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1.
ACS Appl Mater Interfaces ; 13(39): 47100-47117, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34579527

RESUMO

Titanium-based substrates are widely used in orthopedic treatments and hard tissue engineering. However, many of these titanium (Ti) substrates fail to interact properly between the cell-to-implant interface, which can lead to loosening and dislocation from the implant site. As a result, scaffold implant-associated complications and the need for multiple surgeries lead to an increased clinical burden. To address these challenges, we engineered osteoconductive and osteoinductive biosubstrates of chitosan (CS)-cross-linked polyaniline (PANI) nanonets coated on titanium nanotubes (TiO2NTs) in an attempt to mimic bone tissue's major extracellular matrix. Inspired by the architectural and tunable mechanical properties of such tissue, the TiO2NTs-PANI@CS-based biofilm conferred strong anticorrosion, the ability to nucleate hydroxyapatite nanoparticles, and excellent biocompatibility with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). An in vitro study showed that the substrate-supported cell activities induced greater cell proliferation and differentiation compared to cell-TiO2NTs alone. Notably, the bone-related genes (collagen-I, OPN, OCN, and RUNX 2) were highly expressed within TiO2NTs-PANI@CS over a period of 14 days, indicating greater bone cell differentiation. These findings demonstrate that the in vitro functionality of the cells on the osteoinductive-like platform of TiO2NTs-PANI@CS improves the efficiency for osteoblastic cell regeneration and that the substrate potentially has utility in bone tissue engineering applications.

2.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445110

RESUMO

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
3.
Prev Nutr Food Sci ; 26(2): 121-131, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34316477

RESUMO

Dysbiosis is a microbial imbalance, which often causes diseases and can be triggered by diet. Here, we deter-mined the effect of a nutritionally balanced diet rich in vegetables and whole grains alone and/or in combination with probiotics on the gut microbiota of healthy adults. We conducted a parallel-group randomized trial enrolling 63 healthy participants who were administered either a balanced diet (B-diet group), a probiotic capsule containing Lactobacillus plantarum PMO 08 (probiotics group), or a balanced diet plus probiotic capsule (synbiotics group) once daily for 2 weeks. The gut microbiota of each participant was analyzed via 16S ribosomal RNA MiSeq-based sequencing. Gastrointestinal symptoms and defecation habits were evaluated using questionnaires. The B-diet group showed significantly reduced Firmicutes-to-Bacteroidetes ratio (P<0.05) and abundances of the genera Blautia (P<0.01), Dorea (P<0.05), and Lachnoclostridium (P<0.05). Furthermore, the abundance of Bacteroides increased (P<0.05) compared to baseline levels. In the synbiotics group, Lactobacillus abundance increased significantly (P<0.05) and defecation difficulty decreased (P<0.05), confirming a synergistic effect of combined intake. All groups showed a significant reduction in the abundance of Clostridiaceae (P<0.001) and alleviation of bloating symptoms (P<0.05). Moreover, the relative abundance of Faecalibacterium significantly increased in the probiotics group (P<0.05). Therefore, the individual or combined intake of a nutritionally balanced diet and L. plantarum PMO 08 beneficially modifies the gut microbiota with the potential to alleviate gastrointestinal symptoms and improve defecation habits.

4.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809267

RESUMO

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Obesidade/tratamento farmacológico , Panax , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Animais , Glicemia/análise , Imunofluorescência , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Insulina/sangue , Leptina/sangue , Masculino , Metagenômica , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , Obesidade/patologia , Pâncreas/patologia , RNA Ribossômico 16S/genética
5.
Nutrients ; 13(4)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919521

RESUMO

The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of Gardenia jasminoides (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome.


Assuntos
Dermatite Atópica/tratamento farmacológico , Gardenia , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pele/microbiologia , Animais , Antibacterianos/efeitos adversos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/microbiologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C
6.
Int Neurourol J ; 25(2): 119-127, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33504132

RESUMO

The incidence of prostate cancer (PCa) is increasing concomitantly with population aging. Accordingly, interest in radiation therapy (RT) and the frequency of RT are also increasing. The types of RT can be broadly divided into external beam RT (EBRT), brachytherapy (BT), and combination therapy (EBRT+BT). Lower urinary tract symptoms (LUTS) after RT for the treatment of PCa are common; however, there are few reviews on the relationship between RT and LUTS. Herein, we review the causes and incidence of LUTS, as well as the evaluation and treatment options. Because of the reported risks of RT, patients undergoing RT should be counseled regarding the challenges of treatment and informed that they may have higher failure rates than nonirradiated patients. Moreover, thorough evaluation and treatment strategies are needed to support treatment recommendations. With a review of the existing literature, this narrative article provides an overview to aid urologists in treating patients presenting with complications associated with RT for the treatment of PCa. Further research is required to provide evidence of the effectiveness and feasibility of the management approach to the care of patients with LUTS after RT for the treatment of PCa.

7.
Nutrients ; 12(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266101

RESUMO

The aim of our study was to evaluate the anti-obesity effects of Lactobacillus sakei (L. sakei) ADM14 administration in a high-fat diet-induced obese mouse model and the resulting changes in the intestinal microbiota. Prior to in vivo testing, L. sakei ADM14 was shown to inhibit adipogenesis through in vitro test and genetic analysis. Subsequently, mice were orally administered 0.85% saline supplemented or not with L. sakei ADM14 to high-fat diet group and normal diet group daily. The results showed that administration of L. sakei ADM14 reduced weight gain, epididymal fat expansion, and total blood cholesterol and glucose levels, and significantly decreased expression of lipid-related genes in the epididymal fat pad. Administration of L. sakei ADM14 showed improvement in terms of energy harvesting while restoring the Firmicutes to Bacteroidetes ratio and also increased the relative abundance of specific microbial taxa such as Bacteroides faecichinchillae and Alistipes, which are abundant in non-obese people. L. sakei ADM14 affected the modulation of gut microbiota, altered the strain profile of short-chain fatty acid production in the cecum and enhanced the stimulation of butyrate production. Overall, L. sakei ADM14 showed potential as a therapeutic probiotic supplement for metabolic disorders, confirming the positive changes of in vivo indicators and controlling gut microbiota in a high-fat diet-induced obese mouse model.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Lactobacillus sakei , Obesidade/terapia , Células 3T3-L1 , Tecido Adiposo/metabolismo , Tecido Adiposo/microbiologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bacteroides/metabolismo , Glicemia/metabolismo , Ceco/metabolismo , Ceco/microbiologia , Colesterol/sangue , Ácidos Graxos Voláteis/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Probióticos/administração & dosagem , Ganho de Peso
8.
Int J Syst Evol Microbiol ; 70(12): 6301-6306, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33141655

RESUMO

A Gram-stain-negative, aerobic, non-spore-forming, motile by single polar flagellum and ovoid or rod-shaped bacterial strain, designated JBTF-M23T, was isolated from tidal flat sediment collected from the Yellow Sea, Republic of Korea. Neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain JBTF-M23T fell within the clade comprising the type strains of Pseudoalteromonas species, clustering with the type strains of P. byunsanensis and P. amylolytica. Strain JBTF-M23T exhibited the highest 16S rRNA gene sequence similarity value (98.6 %) to the type strain of P. rubra and sequence similarities of 98.3 and 97.7 % to the type strains of P. byunsanensis and P. amylolytica, respectively. The DNA G+C content of strain JBTF-M23T from genomic sequence data was 41.98 %. The ANI and dDDH values between strain JBTF-M23T and the type strains of P. rubra, P. byunsanensis and P. amylolytica were 71.3-76.6 and 19.4-19.9 %, respectively. Strain JBTF-M23T contained Q-8 as the predominant ubiquinone and C16 : 1 ω7c and/or C16 : 1 ω6c, C16 : 0 and C18 : 1 ω7c as the major fatty acids. The major polar lipids of strain JBTF-M23T were phosphatidylethanolamine and one unidentified aminolipid. Distinguished phenotypic properties, along with the phylogenetic and genetic distinctiveness, revealed that strain JBTF-M23T is separated from recognized Pseudoalteromonas species. On the basis of the data presented, strain JBTF-M23Tis considered to represent a novel species of the genus Pseudoalteromonas, for which the name Pseudoalteromonas caenipelagi sp. nov. is proposed. The type strain is JBTF-M23T(=KACC 19900T=NBRC 113647T).


Assuntos
Sedimentos Geológicos/microbiologia , Filogenia , Pseudoalteromonas/classificação , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfatidiletanolaminas/química , Pseudoalteromonas/isolamento & purificação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Ubiquinona/química
9.
Int J Mol Sci ; 21(20)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066004

RESUMO

The mortality rate of ovarian cancer (OC) worldwide increases with age. OC is an often fatal cancer with a curative rate of only 20-30%, as symptoms often appear after disease progression. Studies have reported that isolinderalactone (ILL), a furanosesquiterpene derivative extracted from the dried root of Lindera aggregata, can inhibit several cancer cell lines' growth. However, the molecular mechanisms underlying ILL activities in human OC cells remain unexplored. This study investigated the antitumor activities of ILL in human OC cells by inducing mitochondrial superoxide (mtSO) and JAK-signal transducer and activator of transcription 3 (STAT3)-dependent cell death. ILL caused cell death in SKOV-3 and OVCAR-3 cells and increased the cell proportion in the subG1 phase. Additionally, ILL significantly induced mtSO production and reduced ROS production. Moreover, ILL downregulated mitochondrial membrane potential and the expression levels of anti-apoptotic Bcl-2 family proteins and superoxide dismutase (SOD)2. Results showed that ILL decreased phosphorylation of serine 727 and tyrosine 705 of STAT3 and expression of survivin, a STAT3-regulated gene. Furthermore, ILL-induced cell death was reversed by pretreatment of Mito-TEMPO, a mitochondria-specific antioxidant. These results suggest that ILL induces cell death by upregulation of mtSO, downregulation of mitochondrial SOD2, and inactivation of the STAT3-mediated pathway.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Antineoplásicos/toxicidade , Neoplasias Ovarianas/metabolismo , Sesquiterpenos/toxicidade , Morte Celular , Linhagem Celular Tumoral , Feminino , Humanos , Janus Quinases/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator de Transcrição STAT3/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
10.
Life (Basel) ; 10(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066563

RESUMO

Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4-6 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose.

11.
Int J Mol Sci ; 21(8)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32340319

RESUMO

An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.


Assuntos
Bioimpressão/métodos , Técnicas de Cultura de Células , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neovascularização Patológica , Impressão Tridimensional , Esferoides Celulares , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis , Microscopia Confocal , Neovascularização Patológica/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos
12.
Int Neurourol J ; 24(1): 66-76, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32252188

RESUMO

PURPOSE: Given the importance of evaluating the severity of overactive bladder (OAB) symptoms and outcomes after treatment, several questionnaires have been developed to evaluate OAB patients. However, only limited questionnaires are available in Korea for use with Korean patients. Therefore, this study aimed to develop Korean versions of OAB questionnaires through a rigorous linguistic validation process. METHODS: The Indevus Urgency Severity Scale, Urgency Perception Scale, Urgency Severity Scale, and Patient Perception of Intensity of Urgency Scale underwent translation and linguistic validation. The linguistic validation procedure consisted of permission for translation, forward translations, reconciliation, back-translation, cognitive debriefing, and proofreading. Two independent bilingual translators translated the original version of each questionnaire, and a panel then discussed and reconciled the 2 initial translations. Next, a third independent bilingual translator performed a backward translation of the reconciled version into English. Five Korean patients diagnosed with OAB were interviewed for cognitive debriefing. RESULTS: Each item of the questionnaires was translated into 2 Korean versions in the forward translation process. Terms such as 'urgency' and 'wetting' were translated into ordinary language by the translators and adjusted by the panel members to more conceptually equivalent terms in a medical context. In the back-translation process, the panel made a few changes regarding details based on a comparison of the back-translated and original versions. During the cognitive debriefing process, 5 patients provided a few pieces of feedback on the naturalness of the wording of the questionnaires, but generally agreed on the translated terms. CONCLUSION: In this study, the panel produced a successful linguistic validation of Korean versions of multiple OAB questionnaires, which can be utilized to evaluate the severity and treatment outcomes of OAB.

13.
J Exp Med ; 217(6)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32267915

RESUMO

Transforming growth factor ß (TGFß) is a crucial factor in fibrosis, and transcriptional intermediary factor 1γ (TIF1γ) is a negative regulator of the TGFß pathway; however, its role in liver fibrosis is unknown. In this study, mesenchymal stem cells derived from human embryonic stem cells (hE-MSCs) that secrete hepatocyte growth factor (HGF) were used to observe the repair of thioacetamide (TAA)-induced liver fibrosis. Our results showed that TIF1γ was significantly decreased in LX2 cells when exposed to TGFß1. Such decrease of TIF1γ was significantly prevented by co-culture with hE-MSCs. Interaction of TIF1γ with SMAD2/3 and binding to the promoter of the α-smooth muscle gene (αSMA) suppressed αSMA expression. Phosphorylation of cAMP response element-binding protein (CREB) and binding on the TIF1γ promoter region induced TIF1γ expression. Furthermore, hepatic stellate cell-specific TIF1γ-knockout mice showed aggravation of liver fibrosis. In conclusion, loss of TIF1γ aggravates fibrosis, suggesting that a strategy to maintain TIF1γ during liver injury would be a promising therapeutic approach to prevent or reverse liver fibrosis.


Assuntos
Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fatores de Transcrição/metabolismo , Actinas/metabolismo , Animais , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Camundongos Knockout , Camundongos Nus , Camundongos Transgênicos , Fosforilação , Regiões Promotoras Genéticas/genética , Ligação Proteica , Reprodutibilidade dos Testes , Proteínas Smad/metabolismo , Tioacetamida , Fatores de Transcrição/genética , Regulação para Cima
14.
J Nanosci Nanotechnol ; 20(9): 5360-5364, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32331104

RESUMO

Stent-mediated therapy is minimally invasive and fairly effective for the specific tissue and organs with tubal structures such as the esophagus, intestine, and blood vessels. Cerebral arteries are one of the most critical tubal structures to maintain the physiological function and the life of the human. Since the retrieval of the implanted vascular stent is difficult and risky, the one-step stent therapy is imperative. However, the placement of a current pipe-typed stent can also limit the nutritional supply to the vascular wall. Also, the non-degradable polymeric layer is possibly sensitized to the recipient as a foreign body after prolonged period after implantation. Herein, we developed PLGA/PCL nanofiber-coated stent for blocking the flow towards the aneurysm cavity as well as allowing nutritional support to the vessel with the biodegradability. The PLGA/PCL nanofiber-coated stent (NCS) was fabricated via electrospinning composite nanofibers onto a self-expandable mater metal stent. The as-fabricated NCS was physicochemically characterized using FT-IR, FE-SEM, and UTM, and experimented in vivo as implanted in porcine models and radiologically and histologically analyzed. The NCS demonstrated improved physicochemical properties for intracranial aneurysmal treatment including enhanced mechanical properties. The bioabsorbability of NCS was confirmed in the animal model.


Assuntos
Nanofibras , Implantes Absorvíveis , Animais , Glicolatos , Glicóis , Humanos , Poliésteres , Espectroscopia de Infravermelho com Transformada de Fourier , Stents , Suínos
15.
Front Oncol ; 10: 62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32133284

RESUMO

In this study, the mechanism of the anticancer effect through which cucurbitacin D (CuD) can overcome gefitinib resistance in NSCLC was investigated. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, and cell migration and growth were observed by wound healing and colony formation assays, respectively. Levels of EGFR family members, protein kinase B, extracellular signal-regulated kinase, poly(ADP-ribose) polymerase, and G2/M phase-related proteins were detected by Western blot analysis. Immunofluorescence analysis was used to detect the intracellular expression of p-EGFR. Induction of apoptosis and cell cycle arrest was measured by flow cytometry. Solid-phase binding assays were used to determine binding to the EGFR family. CuD inhibits the phosphorylation of EGFR in gefitinib-resistant NSCLC cells and induces cell death via cell cycle arrest and apoptosis. CuD treatment or EGFR knockdown also suppressed the growth of gefitinib-resistant NSCLC cells. In addition, CuD overcame resistance by blocking EGF binding to EGFR in gefitinib-resistant NSCLC cells. In conclusion, we demonstrate that CuD overcomes gefitinib resistance by reducing the activation of EGFR-mediated survival in NSCLC and by inhibiting the combination of EGF and EGFR.

16.
Cancer Lett ; 478: 71-81, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32173479

RESUMO

Glioblastoma multiforme (GBM) is a lethal and highly vascular type of brain tumor. We previously reported that isolinderalactone enhances GBM apoptosis in vitro and in vivo, but its role in tumor angiogenesis is unknown. Here, we investigated the anti-angiogenic activity of isolinderalactone and its mechanisms. In a human GBM xenograft mouse model, isolinderalactone significantly reduced tumor growth and vessels. Isolinderalactone decreased the expression of vascular endothelial growth factor (VEGF) mRNA, protein, and VEGF secretion in hypoxic U-87 GBM cells and also in xenograft GMB tissue. In addition, we demonstrated that isolinderalactone significantly inhibited the proliferation, migration, and capillary-like tube formation of human brain microvascular endothelial cells (HBMECs) in the presence of VEGF. We also found that isolinderalactone decreased sprout diameter and length in a 3D microfluidic chip, and strongly reduced VEGF-triggered angiogenesis in vivo Matrigel plug assay. Isolinderalactone downregulated hypoxia-inducible factor-1α (HIF-1α) and HIF-2α proteins, decreased luciferase activity driven by the VEGF promoter in U-87 cells under hypoxic conditions, and suppressed VEGF-driven phosphorylation of VEGFR2 in HBMECs. Taken together, our results suggest that isolinderalactone is a promising candidate for GBM treatment through tumor angiogenesis inhibition.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Dispositivos Lab-On-A-Chip , Masculino , Camundongos , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Brain Behav Immun ; 87: 765-776, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32201254

RESUMO

Although over one-third of stroke patients may develop post-stroke cognitive impairment (PSCI), the mechanisms underlying PSCI remain unclear. We explored here, the involvement of post-stroke inflammasomes in long-term PSCI development, using a 45 min-middle cerebral artery occlusion (MCAO)/reperfusion-induced PSCI model. Immunohistological assessment on day 1, 3, and 7 was followed by cognitive function test 28 days post-stroke. Evaluation of inflammasome sensor gene expression in aged mouse brains showed dominant expression of absent in melanoma 2 (Aim2) in 6-, 12-, and 18-month-old mouse brains. AIM2 mRNA and protein increased until 7 days post-stroke. PSCI decreased anxiety in elevated plus maze test and impaired spatial learning and memory functions in Morris water maze test 28 days post-stroke. AIM2 and other inflammasome subunit immunoreactivities, including those for caspase-1, interleukin (IL)-1ß, and IL-18, were higher in the hippocampus and cortex of the PSCI than in those of the sham group 7 days post-stroke. AIM2 immunoreactivity of the PSCI group was primarily co-localized with Iba-1 (microglial marker) and CD31 (endothelial cell marker) immunoreactivities but not NeuN (neuronal marker) and GFAP (astrocyte marker) immunoreactivities, suggesting that microglia or endothelial cell-induced AIM2 production mediated PSCI pathogenesis. Additionally, inflammasome-induced pyroptosis might contribute to acute and chronic neuronal death after stroke. AIM2 knockout (KO) and Ac-YVAD-CMK-induced caspase-1 inhibition in mice significantly improved cognitive function and reversed brain volume in the hippocampus relative to those in stroke mice. Conclusively, AIM2 inflammasome-mediated inflammation and pyroptosis likely aggravated PSCI; therefore, targeting and controlling AIM2 inflammasome could potentially treat PSCI.


Assuntos
Lesões Encefálicas , Disfunção Cognitiva , Acidente Vascular Cerebral , Animais , Disfunção Cognitiva/etiologia , Proteínas de Ligação a DNA , Inflamassomos , Camundongos , Acidente Vascular Cerebral/complicações
18.
Polymers (Basel) ; 12(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069827

RESUMO

Herein, we describe precisely a covalent modification of pure magnesium (Mg) surface and its application to induce in vitro osteogenic differentiation. The new concept of a chemical bonding method is proposed for developing stable chemical bonds on the Mg surface through the serial assembly of bioactive additives that include ascorbic acid (AA) and bovine serum albumin (BSA). We studied both the physicochemical and electrochemical properties using scanning electron microscopy and other techniques to confirm how the covalent bonding of BSA on Mg can, after coating, significantly enhance the chemical stability of the substrate. The modified Mg-OH-AA-BSA exhibits better anti-corrosion behavior with high corrosion potential (Ecorr = -0.96 V) and low corrosion current density (Icorr = 0.2 µA cm-2) as compared to the pure Mg (Ecorr = -1.46 V, Icorr = 10.42 µA cm-2). The outer layer of BSA on Mg protects the fast degradation rate of Mg, which is the consequence of the strong chemicals bonds between amine groups on BSA with carboxylic groups on AA as the possible mechanism of peptide bonds. Collectively, the results suggest that the surface-modified Mg provides a strong bio-interface, and enhances the proliferation and differentiation of pre-osteoblast (MC3T3-E1) cells through a protein-lipid interaction. We therefore conclude that the technique we describe provides a cost-effective and scalable way to generate chemically stable Mg surface that inherits a biological advantage in orthopedic and dental implants in clinical applications.

19.
J Gerontol A Biol Sci Med Sci ; 75(4): 631-639, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-30346494

RESUMO

Photobiomodulation using low-level light-emitting diode can be rapidly applied in neurological and physiological disorders safely and noninvasively. Photobiomodulation is effective for chronic diseases because of fewer side effects than drugs. Here we investigated the effects of photobiomodulation using light-emitting diode on amyloid plaques, gliosis, and neuronal loss to prevent and/or recover cognitive impairment, and optimal timing of photobiomodulation initiation for recovering cognitive function in a mouse model of Alzheimer's disease. 5XFAD mice were used as an Alzheimer's disease model. Animals receiving photobiomodulation treatment were divided into two groups: an early group starting photobiomodulation at 2 months of age (5XFAD+Early), and a late group starting photobiomodulation at 6 months of age (5XFAD+Delay). Both groups received photobiomodulation 20 minutes per session three times per week for 14 weeks. The Morris water maze, passive avoidance, and elevated plus maze tests were performed at 10 months of age. Immunohistochemistry and Western blot were performed after behavioral evaluation. The results showed that photobiomodulation treatment at early stages reduced amyloid accumulation, neuronal loss, and microgliosis and alleviated the cognitive dysfunction in 5XFAD mice, possibly by increasing insulin degrading enzyme related to amyloid-beta degradation. Photobiomodulation may be an excellent candidate for advanced preclinical Alzheimer's disease research.


Assuntos
Doença de Alzheimer/radioterapia , Terapia com Luz de Baixa Intensidade , Fatores Etários , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Aprendizagem da Esquiva/efeitos da radiação , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/efeitos da radiação , Cognição/efeitos da radiação , Modelos Animais de Doenças , Gliose/patologia , Gliose/prevenção & controle , Humanos , Lasers Semicondutores/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos da radiação , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos da radiação , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto , Proteólise/efeitos da radiação
20.
Mol Ther ; 28(1): 142-156, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31606324

RESUMO

Hypoxic microenvironments exist in developing embryonic tissues and determine stem cell fate. We previously demonstrated that hypoxic priming plays roles in lineage commitment of embryonic stem cells. In the present study, we found that hypoxia-primed embryoid bodies (Hyp-EBs) efficiently differentiate into the myogenic lineage, resulting in the induction of the myogenic marker MyoD, which was not mediated by hypoxia-inducible factor 1α (HIF1α) or HIF2α, but rather by Sp1 induction and binding to the MyoD promoter. Knockdown of Sp1 in Hyp-EBs abrogated hypoxia-induced MyoD expression and myogenic differentiation. Importantly, in the cardiotoxin-muscle injury mice model, Hyp-EB transplantation facilitated muscle regeneration in vivo, whereas transplantation of Sp1-knockdown Hyp-EBs failed to do. Moreover, we compared microRNA (miRNA) expression profiles between EBs under normoxia versus hypoxia and found that hypoxia-mediated Sp1 induction was mediated by the suppression of miRNA-92a, which directly targeted the 3' untranslated region (3' UTR) of Sp1. Further, the inhibitory effect of miRNA-92a on Sp1 in luciferase assay was abolished by a point mutation in specific sequence in the Sp1 3' UTR that is required for the binding of miRNA-92a. Collectively, these results suggest that hypoxic priming enhances EB commitment to the myogenic lineage through miR-92a/Sp1/MyoD regulatory axis, suggesting a new pathway that promotes myogenic-lineage differentiation.


Assuntos
Diferenciação Celular/genética , Hipóxia Celular/genética , Linhagem da Célula/genética , MicroRNAs/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Desenvolvimento Muscular/genética , Proteína MyoD/metabolismo , Fator de Transcrição Sp1/metabolismo , Regiões 3' não Traduzidas , Animais , Células Cultivadas , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Regiões Promotoras Genéticas , Fator de Transcrição Sp1/genética , Transfecção
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