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We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.
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We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.
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Human hair, flue gas and fly ash from a municipal solid waste incinerator (MSWI) in south China were collected and analyzed for polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF). The ΣPCDD/F level in hair from male workers were higher than those from residents. The Principal Component Analysis (PCA) suggested that ΣPCDD/F in flue gas is an external source of male workers' hair ΣPCDD/F. Results of daily intake of ΣPCDD/F by inhaling flue gas suggested that the inhalation exposure of ΣPCDD/F was at a slight health risk. For the male workers directly exposed to the MSWI power plant, ΣPCDD/F levels in their hair were significantly higher than those who were non-directly exposed. Moreover, a significantly positive relationship was obtained between ΣPCDD/F levels in male workers' hair and the working time. The result of correlation analysis suggested that 1,2,3,4,6,7,8-HpCDD and OCDD could be level indicator congeners to estimate ΣPCDD/F levels. In addition, 2,3,7,8-TCDD could be applied as TEQ indicator congener to characterize the hair of MSWI male workers.
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Dibenzofuranos Policlorados/análisis , Cabello/química , Incineración , Exposición por Inhalación/análisis , Exposición Profesional/análisis , Dibenzodioxinas Policloradas/análisis , China , Ceniza del Carbón/análisis , Humanos , Masculino , Residuos Sólidos/análisisRESUMEN
BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.
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Brotes de Enfermedades , Poliomielitis/epidemiología , Vacuna Antipolio Oral , Poliovirus/genética , Adolescente , Adulto , Distribución por Edad , Proteínas de la Cápside/genética , Niño , Preescolar , China/epidemiología , Brotes de Enfermedades/prevención & control , Femenino , Humanos , Incidencia , Lactante , Masculino , Filogenia , Poliomielitis/diagnóstico , Poliomielitis/prevención & control , Poliomielitis/transmisión , Poliovirus/aislamiento & purificación , Vacuna Antipolio Oral/administración & dosificación , Vigilancia de la Población , Práctica de Salud Pública , Distribución por SexoRESUMEN
As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway.
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Infecciones por Enterobacteriaceae/veterinaria , Enfermedades de los Peces/genética , Regulación de la Expresión Génica , Infecciones por Rhabdoviridae/veterinaria , Transducción de Señal , Proteínas de Pez Cebra/genética , Pez Cebra , Secuencia de Aminoácidos , Animales , Antivirales/metabolismo , Línea Celular , Clonación Molecular , ADN Complementario/genética , ADN Complementario/metabolismo , Edwardsiella tarda/fisiología , Infecciones por Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/virología , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/virología , Interferón Tipo I/genética , Interferón Tipo I/metabolismo , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Rhabdoviridae/fisiología , Infecciones por Rhabdoviridae/genética , Infecciones por Rhabdoviridae/metabolismo , Infecciones por Rhabdoviridae/virología , Alineación de Secuencia/veterinaria , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/metabolismoRESUMEN
BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.
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Brotes de Enfermedades , Poliomielitis/epidemiología , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , China/epidemiología , Trazado de Contacto , Brotes de Enfermedades/prevención & control , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Poliomielitis/diagnóstico , Poliomielitis/prevención & control , Vigilancia en Salud Pública , Estudios Retrospectivos , Adulto JovenRESUMEN
Melanoma differentiation-associated gene 5 (MDA5) is one of the three members in the retinoic acid-inducible gene I-like receptor (RLR) family, which are cytoplasmic pathogen recognition receptors recognizing intracellular viruses. In the present study, MDA5 and its spliced shorter forms, named as MDA5a and MDA5b, were identified in zebrafish. MDA5a and MDA5b can be up-regulated in cell lines following the infection of a negative ssRNA virus, the spring viraemia of carp virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, implying that the RLR may also be able to sense elements released from bacteria. The over-expression of MDA5a and MDA5b in fish cells resulted in significant induction of type I interferon promoter activity and enabled the protection of transfected cells against SVCV infection. Furthermore, the shorter spliced form, MDA5b when co-transfected with MDA5a or mitochondrial antiviral signalling protein (MAVS), induced a significantly higher level of interferon promoter activity, indicating that MDA5b may function as an enhancer in the interaction between MDA5 and MAVS.
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ARN Helicasas DEAD-box/fisiología , Interferón Tipo I/genética , Regiones Promotoras Genéticas , Proteínas de Pez Cebra/metabolismo , Proteínas Adaptadoras Transductoras de Señales/fisiología , Secuencia de Aminoácidos , Animales , Línea Celular , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Células HEK293 , Humanos , Helicasa Inducida por Interferón IFIH1 , Datos de Secuencia Molecular , Transducción de Señal , Virosis/prevención & control , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
BACKGROUND: After being polio free for more than 10 years, an outbreak occurred in China in 2011 in Xinjiang Uygur Autonomous Region (Xinjiang) following the importation of wild poliovirus (WPV) originating from neighboring Pakistan. METHODS: To strengthen acute flaccid paralysis (AFP) surveillance in Xinjiang, "zero case daily reporting" and retrospective searching of AFP cases were initiated after the confirmation of the WPV outbreak. To pinpoint all the polio cases in time, AFP surveillance system was expanded to include persons of all ages in the entire population in Xinjiang. RESULTS: Totally, 578 AFP cases were reported in 2011 in Xinjiang, including 21 WPV cases, 23 clinical compatible polio cases and 534 non-polio AFP cases. Of the 44 polio cases, 27 (61.4%) cases were reported among adults aged 15-53 years. Strengthening AFP surveillance resulted in an increase in the number of non-polio AFP cases in 2011 (148 children < 15 years) compared with 76 cases < 15 years in 2010. The AFP surveillance system in Xinjiang was sensitive enough to detect polio cases, with the AFP incidence of 3.28/100,000 among children < 15 years of age. CONCLUSIONS: Incorporating adult cases into the AFP surveillance system is of potential value to understand the overall characteristics of the epidemic and to guide emergency responses, especially in countries facing WPV outbreak following long-term polio free status. The AFP surveillance system in Xinjiang was satisfactory despite limitations in biological sample collection.
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Brotes de Enfermedades , Parálisis/virología , Poliomielitis/epidemiología , Poliovirus , Adolescente , Adulto , Niño , Preescolar , China/epidemiología , Monitoreo Epidemiológico , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Pakistán , Parálisis/epidemiología , Poliomielitis/virología , Estudios Retrospectivos , Adulto JovenRESUMEN
Type I interferons (IFNs) are critical cytokines for the establishment of antiviral status in fish, amphibian, avian and mammal, but the knowledge on type I IFNs is rather limited in reptile. In this study, seven type I IFN genes, designed as IFN1 to IFN7, were identified from a reptile species, the Chinese soft-shelled turtle (Pelodiscus sinensis). These identified type I IFNs have relatively low protein identity, when compared with those in human and chicken; but they possess conserved cysteines, predicted multi-helix structure and N-terminal signal peptide. The Chinese soft-shelled turtle IFN1 to IFN5 have two exons and one intron, but IFN6 and IFN7 are the single-exon genes. Chinese soft-shelled turtle type I IFNs are located respectively on the two conserved reptile-bird loci, named as Locus a and Locus c, and are clustered into the four of the five reptile-bird groups (named as Groups I-V) based on phylogenetic evidence, due to the lack of IFNK in the turtle. Moreover, the Chinese soft-shelled turtle type I IFNs can be induced by soft-shelled turtle iridovirus (STIV) infection and show antiviral activity in soft-shelled turtle artery (STA) cells, except IFN6. In addition, due to the difference in genome organizations, such as the number of exons and introns of type I IFN genes from fish to mammal, the definition and evolution of 'intronless' type I IFN genes were discussed in lineages of vertebrates. Thus, the finding of type I IFNs on two different loci in P. sinensis sheds light on the evolution of type I IFN genes in vertebrates.
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Interferón Tipo I , Tortugas , Animales , Antivirales/metabolismo , China , Interferón Tipo I/genética , Mamíferos , Filogenia , Reptiles , Sintenía , Tortugas/genética , Tortugas/metabolismoRESUMEN
The pollution level, emission characteristics, and emission factors of PCDD/Fs from a number of steel plants were investigated in a particular province of China. The results showed that the concentration of PCDD/Fs was at a low level and decreased by 1-2 orders of magnitude compared with that in 2005-2019. In detail, the concentrations of PCDD/Fs ranged from 0.003-0.557 ng·m-3(I-TEQ), and the mean value was 0.165 ng·m-3 for the sintering process. Moreover, the concentrations of PCDD/Fs ranged from 0.006 to 0.057 ng·m-3, and the mean value was 0.025 ng·m-3 for the electric furnace process. In addition, the concentration of PCDD/Fs in the iron and steel industry from 2005 to 2020 increased first and then decreased, especially after the implementation of the new emission standard and the ultra-low emission control of conventional pollutants such as smoke, showing a significant decline. The results of fingerprint analysis showed that 2,3,7,8-TCDF was the largest congener contributing to the mass concentration, and lower chlorinated PCDFs were increased. This result differed from those of previous studies in which highly chlorinated PCDFs and PCDDs dominated, indicating that the generation source of PCDD/Fs had changed. The congener and isomer profiles of PCDD/Fs in flue gas from the sintering process were similar to those in the flue gas from the electric furnace process. Additionally, showing the characteristics of the typical high-temperature thermal process, the de novo synthesis may be the dominant mechanism of formation of PCDD/Fs in the sintering process and electric furnace process. The emission factor was 0.003-0.5 µg·t-1 (I-TEQ), and the average emission factor was (0.18±0.22) µg·t-1 for the sintering process. The emission factor was 0.04-0.5 µg·t-1, and the average emission factor was (0.27±0.23) µg·t-1 for the electric furnace process. These values were far lower than those of the standard toolkit for identification and quantification of dioxin and furan emissions released by UNEP in 2013 and the emission factors in the dioxin emission inventory of China in 2004. It is suggested that the emission factors of PCDD/Fs in the iron and steel industry of China should be studied and updated.
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Contaminantes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Contaminantes Atmosféricos/análisis , Dibenzofuranos/análisis , Dibenzofuranos Policlorados/análisis , Dioxinas/análisis , Monitoreo del Ambiente , Incineración , Hierro/análisis , Dibenzodioxinas Policloradas/análisis , Acero/análisisRESUMEN
As a member of a newly discovered protein family, the suppressor of cytokine signalling 3 (SOCS-3) has been shown to regulate the responses of many immune cytokines in a negative auto-regulatory manner. The full-length cDNA of common carp SOCS-3 was 1603 bp and contained a 630 bp open reading frame (ORF) coding for a protein of 209 amino acids. Carp SOCS-3 molecule was well conserved especially in the SRC homology 2 (SH2) and the SOCS box. The kinase inhibitory region (KIR) and ESS domains, upstream of the SH2 domain, were conserved in carp SOCS-3, except for a specific insertion (PHRYK) in the KIR domain at the N-terminal region. Three conserved cysteine (Cys-102, 124 and 193) residues, and one additional cysteine (Cys-168) residue, were also found in carp SOCS-3. The 2015 bp genomic DNA of carp SOCS-3 contained two exons and one intron. Phylogenetic analysis showed that carp SOCS-3 sequence grouped with other known fish SOCS-3 sequences with zebrafish SOCS-3 as the closest neighbour. RT-PCR analysis showed that carp SOCS-3 was initially expressed at 4 h pf (post-fertilization) and gradually increased up to 4 w pf during embryogenesis. By RT-qPCR analysis, carp SOCS-3 gene was predominantly detected in gill, head kidney, thymus and skin, followed by spleen and peripheral blood, lower expression level was detected in kidney, intestine, liver and muscle; the SOCS-3 transcript was significantly increased in thymus, head kidney, spleen and intestine of GH (growth hormone)-transgenic carp; after SVCV (spring viraemia of carp virus) infection, the carp SOCS-3 transcript was significantly up-regulated in gill, intestine, thymus, spleen, head kidney and kidney tissues in a time-dependent manner. These results suggest that teleost SOCS-3 may play an active role in the modulation of viral-induced innate immune response and in preventing the overaction of some cytokines with viral stimulation.
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Carpas/genética , Carpas/inmunología , Enfermedades de los Peces/inmunología , Regulación de la Expresión Génica , Infecciones por Rhabdoviridae/veterinaria , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Carpas/embriología , Carpas/virología , Clonación Molecular , Desarrollo Embrionario/inmunología , Perfilación de la Expresión Génica , Hormona del Crecimiento/genética , Datos de Secuencia Molecular , Filogenia , Infecciones por Rhabdoviridae/inmunología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Vesiculovirus/inmunologíaRESUMEN
OBJECTIVE: A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs). METHODS: A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used. RESULTS: Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval. CONCLUSION: Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.
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The emissions characteristics of 16 kinds of polycyclic aromatic hydrocarbons (PAHs) in ambient air during the waste tire retreading process (open-air storage, mixing, vulcanization, and grinding processes) and in workers' dormitory were analyzed. In addition, the occupational health risk of the workers was evaluated. Results showed that PAHs were detected in all retreading processes and in the workers' dormitory. The highest concentration site was the mixing process, followed by open-air storage and vulcanization process. The lowest concentration point was in the grinding process. The average concentration of PAHs in the workers' dormitory was 11.1 ng·m-3. The PAHs at all sampling points were largely phenanthrene (Phe), fluoranthene (Flu), anthracene (Ant), and pyrene (Pry), which also had a stronger linear correlation with the total PAH concentration. An analysis of the benzene rings showed that three ring and four ring were the majority, while two ring, five ring, and six ring components accounted for less than 10%. Results of the possible influencing factors of the PAHs revealed that the open-air storage and dormitory might be affected by a combustion source, but the mixing, vulcanization, and grinding processes might be affected by rubber oil. The principal component analysis (PCA) and cluster analysis showed that the spatial location of all sites would significantly influence the distribution of PAHs during the tire retreading process. The health risk assessment showed that occupational workers had a lower risk of lifelong cancer, and there was little influence on life expectancy.
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Contaminantes Atmosféricos/efectos adversos , Exposición Profesional/análisis , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Reciclaje , Residuos Sólidos , Monitoreo del Ambiente , Humanos , Medición de RiesgoRESUMEN
Erxian Tang is a Chinese herbal formula developed for the treatment of menopausal syndrome in women. In the past 50 years, EXT has shown positive efficacy in the treatment of many chronic diseases in TCM, involving syndrome types of Shen yin-yang deficiency, yin-deficiency caused yang-flourishing, and disharmony of Chong-Ren meridian. Experimental studies have revealed that EXT has multiple pharmacological actions on such multiple targets as hypothalamus-pituitary-target gland axis, immune function and free radical metabolism, etc.
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Investigación Biomédica , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Animales , Radicales Libres/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inmunidad/efectos de los fármacos , Menopausia/efectos de los fármacosRESUMEN
In this study, the inhibitory effect and mechanism of rifampicin on the activity of tyrosinase were investigated for developing a novel tyrosinase inhibitor. It was found to have a significant inhibition on the activity of tyrosinase (IC50=90±0.6µM). From the kinetics analysis, it was proved to be a reversible and noncompetitive type inhibitor of the enzyme with the KI value of 94±3.5µM. The results obtained from intrinsic fluorescence quenching indicated that rifampicin could interact with tyrosinase. In particular, the drastic decrease of fluorescence intensity was due to the formation of a rifampicin-enzyme complex in a static procedure which was mainly driven by hydrophobic forces and hydrogen bonding. Moreover, the ANS-binding fluorescence analysis suggested that rifampicin binding to tyrosinase changed the polarity of the hydrophobic regions. Molecular docking analysis further revealed that the hydrogen bonds were generated between rifampicin and amino residues Leu7, Ser52, and Glu107 in the B chain of the enzyme. And the hydrophobic forces produced through the interaction of rifampicin with B chain residues Pro9, Pro14, and Trp106. This work identified a novel tyrosinase inhibitor and potentially contributed to the usage of rifampicin as a potential hyperpigmentation drug.
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Inhibidores Enzimáticos/farmacología , Monofenol Monooxigenasa/antagonistas & inhibidores , Rifampin/farmacología , Agaricales/enzimología , Inhibidores Enzimáticos/metabolismo , Cinética , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/química , Monofenol Monooxigenasa/metabolismo , Conformación Proteica , Rifampin/metabolismoRESUMEN
This paper analyzed 17 polychlorinated dibenzo-p-dioxins and dibenzofurans(PCDD/Fs) by HRGC/HRMS in the flue gas of a certain municipal solid waste incinerator(MSWI) and its surrounding air and other possible sources in Guangdong. It discussed the feature of homologs and main toxic monomers in all samples. It also investigated the relationship among surrounding area, MSWI and possible sources using principle component analysis (PCA) and cluster analysis. The results showed that the concentration of PCDD/Fs was higher in the flue gas than the ambient air, moreover non-effect suffered by prevailing wind direction. The possible sources might be tyre factory and open burning based on spot survey. The concentration of PCDD/Fs was lower in tyre factory than upwind station, but higher at open burning spot than outdrop monitoring station. The analysis of homologs showed that OCDD, 1,2,3,4,6,7,8-HpCDD and 1,2,3,4,6,7,8-HpCDF were the main materials in the flue gas and air, meanwhile OCDF was also found in atmosphere. There was similar feature of 17 PCDD/Fs between surrounding monitoring station and tyre factory, and the same between flue gas and open burning. The further analysis showed that the linearly dependent coefficients of 1,2,3,7,8-PeCDD and 2,3,4,6,7,8-HxCDF were 0.95 and 0.75, respectively. It showed the strong correlation of two monomers in all ambient air samples. The PCA and cluster analysis showed that MSWI influenced the surrounding air, tyre factory had an impact on upwind station, and open burning had a lower effect on outdrop monitoring station.
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IFN-λ (IFNL), i.e. type III IFN genes were found in a conserved gene locus in tetrapod vertebrates. But, a unique locus containing IFNL was found in avian. In turtle and crocodile, IFNL genes were distributed in these two separate loci. As revealed in phylogenetic trees, IFN-λs in these two different loci and other amniotes were grouped into two different clades. The conservation in gene presence and gene locus was also observed for the receptors of IFN-λ, IFN-λR1 and IL-10RB in tetrapods. It is further revealed that in North American green anole lizard Anolis carolinensis, a single IFNL gene was situated collinearly in the conserved locus as in other tetrapods, together with its receptors IFN-λR1 and IL-10RB also identified in this study. The IFN-λ and its receptors were expressed in all examined organs/tissues, and their expression was stimulated following the injection of polyI:polyC. The ISREs in promoter of IFN-λ in lizard were responsible to IRF3 as demonstrated using luciferase report system, and IFN-λ in lizard functioned through the receptors, IFN-λR1 and IL-10RB, as the up-regulation of ISGs was observed in ligand-receptor transfected, and also in recombinant IFN-λ stimulated, cell lines. Taken together, it is concluded that the mechanisms involved in type III IFN ligand-receptor system, and in its signalling pathway and its down-stream genes may be conserved in green anole lizard, and may even be so in tetrapods from xenopus to human.
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Factor 3 Regulador del Interferón/metabolismo , Interleucinas/genética , Lagartos/inmunología , Filogenia , Receptores de Interferón/metabolismo , Caimanes y Cocodrilos/inmunología , Animales , Evolución Biológica , Línea Celular , Humanos , Factor 3 Regulador del Interferón/genética , Poli I-C/inmunología , Regiones Promotoras Genéticas/genética , Transducción de Señal , Tortugas/inmunología , XenopusRESUMEN
CXC195 exhibits strong protective effects against neuronal apoptosis by exerting antioxidant activity. However, the pharmacological function of CXC195 in cancer remains to be elucidated. The present study demonstrated that CXC195 exhibited significant cytotoxic effects, and induced cell cycle arrest and apoptosis in HepG2 human hepatocellular carcinoma (HCC) cell lines. Following treatment of HepG2 cells with 150 µΜ CXC195 for 24 , cell viability and the apoptotic rate were assessed using an MTT assay and Annexin V/propidium iodide staining followed by ï¬ow cytometric analysis. Molecular markers of the cell cycle, apoptosis, mitochondrial function and endoplasmic reticulum (ER) stress were analyzed by western blot or polymerase chain reaction analysis. Caspase activation, cytochrome c and apoptosisinducing factor release, and analysis of the B cell lymphoma 2 (Bcl2)associated X protein/Bcl2 ratio demonstrated that the anticancer effects of CXC195 in HepG2 cells were mediated by caspase and mitochondriadependent apoptosis. CXC195 also induced the expression of ER stressassociated proteins, including CCAATenhancerbinding protein homologous protein, and glucoseregulated proteins 94 and 78, and led to the activation of multiple branches of ER stress transducers, including inositolrequiring enzyme 1αapoptosis signalregulating kinasep38/cJun Nterminal kinase, and protein kinase Rlike endoplasmic reticulum kinaseeukaryotic translation initiation factor 2αactivating transcription factor (ATF)4 and ATF6, in the HepG2 cells. In addition, CXC195 inhibited the phosphorylation of phosphoinositide 3kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) in the HepG2 cells. These effects were enhanced following treatment with selected inhibitors of PI3K (LY294002), Akt (SH6) and mTOR (rapamycin). Furthermore, these inhibitors enhanced the proapoptotic effects of CXC195 in the HepG2 cells. In conclusion, the results of the present study indicated that CXC195 induced apoptosis and ER stress in HepG2 cells through the inhibition of the PI3K/Akt/mTOR signaling pathway.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Piperazinas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pirazinas/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Piperazinas/química , Pirazinas/química , Transducción de Señal/efectos de los fármacosRESUMEN
D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.
Asunto(s)
Envejecimiento/genética , Galactosa/farmacología , Metaboloma/efectos de los fármacos , Metabolómica , Transcripción Genética/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos ICR , Análisis Multivariante , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los ResultadosRESUMEN
To analysis the influencing factors for the emssions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) as structure of crematory, air pollution control device (APCD) and funeral objects, etc, we collected and measured the PCDD/Fs emissions in flue gas from 13 crematories in China. Then we proposed some supervision suggestions on measures of pollution control and management. The results indicated that the emission levels of PCDD/Fs (as the toxic equivalent concentration, TEQ) was ranged in a large gap from 0.027 to 15.8 ng x m(-3), and the average was 3.2 ng x m(-3). Emissions factor of PCDD/Fs (as TEQ) from 13 crematories varied between 45.9 and 22 236 ng x body(-1), and the average was 4 738 ng x body(-1). The emissions of PCDD/Fs from flat incinerators were generally lower, whereas higher ratio up to the national discharge standard, than that of car type incinerators. Congener distribution of PCDD/Fs in flue gas from 13 crematories were different from each other. Since the emission of PCDD/Fs from some crematories remains in high level, it is necessary to control pollution from the source, improve the pollution control technology, and strengthen government supervision, by following measures: 11 cremating funeral objects separately from corpse; 22 adding one