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1.
J Bone Miner Metab ; 40(4): 581-593, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35648221

RESUMO

INTRODUCTION: Osteosarcoma (OS) is the most aggressive malignancy among the bone tumors in the world. Circular RNAs (circRNAs) have been reported to be participated in multiple cancers, including OS. Meanwhile, circPVT1 has been proved to be upregulated in OS. However, the mechanism by which circPVT1 mediates the tumorigenesis of OS remains to be further explored. MATERIALS AND METHODS: Protein and gene expressions in OS cells were measured by western blot and RT-qPCR, respectively. Cell growth was assessed by flow cytometry and colony formation, respectively. In addition, cell migration was assessed by wound healing, and invasion was evaluated by Transwell assay. Meanwhile, the correlation among circPVT1, miR-26b-5p and CCNB1 was explored by RNA pull-down and dual luciferase assay. Finally, in vivo model was established to explore the role of circPVT1 in OS in vivo. RESULTS: CircPVT1 and CCNB1 were significantly upregulated in OS cells, while miR-26b-5p was downregulated. Knockdown of circPVT1 notably inhibited proliferation and induced apoptosis of OS cells. CircPVT1 shRNA significantly suppressed the OS cell invasion and migration. Meanwhile, circPVT1 sponged miR-26b-5p and CCNB1 was found to be the direct target of miR-26b-5p. Furthermore, silencing of circPVT1 inhibited the growth and metastasis of OS in vivo. CONCLUSION: Silencing of circPVT1 notably suppressed the tumorigenesis and metastasis of OS via miR-26b-5p/CCNB1 axis. Therefore, circPVT1 might be used as a target for OS treatment.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Neoplasias Ósseas/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina B1/genética , Ciclina B1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia
2.
Support Care Cancer ; 29(12): 7315-7322, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34046726

RESUMO

PURPOSE: This study aims to explore the characteristics and related factors of insomnia of patients after operation for gastric cancer. METHODS: A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer-related information, sleep quality, and other symptoms were investigated. RESULTS: ① The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11-15 points, and the sleep quality rating was "poor". ② The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue, and depression. ③ The probability of reduced sleep quality with the number of chemotherapy cycles >6 is 3.640 times that of ≤6. The probability of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. CONCLUSION: Attention to related factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Neoplasias Gástricas , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Fadiga , Humanos , Sono , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia
3.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2766-2772, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296574

RESUMO

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.

4.
J Cell Mol Med ; 24(19): 11524-11534, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32862562

RESUMO

Bone fracture is one of the most common injuries. Despite the high regenerative capacity of bones, failure of healing still occurs to near 10% of the patients. Herein, we aim to investigate the modulatory role of neurofibromatosis type I gene (NF1) to osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and new bone formation after fracture in a rat model. We studied the NF1 gene expression in normal and non-union bone fracture models. Then, we evaluated how NF1 overexpression modulated osteogenic differentiation of BMSCs, autophagy activity, mTORC1 signalling and osteoclastic bone resorption by qRT-PCR, Western blot and immunostaining assays. Finally, we injected lentivirus-NF1 (Lv-NF1) to rat non-union bone fracture model and analysed the bone formation process. The NF1 gene expression was significantly down-regulated in non-union bone fracture group, indicating NF1 is critical in bone healing process. In the NF1 overexpressing BMSCs, autophagy activity and osteogenic differentiation were significantly enhanced. Meanwhile, the NF1 overexpression inhibited mTORC1 signalling and osteoclastic bone resorption. In rat non-union bone fracture model, the NF1 overexpression significantly promoted bone formation during fracture healing. In summary, we proved the NF1 gene is critical in non-union bone healing, and NF1 overexpression promoted new bone formation after fracture by enhancing autophagy and inhibiting mTORC1 signalling. Our results may provide a novel therapeutic clue of promoting bone fracture healing.


Assuntos
Autofagia/genética , Fraturas Ósseas/genética , Fraturas Ósseas/patologia , Genes da Neurofibromatose 1 , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Osteogênese/genética , Transdução de Sinais , Animais , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Diferenciação Celular/genética , Modelos Animais de Doenças , Consolidação da Fratura/genética , Fraturas não Consolidadas/genética , Fraturas não Consolidadas/patologia , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Ratos Sprague-Dawley
6.
Int J Legal Med ; 131(3): 885-894, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28058571

RESUMO

Preadult development of necrophagous flies is commonly recognized as an accurate method for estimating the minimum postmortem interval (PMImin). However, once the PMImin exceeds the duration of preadult development, the method is less accurate. Recently, fly puparial hydrocarbons were found to significantly change with weathering time in the field, indicating their potential use for PMImin estimates. However, additional studies are required to demonstrate how the weathering varies among species. In this study, the puparia of Chrysomya rufifacies were placed in the field to experience natural weathering to characterize hydrocarbon composition change over time. We found that weathering of the puparial hydrocarbons was regular and highly predictable in the field. For most of the hydrocarbons, the abundance decreased significantly and could be modeled using a modified exponent function. In addition, the weathering rate was significantly correlated with the hydrocarbon classes. The weathering rate of 2-methyl alkanes was significantly lower than that of alkenes and internal methyl alkanes, and alkenes were higher than the other two classes. For mono-methyl alkanes, the rate was significantly and positively associated with carbon chain length and branch position. These results indicate that puparial hydrocarbon weathering is highly predictable and can be used for estimating long-term PMImin.


Assuntos
Dípteros/química , Hidrocarbonetos/análise , Mudanças Depois da Morte , Pupa/química , Animais , Restos Mortais , Entomologia , Comportamento Alimentar , Ciências Forenses/métodos , Cromatografia Gasosa-Espectrometria de Massas , Tempo (Meteorologia)
7.
Tumour Biol ; 37(10): 14165-14171, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27542674

RESUMO

Acquired evidence indicated that microRNAs (miRNAs) played essential roles in cancer development, including hepatocellular carcinoma (HCC). Functions and mechanisms of miRNAs involved in HCC remain largely unknown. Here, we found that miR-384 was significantly downregulated in HCC cells and tissues by RT-PCR. Gain and loss of function studies revealed that miR-384 significantly suppressed HCC cell proliferation. Insulin receptor substrate 1(IRS1) was identified as a direct and functional target of miR-384. Moreover, miR-384 decreased IRS1 expression, subsequently downregulating cyclin D1 and upregulating p21 and p-Rb expression. In addition, promotion of cell proliferation caused by miR-384-in was counteracted by silencing IRS1 expression with siRNAs. Taken together, our data provided convincing evidence that miR-384 exerted suppressive effect on HCC cell proliferation through the direct inhibition of IRS1 expression, suggesting miR-384 may serve as a potential therapeutic target for HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Apoptose , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas
8.
Pharmacology ; 97(5-6): 218-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26872133

RESUMO

The aim of this study was to assess the influence of evodiamine on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1 week with evodiamine or physiological saline (control group) by oral administration, probe drugs phenacetin (5.0 mg/kg; CYP1A2 activity), tolbutamide (1.0 mg/kg; CYP2C9 activity), omeprazole (10 mg/kg; CYP2C19 activity), metoprolol (20 mg/kg; CYP2D6 activity) and midazolam (10 mg/kg; CYP3A4 activity) were administered to rats by oral administration. The blood was then collected at different times for ultra-performance liquid chromatography-tandem mass spectrometry analysis. The data showed that evodiamine exhibits an inhibitory effect on CYP1A2, CYP2C9 and CYP2D6 by increasing t(1/2), Cmax and AUC(0-∞), and decreasing CL/F compared with those of the control group. However, no significant changes in CYP2C19 and CYP3A4 activities were observed. In conclusion, the results indicated that evodiamine could inhibit CYP1A2, CYP2C9 and CYP2D6, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related herb-drug interactions in the clinic.


Assuntos
Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Ervas-Drogas , Quinazolinas/farmacologia , Administração Oral , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metoprolol/sangue , Metoprolol/farmacocinética , Midazolam/sangue , Midazolam/farmacocinética , Omeprazol/sangue , Omeprazol/farmacocinética , Fenacetina/sangue , Fenacetina/farmacocinética , Ratos Sprague-Dawley , Tolbutamida/sangue , Tolbutamida/farmacocinética
9.
BMC Musculoskelet Disord ; 17(1): 443, 2016 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-27770774

RESUMO

BACKGROUND: The purpose of this study was to investigate the initial union rate, refracture rate and residual deformities of congenital pseudarthrosis of the tibia (CPT), using combined surgery including pseudarthrosis resection, intramedullary rodding, autogenous iliac bone grafting and Ilizarov's fixator, with a mean 5.2 years follow-up. METHODS: We retrospectively reviewed the records and diagrams of patients with Crawford type IV congenital pseudarthrosis of the tibia between February 2007 and March 2010. Patients managed by pseudarthrosis resection, intramedullary rod of the tibia, wrapping autogenous iliac bone grafting and Ilizarov's fixator were enrolled. We evaluated the bone union rate, tibial alignment, limb length discrepancy (LLD), valgus deformity of the ankle and the frequencies of refracture during period of follow-up. RESULTS: There were 56 cases enrolled in the study, with a mean follow-up 5.2 years (range, 3 to 6.7 years). The mean age of the patients at surgery was 3.5 years (range, 1.5 to 12.4 years). Fifty (89.2 %) of the 56 patients had primary bone union at site of pseudarthrosis, while 5 obtained union after second surgery and 1 failed. The average time spent to obtain pseudarthrosis initial union was 4.5 months (range, 3.0 to 10.0 months) and mean duration of Ilizarov treatment was 4.7 months (range, 3.2 to 10.4 months). Eleven (19.6 %) patients had proximal tibial valgus with a mean angle of 9.5° (range, 5 to 24°), while 10 (17.9 %) patients had ankle valgus deformities with a mean of 12.3° (range, 6 to 21°). Sixteen (28.6 %) patients had an average 2.2 cm LLD (range, 1.5-4.2 cm). Of the 50 cases who obtained initial bone union of pseudarthrosis, 13 (26.0 %) had refracture which need cast immobilization or secondary surgery. CONCLUSIONS: This combined surgery obtained initial union rate of 89.2 % at primary surgery while the refracture rate is 26.0 %. However, residual deformities such as proximal tibial valgus, LLD and ankle valgus were also existed which should be pay more attention to and dealt with. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov under the name "The Effect of Combined Surgery in Management of Congenital Pseudarthrosis of Tibia" ( NCT02640040 ), which was released on August 31, 2015.


Assuntos
Transplante Ósseo/métodos , Fixação Intramedular de Fraturas/métodos , Técnica de Ilizarov , Pseudoartrose/congênito , Fraturas da Tíbia/cirurgia , Moldes Cirúrgicos , Criança , Pré-Escolar , Feminino , Seguimentos , Fixação Intramedular de Fraturas/instrumentação , Humanos , Ílio/transplante , Lactente , Fixadores Internos , Masculino , Pseudoartrose/diagnóstico por imagem , Pseudoartrose/cirurgia , Radiografia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Transplante Autólogo/métodos
10.
Drug Metab Dispos ; 43(4): 561-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25614704

RESUMO

Our previous study detected totally 35 CYP2C9 allelic variants in 2127 Chinese subjects, of whom 21 novel alleles were reported for the first time in Chinese populations. The aim of the present study was to characterize the 13 CYP2C9 allelic variants both in vitro and in vivo. Different types of CYP2C9 variants were highly expressed in COS-7 cells, and 50 µM tolbutamide was added as the probing substrate to evaluate their metabolic abilities in vitro. Subsequently, the concentrations of tolbutamide and its metabolite in the plasma and urine within individuals with different types of genotypes were determined by HPLC to evaluate the catalytic activity of the 13 mutant CYP2C9 proteins in vivo. Our results showed that compared with *1/*1 wild-type subjects, subjects with *1/*40 genotype showed increased oral clearance (CL/F), whereas individuals with *1/*3, *1/*13, *3/*3, *3/*13, *1/*16, *1/*19, *1/*34, *1/*42, *1/*45, *1/*46, and *1/*48 genotype exhibited significantly decreased CL/F, and those with *1/*27, *1/*29, *1/*40, and *1/*41 genotype presented similar CL/F value. When expressed in COS-7 cells, the CYP2C9 variants showed similar pattern to the results in clinical study. The study suggests that, besides two typical defective alleles, *3 and *13, seven CYP2C9 allelic variants (*16, *19, *34, *42, *45, *46, and *48) cause defective effects on the enzymatic activities both in vitro and in vivo. In clinic, patients with these defective alleles should be paid close attention to.


Assuntos
Alelos , Povo Asiático/genética , Citocromo P-450 CYP2C9/genética , Frequência do Gene , Variação Genética , Animais , Área Sob a Curva , Células COS , Chlorocebus aethiops , Cromatografia Líquida de Alta Pressão , Frequência do Gene/genética , Genética Populacional , Genótipo , Humanos , Plasmídeos , Tolbutamida/sangue , Tolbutamida/urina , Transfecção
11.
Hepatol Res ; 45(2): 201-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24655315

RESUMO

AIM: Although perioperative short-term administration of steroids can attenuate surgical stress response following liver resection, there is no consensus concerning the effect on postoperative complications. This study aims to use meta-analysis to quantitatively investigate the effect of perioperative short-term administration of steroids on postoperative complications following liver resection. METHODS: A systematic published work search was performed to detect randomized controlled trials (RCT) assessing the effect of perioperative short-term administration of steroids on outcomes following liver resection. Parameters of surgical stress, hospital stay and postoperative complications were analyzed. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan version 5 and meta-analyses were performed using a random-effects model. RESULTS: Five RCT published between 2001 and 2011 containing a total of 379 patients were eligible for final analysis. Serum total bilirubin, interleukin-6 and C-reactive protein were significantly lower in the steroid than in the control group on postoperative day 1 (P = 0.02, 0.004 and 0.02, respectively). There was no difference in duration of hospital stay between the steroid and control group (P = 0.37). The analysis of end-points including infective complications (odds ratio [OR], 0.95), wound complications (OR, 0.67), bile leakage (OR, 0.58) and overall complications (OR, 0.50) revealed no difference between steroid administration and no treatment. There was no postoperative death or adverse effect attributable to steroid treatment in all patients. CONCLUSION: On currently available evidence, short-term administration of steroids does not increase incidence of complications in patients undergoing liver resection.

12.
BMC Musculoskelet Disord ; 16: 216, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26293924

RESUMO

BACKGROUND: The purpose of our retrospective study was to evaluate the preliminary result of distraction osteogenesis in patient with tibial shortening after initial union of Congenital Pseudarthrosis of the Tibia (CPT). METHODS: All the CPT cases with tibial shortening after initial union managed by proximal tibial lengthening using Ilizarov technique were identified. All the patient charts and radiograms were reviewed. RESULTS: Between March 2007 and January 2012, 11 CPT cases were included with an average follow-up of 41 months (range, 34-51 months). The mean age at surgery was 8.5 years (range, 3.9-14.5y). The average length of discrepancy was 5.6 cm (range, 2.0-8.2 cm). Eight (8) cases had radiological findings of proximal tibial dysplasia, while the other 3 cases had not. The average distraction length gained was 5.3 cm (range, 3.5-8.0 cm) with a mean elongation rate of 21.4% (range, 15-30%). The Healing Index (HI) was 63.1 d/cm (range, 47-77 d/cm). In the 8 patients with proximal tibial dysplasia, 5 cases had lateral callus, 3 had central callus, and poor bone regeneration was observed in all of them with an average HI of 67 d/cm. In the other 3 patients without proximal tibial dysplasia, concave shaped callus was identified with an average HI of 52.7 d/cm. None of the patients had re-fracture, nonunion, axis deviation or angulation of the distraction area. Ankle joint stiffness was found in 2 of the patients. No evidence of knee contracture was detected. There were 5 cases with pin-tract infection which was managed by pin-tract nurse and oral administration of antibiotics. CONCLUSIONS: We concluded that proximal tibial lengthening after initial union of CPT was effective for management of tibial shortening, however it was characterized by poor bone regeneration with different types of callus from normal, greater healing index and prolonged fixator wearing. We recommended that tibial lengthening could be considered when the limb length discrepancy (LLD) was more than 4 cm in younger children after primary union of CPT.


Assuntos
Desigualdade de Membros Inferiores/cirurgia , Osteogênese por Distração , Complicações Pós-Operatórias/cirurgia , Pseudoartrose/congênito , Tíbia/cirurgia , Adolescente , Fatores Etários , Regeneração Óssea , Calo Ósseo/patologia , Criança , Pré-Escolar , Contratura/etiologia , Contratura/prevenção & controle , Feminino , Humanos , Técnica de Ilizarov , Desigualdade de Membros Inferiores/etiologia , Masculino , Neurofibromatose 1/complicações , Aparelhos Ortopédicos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Pseudoartrose/etiologia , Pseudoartrose/cirurgia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/enfermagem , Tíbia/anormalidades
13.
Drug Dev Ind Pharm ; 41(9): 1512-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25250618

RESUMO

The present study aimed to investigate the effect of clopidogrel (CLO) on pharmacokinetics of ivabradine (IVA) and its metabolite in rats and develop a reliable method to determine IVA and its metabolite N-demethyl ivabradine in serum. Healthy male SD rats were randomized to be given 0.8 mg/kg IVA or IVA combined with 8 mg/kg CLO. Blood samples were collected at 0.083, 0.16, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after administration. The serum concentrations of IVA and N-demethyl ivabradine were determined by ultra-performance liquid chromatography-mass spectrometry and pharmacokinetic parameters were calculated using DASver3.0 software. The parameters of AUC(0 - t), AUC(0 - ∞), and Cmax for IVA in the group of IVA + CLO were significantly higher than those in the group of IVA (p < 0.01); the half-time (t1/2) in the IVA + CLO group was extended compared to IVA (p < 0.01) and CL/F was dropped obviously (p < 0.01). The decreases in AUC(0 - t), AUC(0 - ∞), and Cmax for N-demethyl ivabradine in the group of IVA + CLO was significantly compared to the group of IVA (p < 0.01). CL/F was higher than IVA (p < 0.01) and the t1/2 was slightly increased. In this study, we find that CLO restrains the metabolism of IVA into N-demethyl ivabradine, which may be related to its competitive inhibition effect on cytochrome P450 isoform 3A4(CYP3A4).


Assuntos
Benzazepinas/farmacocinética , Fármacos Cardiovasculares/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Clopidogrel , Citocromo P-450 CYP3A/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações Medicamentosas , Meia-Vida , Ivabradina , Masculino , Espectrometria de Massas , Ratos , Ratos Sprague-Dawley , Ticlopidina/farmacologia
14.
Arch Biochem Biophys ; 545: 162-6, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24495782

RESUMO

The pathogenesis of hepatic fibrosis is to be further investigated. Protease-activated receptor-2 (PAR2) plays a role in hepatic fibrosis. This study aims to elucidate the role of activation of PAR2 in the regulation of hepatic stellate cell activities. In this study, the expression of PAR2, Fas and caveolin-1 in human hepatic stellate cell line, HHStec cell (HHStecs) was assessed by real time RT-PCR and Western blot. The levels of collagen were determined by enzyme-linked immunosorbent assay. The PAR2 gene was silenced in HHStecs using RNA interference. Apoptosis of HHStecs was assessed by flow cytometry. The results showed that HHStecs expressed PAR2, which was up regulated by activation with phorbol myristate acetate (PMA). Activation of PAR2 increased the release of collagen from HHStecs. Exposure to PMA induced HHStec apoptosis, which was significantly inhibited by activation of PAR2. The PAR2 activation also suppressed the expression of caveolin-1 and Fas in HHStecs. Over expression of caveolin-1 in HHStecs blocked PAR2-reduced apoptosis. We conclude that HHStecs express PAR2. Activation of PAR2 increases HHStecs to release collagen and reduces the activation-induced HHStec apoptosis, which can be inhibited by the over expression of caveolin-1.


Assuntos
Apoptose , Colágeno/metabolismo , Células Estreladas do Fígado/metabolismo , Receptor PAR-2/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular , Ativação Enzimática , Expressão Gênica , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Receptor PAR-2/genética , Regulação para Cima
15.
World J Gastrointest Oncol ; 16(2): 300-313, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425402

RESUMO

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.

16.
Dig Dis Sci ; 58(12): 3503-15, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23979441

RESUMO

BACKGROUND: Intratumoral hypoxia and epithelial-mesenchymal transition are involved in tumor invasion and metastasis. AIMS: This study investigated the molecular mechanisms that relay the hypoxia signal into the epithelial-mesenchymal transition and metastasis. METHODS: Morphology analysis and tumor cell migration and invasion assays were performed to detect phenotypic changes of pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral HIF-1α shRNA transfection. Quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry were used to detect gene expression in pancreatic cancer cell lines and tissues or normal pancreatic tissues. Luciferase, gel shift, and ChIP assays were used to assess gene regulation. RESULTS: Under hypoxic conditions, these tumor cells underwent typical morphological and molecular changes to epithelial-mesenchymal transition. Moreover, Snail expression was induced by hypoxic conditions and was regulated by HIF-1α expression at the transcriptional level through HIF-1α-binding to the second site of hypoxia-responsive elements of the Snail gene promoter. In addition, Snail expression was associated with HIF-1α expression in pancreatic cancer tissues, and expression of both was associated with tumor metastasis and poor patient survival. CONCLUSIONS: Our study provides key evidence that HIF-1α and Snail are responsible for hypoxia-induced metastasis phenotypes in pancreatic cancer and that HIF-1α and Snail expression can be used as biomarkers to predict tumor metastasis and patient survival.


Assuntos
Carcinoma/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Hipóxia/metabolismo , Neoplasias Pancreáticas/metabolismo , Fatores de Transcrição/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fatores de Transcrição da Família Snail , Fatores de Transcrição/biossíntese
17.
J Cancer ; 13(2): 465-480, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35069895

RESUMO

Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust. Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma. Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

18.
Risk Manag Healthc Policy ; 15: 331-337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250319

RESUMO

AIM: To investigate the status of the family resilience score of caregivers of children with congenital pseudarthrosis of the tibia (CPT) and analyse its influencing factors to provide a reference and basis for clinical formulation of a family resilience intervention programme. METHODS: A total of 379 families of children with CPT were included in this study, which used a combination questionnaire to investigate the families of children with CPT. The researchers sent a link to the questionnaire to all eligible subjects to conduct a survey on the characteristics of families of children with CPT. Single factor analysis was used to compare the total scores of family resilience. Multiple linear regression was used to determine meaningful variables for single factor analysis. RESULTS: The average family resilience score was 151.79 ± 30.79, the lowest score was 20 and the highest score was 231. The CPT usually occurred in unilateral limbs (37.63%). The payment methods of medical expenses were through a rural cooperative medical system (44.85%). The caregivers were mostly the mothers (62.80%) and caregivers were 31-40 years old (62.27%). Most caregivers were farmers (30.34%). The average monthly income of the families in the past year was 1000-5000 yuan (54.09%). There were significant differences in family resilience scores between caregivers' working conditions (P = 0.039) and average monthly incomes in the past year (P = 0.008). The working conditions of caregivers and the average monthly income of families in the past year were the main factors affecting the family resilience of caregivers of children with CPT. CONCLUSION: The caregivers' working conditions and the average monthly income of families were the influencing factors in the family resilience score.

19.
Rev Assoc Med Bras (1992) ; 68(7): 893-897, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35946764

RESUMO

OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.


Assuntos
Comportamento Problema , Pseudoartrose , Ansiedade , Criança , Humanos , Pseudoartrose/congênito , Tíbia
20.
Dig Dis Sci ; 56(4): 1090-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20927591

RESUMO

BACKGROUND: CD151, c-Met, and integrin alpha3/alpha6 are all involved in the hepatocyte growth factor (HGF)/c-Met signal pathway, which plays an important role in the malignant progression of tumors. AIMS: The purpose of this study was to explore the expression and prognostic significance of these proteins in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used immunohistochemical methods to investigate the expression patterns of CD151, c-Met, and integrin alpha3/alpha6proteins in 71 patients with PDAC and in ten samples of normal pancreatic tissue. We also assessed correlations between these proteins and clinicopathological parameters and survival of PDAC patients using various statistical methods. RESULTS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met overexpressions were significantly associated with TNM stage (p=0.001 and p=0.038, respectively) and lymph node invasion (p=0.000, p=0.012, respectively). A significant positive linear correlation was found between CD151 and c-Met (r=0.583; p=0.000), integrin alpha3 (r=0.457; p=0.000), and integrin alpha6 (r=0.671; p=0.000). Overexpression of CD151, c-Met, integrin alpha3, or integrin alpha6 was related to poor survival of PDAC patients (p=0.000, p=0.000, p=0.005, and p=0.003, respectively), and CD151 and c-Met were independent factors in prognosis of PDAC. CONCLUSIONS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met might be new molecular markers to predict the prognosis of PDAC patients.


Assuntos
Antígenos CD/biossíntese , Carcinoma Ductal Pancreático/diagnóstico , Integrina alfa3/biossíntese , Integrina alfa6/biossíntese , Neoplasias Pancreáticas/diagnóstico , Proteínas Proto-Oncogênicas c-met/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Tetraspanina 24
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