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1.
Curr Med Sci ; 44(3): 529-544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38809379

RESUMO

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.


Assuntos
Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Mapas de Interação de Proteínas , Trocadores de Sódio-Hidrogênio , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes , Genes Supressores de Tumor , Prognóstico , Mapas de Interação de Proteínas/genética , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo
2.
Mol Neurobiol ; 60(10): 5725-5737, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37338804

RESUMO

Microglia-induced neuroinflammation is a contributing factor to neurodegenerative diseases. Jatrorrhizine (JAT), an alkaloid isolated from Huanglian, has been shown to have neuroprotective effects against various neurodegenerative diseases, but its impact on microglia-induced neuroinflammation remains unclear. In this study, we investigated the role of JAT in MAPK/NF-κB/NLRP3 signaling pathway in an H2O2-induced oxidative stress model using microglia (N9 cells). We divided cells into six groups, including control, JAT, H2O2, H2O2 + 5 µmol/L JAT, H2O2 + 10 µmol/L JAT, and H2O2 + 20 µmol/L minocycline groups. Cell viability was measured using MTT assay and TNF-α levels were detected with an ELISA Kit. Western blot was used to detect NLRP3, HMGB1, NF-κB, p-NF-κB, ERK, p-ERK, p38, p-p38, p-JNK, JNK, IL-1ß, and IL-18 expressions. Our results showed that JAT intervention improved H2O2-induced cytotoxicity in N9 cells and reduced the elevated expression of TNF-α, IL-1ß, IL-18, p-ERK/ERK, p-p38/p38, p-JNK/JNK, p-p65/p65, NLRP3, and HMGB1 in H2O2 group. Furthermore, treatment with ERK inhibitor SCH772984 specifically blocked ERK phosphorylation, resulting in decreased protein levels of p-NF-κB, NLRP3, IL-1ß, and IL-18 in H2O2 group. These results suggest that the MAPK/NF-κB signaling pathway may regulate the protein levels of NLRP3. Overall, our study indicates that JAT may have a protective effect on H2O2-treated microglia via inhibition the MAPK/NF-κB/NLRP3 pathway and could be a potential therapeutic approach for neurodegenerative diseases.


Assuntos
Proteína HMGB1 , NF-kappa B , Humanos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Proteína HMGB1/metabolismo , Peróxido de Hidrogênio/toxicidade , Fator de Necrose Tumoral alfa , Doenças Neuroinflamatórias , Microglia/metabolismo , Transdução de Sinais
3.
Curr Med Sci ; 43(1): 104-114, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36459303

RESUMO

OBJECTIVE: This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS: A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS: The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION: In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinógenos , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Hepáticas/genética
4.
Curr Med Sci ; 42(2): 357-372, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35325407

RESUMO

OBJECTIVE: Gastric cancer (GC) is a deadly cancer and a challenging public health problem globally. This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer. METHODS: This work selected the overlapping differentially expressed genes (DEGs) in GC from four datasets, the GSE29272, GSE29998, GSE54129 and GSE118916 Gene Expression Omnibus databases. These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched, the relative expression levels and immune infiltrates, the prognostic characteristics and the interaction network. RESULTS: In total, 55 DEGs increased while 98 decreased in their expression levels. For those DEGs with increased expression, they were mostly concentrated on "focal adhesion" and "ECM-receptor interaction", whereas DEGs with decreased expression were mostly associated with "gastric acid secretion" and "drug metabolism cytochrome P450". MCODE and ClueGO results were then integrated to screen 10 hub genes, which were FN1, COL1A1, COL3A1, BGN, TIMP1, COL1A2, LUM, VCAN, COL5A2 and SPP1. Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients. TIMP1 was most significantly related to neutrophils, CD8+ T cells, as well as dendritic cells, while LUM was most significantly related to macrophages. CONCLUSION: Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.


Assuntos
Neoplasias Gástricas , Linfócitos T CD8-Positivos/patologia , Carcinogênese , Biologia Computacional/métodos , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
5.
Curr Med Sci ; 42(1): 100-107, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34985612

RESUMO

OBJECTIVE: The eukaryotic release factor 3a (eRF3a), a member of the eukaryotic peptide chain release factor family, is overexpressed in several types of cancer. This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer. METHODS: Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. RESULTS: eRF3a was significantly highly expressed in liver cancer cells, and its expression level was negatively correlated with the clinical prognosis of patients. In addition, in vitro experiments showed that eRF3a could promote the proliferation and migration of liver cancer cells through the ERK and JNK signaling pathways. CONCLUSION: This study suggests that eRF3a may be a potential prognostic marker for liver cancer and act as an oncogene by activating JNK and ERK signaling; therefore, eRF3a may be a new target for the treatment of liver cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Fatores de Terminação de Peptídeos/metabolismo , Linhagem Celular Tumoral , Humanos
6.
Curr Med Sci ; 41(5): 1012-1022, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34542829

RESUMO

OBJECTIVE: The present study was aimed to identify novel key genes, prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer. METHODS: The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes. Meanwhile, another microarray data GSE17536 was performed for weighted gene co-expression network analysis (WGCNA). RESULTS: In present study, 12 co-expressed gene modules associated with tumor progression were identified for further studies. The red module showed the highest association with pathological stage by Pearson's correlation analysis. Functional enrichment analysis revealed that genes in red module focused on cell division, cell proliferation, cell cycle and metabolic related pathway. Then, a total of 26 key hub genes were identified, and GEPIA database was subsequently selected for validation. Holliday junction-recognizing protein (HJURP) and cell division cycle 25 homolog C (CDC25C) were identified as effective prognosis biomarkers, which were all detrimental to prognosis. Gene set enrichment analyses (GSEA) found the two hub genes were enriched in "oocyte meiosis", "oocyte maturation that are progesterone-mediated", "p53 signaling pathway", and "cell cycle". Furthermore, the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue. CONCLUSION: HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA, which might influence the prognosis by regulating cell cycle pathways.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica/métodos , Fosfatases cdc25/genética , Estudos de Casos e Controles , Biologia Computacional , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Transdução de Sinais
7.
J Cancer ; 11(17): 5042-5055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742452

RESUMO

Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) is an important mitochondrial complex III subunit. This study investigated the role of UQCRC2 in gastric cancer (GC) and its upstream regulatory microRNAs (miRNAs). UQCRC2 expression levels were lower in GC tissues than non-carcinoma tissues. Furthermore, UQCRC2 levels were negatively correlated with lymph node metastasis, relapse, and tumor grade. Bioinformatics analysis predicted UQCRC2 as the target gene for miR-370, and this was verified in luciferase reporter assays. MiR-370 levels were inversely correlated with UQCRC2 levels in GC. UQCRC2 overexpression suppressed GC cell migration and invasion in vitro and in vivo, whereas up-regulating miR-370 reversed these effects. Western blotting analysis showed that miR-370 targeted UQCRC2 and positively regulated the epithelial-mesenchymal transition (EMT) signaling pathway in GC cells. Therefore, the miR-370/UQCRC2 axis may regulate EMT signaling pathways to affect tumor proliferation and metastasis and is, thus, a potential target for GC treatment.

8.
Curr Med Sci ; 39(6): 978-983, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845230

RESUMO

This study aims to explore the expression of stanniocalcin 2 (STC2) gene in breast cancer and its clinical significance. Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March 2014 to October 2014 were enrolled in this study. All the tissues used in this experiment included 50 cases of breast cancer tissues and corresponding 50 cases of paracancer normal breast tissues with complete patients' information. The real-time quantitative polymerase chain reaction (qPCR) was applied to detect the expression of STC2 gene in 50 cases of breast cancer and paracancer normal breast tissues. The results showed that the expression level of STC2 gene in 50 cases of breast cancer tissues was significantly higher than that in paracancer normal breast tissues (P<0.001). The expression of STC2 gene was correlated with lymph node metastasis, distant metastasis, TNM stage and histological grade (P<0.001). The expression level of STC2 gene was significantly higher in breast cancer tissues with higher expression of Ki-67 (P<0.001). The expression level of STC2 gene was significantly higher in estrogen receptor (ER) positive breast cancer tissues than in ER negative ones (P<0.001). However, different groups of age, pathological type, tumor size, PR expression and human epidermal growth factor receptor-2 (HER2) expression did not show significant differences in STC2 expression (P>0.05). In conclusion, the abnormal overexpression of STC2 gene may play a role in the development and progression of breast cancer, and it can be used as an independent metastasis and prognostic factor of breast cancer. In addition, STC2 gene probably promotes the development and metastasis of breast cancer by interacting with estrogen and ER, and it may become a new direction for breast cancer endocrine therapy.


Assuntos
Neoplasias da Mama/patologia , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Regulação para Cima , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/metabolismo
9.
Sci Rep ; 9(1): 19575, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862965

RESUMO

Alzheimer's disease (AD) is a complex disorder influenced by both genetic and environmental components and has become a major public health issue throughout the world. Oxidative stress and inflammation play important roles in the evolution of those major pathological symptoms. Jatrorrhizine (JAT), a main component of a traditional Chinese herbal, coptidis rhizome, has been shown to have neuroprotective effects and we previously showed that it is also able to clear oxygen free radicals and reduce inflammatory responses. In this study, we demonstrated that JAT administration could alleviate the learning and memory deficits in AD. Furthermore, we also found that JAT treatment reduced the levels of Aß plaques in the cortex and hippocampus of APP/PS1 double-transgenic mice. Other studies suggest that there are gut microbiome alterations in AD. In order to explore the underlying mechanisms between gut microbiota and AD, DNA sequencing for 16s rDNA V3-V4 was performed in fecal samples from APP/PS1 transgenic mice and C57BL/6 wild-type (WT) mice. Our results indicated that APP/PS1 mice showed less Operational Taxonomic Units (OTUs) abundance in gut microbiota than WT mice and with different composition. Furthermore, JAT treatment enriched OTUs abundance and alpha diversity in APP/PS1 mice compared to WT mice. High dose of JAT treatment altered the abundance of some specific gut microbiota such as the most predominant phylum Firmicutes and Bacteroidetes in APP/PS1 mice. In conclusion, APP/PS1 mice display gut dysbiosis, and JAT treatment not only improved the memory deficits, but also regulated the abundance of the microbiota. This may provide a therapeutic way to balance the gut dysbiosis in AD patients.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Berberina/análogos & derivados , Microbioma Gastrointestinal/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Peptídeos beta-Amiloides/genética , Análise de Variância , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Berberina/uso terapêutico , DNA Ribossômico/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Amiloide/metabolismo
10.
Pharmacology ; 103(5-6): 263-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30783055

RESUMO

BACKGROUND: Crocetin is a carotenoid extracted from the traditional Chinese medical herb saffron. Previous studies have demonstrated that crocetin possesses anticancer properties that are effective against various cancers. As an extension of our earlier study, the present study explored the underlying mechanisms in crocetin's anticancer effect on KYSE-150 cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), Mitogen-activated protein kinases (MAPK), and p53/p21 signal pathways play an important role in carcinogenesis, progression, and metastasis of carcinoma cells. Thus, we investigated crocetin's effects on the PI3K/AKT, MAPK, and p53/p21 pathways in esophageal squamous carcinoma cell line KYSE-150 cells. METHODS: KYSE-150 cells were treated with various concentrations of crocetin. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide assay, Annexin V/PI stain as well as Rh123 stain were used to evaluate the cell viability, apoptosis, and MMP. Western blot was used to detect the expression of PI3K, AKT, ERK1/2, p38, c-Jun NH-terminal kinase (JNK), P53, P21, Bcl-2, Bax, and cleaved caspase-3, which were associated with cell proliferation and apoptosis. RESULTS: Our results showed that crocetin significantly inhibited the proliferation of KYSE-150 cells in a dose- and time-dependent manner. Crocetin also markedly induced cell apoptosis. Furthermore, we have found that crocetin not only inhibited the activation of PI3K/AKT, extracellular signal-regulated kinase-1/2 (ERK1/2), and p38 but also upregulated the p53/p21 level. These regulations ultimately triggered the mitochondrial-mediated apoptosis pathway with an eventual disruption of MMP, increased levels of Bax and cleaved caspase-3, and decreased levels of Bcl-2. CONCLUSIONS: These findings suggested that crocetin interfered with multiple signal pathways in KYSE-150 cells. Therefore, this study suggested that crocetin could potentially be used as a therapeutic candidate for the treatment of esophageal cancer.


Assuntos
Anticarcinógenos/farmacologia , Carotenoides/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Anticarcinógenos/administração & dosagem , Apoptose/efeitos dos fármacos , Carotenoides/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Vitamina A/análogos & derivados
11.
Shanghai Kou Qiang Yi Xue ; 27(3): 270-274, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30411122

RESUMO

PURPOSE: This study was performed to investigate the changes of upper airway before and after functional correction in ClassⅡmalocclusion children with high mandibular plane angle at growth and development peak. METHODS: Cone-beam CT (CBCT) data of the upper airway were inputted into Minics 17.0 software for measurement of changes in the upper airway before and after functional treatment by high headgear-activator. The changes of upper airway before and after treatment were analyzed with SPSS22.0 software package. RESULTS: The change of the total volume of the upper airway, the volume of the velopharynx, glossopharynx, laryngopharynx; the sectional area of the tip of soft palate, roof of the epiglottis, the minimum sectional area of the oropharynx were significant (P<0.05). The upper airway morphology tended to be circular in the soft palate tip plane(P<0.05), but there was no significant difference in the plane of epiglottis(P>0.05). CONCLUSIONS: High headgear-activator corrected mandibular hypoplasia in children with increased airway volume, increased ventilation, improved respiratory function to prevent occurrence of obstructive sleep apnea hypopnea syndrome after adult.


Assuntos
Palato Mole , Faringe , Apneia Obstrutiva do Sono , Adulto , Criança , Tomografia Computadorizada de Feixe Cônico , Humanos , Orofaringe , Palato Mole/anatomia & histologia , Palato Mole/diagnóstico por imagem , Apneia Obstrutiva do Sono/diagnóstico por imagem
12.
Shanghai Kou Qiang Yi Xue ; 27(2): 117-122, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30146635

RESUMO

PURPOSE: To evaluate the biomechanical effect of arch wire deformation, height of micro-implant and lever-arm on movement of the maxillary anterior teeth in the lingual retraction force system. METHODS: Nonlinear 3-D finite element model of lingual orthodontic force system with micro-implant was constructed. When the arch-wire was set to be flexible body and rigid body, lingual retraction force system using sliding mechanism, the height of micro-implant and lever-arm was 0, 3, 5, 7 mm to alveolar ridge crest of the middle point of maxillary second premolars and maxillary first molars. The initial movement and hydrostatic pressure of anterior teeth were calculated. RESULTS: In the lingual retraction force system with micro-implant using sliding mechanism, when the wire was set to be flexible body, retroclination primary displacements of maxillary anterior teeth were found because of wire deformation. The maxillary lateral incisor's primary displacement became larger with the height of micro-implant increased. When the wire was set to be rigid body, the teeth tended to be slightly tipping, and with the increase of height of micro-implant, the change of movement tendency was not obvious. High value of periodontal ligament hydrostatic pressure was observed in the lingual retraction force system of maxillary anterior teeth with micro-implant when the wire was flexible, exceeding the capillary pressure. When the wire was rigid, the value of periodontal ligament hydrostatic pressure was small within the upper limit value of capillary pressure. CONCLUSIONS: Deformation of wire has a great influence on initial teeth movement and periodontal hydrostatic pressure. In clinic, using more rigid wire and reducing the initial force may reduce the risk of orthodontic root absorption.


Assuntos
Análise de Elementos Finitos , Procedimentos de Ancoragem Ortodôntica , Técnicas de Movimentação Dentária , Dente Pré-Molar , Incisivo , Maxila , Dente Molar
13.
Shanghai Kou Qiang Yi Xue ; 27(2): 150-155, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30146641

RESUMO

PURPOSE: The aim of this clinical study was to evaluate the changes of alveolar bone morphology before and after upper incisors retraction with mini implant anchorage using cone-beam CT (CBCT). METHODS: Twenty-two young patients with dentoalveolar maxillary protrusion and extraction of 2 maxillary first premolars were evaluated with CBCT. CBCT scans were obtained before treatment and 3 months after retraction of the incisors. The movement patterns of the upper incisors were assessed with Mimics15.0. The labial and palatal alveolar plates at crest level, midroot level, and apical level for bone-thickness changes and labial and palatal vertical bone level during retraction of the maxillary anterior segments were assessed with Invivo5.0. Paired t tests were used to evaluate the changes. RESULTS: The edge of the maxillary incisor and the root apex appeared lingual movement horizontally, but the moving distance was larger than the root apex. The edge of the incisors was moved downward, and the root apex was moved upward obviously. The palatal thickness and total thickness of the alveolar bone showed significant decrease at the crest level and midroot level after retraction while the apical level showed significant increase(P<0.05). The palatal vertical bone level also showed great loss (P<0.05). CONCLUSIONS: After extensive retraction of the maxillary incisors, tilt movements are controlled with high traction hooks and microscrew implants. The decreases in palatal bone thickness are much more significant compared with the increases in labial bone thickness. Alveolar bone remodeling doesn't follow the movement of tooth, suggesting that the limitation of anterior teeth retraction should be taken into consideration.


Assuntos
Incisivo , Maxila , Técnicas de Movimentação Dentária , Dente Pré-Molar , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila/diagnóstico por imagem
14.
Int J Mol Med ; 41(2): 1138-1146, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207020

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by aberrant tau protein hyperphosphorylation, which eventually leads to the formation of neurofibrillary tangles. Hyperphosphorylated tau protein is considered as a vital factor in the development of AD and is highly associated with cognitive impairment. Therefore, it is recognized to be a potential therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound. In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced tau protein hyperphosphorylation in HT22 cells was explored. Western blotting results indicated that QUE significantly attenuated OA­induced tau protein hyperphosphorylation at the Ser396, Ser199, Thr231 and Thr205 sites. Further experiments demonstrated that QUE inhibited the activity of cyclin­dependent kinase 5 (CDK5), a key enzyme in the regulation of tau protein, and blocked the Ca2+­calpain­p25­CDK5 signaling pathway. These observations indicate the ability of QUE to decrease tau protein hyperphosphorylation and thereby attenuate the associated neuropathology. In conclusion, these results support the potential of QUE as a therapeutic agent for AD and other neurodegenerative tauopathies.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Quercetina/administração & dosagem , Proteínas tau/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Cálcio/metabolismo , Calpaína/genética , Calpaína/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ácido Okadáico/toxicidade , Fosforilação/efeitos dos fármacos , Proteínas tau/genética
15.
Shanghai Kou Qiang Yi Xue ; 26(4): 414-418, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29199337

RESUMO

PURPOSE: To study the aesthetic appearance of skeletal Class Ⅱ patients with maxillary protrusion and mandibular retrusion treated with different methods. METHODS: The facial profile photographs and lateral cephalometric radiographs of a Chinese woman suffering from skeletal Class Ⅱ with maxillary protrusion and mandibular retrusion was digitized.The digital images were modified to obtain orthodontic compensatory treatment, genioplasty with different advancement ranges and orthognathic treatment comprising 6 profiles by Photoshop software,orthodontic professionals and non-professionals were chosen to score the pictures. Post hoc tests were done with ANONA and the Student Keuls method to analyze the data Using SPSS22.0 software package. RESULTS: The profile with the highest score was the picture treated by orthognathic and orthodontic treatment. The profile with genioplasty (advancement of 4 mm) took the second place. When the advancement distance of genioplasty was 8 mm, the score was under the score of orthodontic compensatory treatment profile. CONCLUSIONS: Orthognathic-orthodontic treatment of skeletal Class Ⅱ is still the best treatment option to improve facial aesthetics. Genioplasty, as a adjuvant treatment, improves the appearance based on compensatory orthodontic treatment to some extent, but not comparable to orthognathic-orthodontic treatment.


Assuntos
Estética Dentária , Mentoplastia , Cefalometria , Feminino , Humanos , Maxila , Retrognatismo/cirurgia , Resultado do Tratamento
16.
Cancer Cell Int ; 17: 98, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093644

RESUMO

BACKGROUND: More than 400,000 patients die from esophageal cancer annually. Considerable efforts have been made to develop new and effective treatments, one of which is directed toward herbal medication. Crocetin is a natural carotenoid dicarboxylic acid isolated from the Chinese herb saffron. We recently reported on the anticancer effects of saffron. This study aimed to determine whether crocetin combined cisplatin has synergistic effect in KYSE-150 cells and explore the underlying mechanism. METHODS: KYSE-150 cells were treated with crocetin and/or cisplatin. The effects on cell viability, cell apoptosis, mitochondrial membrane potential (MMP), as well as the expression levels of PI3K/AKT, MAPKs, p53/p21, and apoptosis-related protein were evaluated. MTT assay, Annexin V-FITC/PI staining, Rh123 staining, and Western blot analysis were used. RESULTS: The cell proliferation significantly decreased and cell apoptosis was induced with combined crocetin and cisplatin, compared with either crocetin only or cisplatin only. The outcome suggested that crocetin combined cisplatin has synergistic effects on inhibition of cell proliferation and pro-apoptotic effect of cisplatin on KYSE-150 cells. Disruption of MMP, upregulation of cleaved caspase-3 expression, and downregulation of Bcl-2 occurred in the group treated with combined treatment. No significant differences in p-PI3K, p-AKT, and MAPKs activity were indicated between combined treatment group and the individual treatment group. However, the expression levels of p53 and p21 were markedly higher in the combined treatment group than in the individual treatment group. The wild-type p53 inhibitor, PFT-α suppressed the overexpression of p53/p21 and the synergistic effect induced by the combination of crocetin and cisplatin. CONCLUSIONS: We concluded that crocetin combined with cisplatin exerts a synergistic anticancer effect by up-regulating the p53/p21 pathway.

17.
CNS Neurol Disord Drug Targets ; 16(5): 617-623, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27401065

RESUMO

OBJECTIVES: This study investigated the neuroprotective effects of Jatrorrhizine in rat cortical neurons. METHOD: The effects of Jatrorrhizine on hydrogen peroxide (H2O2)-induced cell lesion, levels of lipid peroxidation and antioxidant enzyme activities were investigated in rat cortical neurons. Levels of mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) were measured by fluorescent rhodamine staining and 2',7'-dichlorfluorescein-diacetate staining, respectively. ATP content was measured by a high performance liquid chromatography. The protein levels for Bax, Bcl2 and cleaved caspase-3 were analyzed by western blot protein expression. RESULTS: There was a significant reduction in cell viability and activities of Superoxide dismutase and glutathione peroxidase for the cortical neurons after exposure to 50µM H2O2 for 12h. The hydrogen peroxide increased the production of malondialdehyde and ROS but decreased MMP and ATP in the neurons. However, pretreatment with different concentrations of Jatrorrhizine (5-20µM) inhibited H2O2-induced neurotoxicity markedly. Jatrorrhizine also attenuated the H2O2-induced Bcl-2/Bax ratio reduction and caspase-3 activation in these neurons. CONCLUSIONS: Our findings suggest that Jatrorrhizine plays a critical neuroprotective role in H2O2 - induced apoptosis through its anti-oxidative actions. This may allow Jatrorrhizine to be a novel therapeutic with its high bioavailability to treat Alzheimer's disease.


Assuntos
Antioxidantes/farmacologia , Berberina/análogos & derivados , Córtex Cerebral/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Berberina/farmacologia , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
18.
PLoS One ; 11(4): e0152371, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27050422

RESUMO

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3ß (PI3K/Akt/GSK3ß) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3ß, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.


Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Neurônios/efeitos dos fármacos , Ácido Okadáico/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Animais , Linhagem Celular , Glutationa Peroxidase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/citologia , Hipocampo/enzimologia , Camundongos , Neurônios/enzimologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Proteínas tau/metabolismo
19.
CNS Neurol Disord Drug Targets ; 14(10): 1334-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26295822

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposit of amyloid plaques and neurofibrillary tangles and oxidative stress plays an essential role in the pathogenesis of AD. Jatrorrhizine (JAT), a Coptidis Rhizome, has multiple biological functions such as anti-oxidation and anti-inflammation. Herein, we investigated the neuroprotective effects of JAT on okadaic acid (OA)- induced cytotoxicity and apoptosis in HT22 cells. Following the exposure to 80 nmol/L OA for 12h, the reduction in cell survival, activities of superoxide dismutase, glutathione peroxidase and mitochondria membrane potential has been shown in HT22 cells. In contrast, OA increased levels of lactate dehydrogenase, malondialdehyde production and intracellular reactive oxygen species. OA also enhanced the expression of Bax but decreased the levels of Bcl-2, OA also upregulated the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinases 1/2, phosphorylated c-Jun N-terminal kinases, phosphorylated p38 and NF-kappa B p65 subunit in HT22 cells and this up-regulation was attenuated by JAT which was pre-incubated for 12h in the cells prior to OA exposure. In conclusion, our data present the protective role of JAT in OA induced cytotoxicity, via its antioxidant and anti-apoptotic properties by inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. These results indicate that JAT may be the potential target to treat AD induced by oxidative stress and apoptosis.


Assuntos
Berberina/análogos & derivados , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ácido Okadáico/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Berberina/química , Berberina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Hipocampo/fisiopatologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Neurônios/fisiologia , Fármacos Neuroprotetores/química , Estresse Oxidativo/fisiologia
20.
Oncol Lett ; 9(3): 1254-1260, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25663893

RESUMO

Crocetin is the main pharmacologically-active component of saffron and has been considered as a promising candidate for cancer chemoprevention. The purpose of the present study was to investigate the anticancer effects of crocetin and the possible mechanisms of these properties in the esophageal squamous cell carcinoma cell line KYSE-150. The KYSE-150 cells were cultured in Dulbecco's modified Eagle's medium and incubated with 0, 12.5, 25, 50, 100 or 200 µmol/l crocetin for 48 h. Cell proliferation was measured using an MTT assay. Hoechst 33258 staining and observation under fluorescent microscopy were used to analyze the proapoptotic effects of crocetin. The migration rate was assessed by a wound-healing assay. The cell cycle distribution was analyzed using flow cytometry analysis subsequent to propidium iodide staining. The expression of B-cell lymphoma-2-associated X protein (Bax) and cleaved caspase 3 was determined by western blot analysis. It was found that treatment of KYSE-150 cells with crocetin for 48 h significantly inhibited the proliferation of the cells in a concentration-dependent manner, and the inhibition of proliferation was associated with S phase arrest. Crocetin was also found to induce morphological changes and cell apoptosis in a dose-dependent manner through increased expression of proapoptotic Bax and activated caspase 3. In addition, crocetin suppressed the migration of KYSE-150 cells. The present study provides evidence that crocetin exerts a prominent chemopreventive effect against esophageal cancer through the inhibition of cell proliferation, migration and induction of apoptosis. These findings reveal that crocetin may be considered to be a promising future chemotherapeutic agent for esophageal cancer therapy.

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