RESUMO
The aim of this study was to investigate the interference of lipemia on measurement of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, HIV Ag/Ab, and anti-TP in serum by chemiluminescent microparticle immunoassay (CMIA) and compare lipemia removing performance between high-speed centrifugation and Lipoclear reagent. Mixed native serum samples (NSs) and hyperlipemia serum samples (HLS) were prepared for the investigated parameters. The levels of these parameters in NS and HLS were determined by CMIA on an Abbott ARCHITECT i2000SR immunoassay analyzer. HBsAg, anti-HBs, and anti-TP were affected with relative bias >12.5% (acceptable limit) when the level of triacylglycerol (TG) was higher than 27.12 mmol/L in HLS. Clinically unacceptable bias were observed for HBeAg and anti-HBe in HLS with TG higher than 40.52 mmol/L. However, anti-HCV and HIV Ag/Ab were not interfered in severe lipemia with TG < 52.03 mmol/L. In addition, the Lipoclear reagent did not reduce the interference of lipemia with relative bias from -62.50% to -18.02%. The high-speed centrifugation under the optimized condition of 12 000g for 10 min successfully removed the interference of lipemia with relative bias from -5.93% to 0% for HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. To conclude, high-speed centrifugation can be used for removing the interference of lipemia to measure HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. Accordingly, a standardized sample preanalytical preparation of the patients and other screening participants as well as a specimen examination procedure for removing lipemia interference on the serological tests was recommended.
Assuntos
Síndrome da Imunodeficiência Adquirida , Hepatite B , Hepatite C , Hiperlipidemias , Sífilis , Humanos , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Indicadores e Reagentes , Sífilis/diagnóstico , Vírus da Hepatite B , Anticorpos Anti-Hepatite B , Imunoensaio , Hepatite C/diagnóstico , Testes Sorológicos , Triglicerídeos , CentrifugaçãoRESUMO
During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.
Assuntos
Níveis de Referência de Diagnóstico , Radiologia Intervencionista , Humanos , Radiologia Intervencionista/métodos , Doses de Radiação , Estudos Retrospectivos , RadiografiaRESUMO
ABSTRACT: Vascular calcification (VC), which currently cannot be prevented or treated, is an independent risk factor for cardiovascular events. We aimed to investigate the ameliorative effect of berberine on VC via the activation of Akt signaling and inhibition of endoplasmic reticulum stress (ERS). The VC model was induced by high-dose Vitamin D 3 in rats and beta-glycerophosphate in primary vascular smooth muscle cells of rat aortas, which were evaluated by Alizarin red staining to determine the calcium content and alkaline phosphatase activity. ERS was determined by the levels of GRP78 and CHOP, whereas that of the Akt signaling pathway was determined by the levels of phosphorylated Akt and GSK3ß. VC was significantly ameliorated by berberine treatment in vivo and in vitro, and the inhibition of ERS and the activation of the Akt/GSK3 signaling pathway. In the vascular smooth muscle cells of primary rats, tunicamycin, an ERS activator, blocked the ameliorative effect of berberine on VC and ERS, but not the activation of Akt/GSK3. The ameliorative effects of berberine on VC, ERS, and the Akt signaling pathway were all prevented by inhibitor IV. Four-phenylbutyric acid, an ERS inhibitor, can restore the ameliorative effect of berberine on VC and ERS that was blocked by inhibitor IV. Our results are the first to demonstrate the ameliorative effect of VC that was mediated by the activation of the Akt signaling pathway and inhibition of ERS. These results may provide a new pharmaceutical candidate for the prevention and treatment of VC.
Assuntos
Berberina , Calcificação Vascular , Animais , Berberina/farmacologia , Estresse do Retículo Endoplasmático , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/farmacologia , Músculo Liso Vascular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Calcificação Vascular/induzido quimicamente , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/prevenção & controleRESUMO
The abuse of buprenorphine and methadone has grown into a rising worldwide issue. After their consumption, buprenorphine, methadone and their metabolites can be found in the human organism. Due to the difficulty in the assessment of these compounds by routine drug screening, the importance of developing highly sensitive analytical approaches is undeniable. Liquid chromatography tandem mass spectrometry is the preferable technique for the determination of buprenorphine, methadone and their metabolites in biological matrices including urine, plasma, nails or oral fluids. This research aims to review a critical discussion of the latest trends for the monitoring of buprenorphine, methadone and their metabolites in various biological specimens.
Assuntos
Buprenorfina , Metadona , Cromatografia Líquida/métodos , Humanos , Metadona/urina , Espectrometria de Massas em Tandem/métodosRESUMO
The dysfunction of bone marrow mesenchymal stem cells (BMSCs) in osteogenic differentiation is one of the main causes of age-related bone loss. Our previous studies have shown that low-magnitude vibration (LMV) induces the osteogenic differentiation of BMSCs derived from ovariectomized osteoporotic rats. To investigate whether LMV promotes osteogenic differentiation of BMSCs and its underlying mechanisms in aged rats, 20-month-old female Sprague-Dawley rats (n = 20) were randomly divided into LMV group (rats were vibrated at 0.3 g and 90 Hz for 30 minutes, once daily, 5 days a week until 12 weeks for subsequent analysis, n = 10), static group (rats were placed in the box on the vibration platform without vibration, n = 10); 6-month-old female Sprague-Dawley rats were used as control (young group, n = 10). The bone mineral density and bone strength of aged rats were significantly decreased compared with the young rats. Furthermore, the primary BMSCs isolated and cultured from the aged rats with the whole-bone marrow differential pasting method showed a decreased ability in osteogenic differentiation compared with that from the young rats. Then the differentially expressed miRNAs between the aged and young rat-derived BMSCs were screened by high-throughput sequencing and verified by qRT-PCR, and we found that miR-378a-3p was significantly downregulated in the aged rat-derived BMSCs compared with the young rat-derived BMSCs. By transfecting miRNA mimics and inhibitors, miR-378a-3p was confirmed to promote the expression levels of osteogenic genes (Runx2, ALP, Col I, and OCN) and ALP activity of the aged rat-derived BMSCs. Meanwhile, the expression levels of osteogenic genes and miR-378a-3p of aged rat-derived BMSCs were significantly upregulated by LMV (cells were vibrated at 0.3 g and 90 Hz for 30 minutes a day, until 5 days for subsequent analysis), while the LMV-induced osteogenic gene expression levels of aged rat-derived BMSCs were suppressed by miR-378a-3p inhibitors. Furthermore, the inhibition of growth factor receptor-bound protein 2 (Grb2) by miR-378a-3p and Grb2-siRNA promoted the LMV-induced osteogenic differentiation of aged rat-derived BMSCs. Additionally, LMV was found to promote bone mineral density and bone strength of aged rats in vivo, as well as upregulating the expression level of miR-378a-3p and downregulating the expression level of Grb2 of BMSCs from aged rats. These results suggest that LMV induces osteogenic differentiation of BMSCs through miR-378a-3p/Grb2 pathway to improve bone mineral density and mechanical properties in a rat model of age-related bone loss.
Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Proteína Adaptadora GRB2/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Osteogênese/genética , Osteoporose/genética , Vibração , Fatores Etários , Animais , Densidade Óssea/genética , Células da Medula Óssea/citologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Proteína Adaptadora GRB2/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Osteoporose/metabolismo , Ratos Sprague-DawleyRESUMO
BACKGROUND AND METHODS: 2019 Corona Virus Disease (COVID-19) caused by SARS-CoV-2 is still pandemic now. RT-qPCR detection was the most common method for the diagnosis of SARS-CoV-2 infection, facilitated by amounts of nucleic acid testing kits. However, the accuracy of nucleic acid detection is affected by various factors such as specimen collection, specimen preparation, reagents deficiency, and personnel quality. RESULTS: In this study, we found that unmatched virus preservation solution will inhibit N gene and OFR-1ab gene (two independent genes of SARS-CoV-2) amplification in one-step detection reagent. CONCLUSIONS: Despite just being a particular phenomenon we found in our work to fight 2019-nCoV, we concluded that unmatched virus preservation solution may have an inhibitory effect on SARS-CoV-2 nucleic acid detection which may lead to incorrect clinical diagnosis.
Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19 , Genes Virais/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , SARS-CoV-2 , Manejo de Espécimes , COVID-19/diagnóstico , COVID-19/virologia , Erros de Diagnóstico/prevenção & controle , Humanos , Kit de Reagentes para Diagnóstico/normas , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Manejo de Espécimes/efeitos adversos , Manejo de Espécimes/métodosRESUMO
BACKGROUND: The obesity-hypertension pathogenesis is complex. From the phenotype to molecular mechanism, there is a long way to clarify the mechanism. To explore the association between obesity and hypertension, we correlate the phenotypes such as the waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), and diastolic blood pressure (DB) with the clinical laboratory data between four specific Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group), and the results may show something. OBJECTIVE: To explore the mechanisms from obesity to hypertension by analyzing the correlations and differences between WC, BMI, SB, DB, and other clinical laboratory data indices in four specific Chinese adult physical examination groups. METHODS: This cross-sectional study was conducted from September 2012 to July 2014, and 153 adult subjects, 34 women and 119 men, from 21 to 69 years, were taken from four characteristic Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group). The study was approved by the ethics committee of Hangzhou Center for Disease Control and Prevention. WC, BMI, SB, DB, and other clinical laboratory data were collected and analyzed by SPSS. RESULTS: Serum levels of albumin (ALB)ï¼alanine aminotransferase (ALT), low density lipoprotein cholesterol (LDLC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), alkaline phosphatase (ALP), uric acid (Ua), and TC/HDLC (odds ratio) were statistically significantly different between the four groups. WC statistically significantly positively correlated with BMI, ALT, Ua, and serum levels of glucose (GLU), and TC/HDLC, and negatively with ALB, HDLC, and serum levels of conjugated bilirubin (CB). BMI was statistically significantly positively related to ALT, Ua, LDLC, WC, and TC/HDLC, and negatively to ALB, HDLC, and CB. DB statistically significantly positively correlated with ALP, BMI, and WC. SB was statistically significantly positively related to LDLC, GLU, serum levels of fructosamine (FA), serum levels of the total protein (TC), BMI, and WC. CONCLUSION: The negative body effects of obesity are comprehensive. Obesity may lead to hypertension through multiple ways by different percents. GGT, serum levels of gamma glutamyltransferase; ALB, serum levels of albumin; ALT, serum levels of alanine aminotransferase; LDLC, serum levels of low density lipoprotein cholesterol; TG, serum levels of triglyceride; HDLC, serum levels of high density lipoprotein cholesterol; FA, serum levels of fructosamine; S.C.R, serum levels of creatinine; IB, serum levels of indirect bilirubin; ALP, serum levels of alkaline phosphatase; CB, serum levels of conjugated bilirubin; UREA, Urea; Ua, serum levels of uric acid; GLU, serum levels of glucose; TC, serum levels of the total cholesterol; TB, serum levels of the total bilirubin; TP, serum levels of the total protein; TC/HDLC, TC/HDLC ratio.
Assuntos
Pressão Sanguínea , Índice de Massa Corporal , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Circunferência da Cintura , Adulto , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Glicemia/metabolismo , China , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Diástole , Feminino , Frutosamina/sangue , Humanos , Hipertensão/sangue , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Fenótipo , Fatores de Risco , Albumina Sérica/metabolismo , Sístole , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto Jovem , gama-Glutamiltransferase/sangueRESUMO
BACKGROUND: Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown. METHODS: A nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped. RESULTS: Carriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes. CONCLUSIONS: Individuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.
Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Doença da Artéria Coronariana/genética , Dislipidemias/genética , Estilo de Vida , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/sangue , Dislipidemias/sangue , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
MicroRNAs (miRNAs) are short non-coding RNA and play crucial roles in a wide array of biological processes, including cell proliferation, differentiation and apoptosis. Our previous studies found that homocysteine(Hcy) can stimulate the proliferation of vascular smooth muscle cells (VSMCs), however, the underlying mechanisms were not fully elucidated. Here, we found proliferation of VSMCs induced by Hcy was of correspondence to the miR-125b expression reduced both in vitro and in the ApoE knockout mice, the hypermethylation of p53, its decreased expression, and DNA (cytosine-5)-methyltransferase 3b (DNMT3b) up-regulated. And, we found DNMT3b is a target of miR-125b, which was verified by the Dual-Luciferase reporter assay and western blotting. Besides, the siRNA interference for DNMT3b significantly decreased the methylation level of p53, which unveiled the causative role of DNMT3b in p53 hypermethylation. miR-125b transfection further confirmed its regulative roles on p53 gene methylation status and the VSMCs proliferation. Our data suggested that a miR-125b-DNMT3b-p53 signal pathway may exist in the VSMCs proliferation induced by Hcy.
Assuntos
DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/genética , Homocisteína/farmacologia , MicroRNAs/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Sequência de Bases , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/genética , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Masculino , Camundongos Knockout , MicroRNAs/genética , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , DNA Metiltransferase 3BRESUMO
BACKGROUND: Noise-induced hearing loss (NIHL) is a complex disease caused by environmental and genetic risk factors. This study explored the relationship between the genetic variations in the CASP gene and the risk of developing NIHL among Chinese workers exposed to occupational noise. METHODS: A case-control study of 272 NIHL workers and 272 normal-hearing workers matched for age, sex and years of noise exposure was conducted. Fifteen single-nucleotide polymorphisms (SNP) in the CASP1, CASP3, CASP4, CASP5, CASP6, CASP8, CASP9, CASP10 and CASP14 genes were genotyped using the polymerase chain reaction-ligase detection reaction method. Using conditional logistic regression models, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of genetic variations associated with NIHL risk were calculated. RESULTS: Two SNPs in the CASP3 gene were associated with NIHL risk. For rs1049216, TT genotype was associated with a decreased risk of NIHL (OR = 0.246, 95% CI = 0.069-0.886) when compared with the CC genotype. For rs6948, the AC and CC genotype were associated with a decreased NIHL risk (OR = 0.568, 95% CI = 0.352-0.916) compared with AA genotype. There were joint effects of working time and CASP3 polymorphisms on NIHL risk (P < 0.05). CONCLUSIONS: Genetic variations in the CASP3 gene and the joint effects of working time and CASP3 polymorphisms may modify the risk of developing NIHL.
Assuntos
Genótipo , Perda Auditiva Provocada por Ruído/genética , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
The purpose of this study was to investigate the effect of biaxial tensile strain on the osteogenic differentiation of rat bone marrow mesenchymal stem cells(rBMSCs)in vitro.The rBMSCs were isolated from tibia and femur of 4weeks-old Sprague-Dawley(SD)rats.The rBMSCs were cultured in DMEM-LG complete culture medium and grew to subconfluence in the cell culture device for loading tensile strain.The biaxial tensile strain was applied to the rBMSCs for periods of 2,4and 6hours every day,respectively,lasting 3days.The amplitude of biaxial tensile strain applied to the rBMSCs were 1%,2% and 5%respectively,at a frequency of 1Hz.Unstrained rBMSCs were used as blank control(control group).The rBMSCs cultured with DMEM-LG complete culture medium containing100nmol/Lß-Estradiol(E2)were used as positive control.The mRNA expression of alkaline phosphatase(ALP),collagen typeâ (Colâ ),Runt-related transcription factor 2(Runx2)and osteocalcin(OCN)was examined with real-time quantitative PCR and the protein expression of ALP,Colâ ,Runx2 and OCN was detected with Western blot method.The results showed as follws:(1)The mRNA and protein expression of the ALP,Colâ ,Runx2,OCN were significantly higher in rBMSCs of the E2 group than those in the control group(P<0.05).(2)The mRNA and protein expression level of the ALP,Runx2 were higher markedly in the 1% tensile strain groups than those in the control group(P<0.05),but lower than those in the E2group(P<0.05).(3)The mRNA and protein expression level of the ALP,Colâ ,Runx2,OCN were significantly higher in the 2% tensile strain groups than those in the control group(P<0.05),and the mRNA and protein expression level of Colâ and Runx2 in the group applied with2% amplitude of tensile strain for 4h/d was significantly higher than those in E2group(P<0.05).(4)The mRNA and protein expression level of the ALP,Colâ ,Runx2 were significantly higher in the groups applied with 5% amplitude of tensile strain for 2h/d or for 4h/d than those in the control group(P<0.05).In our study,E2 and mechanical stimulation played an important role in the regulation of differentiation of rBMSCs into osteoblasts,and the manner applied with the 2%amplitude of tensile strain for 4h/d,lasting 3days was an optimal stimulus for up-regulating the mRNA and protein expression of ALP,Colâ ,Runx2,OCN of rBMSCs.
Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Estresse Mecânico , Fosfatase Alcalina/metabolismo , Animais , Medula Óssea , Células da Medula Óssea/citologia , Proliferação de Células , Células Cultivadas , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/química , Osteocalcina/metabolismo , Osteogênese , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
The aim of the present study is to explore the role of miR-124 and its promoter region DNA methylation in homocysteine (Hcy)-induced atherosclerosis. ApoE(-/-) mice were fed with hypermethionine diet for 16 weeks to duplicate hyperhomocysteinemia model. Meanwhile, a normal control group (C57BL/6J mice fed with normal diet, N-control) and a model control group (ApoE(-/-) mice fed with normal diet, A-control) were set. The degree of atherosclerosis was observed by HE and oil red O staining. Automatic biochemical analyzer was used to detect the serum levels of Hcy. Foam cell model was duplicated and oil red O staining was used to confirm whether the model was successfully established. And foam cells were stimulated with 0, 50, 100, 200, 500 µmol/L Hcy and 50 µmol/L Hcy + 10 µmol/L AZC respectively. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-124 in mice aorta and foam cells; Nested landing methylation specific PCR (nMS-PCR) was used to detect the levels of miR-124 promoter DNA methylation in mice aorta and foam cells. Meanwhile, the effects of DNA methylation inhibitor AZC on miR-124 expression were observed at the cellular level. The effect of miR-124 promoter DNA methylation status on lipid accumulation in foam cells was observed by oil red O staining. The results showed that compared with model control group, the serum levels of Hcy in high methionine group were significantly increased (P < 0.01) and developed aortic atherosclerotic plaque, the expression of miR-124 was markedly decreased (P < 0.01), while the levels of miR-124 promoter DNA methylation were significantly increased (P < 0.01). Given different levels of Hcy, the expression of miR-124 in foam cells was decreased, while the levels of miR-124 promoter DNA methylation were increased in a dose-dependent manner (P < 0.05, P < 0.01). AZC reversed the results of mentioned indices as above markedly (P < 0.05). Downregulation of miR-124 may play a role in Hcy-induced atherosclerosis and its promoter DNA methylation status may be an important mechanism in this process.
Assuntos
Aterosclerose/genética , Metilação de DNA , MicroRNAs/genética , Animais , Aorta/metabolismo , Apolipoproteínas E , Aterosclerose/induzido quimicamente , Dieta , Células Espumosas/metabolismo , Homocisteína/efeitos adversos , Hiper-Homocisteinemia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras GenéticasRESUMO
Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease and has a strong correlation with heart failure. However, the effects of HHcy on cardiac tissue remain less well understood. To elucidate the role of p53-dependent apoptosis in HHcy-induced cardiac injury, we fed ApoE(-/-) mice with high methionine diet to establish HHcy model. Serum Hcy, cardiac enzymes, and lipids were measured. The protein levels of Noxa, DNMT1, caspases-3/9, and p53 were determined by enzyme-linked immunosorbent assay. Bcl-2 and Bax proteins were detected by immunohistochemistry staining. S-adenosyl methionine and S-adenosyl homocysteine concentrations were determined by high-performance liquid chromatography. The mRNA levels of p53 and DNMT1 were analyzed by real-time polymerase chain reaction (PCR) and the methylation levels of p53 were analyzed by nested methylation-specific-PCR. Our data showed that the concentrations of serum Hcy and lipids were increased in Meth group compared with the N-control group, which indicated that the model was established successfully. The expression levels of p53 and Noxa were increased in Meth group, while the methylation status of p53 was hypomethylation. The activities of caspase-3/9 were increased in Meth group compared with the N-control group. In addition, immunohistochemistry staining showed that the expression of Bax was significantly increased in Meth and Meth-F group compared with the N-control group. In summary, HHcy induces cardiac injury by up-regulation of p53-dependent pro-apoptotic related genes Noxa and Bax, while p53 DNA hypomethylation is a key molecular mechanism in pathological process induced by HHcy.
Assuntos
Apolipoproteínas E/deficiência , Cardiomiopatias/etiologia , Hiper-Homocisteinemia/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/biossíntese , Animais , Cardiomiopatias/fisiopatologia , Caspase 3/metabolismo , Caspase 9/metabolismo , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/biossíntese , Metilação de DNA , Masculino , Camundongos , Regulação para CimaRESUMO
Primary intestinal malignancies account for only 1%-3% of all malignant gastrointestinal tumors. Adenocarcinomas are uncommonly located in the ileum. Ileal adenocarcinoma (IA) is rare and difficult to diagnose because of its location. IA is common in older men and rare in young pregnant women. A 23-year-old pregnant woman was hospitalized several times for repeated vomiting and abdominal pain. Her symptoms were relieved after symptomatic treatment. She exhibited no typical manifestations of intestinal obstruction, such as abdominal distension, difficulty passing gas and defecation. Unfortunately, she was misdiagnosed with acute gastroenteritis. On the second day after delivery, the patient stopped passing gas and computed tomography (CT) revealed an intestinal obstruction. She was treated as paralytic ileus. However, in view of failed conservative management, she was decided for an exploratory laparotomy. A malignant ileal tumor 5cm from the ileocecal valve was found incidentally and was surgically excised accompanied with End-to-side anastomosis of ileal and transverse colon. The operation lasted 195 minutes. Pathological examination revealed an IA. Pregnant woman who experience symptoms of intestinal obstruction should be alert to the possibility of malignancy in the small intestine. IA is an insidious tumor in pregnant women. An "IA triad" can be defined as refractory vomiting, vague abdominal pain, and weight loss (or inadequate weight gain in pregnant women). Pregnant women with an IA triad should undergo investigation with endoscopy or, if necessary, magnetic resonance imaging (MRI).
RESUMO
BACKGROUND: Quantitative studies on the changes in inflammation-related content in tears, especially the effect of diabetes, are lacking. In this study, we measured the preoperative and postoperative tear inflammatory mediator levels in cataract patients, focusing on the expression of inflammatory factors in postoperative cataracts in the diabetic, and investigated the effect of drugs on the control of postoperative inflammation. AIM: To study the expression of inflammatory factors in elderly people with type 2 diabetes after cataract surgery. METHODS: Patients with a mean age of 70.3 ± 6.3 years were divided into group A (composed of elderly patients with cataracts and type 2 diabetes, n = 20 eyes) and group B (patients with age-related cataract, n = 20 eyes). Their tears were collected before each operation and on days 1 and 3, and weeks 1, 2, 3, and 4 post-surgery. Saline (150 µL) was dropped into the conjunctival sac of the surgical eye, followed by oculogyration in four directions. The fluid in the conjunctival sac was extracted using a sterile syringe and stored in Eppendorf tubes at -80 °C until measurement. The expression levels of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, interleukin-6 (IL-6), and IL-20 in tear fluid were measured using enzyme-linked immunosorbent assays. RESULTS: The postoperative expression levels of MMP-2, MMP-9, TIMP-2, IL-6, and IL-20 in group A were significantly higher than those in group B, whereas the concentration of TIMP-1 in group A remained lower than that in group B. The levels of MMP-2 and IL-6 in both groups continuously increased until the peak in the first postoperative week, and then gradually decreased over the next three weeks. Ultimately, MMP-2 declined to a lower level than that preoperatively at week 4, but IL-6 decreased to the same level as that preoperatively. The level of MMP-9 peaked in the first two weeks postoperative and then returned to the same level as 1-day post-operation. The concentration of TIMP-1 post-operation remained constant at a lower level than before surgery, and TIMP-2 Levels remained stable in both groups. IL-20 content started to increase in the third week after surgery. CONCLUSION: Inflammatory factor levels in tears fluctuated before and post-operation, which indicated more severe postoperative inflammation in the first two weeks.
RESUMO
Metastasis is a major cause of treatment failure and poor outcomes in cancer patients. The data used in the current study was downloaded from TCGA and GEO databases. Differentially expressed metastasis-related genes were identified and the biological functions were implemented. Kaplan-Meier analysis univariate, and, multivariate Cox regression analyses were performed to identify robust prognostic biomarkers, followed by construction of the risk model and nomogram. Gene set enrichment analysis was performed to identify pathways enriched in low- and high-risk groups. POLR2J3 and MYH11 were treated as prognostic biomarkers in LSCC and the risk model was constructed. Receiver operating characteristic curves revealed the good performance of the risk model. A nomogram with high accuracy was constructed, as evidenced by calibration and decision curves. Moreover, we found that the expressions of POLR2J3 and MYH11 was significantly higher in metastasis tissues compared with those in non-metastasis tissues by RT-qPCR and IHC. Our study identified novel metastasis-related prognostic biomarkers in LSCC and constructed a unique nomogram for predicting the prognosis of LSCC patients. Moreover, we explored the related mechanisms of metastasis-related genes in regulating LSCC.
Assuntos
Neoplasias de Cabeça e Pescoço , Nomogramas , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , BiomarcadoresRESUMO
Spider silk protein has attracted much attention on account of its excellent mechanical properties, biodegradability, and biocompatibility. As the main protein component of spider silk, spidroin plays important role in spider spinning under natural circumstances and biomaterial application in medicine as well. Compare to the native spidroin which has a large molecular weight (>300 kDa) with highly repeat glycine and polyalanine regions, the recombinant spidroin was maintained the core amino motifs and much easier to collect. Here, we reviewed the application of recombinant spider silk protein eADF4(C16), major ampullate spidroin (MaSp), minor ampullate spidroin (MiSp), and the derivatives of recombinant spider silk protein in drug delivery system. Moreover, we also reviewed the application of spider silk protein in the field of alternative materials, repairing materials, wound dressing, surgical sutures along with advances in recombinant spider silk protein.
Assuntos
Fibroínas/farmacologia , Fibroínas/uso terapêutico , Seda , Sequência de Aminoácidos , Animais , Portadores de Fármacos , Fibroínas/genética , Proteínas Recombinantes , Aranhas/metabolismoRESUMO
ABSTRACT: A 42-year-old woman underwent 131I radiotherapy for thyroid papillary cancer. A focal elevated 131I activity in the right kidney was revealed on the initial whole-body posttherapeutic images, which was located in the region of a renal stone. However, on the follow-up 131I images acquired 6 months later, there was no longer any increased activity in the region of this stone, which had moved into right ureter. Our case indicates that the 131I activity accumulated in the region of urinary stone is due to stagnated radioactive urine rather than due to the stone per se.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Cálculos Renais/complicações , Câncer Papilífero da Tireoide/complicações , Câncer Papilífero da Tireoide/radioterapia , Adulto , Feminino , Humanos , Câncer Papilífero da Tireoide/cirurgia , TireoidectomiaRESUMO
OBJECTIVE: To analyze the bacterial biofilm (BF) formation in patients with malignancy undergoing double J stent indwelling and its influencing factors. METHODS: A total of 167 patients with malignant tumors who received double J stent indwelling in the hospital from January 2018 to January 2021 were included in the study. The urine and double J stent samples were collected for bacterial identification and observed for BF formation on the surface of the urinary catheter under a scanning electron microscope (SEM). Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of BF. RESULTS: The BF formation rate was 34.73% (58/167). The BF formation rate of positive specimens cultured in urine and double J stent was significantly higher than that of negative ones (P<0.05). Staphylococcus was the main BF bacteria in double J stent and urine culture specimens, followed by Enterococcus, Pseudomonas, Enterobacter, and Acinetobacter. Compared with the non-BF group, the number of viable bacteria in the double J stent and urine and the catheterization time in the BF group rose markedly (P<0.05). Advanced age, chemotherapy, anemia, indwelling time ≥90d, and urinary tract infection were risk factors for BF formation in patients with malignancy undergoing double J stent indwelling (P<0.05). CONCLUSION: There is a high rate of BF formation in patients with malignancy undergoing double J stent indwelling, with Staphylococcus as the dominant species. Treatment requires enhanced urinary catheter management and nutritional status to inhibit BF formation and lower the rate of urinary catheter-related infections.
RESUMO
Aim: Metabolic syndrome (MS) screening is essential for the early detection of the occupational population. This study aimed to screen out biomarkers related to MS and establish a risk assessment and prediction model for the routine physical examination of an occupational population. Methods: The least absolute shrinkage and selection operator (Lasso) regression algorithm of machine learning was used to screen biomarkers related to MS. Then, the accuracy of the logistic regression model was further verified based on the Lasso regression algorithm. The areas under the receiving operating characteristic curves were used to evaluate the selection accuracy of biomarkers in identifying MS subjects with risk. The screened biomarkers were used to establish a logistic regression model and calculate the odds ratio (OR) of the corresponding biomarkers. A nomogram risk prediction model was established based on the selected biomarkers, and the consistency index (C-index) and calibration curve were derived. Results: A total of 2,844 occupational workers were included, and 10 biomarkers related to MS were screened. The number of non-MS cases was 2,189 and that of MS was 655. The area under the curve (AUC) value for non-Lasso and Lasso logistic regression was 0.652 and 0.907, respectively. The established risk assessment model revealed that the main risk biomarkers were absolute basophil count (OR: 3.38, CI:1.05-6.85), platelet packed volume (OR: 2.63, CI:2.31-3.79), leukocyte count (OR: 2.01, CI:1.79-2.19), red blood cell count (OR: 1.99, CI:1.80-2.71), and alanine aminotransferase level (OR: 1.53, CI:1.12-1.98). Furthermore, favorable results with C-indexes (0.840) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. Conclusions: The risk assessment model based on the Lasso logistic regression algorithm helped identify MS with high accuracy in physically examining an occupational population.