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1.
BMC Nurs ; 23(1): 659, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285272

RESUMO

BACKGROUND: Clinical nurses face high-pressure situations requiring rapid decision-making and skilled intervention, impacting their psychological responses and emergency capabilities. Understanding the relationships between psychological factors like gratitude and meaning in life is crucial for improving nurses' performance in emergencies. This study explores the mediating role of gratitude and meaning in life in the impact of psychological responses on clinical nurses' emergency capabilities, aiming to enhance their effectiveness in such situations. METHODS: This study is a multi-center cross-sectional survey. A questionnaire survey was conducted among 1833 clinical nurses in five tertiary hospitals in Anhui Province, China including general information questionnaire, nurses' emergency capability scale, Meaning in life scale, Gratitude scale and Psychological response questionnaire. According to the results of the questionnaire survey, a chain mediating model was constructed and tested. RESULTS: The total score of emergency capability of 1833 clinical nurses was (71.65 ± 10.77), the total score of meaning in life was (50.67 ± 9.04), the total score of gratitude was (30.96 ± 3.57), and the total score of psychological response was 13.00 (6.00, 20.00). The emergency capability of subjects was positively correlated with the meaning in life, the total score of gratitude scale and the scores of each dimension of the two scales, and negatively correlated with the total score of psychological response scale and each dimension of this scale (all P < 0.05). The total effect coefficient, direct effect coefficient and indirect effect coefficient of psychological response on nurses' emergency capability are - 0.230, -0.110 and - 0.120 respectively, that is, the indirect effect accounts for 52.17% of the total effect. Among the indirect effects, the specific mediating effects of gratitude and meaning in life account for 22.50% and 62.50% respectively, and the chain mediating effects of gratitude and meaning in life account for 15.00%. CONCLUSION: Gratitude and meaning in life have multiple mediating roles in the mechanism of psychological response that affecting clinical nurses' emergency capability. Therefore, it is very important to pay attention to dynamically evaluating the psychological response level of clinical nurses, and strive to improve their gratitude and meaning in life, so as to further enhance their emergency response ability.

2.
Nutr J ; 23(1): 14, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38291391

RESUMO

BACKGROUND: The role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chinese girls. METHODS: In this case-control study, we enrolled 185 precocious puberty girls and 185 age-matched controls. Their dietary intake was assessed through a semi-quantitative food frequency questionnaire. Their sociodemographic and lifestyle data were collected. The associations between dietary intake and risk of precocious puberty were assessed by conditional logistic regression models. RESULTS: After multivariate adjustment, consuming a higher amount of red meat was associated with higher precocious puberty risk (OR = 2.74, 95% CI: 1.25-6.02), while a higher frequency of fruit ( P for trend = 0.024) and amount of vegetable intake was associated with a lower risk of precocious puberty (P for trend = 0.002). The high vegetable and protein dietary pattern was significantly negatively associated with precocious puberty (OR = 0.78, 95% CI: 0.63-0.97), whereas the high animal food and fruits dietary pattern was remarkably positively associated with precocious puberty (OR = 1.36, 95% CI: 1.09-1.69), after adjusting for age and body mass index. CONCLUSIONS: High vegetable and protein dietary pattern is a protective factor against precocious puberty, while high animal food and fruits dietary pattern is a risk factor for precocious puberty in Chinese girls. Attentions should be paid to a reasonable intake of red meat, eggs, and fruits in children's daily diet, increase their intake of vegetables, in order to reduce the risk of precocious puberty.


Assuntos
Padrões Dietéticos , Puberdade Precoce , Feminino , Animais , Criança , Humanos , Estudos de Casos e Controles , Puberdade Precoce/epidemiologia , Dieta , Fatores de Risco , Frutas , Verduras , China/epidemiologia
3.
Stem Cell Res ; 73: 103227, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37931536

RESUMO

Desmin (DES) is an important intermediate filament protein associated with the extrasarcomeric cytoskeleton and cellular function that was first reported to be associated with cardiac conduction disease and cardiomyopathy in 1998. We generated an induced pluripotent stem cell (iPSC) line from the left bundle branch block (LBBB) patient's peripheral blood mononuclear cells using Sendai virus-mediated reprogramming. The iPSCs exhibited stable amplification, expressed pluripotent markers, and spontaneously differentiated into three layers in vitro. Additionally, it showed a normal diploid karyotype and maintained the pathogenic mutation in DES. Hence, the iPSC line provided a platform for exploring LBBB mechanisms associated with DES mutations.


Assuntos
Células-Tronco Pluripotentes Induzidas , Criança , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Bloqueio de Ramo/metabolismo , Leucócitos Mononucleares/metabolismo , Diferenciação Celular/genética , Mutação , China
4.
MAbs ; 15(1): 2215364, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37229604

RESUMO

Aspartic acid (Asp) isomerization is a spontaneous non-enzymatic post-translation modification causing a change in the structure of the protein backbone, which is commonly observed in therapeutic antibodies during manufacturing and storage. The Asps in Asp-Gly (DG), Asp-Ser (DS), and Asp-Thr (DT) motifs in the structurally flexible regions, such as complementarity-determining regions (CDRs) in antibodies, are often found to have high rate of isomerization, and they are considered "hot spots" in antibodies. In contrast, the Asp-His (DH) motif is usually considered a silent spot with low isomerization propensity. However, in monoclonal antibody mAb-a, the isomerization rate of an Asp residue, Asp55, in the aspartic acid-histidine-lysine (DHK) motif present in CDRH2 was found to be unexpectedly high. By determining the conformation of DHK motif in the crystal structure of mAb-a, we found that the Cgamma of the Asp side chain carbonyl group and the back bone amide nitrogen of successor His were in proximal contact, which facilitates the formation of succinimide intermediate, and the +2 Lys played an important role in stabilizing such conformation. The contributing roles of the His and Lys residues in DHK motif were also verified using a series of synthetic peptides. This study identified a novel Asp isomerization hot spot, DHK, and the structural-based molecular mechanism was revealed. When 20% Asp55 isomerization in this DHK motif occurred in mAb-a, antigen binding activity reduced to 54%, but the pharmacokinetics in rat was not affected significantly. Although Asp isomerization of DHK motif in CDR does not appear to have a negative impact on PK, DHK motifs in the CDRs of antibody therapeutics should be removed, considering the high propensity of isomerization and impact on antibody activity and stability.


Assuntos
Ácido Aspártico , Peptídeos , Animais , Ratos , Isomerismo , Ácido Aspártico/química , Peptídeos/química , Regiões Determinantes de Complementaridade/química , Anticorpos Monoclonais/química
5.
Front Pediatr ; 10: 947963, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452351

RESUMO

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of -0.9211 and -0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.

6.
Molecules ; 27(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364285

RESUMO

The treatment of oilfield wastewater with high crude oil content and complex composition is a problem requiring considerable attention. In order to effectively remove crude oil contained in wastewater, in this work, rice straw, as an oil-absorbing material, was modified and used as a sorbent for crude oil. Rice straw was modified with alkali and cetyltrimethylammonium chloride (CTAC) by simple substitution reaction. The adsorption capacity of modified rice straw for oil was evaluated. The results illustrate that the adsorption rate of rice straw for crude oil was increased from 0.83 to 8.49 g/g, with the optimal conditions of 18% NaOH reacted for 90 min at 50 °C and 2% CTAC reacted for 60 min at 20 °C. The proposed modification method could be used for different materials to enhance the adsorption rate. The results of the contact angle test show that the modified straw changed from hydrophilic to hydrophobic, which may be the main reason for the improvement in the oil absorption rate. Finally, the surface structure of rice straw was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and N2 adsorption-desorption isotherms, which further confirmed the hydrophobicity of the modified rice straw.


Assuntos
Oryza , Petróleo , Purificação da Água , Campos de Petróleo e Gás , Águas Residuárias/química , Purificação da Água/métodos , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Oryza/química
7.
Br J Clin Pharmacol ; 88(3): 1179-1188, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34450681

RESUMO

AIMS: Early-onset sepsis (EOS) is a common disease in neonates with a high morbidity and mortality rate. Piperacillin/tazobactam has been used extensively and empirically for EOS treatment without clinically validated dosing regimens, although the population pharmacokinetics (PPK) of piperacillin in neonates has been reported. Therefore, we wanted to study the effectiveness and tolerance of a PPK model-based dosing regimen of piperacillin/tazobactam in EOS patients. METHODS: A prospective, single-centre, phase II clinical study of piperacillin/tazobactam in neonates with EOS was conducted. The dosing regimen (90 mg·kg-1 , q8h) was determined based on a previous piperacillin PPK model in young infants using NONMEM v7.4. The pharmacodynamics (PD) target (70%fT > MIC, free drug concentration above MIC during 70% of the dosing interval) attainment was calculated using NONMEM combined with an opportunistic sampling design. The clinical treatment data were collected. RESULTS: A total of 52 neonates were screened and 49 neonates completed their piperacillin/tazobactam treatment course and were included in this analysis. The median (range) values of postmenstrual age were 33.57 (range 26.14-41.29) weeks. Forty-seven (96%) neonates reached their PD target. Eight (16%) neonates experienced treatment failure clinically. The mean (SD, range) duration of treatment and length of hospitalization were 100.1 (62.2, 36.2-305.8) hours and 31 (30, 5-123) days. There were no obvious adverse events and no infection-related deaths occurred in the first month of life. CONCLUSIONS: A model-based dosing regimen of piperacillin/tazobactam was evaluated clinically, was tolerated well and was determined to be effective for EOS treatment.


Assuntos
Piperacilina , Sepse , Antibacterianos , Humanos , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Piperacilina/efeitos adversos , Piperacilina/farmacocinética , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Sepse/tratamento farmacológico
8.
Prehosp Disaster Med ; 35(3): 335-340, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32200770

RESUMO

BACKGROUND: The aim of this study was to analyze the profile of chest injuries, oxygen therapy for respiratory failure, and the outcomes of victims after the Jiangsu tornado, which occurred on June 23, 2016 in Yancheng City, Jiangsu Province, China. METHODS: The clinical records of 144 patients referred to Yancheng City No.1 People's Hospital from June 23 through June 25 were retrospectively investigated. Of those patients, 68 (47.2%) sustained major chest injuries. The demographic details, trauma history, details of injuries and Abbreviated Injury Scores (AIS), therapy for respiratory failure, surgical procedures, length of intensive care unit (ICU) and hospital stay, and mortality were analyzed. RESULTS: Of the 68 patients, 41 (60.3%) were female and 27 (39.7%) were male. The average age of the injured patients was 57.1 years. Forty-six patients (67.6%) suffered from polytrauma. The mean thoracic AIS of the victims was calculated as 2.85 (SD = 0.76). Rib fracture was the most common chest injury, noted in 56 patients (82.4%). Pulmonary contusion was the next most frequent injury, occurring in 12 patients (17.7%). Ten patients with severe chest trauma were admitted to ICU. The median ICU stay was 11.7 (SD = 8.5) days. Five patients required intubation and ventilation, one patient was treated with noninvasive positive pressure ventilation (NPPV), and four patients were treated with high-flow nasal cannula (HFNC). Three patients died during hospitalization. The hospital mortality was 4.41%. CONCLUSIONS: Chest trauma was a common type of injury after tornado. The most frequent thoracic injuries were rib fractures and pulmonary contusion. Severe chest trauma is usually associated with a high incidence of respiratory support requirements and a long length of stay in the ICU. Early initiation of appropriate oxygen therapy was vital to restoring normal respiratory function and saving lives. Going forward, HFNC might be an effective and well-tolerated therapeutic addition to the management of acute respiratory failure in chest trauma.


Assuntos
Traumatismo Múltiplo/diagnóstico , Oxigenoterapia , Síndrome do Desconforto Respiratório/diagnóstico , Traumatismos Torácicos/diagnóstico , Tornados , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , China , Serviços Médicos de Emergência , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Traumatismo Múltiplo/terapia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Traumatismos Torácicos/mortalidade , Traumatismos Torácicos/terapia
9.
Disaster Med Public Health Prep ; 14(2): 208-213, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31237228

RESUMO

OBJECTIVE: The aim of this study is to characterize the injury profiles and outcomes of victims of a tornado in Jiangsu Province, China. METHODS: This study retrospectively investigated the clinical records of 144 patients treated at a teaching hospital due to a tornado. Each patient's demographic data, diagnosis, injury types, causes of injury, infection status, and outcomes were all reviewed. RESULTS: Of the 144 patients, 64 (44.4%) were male, and 80 (55.6%) were female. The patients' ages ranged from 2 months to 94 years; 91 (63.19%) were admitted within the first 12 h after the disaster. The most frequently injured sites were the body surfaces (24.48%), followed by the limbs and pelvis (21.79%) and chest (20.3%). Soft-tissue injuries and fractures were the most frequent injuries. Traumatic brain injuries were the main causes of death. Tornado-related injuries were primarily caused by flying/falling bricks, wood, and glass. Twenty-three (15.9%) patients suffered from infections, which consisted mainly of skin/soft tissue infections and pneumonia. CONCLUSIONS: Destructive tornadoes often cause heavy casualties with little warning. Medical aid agencies must be prepared to accommodate the massive numbers of injured patients after a catastrophe. Proper triage and prompt treatment of injured victims may decrease mortality. (Disaster Med Public Health Preparedness. 2019;xx:xxx-xxx).


Assuntos
Tornados/estatística & dados numéricos , Resultado do Tratamento , Ferimentos e Lesões/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitais de Ensino/organização & administração , Hospitais de Ensino/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Retrospectivos , Ferimentos e Lesões/epidemiologia
10.
Cancer Lett ; 452: 38-50, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-30904618

RESUMO

The great therapeutic potential of peptides has not yet been achieved, mainly due to their remarkably short in vivo half-life. Although conjugation to macromolecules has been an effective way of improving protein in vivo half-life, the steric hindrance of macromolecules usually reduces the in vivo efficacy of peptides. Here we report a complex delivery system made from PsTag polypeptide, polyglutamic acid chain, matrix metalloproteinase 2 (MMP2)-degradable domain and cationic cell penetrating peptide for anticancer peptide delivery. Clear evidence was shown in vitro and in vivo to demonstrate that this multifunctional protein fusing a pro-apoptotic KLAKLAKKLAKLAK (KLA), named PAK, can increase circulation time in blood, enhance accumulation at tumor sites, eliminate the PsTag domain and the polyanionic sequence when triggered by tumor overexpressing MMP2, and then expose the cell penetrating peptide to realize the potent cellular uptake of KLA. Treatment of tumor-bearing mice with PAK could markedly induce tumor cells apoptosis and inhibit tumor growth, with no significant adverse effects. These results suggest our fusion protein can be a potential delivery system for peptide delivery in cancer treatments.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Peptídeos Penetradores de Células/farmacologia , Portadores de Fármacos , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/farmacocinética , Feminino , Células Hep G2 , Humanos , Células MCF-7 , Metaloproteinase 2 da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Terapia de Alvo Molecular , Neoplasias/enzimologia , Neoplasias/patologia , Fragmentos de Peptídeos/metabolismo , Ácido Poliglutâmico/metabolismo , Domínios Proteicos , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Bioconjug Chem ; 30(3): 898-906, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30802405

RESUMO

Successful and efficient delivery of Cas9 protein and gRNA into cells is critical for genome editing and its therapeutic application. In this study, we developed an improved supercharged polypeptide (SCP) mediated delivery system based on dithiocyclopeptide linker to realize the effective genome editing in tumor cells. The fusion protein Cas9-linker-SCP (Cas9-LS) forms positively charged complexes with gRNA in vitro to provide possibilities for gRNA delivery into cells. Under the microenvironment of tumor cells, the dithiocyclopeptide linker, containing matrix metalloproteinase 2 (MMP-2) sensitive sequence and an intramolecular disulfide bond, can be completely disconnected to promote the release of Cas9 protein with the nuclear localization sequence (NLS) in the cytoplasm and transfer to the cell nucleus for highly efficient genome editing, resulting in an obvious increase of indel efficiency in comparison to fusion protein without dithiocyclopeptide linker (Cas9-SCP). Furthermore, Cas9-LS shows no significant cytotoxicity and minimal hemolytic activity. We envision that the microenvironment-responsive Cas9 protein delivery system can facilitate more efficient genome editing in tumor cells.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Sistemas CRISPR-Cas , Endonucleases/metabolismo , Edição de Genes/métodos , Microambiente Tumoral , Humanos , Metaloproteinase 2 da Matriz/metabolismo , RNA Guia de Cinetoplastídeos/genética
12.
J Am Chem Soc ; 140(49): 17234-17240, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30398334

RESUMO

The efficient delivery of proteins into cells is needed to fully realize the potential of protein-based therapeutics. Current protein delivery strategies generally suffer from poor endosomal escape and low tolerance for serum. Here, the genetic fusion of a supercharged polypeptide, called SCP, to a protein provides a generic method for intracellular protein delivery. It allows efficient protein endocytosis and endosomal escape and is capable of potently delivering various proteins with a range of charges, sizes, and bioactivities into the nucleus of living cells. SCP is discovered to bind directly to the nuclear import protein importin ß1 and gains access to the nucleus. Furthermore, SCP shows minimal hemolytic activity and stability in serum and lacks toxicity and immunogenicity in vivo. Effective gene editing can be achieved by SCP-mediated delivery of Cas9 protein and guide RNA. This study may provide an efficient and useful tool for the design and development of cell-nuclear-targeted drug delivery.


Assuntos
Peptídeos Penetradores de Células/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Peptídeos Penetradores de Células/sangue , Peptídeos Penetradores de Células/genética , Peptídeos Penetradores de Células/toxicidade , Endocitose/fisiologia , Escherichia coli/genética , Feminino , Humanos , Camundongos Endogâmicos BALB C , Estabilidade Proteica , Proteínas Recombinantes de Fusão/sangue , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/toxicidade , beta Carioferinas/metabolismo
13.
ACS Synth Biol ; 7(5): 1291-1302, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29668266

RESUMO

Escherichia coli extracellular expression systems have a number of advantages over other systems, such as lower pyrogen levels and a simple purification process. Various approaches, such as the generation of leaky mutants via chromosomal engineering, have been explored for this expression system. However, extracellular protein yields in leaky mutants are relatively low compared to that in intracellular expression systems and therefore need to be improved. In this work, we describe the construction, characterization, and mechanism of enhanced extracellular expression in Escherichia coli. On the basis of the localizations, functions, and transcription levels of cell envelope proteins, we systematically elucidated the effects of multiple gene deletions on cell growth and extracellular expression using modified CRISPR/Cas9-based genome editing and a FlAsH labeling assay. High extracellular yields of heterologous proteins of different sizes were obtained by screening multiple gene mutations. The enhancement of extracellular secretion was associated with the derepression of translation and translocation. This work utilized universal methods in the design of extracellular expression systems for genes not directly associated with protein synthesis that were used to generate strains with higher protein expression capability. We anticipate that extracellular expression systems may help to shed light on the poorly understood aspects of these secretion processes as well as to further assist in the construction of engineered prokaryotic cells for efficient extracellular production of heterologous proteins.


Assuntos
Sistemas CRISPR-Cas , Escherichia coli/genética , Engenharia Genética/métodos , Escherichia coli/crescimento & desenvolvimento , Matriz Extracelular/genética , Fluorescência , Deleção de Genes , Perfilação da Expressão Gênica/métodos , Interferon-alfa/genética , Interferon-alfa/metabolismo , Microrganismos Geneticamente Modificados , Peso Molecular , Mutação , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
14.
Sci Rep ; 6: 31056, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27491820

RESUMO

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system. However, the mechanisms underlying its tumor initiation, progression, and metastasis are not yet fully understood. The annexin A4 (ANXA4) gene is highly expressed in GBC tissues and may play an important role in the initiation and progression of this disease. In this study, we examined the up-regulation of ANXA4 in human GBC tissues and cell lines. Elevated ANXA4 correlated well with invasion depth in GBC patients and predicted a poor prognosis. In vitro, GBC-SD and NOZ cells with ANXA4 knockdown demonstrated increased apoptosis and inhibited cell growth, migration, and invasion. Interactions between ANXA4 and nuclear factor-κB (NF-κB) p65 proteins were detected. In vivo, ANXA4 knockdown inhibited tumor growth of GBC cells in nude mice and down-regulated the expression of downstream factors in the NF-κB signaling pathway. Taken together, these data indicate that up-regulation of ANXA4 leads to activation of the NF-κB pathway and its target genes in a feedback regulatory mechanism via the p65 subunit, resulting in tumor growth in GBC.


Assuntos
Anexina A4/metabolismo , Neoplasias da Vesícula Biliar/patologia , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Humanos , Camundongos Nus , Ligação Proteica
15.
Mol Carcinog ; 55(5): 458-72, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25808746

RESUMO

Hepatocyte nuclear factor 4-α (HNF4α), a nuclear receptor, is expressed at lower levels in colon carcinoma tissues than in adjacent normal tissues. However, the relation between HNF4α and colon cancer progression and the underlying molecular mechanisms remain unclear. Here, we investigated the role of HNF4α in the progression of colon carcinoma. We showed that HNF4α mRNA and protein were downregulated in colon carcinoma specimens. HNF4α expression was related to pT classification (P < 0.001), lymph node metastasis (P = 0.002), distant metastasis (P < 0.001) and clinical stage (P < 0.001) in colon carcinoma patients. Patients with low or negative HNF4α expression had worse 3-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.005) than patients with high HNF4α expression. Low HNF4α expression was an independent prognostic factor for 3-year PFS (hazard ratio 2.94; 95% confidence interval 1.047-8.250; P = 0.041). Ectopic expression of HNF4α inhibited colon carcinoma cell (HT29, LoVo, and SW480) proliferation, migration, and invasion, induced G2/M phase arrest and promoted apoptosis. Ectopic expression of HNF4α upregulated E-cadherin and downregulated vimentin in vitro, and suppressed SW480 xenograft tumor growth and liver metastasis in vivo. Furthermore, HNF4α overexpression downregulated the expression of snail, slug and twist. HNF4α inhibited EMT through its effect on the Wnt/ß-catenin signaling pathway, and HNF4α downregulation may be mediated by promoter methylation in cancer tissues. Our results suggest that downregulation of HNF4α plays a critical role in the aggravation of colon carcinoma possibly by promoting EMT via the Wnt/ß-catenin signaling pathway and by affecting apoptosis and cell cycle progression.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/metabolismo , Progressão da Doença , Regulação para Baixo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Análise de Sobrevida , beta Catenina/metabolismo
16.
Int J Surg ; 13: 102-110, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25486261

RESUMO

BACKGROUND: Perioperative allogeneic blood transfusion (ABT) may be a deleterious predictor on the prognosis of gastric cancer (GC) for subjects who had undergone curative surgeries. In this article we proposed to figure out the effect of ABT with a systematic review and meta-analysis. METHODS: Relevant articles were identified by searching Pubmed and Embase to March 2014. A random-effects model or fixed-effects model was used to calculate pooled odds ratios (ORs). Sensitivity analysis, meta-regression, stratified analysis, dose-response meta-analysis were conducted, and publication bias tested. RESULTS: Eighteen studies (9120 GC patients) were included, of which 36.3% received transfusions. ABT was associated with increased all-cause mortality (OR, 2.17; 95% confidence interval [CI], 1.72-2.74; p<0.001; I2=75%). Sensitivity analysis showed significant changes in ORs while meta-regression had little influence on ORs. Galbraith plot revealed the OR reduced to 2.10 (95% CI, 1.86-2.37; p<0.001) with tau2 reduced to 0.00 and I2 reduced to 0%. RESULTS of stratified analysis were robust and consistent. Dose-response meta-analysis revealed that all-cause mortality was significantly lower in patients transfused with ≤800 mL of blood than those transfused with >800 mL (OR, 0.58; 95% CI, 0.37-0.92; p=0.02; I2=54%). ABT was also associated with increased cancer-related mortality (OR, 2.57, p=0.011) and recurrence (OR, 1.52, p=0.017). CONCLUSIONS: In GC patients undergoing curative surgeries, ABTs are associated with a worse prognosis, including all-cause mortality, cancer-related mortality and recurrence. Patient blood management should be investigated further to minimize use of ABT.


Assuntos
Transfusão de Sangue/mortalidade , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Reação Transfusional , Causas de Morte , Humanos , Recidiva Local de Neoplasia , Razão de Chances , Prognóstico , Fatores de Risco , Resultado do Tratamento
17.
World J Gastroenterol ; 20(18): 5511-8, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24833881

RESUMO

AIM: To identify potential biomarkers of primary gallbladder cancer (PGC). METHODS: Fresh PGC, cholecystitis and normal gallbladder tissue specimens collected from 10 patients, respectively, were subjected to comparative proteomic analysis. The proteomic patterns of PGC were compared with those of cholecystitis and normal gallbladder tissues using two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were then identified using a MALDI-TOF mass spectrometer (MS) and database searches. To further validate these proteins, 20 samples of PGC tissues and normal tumor-adjacent tissues were collected for Western blot, quantitative real-time PCR, and immunohistochemical staining assay. RESULTS: Seven differentially expressed protein spots were detected by 2-ED analysis by comparing the average maps of PGC, cholecystitis and normal gallbladder tissues. Six of the seven differentially expressed proteins were identified using MALDI-TOF MS, with three overexpressed and three underexpressed in PGC tissue. Protein levels of annexin A4 (ANXA4) were significantly elevated, and heat shock protein 90-beta (Hsp90ß) and dynein cytoplasmic 1 heavy chain 1 (Dync1h1) were decreased in PGC tissues relative to the normal tumor-adjacent tissues as shown by Western blot analysis. However, levels of actin, aortic smooth muscle and gamma-actin were unchanged. In addition, the mRNA levels of all 5 proteins showed similar changes to those of the protein levels (P < 0.01). Further validation by immunohistochemical analysis showed the upregulated expression of ANXA4 and decreased expression of Hsp90ß and Dync1h1 in the cytoplasm of PGC tissues relative to the normal tumor-adjacent tissues. CONCLUSION: Three proteins are identified as potential biomarkers of PGC using proteomic analysis. The functions of these proteins in the carcinogenesis of PGC remain to be studied.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Vesícula Biliar/química , Proteínas de Neoplasias/análise , Proteômica , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Estudos de Casos e Controles , Bases de Dados de Proteínas , Eletroforese em Gel Bidimensional , Feminino , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Valor Preditivo dos Testes , Proteômica/métodos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
18.
Acta Crystallogr C ; 69(Pt 10): 1108-11, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24096495

RESUMO

2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole (L), C26H20N4O, forms one-dimensional chains via two types of intermolecular π-π interactions. In catena-poly[[dichloridozinc(II)]-µ-2,5-bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole], [ZnCl2(C26H20N4O)]n, synthesized by the combination of L with ZnCl2, the Zn(II) centres are coordinated by two Cl atoms and two N atoms from two L ligands. [ZnCl2L]n forms one-dimensional P (plus) and M (minus) helical chains, where the L ligand has different directions of twist. The helical chains stack together via interchain π-π and C-H···π interactions.

19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 255-9, 2013 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-23591347

RESUMO

OBJECTIVE: To investigate the current status of osteoarthritis medications of outpatients for arthritis treatment guidelines, and provide references for the promotion and popularization of traditional Chinese and western medicine in treatment of arthritis. METHODS: The outpatient prescriptions for the treatment of osteoarthritis from all the rheumatology and orthopedics specialists from 2007 February to May in Peking University People's Hospital were chosen and analyzed statistically. RESULTS: There were a total of 2 145 osteoarthritis prescription in this study, including 8 categories: joint lubricants, non-steroid anti-inflammatory drugs (NSAIDs), local anesthetics, cartilage protective agent, adrenal corticosteroids, vitamin AD, analgesic drugs and traditional Chinese medicine. The Chinese medicines were among the drugs with the most species amounted up to 35. The most common route of medication was oral administration (73.2%), which was used more in the department of rheumatology and immunology than in orthopedics. And in oral drugs, the biggest consumption was NSAIDs, accounting for 29.9%. There was no significantly difference between the rheumatology and orthopedic specialists when using non-specific cyclooxygenase (COX) inhibitors. But orthopedic specialists prescribed more COX-1 specific inhibitor than rheumatology specialists. CONCLUSION: Recently the arthritis treatment guidelines have been issued one after another. Many experts have already accepted the treatment of pain. However, in the implementation, the large differences still exist. The use of the Chinese medicine is still very chaotic; there are no clear-cut norms to be followed. Therefore, the implementation of the arthritis treatment guidelines and treatments of arthritis by traditional Chinese medicine are urgent to be standardized.


Assuntos
Prescrições de Medicamentos , Uso de Medicamentos/estatística & dados numéricos , Osteoartrite/tratamento farmacológico , Guias de Prática Clínica como Assunto , Corticosteroides/uso terapêutico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais
20.
Inorg Chem ; 52(6): 3225-35, 2013 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-23461490

RESUMO

A series of Cd(II) coordination frameworks that are constructed from a new oxadiazole-bridged ligand 3,5-bis(3-pyridyl-3-(3'-methylphenyl)-1,3,4-oxadiazole (L) and CdX2 (X = NO3(-), Cl(-), Br(-), I(-), N3(-), and SCN(-)) were synthesized. The NO3(-) anion of the solid CdL2(NO3)2·2THF (1) is able to be quantitatively exchanged with Cl(-), Br(-), I(-), SCN(-), and N3(-) in the solid state. For Cl(-) and Br(-), the anion exchange resulted in a anion-induced structural transformation to form the structures of 2 and 3, respectively. In addition, the Cd(II) structure herein exhibits the anion-responsive photoluminescence, which could be a useful method to monitor the anion-exchange process. Notably, compound 1 can recognize and completely separate SCN(-)/N3(-) with similar geometry.


Assuntos
Cádmio/química , Medições Luminescentes , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Técnicas de Química Sintética , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Conformação Molecular
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