to increased job satisfaction and decreased attrition on a subset of measures, with little effect on motivation. The C1 group also experienced some positive effects on job satisfaction. The null results of the quantitative assessment of motivation cohere with those of the qualitative assessment, which revealed that workers remain motivated by their dedication to the profession and to provide health care to the community rather than by financial incentives. The qualitative evidence also provides two explanations for higher overall job satisfaction in the C1 than in the PBF group: better working conditions and more effective supervision from the District Medical Office. The PBF group had higher satisfaction with compensation than both control groups because they have higher compensation and financial autonomy, which was intended to be part of the PBF intervention. While PBF could not address all the reasons for attrition, it did lower turnover because those health centers were staffed with qualified personnel and the personnel had role clarity. CONCLUSIONS: In Zambia, the implementation of PBF schemes brought about a significant increase in job satisfaction and a decrease in attrition, but had no significant effect on motivation. Enhanced health financing also increased stated job satisfaction.


Assuntos
Pessoal de Saúde , Satisfação no Emprego , Motivação , Reorganização de Recursos Humanos , Qualidade da Assistência à Saúde , Reembolso de Incentivo , Desempenho Profissional , Adulto , Altruísmo , Atitude do Pessoal de Saúde , Atenção à Saúde , Feminino , Humanos , Masculino , Gestão de Recursos Humanos , Inquéritos e Questionários , Local de Trabalho , Zâmbia
20.
J Am Chem Soc ; 138(3): 920-5, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26709448

RESUMO

Recently, polymer-metal-organic frameworks (polyMOFs) were reported as a new class of hybrid porous materials that combine advantages of both organic polymers and crystalline MOFs. Herein, we report a bridging coligand strategy to prepare new types of polyMOFs, demonstrating that polyMOFs are compatible with additional MOF architectures besides that of the earlier reported IRMOF-1 type polyMOF. Gas sorption studies revealed that these polyMOF materials exhibited relatively high CO2 sorption but very low N2 sorption, making them promising materials for CO2/N2 separations. Moreover, these polyMOFs demonstrated exceptional water stability attributed to the hydrophobicity of polymer ligands as well as the cross-linking of the polymer chains within the MOF.

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