RESUMO
Hepatocellular carcinoma (HCC), the third leading cause of cancer-associated mortality worldwide, is a major public health problem. Zinc finger protein A20 (A20), an acute phase response gene, is a potent inhibitor of NF-κB signaling. A20 serves a critical role in liver protection, including limiting inflammation following hepatic injury, stimulating hepatocyte growth, and preventing hepatic ischemia-reperfusion injury. A20 is also involved in different processes, including tumorigenesis, progression, and metastasis through multiple mechanisms. Accumulated studies have reported the clinical implications and biological relevance of A20 in the development and progression of HCC. The underlying mechanisms of A20 in HCC include inhibition of epithelial-mesenchymal transition, protein tyrosine kinase 2 activation and Rac family GTPase 1 activity. Combining liver protection with tumor inhibition is a unique advantage of A20, which has the potential to be a novel treatment for promoting liver regeneration following liver resection in patients with HCC with liver cirrhosis. This review discusses the hepato-protective effect of A20 on hepatocytes and its potential role in cancer development, particularly its suppressor effect on HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Transição Epitelial-Mesenquimal/fisiologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Regeneração Hepática/fisiologiaRESUMO
Legacy organic contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), and several currently used organic contaminants, such as novel brominated retardants (NBFRs), organophosphate flame retardants (OPFRs), and Dechlorane Plus (DPs), were measured in the segmented hair and hand wipes of e-waste dismantling workers and in the dust from their workplace in an e-waste recycling site in South China to assess the accumulation and sources of organic contaminants in the hair shaft. The median concentrations of DPs, PBDEs, NBFRs, PCBs and OPFRs in hair samples were 23.5, 154, 156, 349, and 371 ng/g, respectively. A linear increase in organic contaminant concentrations was found along the hair shaft, with significant differences among each segment, while the age-related patterns were similar among the 7 hair segments. A linear relationship was found between the accumulation rates and the log KOW, indicating that the accumulation rates of organic contaminants along the hair shaft decreased with increasing log KOW values. Enantiomer fraction (EF) values of PCB-132 in distal segments were close to those in dust and air, while EFs in proximal segments were close to those in serum. The contributions of PCBs from external sources to hair increased with the distance from the scalp of hair segments, from 67.8% in 0-3 cm segments to 95.9% in 18-21 cm segments.
Assuntos
Resíduo Eletrônico , Retardadores de Chama , Bifenilos Policlorados , China , Poeira , Monitoramento Ambiental , Feminino , Cabelo , Éteres Difenil Halogenados , Humanos , Local de TrabalhoRESUMO
Brominated flame retardants (BFRs) and Dechlorane Plus (DP) were measured in both human hair and paired serum samples from a cohort of university students in South China. Segmental analysis was conducted to explore gender difference and the relationships between the hair and serum. The concentrations of total PBDEs in the hair and serum samples were in a range of 0.28-34.1ng/g dry weight (dw) and 0.16-156ng/g lipid weight (lw), respectively. Concentrations of ∑DPs (sum of the syn-DP and anti-DP isomers) in all hair samples ranged from nd-5.45ng/g dry weight. Concentrations of most PBDEs and decabromodiphenylethane (DBDPE) in distal segments (5-10cm from the scalp) were higher than those in the proximal segments (0-5cm from the scalp) (t-test, p < 0.05), which could be due to the longer exposure time of distal segments. The proximal segments exhibited a unique congener profile, more close to that in the serum rather than the distal segments of hair. An obvious gender difference was found in the levels of ∑PBDEs using integrated hair samples, while the difference disappeared when considering alone the proximal segments of hair (0-5cm from scalp) for both genders. This paper provides supplement to the current knowledge on sources of BFRs and DPs in hair and declares the importance of segmental analysis.
Assuntos
Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Cabelo/química , Éteres Difenil Halogenados/sangue , Hidrocarbonetos Bromados/sangue , Hidrocarbonetos Clorados/sangue , Compostos Policíclicos/sangue , China , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/análise , Humanos , Hidrocarbonetos Bromados/análise , Hidrocarbonetos Clorados/análise , Masculino , Compostos Policíclicos/análise , Fatores SexuaisRESUMO
Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non-tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR-203 overexpression further promoted the regeneration of the non-tumorous liver by upregulating Ki67 expression and enhancing IL-6/SOCS3/STAT3 pro-proliferative signals. Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR-203 overexpression reversed the epithelial-mesenchymal transition induced by hepatectomy through targeting IL-1ß, Snail1 and Twist1. In conclusion, our results suggested that miR-203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial-mesenchymal transition.
Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Animais , Calpaína/biossíntese , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Hepatectomia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Antígeno Ki-67/biossíntese , Fígado/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Recidiva Local de Neoplasia/genética , Ratos , Ratos Wistar , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 1 Relacionada a Twist/metabolismoRESUMO
BACKGROUND: Liver resection or partial hepatectomy (PH) is still the most commonly used therapeutic option for hepatocellular carcinoma (HCC) at present. However, the impaired regenerative ability induced by the accompanied liver cirrhosis is an important risk factor of posthepatectomy liver failure, and posthepatectomy liver failure is a feared complication that accounts for up to 75% of mortality after extensive liver resection. MicroRNA(miR)-203 is a tumor suppressor of HCC and may act as a positive intermediary in A20-enhanced interleukin (IL-6)/signal transducer and activator of transcription 3 (STAT3) pro-proliferative signals, which may promote liver regeneration after PH. However, its direct pro-proliferative effect on cirrhotic liver after hepatectomy is unknown. MATERIALS AND METHODS: Liver cirrhosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution in adult male Wistar rat. Rats with liver cirrhosis received portal vein injection of physiological saline, miR-203 lentivirus, or control empty lentivirus, and then 70% PH was performed under ether anesthesia 7 d later. Liver samples were harvested at 0, 24, 36, and 72 h after 70% PH. Hepatic expressions of cyclin D1 and Ki67 were checked to evaluate the liver regenerative ability. Hepatic expressions of IL-6, suppressor of cytokine signaling 3 (SOCS3), and phospho-STAT3 were also tested to clarify the mechanisms of miR-203 in liver regeneration. RESULTS: The regeneration of miR-203 overexpression cirrhotic liver after 70% PH was enhanced and peaked at 24 and 36 h after 70% PH. The cyclin D1-positive liver cells/high-power field (HPF) in miR-203 overexpression liver markedly increased at 24 and 36 h after 70% PH compared with 0-h samples. When comparing with the control groups, cyclin D1-positive liver cells/HPF in miR-203 overexpression liver were also significantly increased at 24 and 36 h after 70% PH. A similar result of the Ki67-positive liver cells/HPF was achieved at 36 h after 70% PH. The hepatic expression of IL-6 showed a rising tendency after 70% PH, and the levels of IL-6 are significantly higher in miR-203 overexpression livers. Hepatic expression of SOCS3 was negatively expressed with hepatic miR-203 expression level, and the reduced expression of SOCS3 facilitated the phosphorylation of STAT3. CONCLUSIONS: By targeting SOCS3 and then enhancing proliferating IL-6/STAT3 signaling pathway, hepatic overexpression of miR-203 can facilitate the initiation of liver regeneration and enhance the potency of liver regeneration after 70% PH in cirrhotic rat. Together with the tumor suppressive effect on HCC, miR-203 would be an ideal candidate for promoting liver regeneration in HCC patients undergoing liver resection without the risk of tumorigenesis or cancer recurrence.
Assuntos
Hepatectomia , Cirrose Hepática/cirurgia , Regeneração Hepática/fisiologia , MicroRNAs/metabolismo , Animais , Biomarcadores/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/fisiopatologia , Masculino , Período Pós-Operatório , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
Human hair has been employed as a biomarker for exposure to persistent organic pollutants (POPs), but information on the source of dichloro-diphenyl-trichloroethane (DDT) and its metabolites in hair is limited. The present study investigated the contamination of DDTs in human hair from a rural area and an urban area of South China and compared with those in human serum and indoor dust. The concentrations of ∑DDTs ranged from 2.30 to 489ng/g, with a median of 21.8ng/g in human hair. The ∑DDT concentrations (median=40.8ng/g) in female hair were significantly higher than those in male hair (median=20.6ng/g). There were significantly positive correlations between the concentrations of DDTs and ages in both the female and male hair, but the age-dependence for DDTs in serum was less significant. The profile of DDT analogues in female hair, differing from that in the male hair, was more similar to that in the indoor dust, suggesting a more important role of exogenous exposure in female hair. We estimated that exogenous source is responsible for approximately 11% and 20% of the burden of DDTs in the male and female hair, respectively. Adjusted multiple linear regression model showed significantly positive association between the p,p'-DDE concentrations in the paired hair and serum samples, indicating that endogenous origins are the primary sources of DDTs in the hair of the residents in the study areas. Our findings demonstrated that human hair is a reliable biomarker for body burden of DDTs and can be used in epidemiology research and retrospective assessment of DDT exposure.
Assuntos
DDT/análise , Poluentes Ambientais/análise , Cabelo/química , Inseticidas/análise , Adolescente , Adulto , Poluição do Ar em Ambientes Fechados/análise , Criança , Pré-Escolar , China , DDT/sangue , Poeira/análise , Monitoramento Ambiental , Poluentes Ambientais/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Inseticidas/sangue , Masculino , Pessoa de Meia-Idade , População Rural , População Urbana , Adulto JovemRESUMO
The concentrations of several organic contaminants (OCs) and heavy metals were measured in indoor dust from e-waste recycling, rural, and urban areas in South China to illustrate the spatial characteristics of these pollutants and to further evaluate human exposure risks. The median concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), and dechlorane plus (DPs) were 38.6-3560, 2360-30,100, 665-2720, and 19.5-1860ng/g, while the median concentrations of Cd, Pb, Cu, Cr, and Zn were 2.46-40.4, 206-1380, 217- 1200, 25.3-134, and 176-212µg/g in indoor dust. The levels of all pollutants, except Zn, in dust from the e-waste recycling area were significantly higher than those from the other areas. Cd, Pb, and most OCs exhibited similar pollution patterns in the three areas, indicating that e-waste recycling activities are the major pollution source. In contrast, Cu, Cr, Zn, and penta-BDE are likely derived from household products in the rural and urban areas. The highest estimated daily intakes (EDIs) of PCBs, PBDEs, DBDPE, and DPs were 0.15-163, 3.97-1470, 1.26-169, and 0.11-134ng/kg bw/day for toddlers and adults. The highest EDIs of BDE 209 and Pb in toddlers in the e-waste recycling area were 16% and 18 times higher than the reference doses, indicating the high exposure risk of these pollutants in the e-waste recycling area.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Resíduo Eletrônico/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Bifenilos Policlorados/análise , Reciclagem , Adulto , Pré-Escolar , China , Éteres Difenil Halogenados/análise , Humanos , Hidrocarbonetos Clorados/análise , Compostos Policíclicos/análise , Saúde da População Rural , Saúde da População UrbanaRESUMO
Hair is a promising, non-invasive, human biomonitoring matrix that can provide insight into retrospective and integral exposure to organic pollutants. In the present study, we measured the concentrations of organophosphate flame retardants (PFRs) in hair and serum samples from university students in Guangzhou, China, and compared the PFR concentrations in the female hair segments using paired distal (5~10cm from the root) and proximal (0~5cm from the root) samples. PFRs were not detected in the serum samples. All PFRs except tricresyl phosphate (TMPP) and tri-n-propyl phosphate (TPP) were detected in more than half of all hair samples. The concentrations of total PFRs varied from 10.1 to 604ng/g, with a median of 148ng/g. Tris(chloroisopropyl) phosphate (TCIPP) and tri(2-ethylexyl) phosphate (TEHP) were the predominant PFRs in hair. The concentrations of most PFRs in the distal segments were 1.5~8.6 times higher than those in the proximal segments of the hair (t-test, p<0.05), which may be due to the longer exposure time of the distal segments to external sources. The values of log (PFR concentrations-distal/PFR concentrations-proximal) were positively and significantly correlated with log KOA of PFRs (p<0.05, r=0.68), indicating that PFRs with a higher log KOA tend to accumulate in hair at a higher rate than PFRs with a lower log KOA. Using combined segments of female hair, significantly higher PFR concentrations were observed in female hair than in male hair. In contrast, female hair exhibited significantly lower PFR concentrations than male hair when using the same hair position for both genders (0-5cm from the scalp). The controversial results regarding gender differences in PFRs in hair highlight the importance of segmental analysis when using hair as an indicator of human exposure to PFRs.
Assuntos
Poluentes Ambientais/análise , Retardadores de Chama/análise , Cabelo/química , Organofosfatos/análise , Adulto , China , Monitoramento Ambiental/métodos , Feminino , Humanos , Masculino , Fatores Sexuais , Adulto JovemRESUMO
Thirty surface sediments and three sediment cores were collected from mangrove wetlands in the Pearl River Estuary of South China to investigate the spatial and vertical distribution of Dechlorane Plus (DP). DP concentrations in the mangrove surface sediments ranged from 0.0130 to 1.504 ng/g dry weight (dw). DP concentrations in sediments from Shenzhen were significantly greater than those from Guangzhou and Zhuhai. Anti-Cl11-DP, the dechlorinated product of anti-DP, was also detected in the mangrove sediments with concentrations ranged from not detected to 0.0198 ng/g dw. Significant positive relationship between anti-Cl11-DP and anti-DP levels was observed in the mangrove sediments, suggesting that photo and/or microbial degradation of anti-DP might occur in the sediments. The f anti values in the mangrove sediments were close to those in the technical DP products, suggesting that stereoselective enrichment of anti-DP may not exist in the mangrove sediments. DP concentrations in the mangrove sediment cores generally showed an increasing trend from the bottom to top layers. This is the first study to report the occurrence of DP and its degradation product in the mangrove wetlands.
Assuntos
Monitoramento Ambiental , Sedimentos Geológicos/química , Hidrocarbonetos Clorados/análise , Compostos Policíclicos/análise , Poluentes Químicos da Água/análise , Áreas Alagadas , ChinaRESUMO
OBJECTIVE: The efficacy and safety of ultrasound-guided abdominal paracentesis drainage ahead of percutaneous catheter drainage as the new second step of a step-up approach are evaluated. DESIGN: The observed parameters were compared between groups including mortality, infection, organ failure, inflammatory factor levels, indexes of further interventions, and drainage-related complications. PATIENTS: This retrospective study included 102 consecutive patients with acute pancreatitis from June 2009 to June 2011. INTERVENTIONS: In this step-up approach, all patients subsequently received medical management, percutaneous catheter drainage (with or without previous abdominal paracentesis drainage), and necrosectomy if necessary according to indications. The patients were divided into two groups: 53 cases underwent abdominal paracentesis drainage followed by percutaneous catheter drainage (abdominal paracentesis drainage + percutaneous catheter drainage group) and 49 cases were managed only with percutaneous catheter drainage (percutaneous catheter drainage-alone group). MEASUREMENTS AND MAIN RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the abdominal paracentesis drainage + percutaneous catheter drainage group (0%) than the percutaneous catheter drainage-alone group (8.2%) (p = 0.050). Compared with the percutaneous catheter drainage-alone group, the laboratory variables of the abdominal paracentesis drainage + percutaneous catheter drainage group decreased more rapidly, the mean number of failed organs was lower, and the interval from the onset of disease to further interventions was much longer. However, there was no significant difference in the prevalence and duration of infections between the two groups. CONCLUSION: Application of abdominal paracentesis drainage ahead of percutaneous catheter drainage is safe and beneficial to patients by reducing inflammatory factors, postponing further interventions, and delaying or avoiding multiple organ failure.
Assuntos
Drenagem/métodos , Pancreatite/terapia , Paracentese/métodos , APACHE , Cavidade Abdominal , Doença Aguda , Drenagem/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Pancreatite/mortalidade , Estudos Retrospectivos , Ultrassonografia de Intervenção/métodosRESUMO
Polychlorinated biphenyls (PCBs) and enantiomer fractions (EFs) of PCB enantiomers (PCBs 95, 132, 135, and 149) were investigated in soil and chicken feed, chicken (Gallus domesticus) tissues, eggs on 0, 7, and 14 days after the onset of incubation, and newborn chick tissues. The EF values of PCBs 95, 132, and 149 changed significantly from soil to chicken tissues, and the values in the liver exhibited the highest deviation from the racemic ratio, indicating enantiomer-selective metabolism in hens. Congeners, which are highly resistant to degradation, such as PCBs 138, 153, and 180, exhibited the highest maternal transfer potentials when muscle and liver were used to assess the maternal transfer. However, uniform transfer ratios were observed for most of the PCB congeners when visceral fat was used. The EFs of chiral PCBs in eggs either did not match with muscle or with liver or were similar to those in visceral fat. These results indicate that hens mainly mobilized visceral fat for egg formation and PCBs were deposited in eggs by associating with these lipid materials. Further enantiomeric enrichment of PCBs 95, 132, and 149 occurred in the newborn chick tissues. However, an opposite enantioselectivity for PCB 135 in newborn chicks was observed. These results indicate that the potential toxicity of PCB enantiomers to newborn chicks may be different from that of adults.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/análise , Ração Animal , Animais , Galinhas/metabolismo , Feminino , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Exposição Materna , Músculos/metabolismo , Óvulo/metabolismo , Solo/química , Estereoisomerismo , Distribuição TecidualRESUMO
Dechlorane plus (DP) is a high-productive volume substance which had been identified as ubiquitous pollutant and has been widely detected in biota. In the present study, common carp (Cyprinus carpio) was exposed to known amounts of commercial DP-25 under laboratory conditions. The gastrointestinal absorption and tissue-specific bioaccumulation of DP and its dechlorinated analogs in common carp were investigated. The higher absorption efficiencies but lower assimilation efficiencies of anti-isomers indicated stereoselective metabolism of anti-isomers in fish. Linear uptake curves were seen in serum and muscle, but the depuration curves for all the four tissues (muscle, serum, liver and gonad) did not follow the first-order kinetics. The liver exhibited a high affinity for anti-isomers during the experiment. Other tissues, such as serum, muscle, and gonad, showed a selective accumulation of syn-DP in the early stages of the experiment, particularly the serum. However, the deviation of fanti between different tissues disappeared at late stages of the experiment, and the fanti values in all tissues were close to that in commercial mixtures. Our results suggest that the bioaccumulation of DP is a complex and multi-factorial process.
Assuntos
Carpas/metabolismo , Retardadores de Chama/análise , Trato Gastrointestinal/metabolismo , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/metabolismo , Compostos Policíclicos/química , Compostos Policíclicos/metabolismo , Poluentes Químicos da Água/análise , Absorção , Animais , Dieta , Retardadores de Chama/metabolismo , Trato Gastrointestinal/química , Hidrocarbonetos Clorados/análise , Isomerismo , Compostos Policíclicos/análise , Poluentes Químicos da Água/químicaRESUMO
Halogenated organic pollutants (HOPs)-including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs), polybromobiphenyls (PBBs), dechlorane plus (DP), tetrabromobisphenol A (TBBPA), and hexabromocyclododecanes (HBCDs) as well as PCB metabolites (methylsulfone [MeSO2-]) and hydroxylated (OH-) PCBs and OH-PBDEs-were determined in the serum of mud carp and northern snakehead from an electronic-waste (e-waste) site in South China. The average concentrations (mean ± SD) of ΣPCBs, ΣPBDEs, ΣOCPs, ΣPBBs, ΣTBBPA, ΣHBCDs, and ΣDP were 1410 ± 324, 70 ± 20, 3.0 ± 0.4, 2.8 ± 0.8, 1.6 ± 0.4, 1.0 ± 0.2, and 0.3 ± 0.03 ng/g wet weight (ww) in mud carp and 6430 ± 781, 468 ± 49, 22.4 ± 1.1, 7.0 ± 0.6, 2.9 ± 2.3, 5.5 ± 1.1, and 4.6 ± 0.6 ng/g ww in northern snakehead, respectively. MeSO2-PCBs, OH-PCBs, and OH-PBDEs were detected at a total concentration of 0.44 ± 0.03 and 9.7 ± 0.3 ng/g ww in mud carp and northern snakehead, respectively. The congener profiles of PCBs, PBDEs, OH/MeSO2-PCBs, and OH-PBDEs were found to be significantly different between the two fish species, possibly as a result of species-specific bioaccumulation and/or metabolism of the HOPs. Chirality of ten PCB congeners and α-HBCD, as well as the f anti values of DP in the serum samples, supported the species-specific biotransformation of HOPs. Furthermore, the presence of covaried and counter-varied enantiomeric fractions of PCBs between the two fish species indicated species- and congener-specific enantiomer enrichment of PCBs.
Assuntos
Resíduo Eletrônico , Monitoramento Ambiental , Peixes/sangue , Poluentes Químicos da Água/sangue , Animais , China , Poluentes Ambientais/metabolismo , Peixes/metabolismo , Éteres Difenil Halogenados/metabolismo , Hidrocarbonetos Clorados/metabolismo , Praguicidas/metabolismo , Bifenilos Policlorados/metabolismo , Poluentes Químicos da Água/metabolismoRESUMO
PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-â , 175 eyes), moderate clinical keratoconus (CKC-â ¡, 204 eyes), and severe clinical keratoconus (CKC-â ¢, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.
Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico , Topografia da Córnea , Córnea , Tonometria Ocular , Pressão Intraocular , Curva ROC , Fenômenos BiomecânicosRESUMO
Iron accumulation is one of the most essential pathological events after subarachnoid hemorrhage (SAH). Ferroportin1 (FPN1) is the only transmembrane protein responsible for exporting iron. Hepcidin, as the major regulator of FPN1, is responsible for its degradation. Our study investigated how the interaction between FPN1 and hepcidin contributes to iron accumulation after SAH. We found that iron accumulation aggravated after SAH, along with decreased FPN1 in neurons and increased hepcidin in astrocytes. After knocking down hepcidin in astrocytes, the neuronal FPN1 significantly elevated, thus attenuating iron accumulation. After SAH, p-Smad1/5 and Smad4 tended to translocate into the nucleus. Moreover, Smad4 combined more fragments of the promoter region of Hamp after OxyHb stimulation. By knocking down Smad1/5 or Smad4 in astrocytes, FPN1 level restored and iron overload attenuated, leading to alleviated neuronal cell death and improved neurological function. However, the protective role disappeared after recombinant hepcidin administration. Therefore, our study suggests that owing to the nuclear translocation of transcription factors p-Smad1/5 and Smad4, astrocyte-derived hepcidin increased significantly after SAH, leading to a decreased level of neuronal FPN1, aggravation of iron accumulation, and worse neurological outcome.
Assuntos
Hepcidinas , Hemorragia Subaracnóidea , Humanos , Hepcidinas/genética , Hepcidinas/metabolismo , Astrócitos/metabolismo , Hemorragia Subaracnóidea/patologia , Ferro/metabolismo , Neurônios/metabolismoRESUMO
BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.
Assuntos
Coenzima A-Transferases , Disfunção Cognitiva , Hipocampo , Neurogênese , Hemorragia Subaracnóidea , Ácido 3-Hidroxibutírico , beta Catenina , Coenzima A-Transferases/genética , Coenzima A-Transferases/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas c-akt , Animais , CamundongosRESUMO
The recycling of electrical and electronic waste(e-waste) in developing countries has attracted much attention as a significant source of brominated flame retardants (BFRs).Gaseous and particle-bound BFRs were measured in the atmosphere at e-waste and rural sites in southern China during 2007-2008. The annual average concentrations in the air were 3260 ± 3370 and 219 ± 192 pg/m³ for polybrominated diphenyl ethers (PBDEs) and were 546 ± 547 and 165 ± 144 pg/m³ for non-PBDE BFRs at the e-waste and rural sites,respectively. PBDEs had unusually high relative concentrations of di- and tribrominated congeners at the e-waste site. The Clausius-Clapeyron (CC) plots showed that the gaseous concentrations of less brominated BFRs (di- through hexa-BFRs) were strongly controlled by temperature-driven evaporation from contaminated surfaces (e.g., e-waste, soils, and recycled e-waste remains) except for winter. However, weak temperature dependence at the rural site suggests that regional or long-range atmospheric transport was largely responsible for the air concentrations. Gas-particle partitioning (KP) of PBDEs correlated well with the subcooled liquid vapor pressure (PL(o)) for most sampling events. The varied slopes of log KP versus log PL(o) plots for the e-waste site (-0.59 to -1.29) indicated an influence of ambient temperature and atmospheric particle properties on the partitioning behavior of BFRs. The flat slopes (-0.23 to -0.80) for the rural site implied an absorption-dominant partitioning. This paper suggests that e-waste recycling in Asian low-latitude regions is a significant source of less brominated BFRs and has important implications for their global transport from warm to colder climate
Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Retardadores de Chama/análise , Estações do Ano , China , Resíduo Eletrônico/análise , Éteres Difenil Halogenados/análise , TemperaturaRESUMO
BACKGROUND: Recent studies have reported that circular RNAs (circRNAs) are involved in the development of hepatocellular carcinoma (HCC). This study evaluated the expression of preoperative peripheral venous blood circRNAs in HCC patients and their predictive ability for microvascular invasion (MVI). METHODS: Seven circRNAs (circMTO1, circ-10720, circZKSCAN1, cSMARCA5, circHIPK3, circSETD3 and ciRS-7) were screened from the literature as circRNAs with reported biological functions in HCC. The expression levels of seven circRNAs in preoperative blood samples and HCC tissues were detected by quantitative reverse transcription polymerase chain reaction. The correlations between the circRNA expressions in blood and the clinicopathological factors of HCC patients were analyzed. The risk factors of MVI were analyzed by univariate and multivariate logistic regression. The functional role of circSETD3 in cell migration and invasion was evaluated by wound healing and Transwell assays in vitro. RESULTS: The expressions of all seven circRNAs were measured in peripheral venous blood samples. The venous expression levels of circHIPK3 and circMTO1 were significantly associated with gender, while circ-10720 and circMTO1 levels were significantly correlated with gross vascular invasion. Furthermore, circMTO1 and cSMARCA5 levels were significantly associated with alpha-fetoprotein level and ciRS-7 was significantly associated with satellite nodules. Importantly, low venous circSETD3 expression was significantly associated with prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) level, MVI, gross vascular invasion, and liver capsule. Furthermore, venous circSETD3 expression had predictive ability for MVI. Knockdown of circSETD3 promoted cell invasion and metastasis in vitro. CONCLUSIONS: CircRNAs were stably present in peripheral venous blood and associated with multiple clinicopathological characteristics of HCC patients. Venous circSETD3 was an independent risk factor of MVI and shows ability to predict MVI in HCC patients before surgery.
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A new species, Pythium subutonaiense, isolated from aquatic environments (lake) in China is being described based on morphological characters and molecular evidence. The isolates grew at temperatures between 5 °C and 38 °C, and the optimum temperature was 30 °C, with a radial growth rate of 17.6 mm at 25 °C per day. It is homothallic and characterized by globose to sub-globose shaped and mostly terminal or sometimes catenulate hyphal swellings, filamentous non-inflated sporangia, and smooth oogonia with hypogynous and monoclinous antheridia that contained one plerotic oospore. In phylogenetic analysis, inferred based on the internal transcribed spacer region of the ribosomal RNA gene and mitochondrial cytochrome c oxidase subunit 1 gene, the new species formed a distinct lineage in Pythium clade B. Differences between the new species and phylogenetically related and morphologically similar species are discussed.
RESUMO
A comparative analysis was conducted using total ozone products derived from monitoring atmospheric composition and climate (MACC) reanalysis data validated with ozone data from the atmospheric infrared sounder (AIRS) satellite and ground-based ozone measurements. The results indicate that the relative deviation of total ozone from the MACC reanalysis data and the ground-based ozone total data is controlled within 17%, and all of the correlation coefficients were between 0.79 and 0.97. The total ozone values from the MACC reanalysis data showed good consistency with the ground-based ozone measurements. With respect to the spatial distribution of multi-year averages, the relative deviation of total ozone values in the MACC reanalysis data and the AIRS satellite data was between -3% and 5%. The total ozone values in the MACC reanalysis data were higher than those from AIRS measurements for the Qinghai-Tibet Plateau and the coastal areas of South China, and were lower for northeast China. Furthermore, the seasonal variations in total ozone values in the MACC reanalysis data were consistent with AIRS data. At Mt. Waliguan station, the monthly averaged trends for near-surface ozone in the MACC reanalysis data were also consistent with surface ozone concentrations; the MACC reanalysis data reflect the observed trends for surface-based ozone measurements in spring, summer, and autumn, but show a large deviation in winter.