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1.
Cancers (Basel) ; 16(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38275895

RESUMO

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

2.
Korean J Gastroenterol ; 82(3): 127-136, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37743811

RESUMO

Background/Aims: Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. Methods: Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models. Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. Results: In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46-2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47-2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32-2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps<0.001). No significant publication bias was observed. Conclusions: Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.


Assuntos
Terapia por Acupuntura , Hepatite C , Neoplasias Hepáticas , Humanos , Hepacivirus , Estudos Transversais , Terapia por Acupuntura/efeitos adversos , Neoplasias Hepáticas/terapia
3.
J Liver Cancer ; 23(2): 362-376, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37705145

RESUMO

BACKGROUND/AIM: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. METHODS: Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. RESULTS: Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P<0.001). In early-stage HCC, surgery yielded significantly lower OS in elderly patients compared to non-elderly patients (median, 97.4 vs. 138.0 months; P<0.001), however, local ablation (median, 82.2 vs. 105.5 months) and transarterial therapy (median, 42.6 vs. 56.9 months) each provided comparable OS between the two groups after inverse probability of treatment weighting (IPTW) analysis (all P>0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). CONCLUSIONS: Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

4.
Int J Biol Macromol ; 222(Pt B): 2144-2157, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36216106

RESUMO

This study shows tunable stress relaxing gellan gum (GG) hydrogel for enhanced cell growth and regenerative medicine. The molecular weight and physical crosslinking density of GG were tuned and characterized with physicochemical analysis and mechanical tests. The result showed that a decrease in the molecular weight of the GG correlated with a decline in the mechanical properties but faster stress relaxing character. We also discovered that human-derived bone marrow stem cells (hBMSC) showed active viability, proliferation, and remodeling in the fast stress relaxing GG hydrogel. In particular, hBMSC showed an enhanced release profile of growth factors and exosomes (Exo) in the fast stress relaxing GG hydrogel. The secretome obtained from hBMSC embedded in hydrogel exhibited similar cytotoxicity and wound healing properties to that of secretome extracted from hBMSC cultured in a tissue culture plate (TCP) a standard culture condition. Thus, this work demonstrates the potential of fast stress relaxing GG hydrogels for medical application.


Assuntos
Células-Tronco Mesenquimais , Polissacarídeos Bacterianos , Humanos , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/química , Hidrogéis/farmacologia , Hidrogéis/química , Osso e Ossos , Engenharia Tecidual
5.
Molecules ; 27(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36080277

RESUMO

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.


Assuntos
Ácido Hialurônico , Hidrogéis , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Células Epiteliais , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Retina , Pigmentos da Retina , Engenharia Tecidual
6.
Expert Opin Pharmacother ; 22(18): 2427-2433, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34392744

RESUMO

INTRODUCTION: Chronic hepatitis B is an important public health concern. Introduction of oral nucleos(t)ide analogs (NAs), inhibitors of hepatitis B virus (HBV) polymerase, was a milestone that lowered the high viral loads associated with an increased risk of liver-related complications. AREAS COVERED: Although the currently available NAs are effective in suppressing viral replication, anti-HBV treatment in principle requires lifelong drug administration, and some patients have limitations such as the incidence of liver cancer and the likelihood of toxicities following long-term treatment despite viral suppression. Besifovir dipivoxil maleate (BSV), an oral nucleotide analog, is a prodrug that is metabolized to its active form. It has consistent and well-characterized pharmacokinetics in animals and human. In clinical studies, BSV exhibits significant and potent viral suppression of HBV replication with maintenance of antiviral efficacy for over 192 weeks without resistance, or renal and bone toxicities. Herein, the authors discuss the data of BSV and provide the reader with their expert opinion. EXPERT OPINION: BSV is a newly developed antiviral agent against HBV. This new agent has strong antiviral activity with low toxicity and a high barrier to resistance. Because there is concern that patients treated with a high dose of BSV require carnitine supplementation, BSV with carnitine supplementation is recommended during antiviral therapy.


Assuntos
Hepatite B Crônica , Organofosfonatos , Animais , Antivirais/efeitos adversos , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Maleatos/uso terapêutico , Organofosfonatos/uso terapêutico
7.
ACS Appl Bio Mater ; 4(2): 1900-1911, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35014459

RESUMO

Bone is the rigid tissue that constitutes the skeleton. The material for bone regeneration has to provide the mechanical stability by maintaining the mechanical loads both in the rest conditions and during the body movements. Bone is dynamic tissue constantly reshaped by the action of cells (osteoblasts and osteoclasts). This activity is normally enough to heal bone injuries; however, in several conditions, when bone is subjected to fatal damages, self-renewal is difficult, if not even impossible, and a medical treatment is required. The transplantation of a biomaterial is one of the common surgical procedures to overcome critical injuries. In this study, we exploited the effect of the use of different sources of demineralized bone powder (DBP) in combination with gellan gum (GG) to form a GG-DBP hydrogel scaffold with the purpose of regenerating the bone tissue. DBP was extracted from the femurs of two typologies of Gallus gallus domesticus (the Yeonsan Ogye, a traditional and rare black chicken from Korea, and the Cornish cross, the most common breeds for industrial meat production) and the Pekin duck. The composite scaffold has been tested both in vitro and in vivo. In vitro studies using rat bone marrow-derived mesenchymal stem cells (rBMSCs) confirmed the cellular suitability of bone-specific gene expression for seeded GG-DBP scaffolds, differentiation capacity, and marked upregulation. The scaffold containing a DBP derived from the Yeonsan Ogye (YO) bone showed higher levels of cell proliferation and osteogenic differentiation in comparison with the scaffold with the DBP obtained from the other studied sources. These results have been related with the higher amount of melanin, studied by fluorescence, of the YO DBP compared to Cornish cross and Pekin duck. Overall, this study clearly shows the use of YO DBP as a promising material in bone tissue regeneration.


Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Hidrogéis/farmacologia , Polissacarídeos Bacterianos/farmacologia , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Hidrogéis/síntese química , Hidrogéis/química , Teste de Materiais , Células-Tronco Mesenquimais/efeitos dos fármacos , Tamanho da Partícula , Polissacarídeos Bacterianos/química , Coelhos , Ratos
8.
Eur J Gastroenterol Hepatol ; 33(6): 885-893, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32541238

RESUMO

OBJECTIVE: The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis. RESULTS: Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests). CONCLUSIONS: The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Antivirais/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Incidência , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
ACS Omega ; 5(29): 18021-18027, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32743175

RESUMO

In this study, silk fibroin microfiber (mSF) was applied to assist spheroid assemblies of rBMSCs (rabbit bone marrow stem cells) (S/B). Alkaline hydrolysis was induced with different times and conditions to manufacture the various sizes of mSF. The mSF was incorporated in the rBMSC with different amounts to optimize proper content for spheroid assembly. The formation of the S/B was confirmed under optical microscopy and SEM. Proliferation and viability were characterized by CCK-8 and live/dead staining. Osteogenesis was analyzed with ALP (alkaline phosphatase) activity studies and real-time polymerase chain reaction. The S/B was successfully produced and displayed uniformly distributed cells and mSF with the presence of a gap in the structure. Proliferation and viability of the S/B significantly increased when compared to rBMSC spheroids (B), which is potentially due to the enhanced transportation of oxygen and nutrients to the cells located in the core region. Additionally, ALP activity and osteogenic markers were significantly upregulated in the optimized S/B under osteogenic media conditions. Overall, a hybrid-spheroid system with a simple 3D cell culture platform provides a potential approach for engineering therapeutic stem cells.

10.
J Tissue Eng Regen Med ; 14(11): 1592-1603, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32767724

RESUMO

Hydrogels have a large amount of water that provides a cartilage-like environment and is used in tissue engineering with biocompatibility and adequate degradation rates. In order to differentiate stem cells, it is necessary to adjust the characteristics of the matrix such as stiffness, stress-relaxing time, and microenvironment. Double network (DN) hydrogels provide differences in cellular biological behavior and have interpenetrating networks that combine the advantages of the components. In this study, by varying the viscous substrate of pullulan (PL), the DN hydrogels of gellan gum (GG) and PL were prepared to determine the cartilage differentiation of bone marrow stem cell (BMSC). The characteristics of GG/PL hydrogel were investigated by examining the swelling ratio, weight loss, sol fraction, compressive modulus, and gelation temperature. The viability, proliferation, and toxicity of BMSCs encapsulated in hydrogels were evaluated. Cartilage phenotype and cartilage differentiation were confirmed by morphology, GAG content, and cartilage-specific gene expression. Overall results demonstrate that GG/PL hydrogels can form cartilage differentiation of BMSCs and can be applied for tissue engineering purposes.


Assuntos
Células da Medula Óssea/citologia , Diferenciação Celular , Condrogênese , Glucanos/farmacologia , Polissacarídeos Bacterianos/farmacologia , Células-Tronco/citologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/ultraestrutura , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Imobilizadas/citologia , Células Imobilizadas/efeitos dos fármacos , Células Imobilizadas/ultraestrutura , Condrogênese/efeitos dos fármacos , DNA/metabolismo , Feminino , Glicosaminoglicanos/metabolismo , Hidrogéis/farmacologia , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Células-Tronco/efeitos dos fármacos , Células-Tronco/ultraestrutura , Viscosidade
11.
Scand J Gastroenterol ; 55(8): 951-957, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32698637

RESUMO

OBJECTIVE: It remains controversial whether certain treatments should apply to HCC patients with ascites due to concerns about worsening liver function. The objective of the present study is to compare the prognostic performance of 4 liver function models currently in use for HCC patients with ascites. METHODS: A total of 437 treatment-naïve, newly diagnosed HCC patients were analyzed. The predictive performance of Child-Pugh, MELD, MELD-Na, and ALBI scores were examined using ROC curve analysis. RESULTS: MELD-Na score showed good performance in predicting 1-, 2-, and 3-year mortality, particularly 1-year mortality. MELD-Na score significantly increased at 30 days after treatment in cases initially receiving best supportive care (14-17, p < .001), TACE (9-11, p < .001), and other treatment (radiotherapy, sorafenib, or systemic chemotherapy) (9-11, p = .021). For patients with advanced tumor stage and MELD-Na score ≥12, HCC-specific treatment did not offer significantly better prognosis compared with only the best supportive care (median survival: 2.2 vs. 1.8 months for HCC-specific treatment vs. best supportive care, p = .15). CONCLUSION: MELD-Na can effectively identify liver functional reserve and prognosis in HCC patients with ascites. MELD-Na, together with the tumor stage, may help establish a therapeutic strategy for them.


Assuntos
Ascite , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ascite/complicações , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Humanos , Cirrose Hepática , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Prognóstico , Curva ROC , Índice de Gravidade de Doença
12.
J Tissue Eng Regen Med ; 14(4): 563-574, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32061025

RESUMO

Bone defects are usually difficult to be regenerated due to pathological states or the size of the injury. Researchers are focusing on tissue engineering approaches in order to drive the regenerative events, using stem cells to regenerate bone. The purpose of this study is to evaluate the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) on biologically derived Gallus gallus domesticus-derived demineralized bone particle (GDD) sponge. The sponges were prepared by freeze-drying method using 1, 2, and 3 wt% GDD and cross-linked with glutaraldehyde. The GDD sponge was characterized using scanning electron microscopy, compressive strength, porosity, and Fourier transform infrared. The potential bioactivity of the sponge was evaluated by osteogenic differentiation of BMSCs using 3(4, dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and quantifying alkaline phosphatase (ALP) activity. in vivo experiments were evaluated through a micro-computerized tomography (µ-CT) and histological assays. The analysis confirmed that an increase in the concentration of the GDD in the sponge leads to a higher bone formation and deposition in rat calvarial defects. Histological assay results were in line with µ-CT. The results reported in this study demonstrated the potential application of GDD sponges as osteoinductor in bone tissue engineering in pathological or nonunion bone defects.


Assuntos
Células da Medula Óssea/metabolismo , Técnicas de Cultura de Células , Células Imobilizadas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Crânio , Alicerces Teciduais/química , Animais , Células da Medula Óssea/patologia , Células Imobilizadas/metabolismo , Células Imobilizadas/patologia , Células Imobilizadas/transplante , Feminino , Células-Tronco Mesenquimais/patologia , Ratos , Ratos Sprague-Dawley , Crânio/lesões , Crânio/metabolismo , Crânio/patologia
13.
J Biomed Mater Res A ; 108(3): 784-794, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794132

RESUMO

Treating critical-sized bone defects is an important issue in the field of tissue engineering and bone regeneration. From the various biomaterials for bone regeneration, collagen is an important and widely used biomaterial in biomedical applications, hence, it has numerous attractive properties including biocompatibility, hyper elastic behavior, prominent mechanical properties, support cell adhesion, proliferation, and biodegradability. In the present study, collagen was extracted from duck's feet (DC) as a new collagen source and combined with quercetin (Qtn), a type of flavonoids found in apple and onions and has been reported to affect the bone metabolism, for increasing osteogenic differentiation. Further, improving osteoconductive properties of the scaffold hydroxyapatite (HAp) a biodegradable material was used. We prepared 0, 25, 50, and 100 µM Qtn/DC/HAp sponges using Qtn, DC, and HAp. Their physiochemical characteristics were evaluated using scanning electron microscopy, compressive strength, porosity, and Fourier transform infrared spectroscopy. To assess the effect of Qtn on osteogenic differentiation, we cultured bone marrow mesenchymal stem cells on the sponges and evaluated by alkaline phosphatase, 3-4-2, 5-diphenyl tetrazolium bromide assay, and real-time polymerase chain reaction. Additionally, they were studied implanting in rat, analyzed through Micro-CT and histological staining. From our in vitro and in vivo results, we found that Qtn has an effect on bone regeneration. Among the different experimental groups, 25 µM Qtn/DC/HAp sponge was found to be highly increased in cell proliferation and osteogenic differentiation compared with other groups. Therefore, 25 µM Qtn/DC/HAp sponge can be used as an alternative biomaterial for bone regeneration in critical situations.


Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Durapatita/farmacologia , Transplante de Células-Tronco Mesenquimais , Alicerces Teciduais , Animais , Materiais Biocompatíveis/química , Células Cultivadas , Colágeno/química , Patos , Durapatita/química , Feminino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Quercetina/química , Coelhos , Ratos Sprague-Dawley , Engenharia Tecidual/métodos , Alicerces Teciduais/química
14.
Int J Biol Macromol ; 134: 749-758, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31054303

RESUMO

The prevalence of bone-related diseases has increased, the population growth as a result of the aging phenomenon requires more effective treatments for regeneration of bone defect. Although an autogenous bone graft was used in traditional operation method, they are very inefficient in current bone defect surgery and very difficult to gather the required amount of bone for operation. It is becoming a gradually growing disease, hence there is a need for developing a new method for preparing biomimetic scaffolds. DBP (demineralized bone powder), a potent bone regeneration material, has a trace amount of ions and bone mineral component. Especially, GD (Gallus gallus var domesticus) DBP has a unique property, which has melanin, for strengthening bones, increasing ALP activity and bone mineralization, compared to other available biomaterials. For that reason, GD DBP was combined with GG (gellan gum). The material was characterized in vitro and in vivo rat model. The first priority in this work was given to assessing the attachment and proliferation rates of BMSCs following the in vivo experiment in rats. The results of 1% sample showed better osteogenic effects that can be used in clinical application after studying in larger animals for better bone regeneration and tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Regeneração Óssea , Osso e Ossos/química , Polissacarídeos Bacterianos/química , Alicerces Teciduais/química , Animais , Técnica de Desmineralização Óssea , Regeneração Óssea/genética , Osso e Ossos/diagnóstico por imagem , Sobrevivência Celular , Células Cultivadas , Galinhas , Feminino , Perfilação da Expressão Gênica , Osteogênese/genética , Coelhos , Células-Tronco/citologia , Células-Tronco/metabolismo , Microtomografia por Raio-X
15.
Mater Sci Eng C Mater Biol Appl ; 97: 347-355, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678920

RESUMO

Tissue engineered scaffolds, made of natural derived materials, have the potential to be used in bone regeneration fields due to the biocompatible and biodegradable features. In this study, we propose duck's feet-derived collagen (DC) sponges blended with hydroxyapatite (HAp), incorporated with different concentrations of silymarin (Smn), for improved bone regeneration. The morphological and structural properties of DC/HAp and DC/HAp loaded with 25, 50 and 100 µM of Smn sponges were analyzed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). In vitro evaluations were carried out on rabbit bone marrow stem cells (rBMSCs) using MTT assay for cell proliferation, ALP assay for osteogenic differentiation and reverse transcription-polymerase chain reaction (RT-PCR) for expression of mRNAs. For the evaluation of new bone formation in vivo, histological analysis and micro computed tomography (µCT) were used. Preliminary results, on Smn/DC/HAp morphology and mechanical properties, showed an interconnected porosity suitable for cells ingrowth and a higher compressive strength with the presence of Smn. Similarly, the cells proliferation and ALP activity modulation were positively influenced by the Smn content. Especially, the 100 µM Smn/DC/HAp sponge efficiently enhances the rBMSCs adhesion, growth and gene expression of osteogenic markers. The enhanced osteoinductive effects of sponges blended with Smn were confirmed using µ-CT and histological evaluations. In conclusion, results suggest that collagen sponges represent an excellent environment for cells growth and proliferation, while Smn plays an important role to improve materials osteogenic properties.


Assuntos
Regeneração Óssea/fisiologia , Colágeno/química , Silimarina/farmacologia , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Células da Medula Óssea/citologia , Regeneração Óssea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Patos , Durapatita/química , Feminino , , Microscopia Eletrônica de Varredura , Osteogênese/genética , Coelhos , Ratos Sprague-Dawley , Silimarina/química , Espectroscopia de Infravermelho com Transformada de Fourier
16.
ACS Appl Mater Interfaces ; 10(39): 32955-32964, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30188112

RESUMO

There is a significant rise in the bone grafts demand worldwide to treat bone defects owing to continuous increase in conditions such as injury, trauma, diseases, or infections. Therefore, development of three-dimensional scaffolds has evolved as a reliable technology to address the current limitations for bone tissue regeneration. Mimicking the natural bone, in this study, we have designed a silk fibroin/hydroxyapatite scaffold inlaid with a bioactive phytochemical (quercetin) at different concentrations for promoting osteogenesis, especially focusing on quercetin ability for enhancing bone health. Characterization of the quercetin/silk fibroin/hydroxyapatite (Qtn/SF/HAp) scaffolds showed an increased pore size and irregular porous microstructure with good mechanical strength. The Qtn (low-content)/SF/HAp scaffold was found to be an efficient cell carrier facilitating cellular growth, osteogenic differentiation, and proliferation as compared to SF/HAp and Qtn (high-content)/SF/HAp scaffolds. However, Qtn (high-content)/SF/HAp was observed to inhibit cell proliferation without any effects on cell viability. In vitro and in vivo outcomes studied using bone marrow-derived mesenchymal stem cells (rBMSCs) confirm the cytocompatibility, osteogenic differentiation ability, and prominent upregulation of the bone-specific gene expressions for the rBMSCs-seeded Qtn/SF/HAp scaffolds. In particular, the implanted Qtn (low-content)/SF/HAp scaffolds at the bone defect site were found to be well-attached and amalgamated with the surrounding tissues with approximately 80% bone volume recovery at 6 weeks after surgery as compared with other groups. Based on the aforementioned observations highlighting the quercetin efficiency for bone regeneration, the as-synthesized Qtn (low-content)/SF/HAp scaffolds can be envisioned to provide a biomimetic bone-like microenvironment promoting rBMSCs differentiation into osteoblast, thus suggesting a potential alternative graft for high-performance regeneration of bone tissues.


Assuntos
Durapatita/química , Fibroínas/química , Quercetina/química , Quercetina/farmacologia , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Microscopia Eletrônica de Varredura , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Espectroscopia de Infravermelho com Transformada de Fourier
17.
J Biomater Sci Polym Ed ; 29(7-9): 984-996, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29207926

RESUMO

Scaffolds mimicking structural and chemical characteristics of the native bone tissues are critical for bone tissue engineering. Herein, we have developed and characterized epigallocatechin gallate/duck's feet collagen/hydroxyapatite (EGCG/DC/HAp) composite sponges that enhanced the bone tissue regeneration. The three-dimensional composite sponges were synthesized by loading various amounts (i.e. 1, 5 and 10 µM) of EGCG to duck feet derived collagen followed by freeze-drying and then coating with hydroxyapatite. Several measuremental techniques were employed to examine the properties of the as-fabricated composite sponges including morphology and structure, porosity, compressive strength, etc. and as well compared with pristine duck feet derived collagen. SEM observations of EGCG/DC/HAp sponges showed the formation of a highly porous collagen matrix with EGCG embodiment. The porosity and pore size of sponges were found to increase by high EGCG content. The compressive strength was calculated as 3.54 ± 0.04, 3.63 ± 0.03, 3.89 ± 0.05, 4.047 ± 0.05 MPa for 1, 5 and 10 µM EGCG/DC/HAp sponges, respectively. Osteoblast-like cell (BMSCs isolated from rabbit) culture and in vivo experiments with EGCG/DC/HAp sponges implanted in nude mouse followed by histological staining showed enhanced cell internalization and attachment, cell proliferation, alkaline phosphatase expressions, indicating that EGCG/DC/HAp sponges have ahigh biocompatibility. Moreover, highEGCG content in the EGCG/DC/HAp sponges have led to increased cellular behavior. Collectively, the 5 µM of EGCG/DC/HAp sponges were suggested as the potential candidates for bone tissue regeneration.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Osso e Ossos/efeitos dos fármacos , Catequina/análogos & derivados , Patos , Durapatita/química , Regeneração/efeitos dos fármacos , Animais , Osso e Ossos/citologia , Osso e Ossos/fisiologia , Catequina/química , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Engenharia Tecidual
18.
Int J Radiat Oncol Biol Phys ; 99(2): 396-406, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28871990

RESUMO

PURPOSE: It is unclear whether the efficacy and safety of concurrent chemoradiation therapy (CCRT) and transarterial radioembolization (TARE) with 90Y are comparable in patients with locally advanced hepatocellular carcinoma. METHODS AND MATERIALS: In total, 209 treatment-naive patients with stage B or C cancer according to the Barcelona Clinic Liver Cancer classification who were treated with TARE or CCRT were analyzed. Propensity scores were calculated and matched at a 1:1 ratio for TARE versus CCRT using age, tumor size, tumor number, portal vein thrombosis, and Barcelona Clinic Liver Cancer staging. In the CCRT group, concurrent hepatic arterial infusion chemotherapy with 5-fluorouracil was delivered at a dosage of 500 mg/d during the first and last 5 days of radiation therapy (median, 45 Gy). Overall survival, freedom from progression, tumor response, and complication rate were compared between the TARE and CCRT groups. RESULTS: Among 209 patients, 124 (62 undergoing TARE and 62 undergoing CCRT) were selected after propensity score matching. Overall survival (TARE vs CCRT, 14.0 months vs 13.2 months, P=.435) and freedom from progression (6.9 months vs 7.8 months, P=.437) were comparable between the 2 groups. Objective response rates at 1 month after treatment were higher for CCRT than for TARE (46.8% vs 16.1%, P<.001), while objective response rates at 3 months were significantly higher for TARE than for CCRT (39.3% vs 21.4%, P=.04). There was no significant difference in long-term response rates (at 6 months and 1 year) between the 2 groups. The CCRT group experienced a higher rate of curative resection or liver transplantation after treatment than the TARE group, although the statistical significance was marginal (24.2% vs 11.3%, P=.060). Treatment-related complications were less frequent after TARE than after CCRT. CONCLUSIONS: Both treatments yielded comparable survival rates and long-term response rates in patients with intermediate- or advanced-stage hepatocellular carcinoma. The role of these modalities as a bridge to curative therapy requires further investigation.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Quimiorradioterapia/métodos , Neoplasias Hepáticas/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Trombose Venosa , Radioisótopos de Ítrio/uso terapêutico
19.
World J Hepatol ; 9(18): 808-814, 2017 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-28706579

RESUMO

Transarterial chemoembolization (TACE) is the current standard of therapy for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE (cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drug-eluting beads (DEBs) have been imposed as novel drug-delivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEB-TACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.

20.
Korean J Gastroenterol ; 69(5): 316-320, 2017 May 25.
Artigo em Coreano | MEDLINE | ID: mdl-28539038

RESUMO

Transarterial chemoembolization (TACE) is a common treatment modality to locally manage hepatocellular carcinoma. Liver abscess and bile duct injury are common complications of TACE. However, hepatobronchial fistula is a rare complication. Herein, we report a case of lung abscess due to hepatobronchial fistula after TACE. A 67-year-old man, who had underwent TACE 6 months ago, presented cough and bile-colored sputum. He was diagnosed with lung abscess and hepatobronchial fistula. We performed endoscopic retrograde cholangiopancreatography; however, there was no improvement in his symptoms. Thereafter, partial hepatectomy and repair of fistula were successively conducted.


Assuntos
Quimioembolização Terapêutica/efeitos adversos , Fístula/diagnóstico , Abscesso Pulmonar/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Colangiopancreatografia Retrógrada Endoscópica , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Fístula/etiologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Abscesso Pulmonar/tratamento farmacológico , Abscesso Pulmonar/etiologia , Abscesso Pulmonar/microbiologia , Masculino , Tomografia Computadorizada por Raios X
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