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1.
J Vasc Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38580159

RESUMO

OBJECTIVE: Although carotid body tumors (CBTs) are rare, they attract particular attention because of their propensity for malignant transformation and the high surgical risk. Because data are scarce and as it is difficult to achieve a large sample size, no study has yet comprehensively analyzed the characteristics, management, or operative complications of CBTs. Therefore, we collected and analyzed all currently available information on CBTs and used the pooled data to derive quantitative information on disease characteristics and management. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science up to December 1, 2022, for studies that investigated the characteristics and management of CBTs. The primary objective was to identify the prevalence of the various characteristics and the incidence of complications. The secondary objective was to compare patients who underwent preoperative embolization (PE) and those who did not (non-PE), as well as to compare patients with different Shamblin grades and those with and without succinate dehydrogenase (SDH) mutations in terms of CBT characteristics and complications. Two reviewers selected studies for inclusion and independently extracted data. All statistical analyses were performed using the standard statistical procedures of Review Manager 5.2 and Stata 12.0. RESULTS: A total of 155 studies with 9291 patients and 9862 tumors were identified. The pooled results indicated that the median age of patients with CBT was 45.72 years, and 65% were female. The proportion of patients with bilateral lesions was 13%. In addition, 16% of patients had relevant family histories, and the proportion of those with SDH gene mutations was 36%. Sixteen percent of patients experienced multiple paragangliomas, and 12% of CBTs had catecholamine function. The incidence of cranial nerve injury (CNI) was 27%, and 14% of patients suffered from permanent CNI. The incidence rates of operative mortality and stroke were both 1%, and 4% of patients developed transient ischemic attacks. Of all CBTs, 6% were malignant or associated with metastases or recurrences. The most common metastatic locations were the lymph nodes (3%) and bone (3%), followed by the lungs (2%). Compared with non-PE, PE reduced the estimated blood loss (standardized mean difference, -0.95; 95% confidence interval [CI], -1.70 to -0.20) and the operation time (standardized mean difference, -0.56; 95% CI, -1.03 to -0.09), but it increased the incidence of stroke (odds ratio, 2.44; 95% CI, 1.04-5.73). Higher Shamblin grade tumors were associated with more operative complications. Patients who were SDH gene mutation-positive were more likely to have a relevant family history and had more symptoms. CONCLUSIONS: CBT was most common in middle-aged females, and early surgical resection was feasible; there was a low incidence of serious operative complications. Routine PE is not recommended because this may increase the incidence of stroke, although PE somewhat reduced the estimated blood loss and operation time. Higher Shamblin grade tumors increased the incidence of operative complications. Patients who were SDH gene mutation-positive had the most relevant family histories and symptoms.

2.
Heliyon ; 9(7): e17841, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37539209

RESUMO

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

3.
Mil Med Res ; 10(1): 21, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143145

RESUMO

BACKGROUND: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections. METHODS: Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2',7'-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-ß-D-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real­time reverse transcription­polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo. RESULTS: Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P < 0.01). In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs, but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype (P < 0.05 or P < 0.01). The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways (P < 0.01). In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model (P < 0.01). CONCLUSIONS: These findings suggest that Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Ratos , Animais , Osseointegração , Titânio/farmacologia , Titânio/química , Óxido Nítrico/farmacologia , Ratos Sprague-Dawley , Osteogênese , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Imunoterapia , Biofilmes
4.
Heliyon ; 9(3): e13831, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36895378

RESUMO

Cuprotosis is a new programmed cell death related to cancer. However, the characteristics of cuprotosis in gastric cancer (GC) remain unknown. Ten cuprotosis molecules from 1544 GC patients were used to identify three GC molecular genotypes. Cluster A was characterized by the best clinical outcome and was significantly enriched in metabolic signaling pathways. Cluster B exhibited elevated immune activation, high immune stroma scores and was significantly enriched in tumor immune signaling pathways. Cluster C was characterized by severe immunosuppression and poor response to immunotherapy. Notably, the citrate cycle, cell cycle, and p53 signaling pathways were enriched in the differentially expressed genes among the three subtypes, which were critical signaling pathways for cell death. We also developed a cuprotosis signature risk score that could accurately predict the survival, immunity, and subtype of GC. This study presents a systematic analysis of cuprotosis molecules and provides new immunotherapeutic targets for GC patients.

8.
Front Immunol ; 13: 992060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311733

RESUMO

Objective: The aim of the study was to propose a signature based on genes associated with antigen processing and presentation (APscore) to predict prognosis and response to immune checkpoint inhibitors (ICIs) in advanced gastric cancer (aGC). Background: How antigen presentation-related genes affected the immunotherapy response and whether they could predict the clinical outcomes of the immune checkpoint inhibitor (ICI) in aGC remain largely unknown. Methods: In this study, an aGC cohort (Kim cohort, RNAseq, N=45) treated by ICIs, and 467 aGC patients from seven cohorts were conducted to investigate the value of the APscore predicting the prognosis and response to ICIs. Subsequently, the associations of the APscore with the tumor microenvironment (TME), molecular characteristics, clinical features, and somatic mutation variants in aGC were assessed. The area under the receiver operating characteristic curve (AUROC) of the APscore was analyzed to estimate response to ICIs. Cox regression or Log-rank test was used to estimate the prognosis of aGC patients. Results: The APscore constructed by principal component analysis algorithms was an effective predictive biomarker of the response to ICIs in the Kim cohort and 467 aGC patients (Kim: AUC =0.85, 95% CI: 0.69-1.00; 467 aGC: AUC =0.69, 95% CI: 0.63-0.74). The APscore also was a prognostic biomarker in 467 aGC patients (HR=1.73, 95% CI: 1.21-2.46). Inhibitory immunity, decreased TMB and low stromal scores were observed in the high APscore group, while activation of immunity, increased TMB, and high stromal scores were observed in the low APscore group. Next, we evaluated the value of several central genes in predicting the prognosis and response to ICIs in aGC patients, and verified them using immunogenic, transcriptomic, genomic, and multi-omics methods. Lastly, a predictive model built successfully discriminated patients with vs. without immunotherapy response and predicted the survival of aGC patients. Conclusions: The APscore was a new biomarker for identifying high-risk aGC patients and patients with responses to ICIs. Exploration of the APscore and hub genes in multi-omics GC data may guide treatment decisions.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Gástricas , Humanos , Prognóstico , Apresentação de Antígeno , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Biomarcadores Tumorais/genética , Mutação , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral
9.
Biomed Pharmacother ; 151: 113143, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35643071

RESUMO

Wound healing is a complex and long-term process consisting of hemostasis, inflammation, proliferation, and maturation/remodeling. These four stages overlap and influence each other; they affect wound healing in different ways, and if they do not function perfectly, they may cause scarring, proliferative scarring and keloid formation. A therapeutic target affecting wound healing in multiple ways will help the healing process proceed more effectively. DPP-4/CD26 is a multifunctional dimorphic glycoprotein widely distributed on the surface of a variety of cells, including fibroblasts and keratin-forming cells. It has been found to affect periwound inflammation, re-epithelialization, extracellular matrix secretion and skin fibrosis and is a potential target for promoting wound healing and inhibiting scar formation. After presenting a brief introduction of the wound healing process and DPP-4/CD26, this paper summarizes the effects of DPP-4/CD26 on cells involved in different stages of wound healing and discusses the feasibility of DPP-4/CD26 as a multifunctional target for the treatment of wound healing and inhibition of scar formation.


Assuntos
Cicatriz , Dipeptidil Peptidase 4 , Cicatriz/patologia , Fibrose , Humanos , Inflamação/patologia , Pele , Cicatrização
10.
Cell Death Dis ; 13(6): 527, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35661105

RESUMO

Inflammation is one of the main pathological features leading to skin fibrosis and a key factor leading to the progression of skin fibrosis. Acidosis caused by a decrease in extracellular pH is a sign of the inflammatory process. Acid-sensing ion channels (ASICs) are ligand-gated ion channels on the cell membrane that sense the drop in extracellular pH. The molecular mechanisms by which skin fibroblasts are regulated by acid-sensing ion channel 3 (ASIC3) remain unknown. This study investigated whether ASIC3 is related to inflammation and skin fibrosis and explored the underlying mechanisms. We demonstrate that macrophage colony-stimulating factor (M-CSF) is a direct target of ASIC3, and ASIC3 activation promotes M-CSF transcriptional regulation of macrophages for M2 polarization. The polarization of M2 macrophages transduced by the ASIC3-M-CSF signal promotes the differentiation of fibroblasts into myofibroblasts through transforming growth factor ß1 (TGF-ß1), thereby producing an ASIC3-M-CSF-TGF-ß1 positive feedback loop. Targeting ASIC3 may be a new treatment strategy for skin fibrosis.


Assuntos
Miofibroblastos , Fator de Crescimento Transformador beta1 , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Diferenciação Celular/fisiologia , Retroalimentação , Fibroblastos/metabolismo , Fibrose , Humanos , Inflamação/metabolismo , Fator Estimulador de Colônias de Macrófagos/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/metabolismo , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
11.
J Healthc Eng ; 2021: 5361415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956571

RESUMO

Objective: To investigate the clinical applications of the Clavien-Dindo classification system (CDCS) in the assessment of perioperative complications in minimally invasive percutaneous nephrolithotomy (MPCNL). Methods: Totally, 390 patients with renal stones in our hospital from March 2015 to March 2020 were included for this study and then were divided into observation group (complication group, 78 cases) and control group (noncomplication group, 312 cases) according to the incidence of perioperative complications in CDCS. Single factor analysis and multivariate logistic regression analysis were used to analyze the risk factors of the perioperative complications of MPCNL. Results: The total incidence of complication in the 390 cases with MPCNL was 20.00% (78 cases) according to CDCS, among which the incidence of complications at grades I, II, III, IV, and V was 6.92% (27 cases), 8.21% (32 cases), 2.82% (11 cases), 1.79% (7 cases), and 0.26% (1 case), respectively. The proportion of patients, that aged >60 years, complicated with comorbidities, sophisticated calculi, the preoperative albumin level (<35 g/L), the operation time (>180 minutes), intraoperative bleeding volume (>300 mL), and hospitalization time (>7 days) in the observation group was significantly higher than that in the control group ((75.64% vs. 61.86%, 38.46% vs. 24.36%, 83.33% vs. 69.55%, 83.33% vs. 69.55%, 70.51% vs. 30.76%, 53.85% vs. 36.54%, and 60.26% vs. 43.27%), all P < 0.05). Multivariate logistic regression analysis showed that gender, associated comorbidities, preoperative albumin level, calculus complexity, operation time, and intraoperative bleeding volume (>300 mL) were correlated with the occurrence of complications (P ≤ 0.001, 0.001, 0.001, 0.001, 0.003, and 0.001 respectively). Conclusion: The CDCS can give standard and more comparative criteria for the assessment of perioperative complications, which will provide reference data for reducing complications and ensuring safety profiles in these high-risk patients.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Resultado do Tratamento
12.
J Cell Physiol ; 236(4): 2290-2297, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32830327

RESUMO

The incidence of acute and chronic wound diseases is rising due to various reasons. With complicated pathogenesis, long course, difficult treatment and high disability, wound diseases have become a major burden for patients, their families, and society. Therefore, the focus of research is to identify new ideas and methods for treatment. Fat grafting has gained increased attention because of its effectiveness in wound treatment, and further analysis has uncovered that the stem cells derived from fat may be the main factor affecting wound healing. We summarize the function of adipose stem cells and analyze their possible mechanisms in tissue repair, helping to provide new ideas for the treatment of wound healing.


Assuntos
Tecido Adiposo/transplante , Medicina Regenerativa , Transplante de Células-Tronco , Células-Tronco/metabolismo , Cicatrização , Ferimentos e Lesões/cirurgia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular , Humanos , Comunicação Parácrina , Fenótipo , Resultado do Tratamento , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
13.
EBioMedicine ; 54: 102715, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32251998

RESUMO

BACKGROUND: Hypertrophic scar (HS) is characterized by the increased proliferation and decreased apoptosis of myofibroblasts. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts. Thus, the stimulation of myofibroblast apoptosis is a possible treatment for HS. We aimed to explore that whether over-activated myofibroblasts can be targeted for apoptosis by anticancer drug elesclomol. METHODS: 4',6-diamidino-2-phenylindole staining, flow cytometry, western blotting, collagen gel contraction and immunofluorescence assays were applied to demonstrate the proapoptotic effect of elesclomol in scar derived myofibroblasts and TGF-ß1 induced myofibroblasts. The therapeutic potential of elesclomol was investigated by establishing rabbit ear hypertrophic scar models. FINDINGS: Both 4',6-diamidino-2-phenylindole staining and flow cytometry indicated that elesclomol targets myofibroblasts in vitro. Collagen gel contraction assay showed that elesclomol inhibited myofibroblast contractility. Flow cytometry and western blot analysis revealed that elesclomol resulted in excessive intracellular levels of reactive oxygen species(ROS), and caspase-3 and cytochrome c proteins. Moreover, compared with the control group, the elesclomol group had a significantly lower scar elevation index in vivo. Immunofluorescence assays for TUNEL and α-smooth muscle actin indicated that elesclomol treatment increased the number of apoptotic myofibroblasts. INTERPRETATION: The above results indicate that elesclomol exerted a significant inhibitory effect on HS formation via targeted myofibroblast apoptosis associated with increased oxidative stress. Thus, elesclomol is a promising candidate drug for the treatment of myofibroblast-related diseases such as HS.


Assuntos
Apoptose , Cicatriz/tratamento farmacológico , Hidrazinas/farmacologia , Miofibroblastos/efeitos dos fármacos , Adolescente , Adulto , Caspase 3/metabolismo , Cicatriz/metabolismo , Feminino , Humanos , Hidrazinas/uso terapêutico , Masculino , Miofibroblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
J Cell Mol Med ; 24(2): 2070-2072, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31802598

RESUMO

N6-methyladenosine (m6 A) is one of the most abundant messenger RNA (mRNA) modifications in eukaryotes and is involved in various key processes of RNA metabolism. In this issue of Nature, Ries et al (2019) described the fundamental features of m6A modification of mRNAs in regulating the composition of the phase-separated transcriptome on the basis of number and distribution, and provide strong evidence that m6A plays a role in regulating phase separation in cells.


Assuntos
Adenosina/análogos & derivados , Proteínas de Ligação a RNA/metabolismo , Adenosina/metabolismo , Animais , Grânulos Citoplasmáticos/metabolismo , Camundongos , Modelos Biológicos , Células-Tronco Embrionárias Murinas/metabolismo
15.
Mar Biotechnol (NY) ; 21(4): 463-474, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30941640

RESUMO

Sexual dimorphism is widespread in fish species. The red-tail catfish (Mystus wyckioides) is a commercially important catfish in the lower reaches of the Lancang River and the Mekong basin, and it shows a growth advantage in males. Here, RNA-seq was for the first time used to explore the gene expression difference between the sexes in the hypothalamus and pituitary of red-tail catfish, respectively. In the hypothalamus, 5732 and 271 unigenes have significantly higher and lower expressions, respectively, in males compared with females. KEGG analysis showed that 212 DEGs were annotated to 216 signaling pathways, and enrichment analysis suggested different levels of cAMP and glutamatergic synapse signaling between male and female hypothalami and some of the DEGs appear involved in gonad development and growth. In the pituitary, we found only 19 differentially expressed unigenes, which were annotated to 32 signaling pathways, most of which play important roles in gonad development.


Assuntos
Peixes-Gato/genética , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Caracteres Sexuais , Transdução de Sinais/genética , Transcriptoma , Animais , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/metabolismo , AMP Cíclico/metabolismo , Feminino , Proteínas de Peixes/classificação , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Ácido Glutâmico/metabolismo , Hipotálamo/crescimento & desenvolvimento , Hipotálamo/metabolismo , Masculino , Anotação de Sequência Molecular , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Hipófise/crescimento & desenvolvimento , Hipófise/metabolismo , Diferenciação Sexual , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
16.
Yi Chuan ; 39(3): 250-262, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420621

RESUMO

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.


Assuntos
Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Platina/uso terapêutico , Polimorfismo Genético/genética , Adulto , Idoso , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Enzimas de Conjugação de Ubiquitina/genética , Proteínas de Transporte Vesicular/genética
17.
Aquat Toxicol ; 175: 1-11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26991749

RESUMO

Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole-mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up-regulated in the embryos. Finally, we found that ROS scavengers NAC, GSH, and DMTU not only inhibited in vivo ROS levels induced by copper, but also significantly decreased high expression of hemoglobin back to almost normal levels in copper exposed embryos, and also helped with copper elimination from the embryos. Our data first demonstrated that ROS mediated copper induced hemoglobin expression in vertebrates, partly revealing the underlying molecular mechanism of copper therapy for anemia. Moreover, we revealed that copper homeostasis was broken by its induced ROS and ROS helped with copper overloading in the body, which could be applied as a novel therapy target for copper-caused diseases.


Assuntos
Cobre/toxicidade , Hemoglobinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Análise de Variância , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Espectrometria de Massas , Análise em Microsséries , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/efeitos dos fármacos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
18.
Stem Cells Dev ; 18(4): 583-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18673019

RESUMO

Dental pulp stem cells from teeth can be used for tooth regeneration. Although nondental stem cells derived from bone marrow can differentiate into odontoblast-like cells when recombined with embryonic oral epithelium, these cells can lose their ability to differentiate after an extended number of cell culture passages. There has been limited research to identify stem cells from other tissue sources to regenerate teeth. As another candidate source for mesenchymal stem cells, hair follicle has obtained much more attention recently because of its easy accessibility. In this study, cultured vibrissae follicle dermal papilla mesenchymal cells (FDPMCs) from adult C57BL/6 GFP mice can differentiate into adipocytes and osteoblasts in vitro. Moreover, in the inductive microenvironment generated by apical bud and dental mesenchyme from 7-day-old C57 mice, FDPMCs in vitro demonstrated odontogenic potential, as indicated by the morphological transformation, cell-cycle change and expression of tooth-specific markers. Under the same microenvironment, FDPMCs were incubated in vivo for 3 weeks. Coexpression of GFP and DSP proteins in the odontoblast layer was detected in the recovered implants, suggesting that GFP(+) FDPMCs can function as odontoblasts in vivo. Together, our data indicate for the first time that whisker FDPMCs from adult mice can differentiate to odontoblast-like cells.


Assuntos
Diferenciação Celular/fisiologia , Folículo Piloso/citologia , Células-Tronco Mesenquimais/fisiologia , Odontogênese/fisiologia , Adipogenia/fisiologia , Animais , Biomarcadores/metabolismo , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL
19.
Acta Pharmacol Sin ; 28(7): 985-93, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17588334

RESUMO

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) in cultured human dental follicle cells (HDFC), and to examine the roles of VEGF in the proliferation, differentiation, and apoptosis of HDFC in vitro. METHODS: Immunocytochemistry, ELISA, and RT-PCR were used to detect the expression and transcription of VEGF in cultured HDFC. The dose-dependent and the time-course effect of VEGF on cell proliferation and alkaline phosphatase (ALP) activity in cultured HDFC were determined by MTT assay and colorimetric ALP assay, respectively. The effect of specific mitogen-activated protein kinase (MAPK) inhibitors (PD98059 and U0126) on the VEGF-mediated HDFC proliferation was also determined by MTT assay. The effect of VEGF on HDFC apoptosis was measured by flow cytometry. RESULTS: VEGF was transcribed and expressed in cultured HDFC. VEGF at 10-300 microg/L significantly increased HDFC proliferation and ALP activity compared to the control. Following 1, 3, 5, or 7 d of stimulation, VEGF induced a significant increase in HDFC proliferation compared with the corresponding control, while VEGF was effective at increasing ALP activity at the incubation time point of 3, 5, or 7 d. PD98059 and U0126 could attenuate the VEGF-mediated HDFC proliferation. Fewer apoptotic cells were observed in the VEGF-treated groups compared to the controls, although the difference was not statistically significant. CONCLUSION: VEGF is expressed in cultured HDFC, and at a proper concentration range can stimulate HDFC proliferation, induce HDFC to differentiate in a "cementoblast/osteoblast" pathway and protect HDFC from apoptosis. The MAPK signaling pathway might be involved in the VEGF-mediated HDFC proliferation.


Assuntos
Saco Dentário , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Saco Dentário/citologia , Saco Dentário/metabolismo , Humanos , Fator A de Crescimento do Endotélio Vascular/genética
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 14(3): 601-4, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16800951

RESUMO

To investigate the alpha-1, 3/4-fucosyltransferase gene (FUT3) polymorphism associated with Lewis blood group in Zhejiang population, the Lewis phenotypes of 183 random samples from Chinese blood donors in Zhejiang province were identified by standard serological techniques. The entire coding region of FUT3 gene were amplified by PCR from genomic DNA of 39 Lewis negative and 9 Lewis positive phenotype samples and sequenced directly. The haplotypes of FUT3 allele were identified by TOPO cloning sequencing method. The results showed that the frequency of true Le (a-b-) phenotype in Zhejiang population was 10.4% according to serological and molecular biological methods. Five nucleotide acid variant sites (59T > G, 202T > C, 314C > T, 508G > A and 1067T > A) were detected in all 48 sequencing samples. Besides the wild type Le allele, 2 common (le(59, 1067) and le(59, 508) and 3 rare non-functional le alleles (le(59), le(1067) and le(202, 314) were found in this population. In conclusion, the polymorphism of non-functional FUT3 allele was found to be relatively variable in Chinese Zhejiang population.


Assuntos
Alelos , Fucosiltransferases/genética , Antígenos do Grupo Sanguíneo de Lewis/genética , Polimorfismo Genético , Adulto , Sequência de Bases , China/etnologia , Feminino , Humanos , Masculino , Dados de Sequência Molecular
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