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1.
Molecules ; 25(3)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050529

RESUMO

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca2+ to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca2+) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses.

2.
Int Immunopharmacol ; 80: 106141, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982825

RESUMO

Neuroinflammation significantly contributes to brain injury and neurological deterioration following intracerebral hemorrhage (ICH). MicroRNA-152(miR-152) was reported to be downregulated in ICH patients and to possess anti-inflammatory properties in other diseases. In this study, we aimed to explore the role of miR-152 in ICH, and the underlying mechanisms, using a collagenase-induced rat ICH model and hemin-exposure as a cell model. We first confirmed that miR-152 was consistently downregulated in both models. Overexpression of miR-152 in microglial BV2 cells reduced hemin-induced inflammatory response and reactive oxygen species (ROS) generation, thus protecting co-cultured neuronal HT22 cells. Moreover, overexpression of miR-152 by intracerebroventricular lentivirus injection in ICH rats significantly alleviated neurodecifits, brain edema, and hematoma. These changes were associated with a marked reduction in ICH-induced neuronal death, as detected by co-staining of NeuN and TUNEL, and ICH-induced neuroinflammation, as revealed by inflammatory cytokine levels as well as by the number of Iba1 positive-stained cells in the perihematomal region. Mechanistically, miR-152 significantly inhibited ICH-induced TXNIP expression, and its overexpression blocked the interaction between TXNIP and NOD-like receptor pyrin domain containing 3(NLRP3), thus inhibiting NLRP3-driven inflammasome activation to attenuate neuroinflammation in vivo and in vitro. Moreover, the results of si-TXNIP transfection further confirmed that TXNIP inhibition was involved in the reduction of NLRP3 inflammasome activation by the overexpression of miR-152. Collectively, the present study demonstrates that miR-152 confers protection against ICH-induced neuroinflammation and brain injury by inhibiting TXNIP-mediated NLRP3 inflammasome activation, indicating a potential strategy for ICH treatment.

3.
J Biomed Mater Res A ; 108(1): 19-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31430044

RESUMO

The objective of this study was to fabricate an acellular sheep periosteum and explore its potential application in guided bone regeneration. Sheep periosteum was collected and decellularized by a modified decellularization protocol. The effectiveness of cell removal was proved by hematoxylin and eosin and 4',6-diamidino-2-phenylindole staining, DNA quantitative test, and agarose gel electrophoresis. After decellularization, its microstructure was found to become more porous while the integrality of collagen fibers remained undamaged, and the contents of collagen and glycosaminoglycan were not decreased significantly. Biomechanical analysis showed that the elastic modulus was significantly declined, while the yield stress was not affected, probably due to the collagen integrality. In vitro study of CCK-8 assay demonstrated that the acellular periosteum not only had no toxic effect to the MC3T3-E1 cells, but benefited the cell proliferation to some degree. In vivo experiment of guided bone regeneration was performed using a rabbit cranial model. Micro-CT and histological results revealed that the acellular periosteum not only effectively prevented the ingrowth of fibrous connective tissues, but also potentially facilitated bone regeneration. In conclusion, acellular sheep periostea, with wider sources, less costs, and more convenient fabrication process, would have great potential in the employment for guided bone regeneration.

4.
Stem Cells Int ; 2019: 2743047, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781236

RESUMO

MicroRNAs (miRNAs) influence stem cell functions, including mobilization, proliferation, and differentiation. miR-150 is abundantly expressed in monocytes. Knockdown of miR-150 promotes bone marrow stem cell migration. The role of miR-150 in adipose-derived stem cells (ADSCs) is unclear. In this study, the effects of miR-150 on adipogenic differentiation and proliferation of ADSCs were investigated. ADSCs were isolated from the inguinal adipose tissue of wild-type (WT) and miR-150 knockout (KO) mice and were induced for adipogenic differentiation. The miR-150 level was detected by real-time PCR. ADSCs were transfected by miR-150 or small-interfering RNA (siRNA) of Notch3. MTT assay and colony formation assay were performed in miR-150 knockdown and control ADSCs. Real-time PCR showed that miR-150 was expressed in ADSCs. miR-150 knockdown significantly decreased the capacity of adipogenic differentiation of ADSCs, as compared with their counterparts from WT mice. It is intriguing that the overexpression of miR-150 significantly increased C/EBPα and PPAR-γ expression and lipid formation in ADSCs with adipogenic induction. Overexpression of miR-150 significantly decreased Notch3 expression in ADSCs compared with the control groups. Furthermore, Notch3 inhibition promoted the adipogenic differentiation in ADSCs. miR-150 also suppressed proliferation potential and the expression of Nanog in ADSCs. In summary, this study demonstrates, for the first time, that miR-150 promotes adipogenic differentiation and inhibits proliferation of ADSCs. miR-150 regulates adipogenic differentiation of ADSCs, likely mediated by the downregulation of Notch3.

5.
Neurotherapeutics ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758411

RESUMO

The repair and regeneration of transected peripheral nerves is an important area of clinical research, and the adhesion of anastomosis sites to surrounding tissues is a vital factor affecting the quality of nerve recovery after nerve anastomosis. This study involves the generation of a novel nerve repair membrane derived from decellularized porcine nerves using a unique, innovative technique. The decellularized nerve matrix was verified to be effective in eliminating cellular components, and it still retained some neural extracellular matrix components and bioactive molecules (collagens, glycosaminoglycans, laminin, fibronectin, TGF-ß, etc.), which were mainly determined by proteomic analysis, histochemistry, immunohistochemistry, and enzyme-linked immunosorbent assay. Cytotoxicity, intracutaneous reactivity, hemolysis, and cell affinity analyses were conducted to confirm the biosecurity of the nerve repair membrane. The in vivo functionality was assessed in a rat sciatic nerve transection model, and indices of functional nerve recovery, including the measurement of the claw-spread reflex, nerve anastomosis site adhesion, electrophysiological properties, and the number of regenerated nerve fibers, were evaluated. The results indicated that the nerve repair membrane could effectively prevent adhesion between the nerve anastomosis sites and the surrounding tissues and enhance nerve regeneration, which could be attributed to its various bioactive components. In conclusion, the novel nerve repair membrane derived from xenogeneic decellularized nerves described in this study shows great potential auxiliary clinical treatment for peripheral nerve injuries.

6.
Biomed Mater ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747647

RESUMO

This study addresses the fabrication of an extracellular matrix material of acellular sheep periosteum, and systematic evaluation of its biocompatibility to explore its potential application in guided bone regeneration. Sheep periosteum was harvested and decellularized by a combined decellularization protocol. The effectiveness of cell removal was proved and residual α-Gal antigen was also quantitively detected. Then, mouse MC3T3-E1 cells were seeded onto the acellular periosteum. Scanning electron microscope (SEM) was used to record the whole process of cell adhesion. CCK-8 assay suggested that the acellular periosteum not only had zero toxic effect on pre-osteoblasts, but played a positive role in cell proliferation. It was also tested that whether the acellular periosteum possess favorable osteogenesis induction activity attributed to ALP assay and quantitative real-time PCR (Col I, Runx2, OCN) assay. In vivo study of subcutaneous implantation test using SD rats was performed to detect the changes of IL-2, IFN-γ, IL-4 in serum and elucidate the host's local response to acellular periosteum through HE and immunohistochemical staining. The results show that acellular sheep periosteum did not elicit a severe immunogenic response via Th1 pathway unlike fresh sheep periosteum. In conclusion, acellular sheep periosteum possesses favorable biocompatibility to be employed for guided bone regeneration.

7.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671678

RESUMO

Nitrogen-doped and undoped titanium dioxide nanoparticles were successfully fabricated by simple chemical method and characterized using x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and transmission electron microscopy (TEM) techniques. The reduction in crystalline size of TiO2 nanoparticles (from 20-25 nm to 10-15 nm) was observed by TEM after doping with N. Antibacterial, antifungal, antioxidant, antidiabetic, protein kinase inhibition and cytotoxic properties were assessed in vitro to compare the therapeutic potential of both kinds of TiO2 nanoparticles. All biological activities depicted significant enhancement as a result of addition of N as doping agent to TiO2 nanoparticles. Klebsiella pneumoniae has been illuminated to be the most susceptible bacterial strain out of various Gram-positive and Gram-negative isolates of bacteria used in this study. Good fungicidal activity has been revealed against Aspergillus flavus. 38.2% of antidiabetic activity and 80% of cytotoxicity has been elucidated by N-doped TiO2 nanoparticles towards alpha-amylase enzyme and Artemia salina (brine shrimps), respectively. Moreover, notable protein kinase inhibition against Streptomyces and antioxidant effect including reducing power and % inhibition of DPPH has been demonstrated. This investigation unveils the more effective nature of N-doped TiO2 nanoparticles in comparison to undoped TiO2 nanoparticles indicated by various biological tests. Hence, N-doped TiO2 nanoparticles have more potential to be employed in biomedicine for the cure of numerous infections.

8.
Micromachines (Basel) ; 10(11)2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31717955

RESUMO

Chitosan is a unique natural resourced polysaccharide derived from chitin with special biocompatibility, biodegradability, and antimicrobial activity. During the past three decades, chitosan has gradually become an excellent candidate for various biomedical applications with prominent characteristics. Chitosan molecules can be chemically modified, adapting to all kinds of cells in the body, and endowed with specific biochemical and physiological functions. In this review, the intrinsic/extrinsic properties of chitosan molecules in skin, bone, cartilage, liver tissue repair, and organ three-dimensional (3D) bioprinting have been outlined. Several successful models for large scale-up vascularized and innervated organ 3D bioprinting have been demonstrated. Challenges and perspectives in future complex organ 3D bioprinting areas have been analyzed.

9.
Int Immunopharmacol ; 76: 105887, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536904

RESUMO

Neuroinflammation plays a critical role in the pathogenesis of intracerebral hemorrhage (ICH), contributing to detrimental brain injury and neurological function deficits. MicroRNA-23b (miR-23b) exerts anti-inflammatory effects in many diseases and is downregulated in patients with ICH. This study aimed to evaluate the involvement of miR-23b in ICH models in vivo and in vitro, using basal ganglia injection of collagenase type VII in rats and hemin stimulation for cells, respectively. Exogenous overexpression of miR-23b by transfection with lentivirus-miR-23b (LV-miR-23b) or miR-23b mimics was evaluated by RT-qPCR. In this study, we found miR-23b was downregulated in the ICH models and its overexpression effectively alleviated neurological deficits, brain edema, hematoma area, and neuronal apoptosis in ICH rats. Western blotting for neuroinflammation markers and immunofluorescence staining for microglial activation demonstrated that miR-23b could alleviate neuroinflammation in ICH in vivo. We also performed an in vitro mechanism study using BV2 microglial cells and HT22 neuronal cell lines to explore how miR-23b modulates neuroinflammation and neuronal protection after ICH. We found that miR-23b significantly decreased hemin-stimulated inflammation response in BV2 cells and attenuated co-cultured HT22 neuronal cell death. Additionally, we verified that miR-23b suppressed inflammation in BV2 cells by targeting inositol polyphosphate multikinase (IPMK) and that autophagy regulation through the Akt/mTOR pathway was involved in miR-23b-regulated inflammation after ICH. Our study illustrated that miR-23b played a protective role in ICH through inhibiting neuroinflammation by targeting IPMK; this mechanism may be related to the regulation of the Akt/mTOR autophagy pathway, making it a potential target for ICH treatment.

10.
Colloids Surf B Biointerfaces ; 173: 860-868, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30551302

RESUMO

This study provided the investigation of the surface structure and volatile compounds of peanut proteins obtained through aqueous buffer (AB) and reverse micelles (RMs) by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and gas chromatography-mass spectrometry (GC-MS). The results showed that RMs could modify the amorphous structure of peanut proteins and change the original structure. Significant differences were between the C, O, and N content in two type protein surfaces (P < 0.05).The O/C ratio from AB was higher than from RMs, but the N/C ratio was lower. These changes suggested that RMs could modify the surface morphology and composition of peanut proteins. Untargeted profiling of volatile compounds showed that the volatile compounds of peanut proteins obtained by AB and RMs were major differences. Such finding suggested that RMs could contribute to improve the flavor properties of peanut protein.


Assuntos
Arachis/química , Carbono/química , Micelas , Oxigênio/química , Proteínas de Plantas/química , Cromatografia Gasosa-Espectrometria de Massas , Lipídeos/química , Espectrometria de Massas , Microscopia Eletrônica de Varredura , Nitrogênio/química , Propriedades de Superfície , Temperatura Ambiente , Água/química , Difração de Raios X
11.
Brain Stimul ; 12(1): 161-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30181106

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia and mainly treated by drugs, while the therapeutic outcomes are very limited. This study aimed to determine the optimized parameters of deep brain stimulation (DBS) which was applied to the treatment of AD and propose the involved mechanisms. METHODS: Amyloid-ß precursor protein/Presenilin1 (APP/PS1) transgenic mice were used and received DBS at nucleus basalis of Meynert (NBM). The optimized parameters of DBS were determined by using different stimulation frequencies, durations and ages of mice under Morris water maze test. The involved mechanisms and the possible signal pathways were also investigated. RESULTS: The optimized parameters for DBS were high frequency (100 Hz) for 21 days starting from early age (4 months old). Under the above parameters, the soluble Aß40 and Aß42 in the hippocampus and cortex were down-regulated significantly. DBS increased survival neurons and reduced apoptotic cells in the hippocampus and cortex. Meanwhile, the apoptosis-related proteins caspase-3, caspase-8 and Bid were down-regulated. Moreover, DBS caused a significant increase of superoxide dismutase, glutathione peroxidase and choline acetyltransferase activity as well as a decrease of methane dicarboxylic aldehyde content and acetylcholine esterase activity. Phosphorylation of Akt (p-Akt)/total Akt (t-Akt) was up-regulated while p-extracellular signal-regulated kinase 1/2 (ERK1/2)/t-ERK1/2 was down-regulated. The neuroprotective effect of DBS was attenuated by their inhibitors. CONCLUSIONS: NBM-DBS starting from 4 months of age for 21 days at a high frequency (100 Hz) has therapeutic effects on AD through activating phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and inhibiting ERK1/2 pathway.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Núcleo Basal de Meynert/fisiologia , Estimulação Encefálica Profunda/métodos , Neuroproteção/fisiologia , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
12.
J Immunol Res ; 2018: 7213760, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967801

RESUMO

Abdominal aortic aneurysm (AAA), a deadly vascular disease in human, is a chronic degenerative process of the abdominal aorta. In this process, inflammatory responses and immune system work efficiently by inflammatory cell attraction, proinflammatory factor secretion and subsequently MMP upregulation. Previous studies have demonstrated various inflammatory cell types in AAA of human and animals. The majority of cells, such as macrophages, CD4+ T cells, and B cells, play an important role in the diseased aortic wall through phenotypic modulation. Furthermore, immunoglobulins also greatly affect the functions and differentiation of immune cells in AAA. Recent evidence suggests that innate immune system, especially Toll-like receptors, chemokine receptors, and complements are involved in the progression of AAAs. We discussed the innate immune system, inflammatory cells, immunoglobulins, immune-mediated mechanisms, and key cytokines in the pathogenesis of AAA and particularly emphasis on a further trend and application of these interventions. This current understanding may offer new insights into the role of inflammation and immune response in AAA.


Assuntos
Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/metabolismo , Imunidade , Imunomodulação , Inflamação/complicações , Inflamação/imunologia , Animais , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/terapia , Citocinas/metabolismo , Humanos , Imunidade Inata , Imunoglobulinas/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Receptores Toll-Like/metabolismo
13.
Polymers (Basel) ; 10(11)2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30961203

RESUMO

Three-dimensional (3D) bioprinting, known as a promising technology for bioartificial organ manufacturing, has provided unprecedented versatility to manipulate cells and other biomaterials with precise control their locations in space. Over the last decade, a number of 3D bioprinting technologies have been explored. Natural polymers have played a central role in supporting the cellular and biomolecular activities before, during and after the 3D bioprinting processes. These polymers have been widely used as effective cell-loading hydrogels for homogeneous/heterogeneous tissue/organ formation, hierarchical vascular/neural/lymphatic network construction, as well as multiple biological/biochemial/physiological/biomedical/pathological functionality realization. This review aims to cover recent progress in natural polymers for bioartificial organ 3D bioprinting. It is structured as introducing the important properties of 3D printable natural polymers, successful models of 3D tissue/organ construction and typical technologies for bioartificial organ 3D bioprinting.

14.
Stem Cell Reports ; 9(4): 1097-1108, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28890164

RESUMO

Our ultimate goal of in vitro derivation of Schwann cells (SCs) from adult bone marrow stromal cells (BMSCs) is such that they may be used autologously to assist post-traumatic nerve regeneration. Existing protocols for derivation of SC-like cells from BMSCs fall short in the stability of the acquired phenotype and the functional capacity to myelinate axons. Our experiments indicated that neuro-ectodermal progenitor cells among the human hBMSCs could be selectively expanded and then induced to differentiate into SC-like cells. Co-culture of the SC-like cells with embryonic dorsal root ganglion neurons facilitated contact-mediated signaling that accomplished the switch to fate-committed SCs. Microarray analysis and in vitro myelination provided evidence that the human BMSC-derived SCs were functionally mature. This was reinforced by repair and myelination phenotypes observable in vivo with the derived SCs seeded into a nerve guide as an implant across a critical gap in a rat model of sciatic nerve injury.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Células de Schwann/citologia , Axônios/metabolismo , Biomarcadores , Células Cultivadas , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Células-Tronco Mesenquimais/metabolismo , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Fatores de Crescimento Neural/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neuritos/metabolismo , Neurogênese , Neurônios/citologia , Neurônios/metabolismo , Fenótipo , Células de Schwann/metabolismo
15.
Mol Med Rep ; 16(4): 4455-4462, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28791384

RESUMO

Angiogenesis is an important process in the pathogenesis of aortic aneurysm. The aim of the present study was to investigate the angiogenic balance and the expression of vascular endothelial growth factor (VEGF) in thoracic aortic aneurysm (TAA). A previous study demonstrated that curcumin exerts a marked effect on aortic aneurysm development. Therefore, the present study determined whether curcumin is able to modulate angiogenesis and inflammatory signaling in TAA by collecting human TAA samples and establishing a rat TAA model using periaortic application of CaCl2. TAA rats were treated with curcumin or 1% carboxymethyl cellulose and were sacrificed 4 weeks after the operation. All tissue specimens were analyzed by histological staining, immunohistochemistry and western blotting. Human TAA samples exhibited increased neovascularization and VEGF expression when compared with normal aortic walls. In rat tissues, treatment with curcumin resulted in reduced aneurysm size and restored the wavy structure of the elastic lamellae. In addition, curcumin decreased neovascularization and the expression of VEGF. Immunohistochemical analysis indicated that curcumin significantly inhibited infiltration of cluster of differentiation (CD)3+ and CD68+ cells in TAA. Furthermore, curcumin treatment decreased the expression of vascular cell adhesion molecule­1, intracellular adhesion molecule­1, monocyte chemoattractant protein­1 and tumor necrosis factor­α. Collectively, the results demonstrated that angiogenesis and VEGF expression were increased in the aortic wall in TAA. Treatment with curcumin inhibited TAA development in rats, which was associated with suppression of VEGF expression. In addition, curcumin attenuated inflammatory cell infiltration and suppressed inflammatory factor expression in the periaortic tissue of TAA.


Assuntos
Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/patologia , Curcumina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Animais , Aneurisma da Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/prevenção & controle , Biomarcadores , Biópsia , Curcumina/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Substâncias Protetoras/uso terapêutico , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
World J Gastroenterol ; 23(30): 5538-5548, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28852313

RESUMO

AIM: To explore the let-7a-mediated anti-cancer effect of Yangzheng Sanjie decoction (YZSJD) in gastric cancer (GC) cells. METHODS: YZSJD-containing serum (YCS) was prepared using traditional Chinese medicine serum pharmacology methods. After YCS treatment, cell proliferation and apoptosis were assessed by cell counting kit-8 assay and flow cytometry, respectively, and miRNA expression profiles were determined using qPCR arrays. Let-7a expression was examined by in situ hybridization in GC tissues and by qPCR in GC cells. c-Myc protein expression was detected by immunohistochemistry in GC tissues, and by Western blot in cell lines. RESULTS: YZSJD significantly inhibited proliferation and induced apoptosis in AGS and HS-746T GC cells. After treatment with YCS, the miRNA expression profiles were altered and the reduced let-7a levels in both cell lines were up-regulated, accompanied by a decrease in c-Myc expression. Moreover, decreased let-7a expression and increased c-Myc expression were observed during the progression of gastric mucosa cancerization. CONCLUSION: YZSJD inhibits proliferation and induces apoptosis of GC cells by restoring the aberrant expression of let-7a and c-Myc.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas/tratamento farmacológico , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Medicamentos de Ervas Chinesas/uso terapêutico , Gastrectomia , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Sprague-Dawley , Estômago/citologia , Estômago/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Regulação para Cima
17.
Exp Ther Med ; 13(5): 1922-1926, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28565787

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis. Cell therapy has been considered within the therapeutic options for IPF. In this study, we explored the potential benefits of human umbilical cord-derived mesenchymal stem cell (HUC-MSC) intravenous infusion in the management of IPF. We describe a case of a 56-year-old man with IPF who was receiving long-term oxygen therapy (LTOT). The patient underwent HUC-MSC intravenous infusion and was followed up for 12 months. Clinical and motor tests, as well as questionnaires assessing quality of life, were performed prior to and following the transplantation. At the end of 12 months, a relevant reduction of LTOT requirement was registered; improvements in terms of physical performance, quality of life, and respiratory parameters were observed in our patient. In conclusion, a program of HUC-MSC intravenous infusion appears to be beneficial to patients with IPF and may be considered as an additional therapeutic option.

18.
Exp Ther Med ; 13(5): 2255-2258, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28565834

RESUMO

Four patients with chronic refractory immune thrombocytopenic purpura (ITP) received human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSC dose was 5×107 to 1×108. Complete remission (CR) was achieved in three patients in 12 months and one patient in 24 months. Three patients received the second hUC-MSC transplantation with the same dose. The median time between hUC-MSC transplantation and response was 12.5 days (range, 7-16). There were no severe adverse events during and post hUC-MSC transplantation. During follow-up (median, 17 months; range, 13-24) no other immunosuppressive drugs were used post-first hUC-MSCs transplantation. In conclusion, hUC-MSC transplantation is a reasonable salvage treatment in chronic refractory ITP. Prospective randomized large-scale clinical trials are needed to further elucidate the efficacy of hUC-MSCs transplantation therapy on ITP.

19.
Sci Rep ; 7: 44002, 2017 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-28287100

RESUMO

In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Transplante de Células/métodos , Quitosana/administração & dosagem , Doenças do Sistema Nervoso Periférico/terapia , Nervo Fibular/patologia , Animais , Comportamento Animal , Medula Óssea , Modelos Animais de Doenças , Cabras , Histocitoquímica , Imagem por Ressonância Magnética , Resultado do Tratamento
20.
Stem Cells Transl Med ; 6(2): 369-381, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28191772

RESUMO

Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission. Subpopulations of the derived neurons were electrically excitable, showing tetrodotoxin-sensitive action potentials in patch-clamp experiments. Coculture of the derived neurons with rat Schwann cells under myelinating conditions resulted in upregulated levels of neuronal neuregulin 1 type III in conjunction with the phosphorylated receptors ErbB2 and ErbB3, consistent with amenability of the neuritic network to myelination. As surrogates of embryonic dorsal root ganglia neurons, the derived sensory neurons provided contact-dependent cues to commit bone marrow-derived Schwann cell-like cells to the Schwann cell fate. Our rapid and efficient induction protocol promises not only controlled differentiation of human iPSCs into sensory neurons, but also utility in the translation to a protocol whereby human bone marrow-derived Schwann cells become available for autologous transplantation and remyelination therapy. Stem Cells Translational Medicine 2017;6:369-381.


Assuntos
Diferenciação Celular , Linhagem da Célula , Células-Tronco Pluripotentes Induzidas/fisiologia , Células-Tronco Neurais/fisiologia , Remielinização , Células de Schwann/fisiologia , Células Receptoras Sensoriais/fisiologia , Potenciais de Ação , Animais , Biomarcadores/metabolismo , Linhagem Celular , Técnicas de Cocultura , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/transplante , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/cirurgia , Fenótipo , Ratos , Células de Schwann/metabolismo , Células de Schwann/transplante , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/transplante , Transdução de Sinais , Transplante de Células-Tronco/métodos
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