Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo...Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.展开更多
To show the risks and harm caused by the occupational exposure to the benzene, toluene, ethylbenzene and xylenes compounds (BTEX), the working conditions of 113 persons employed at gas stations in the cities of Riach?...To show the risks and harm caused by the occupational exposure to the benzene, toluene, ethylbenzene and xylenes compounds (BTEX), the working conditions of 113 persons employed at gas stations in the cities of Riach?o do Jacuipe, Feira de Santana and Salvador in the state of Bahia, Brazil were investigated by experts who correlated protection measures required by law and those applied to the workers. Data collection was performed by help of a questionnaire and non-participant observation record. The age groups of the workers in the three cities surveyed were between 18 to 25 years (30.08%) and 26 to 33 years (34.51%) of the total. The study revealed an association between occupational habits of workers at gas stations and the prevalence of symptoms due to the exposure to the BTEX compounds. Regarding the use of Personal Protective Equipment (PPE) most workers wear boots. The data show that these workers reported symptoms such as headache, rhinitis, leg pain, drowsiness, cough, fatigue, insomnia, tremors and palpitations. These disorders are related back to previous exposure to BTEX compounds which is associated with inadequate occupational habits of the workers which potentiate chemical contamination in their respective environment.展开更多
Objective: To evaluate the toxicological and psychotropic properties of Calotropis(C.) procera. Methods: C. procera leaves and root-bark aqueous extracts were evaluated for their toxic and behavioral effects using adu...Objective: To evaluate the toxicological and psychotropic properties of Calotropis(C.) procera. Methods: C. procera leaves and root-bark aqueous extracts were evaluated for their toxic and behavioral effects using adult mice. Toxicity studies were carried out using Organisation for Economic Cooperation and Development guidelines 423 and 407 for acute and subacute evaluation. Behavioral studies were performed using traction test, fireplace test, hole-board test and forced-swimming test to evaluate the sedative, anxiety and depressive-like activities of the extracts. Results: Very low acute toxicity was observed in mice that received both leaves and rootbark extracts. The subacute test showed some morphological, biochemical and hematological changes in the treated groups. Behavioral assessment demonstrated anxiety effects on mice for C. procera leaf extract(400 mg/kg of body weight). Conclusions: The acute use of C. procera(leaves and root-barks) aqueous extracts could be considered as low toxic. However, their repeated uses could have harmful effect on some organs. Likewise, a single dose up to 400 mg/kg body weight of these extracts produce no sedative or depressive-like effect, but they possess possible dose dependent anxiety effect. Yet, more studies are necessary to relate these results to the chemical profile of the plant extracts.展开更多
Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortal...Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.展开更多
Nocardiosis diagnosis is a major challenge. The clinical features and radiological findings are nonspecific. Traditionally, Nocardia identification is based on colonial and microscopical morphology and biochemical tes...Nocardiosis diagnosis is a major challenge. The clinical features and radiological findings are nonspecific. Traditionally, Nocardia identification is based on colonial and microscopical morphology and biochemical tests. However, molecular biology techniques allow a better characterization of species and biotypes. PCR-RFLP of the 65-kDa heat shock protein (HSP) gene provides a rapid, sensitive, and time and labor-efficient method for this proposal. Using this technique, six of eight isolates tested were identified as Nocardia asteroides type VI. PCR-RFLP of the 65-kDa HSP gene could be very useful for determining the incidence of this pathogen in different population groups and its association with susceptibility/resistance profiles to the drugs of choice for treatment. This work is the first molecular detection of Nocardia species in Cuba.展开更多
Objectives To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1(ISM1)and obesity-related phenotypes in a population of Spanish children and to investigate ...Objectives To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1(ISM1)and obesity-related phenotypes in a population of Spanish children and to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.Methods The study population is a sub-cohort of the PUBMEP research project,consisting of a cross-sectional population of 119 pubertal children with overweight(17 boys,19 girls),obesity(20 boys,25 girls),and normal weight(17 boys,21 girls).All subjects were classified into experimental groups according to their sex,obesity,and insulin resistance(IR)status.They were counted anthropometry,glucose and lipid metabolism,inflammation and cardiovascular biomarkers as well as isthmin-1(ISM1)serum levels.This population was intended as a discovery population to elucidate the relationship between obesity and ISM1 levels in children.Furthermore,the study population had blood whole-genome DNA methylation examined,allowing deepening into the obesity–ISM1 molecular relationship.Results Higher serum ISM1 levels were observed in boys with obesity than in normal weight(P=0.004)and overweight(P=0.007)boys.ISM1 serum levels were positively associated with body mass index(BMI)Z-score(P=0.005)and fat mass(P=0.058)and negatively associated with myeloperoxidase(MPO)(P=0.043)in boys.Although we did not find associations between ISM1 serum levels and metabolic outcomes in girls,which may indicate a putative sexual dimorphism,fat mass was positively associated in all children,including boys and girls(P=0.011).DNA methylation levels in two-enhancer-related CpG sites of ISM1(cg03304641 and cg14269097)were associated with serum levels of ISM1 in children.Conclusions ISM1 is associated with obesity in boys at the pubertal stage,elucidating how this protein might be of special relevance as a new biomarker of obesity in children.Further studies including a longitudinal design during puberty are needed.展开更多
Vascular smooth muscle cells（VSMCs） are the major component of vascular wall which are often stretched and compressed by pounding intravascular pressure.These mechanical signals are usually transformed to electrical...Vascular smooth muscle cells（VSMCs） are the major component of vascular wall which are often stretched and compressed by pounding intravascular pressure.These mechanical signals are usually transformed to electrical signals by the opening or closing of ion channels in VSNCs and endothelial cells.Intravascular pressure causes a graded membrane potential depolarization of the VSMCs and leads to vasoconstriction（i.e.,myogenic response）,independent of the vascular endothelium. Although the important role of cation channels including L-type Ca<sup>2+</sup> channels,K<sup>+</sup> channels,and TRP channels in the regulation of vascular tone has been well established the functional roles played by Cl<sup>-</sup> channels in the regulation of the membrane potential and vascular tone remain essentially obscure. Recent emerging evidence implicates very important roles of Cl<sup>-</sup> channels in vascular function ranging from the control of membrane potential equilibrium, vascular contraction and relaxation to the regulation of intracellular pH,cell volume homeostasis,cell proliferation,migration,and apoptosis.展开更多
In a recent paper in Science,Bruchez et al.1 provide new insights how host cells can fight virus infection.They show that an MHC class II transactivator(CIITA)—which normally operates as part of the interferon(IFN)-s...In a recent paper in Science,Bruchez et al.1 provide new insights how host cells can fight virus infection.They show that an MHC class II transactivator(CIITA)—which normally operates as part of the interferon(IFN)-stimulated immune response—is also involved in an antiviral response,beyond its well-known function of antigen presentation.展开更多
Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （holl...Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.展开更多
The rusty-necklaced partridge(Alectoris magna)and the chukar partridge(Alectoris chukar)are the most common gamebirds in northern China.Previous comparisons of mitochondrial DNA(mtDNA)have revealed an intr...The rusty-necklaced partridge(Alectoris magna)and the chukar partridge(Alectoris chukar)are the most common gamebirds in northern China.Previous comparisons of mitochondrial DNA(mtDNA)have revealed an introgression phenomenon between 2 species of partridge in the Liupan Mountain region of China.mtDNA is maternally inherited,making it difficult to determine the origin of parental genes.We assessed the genetic variation and gene flow between these 2 species of partridges using 8 microsatellite loci as neutral diagnostic markers in 171 samples from the hybrid zone.Our data revealed an extensive divergence of genetic structure between populations of rusty-necklaced partridges and chukar partridges.In this study,we found that 19 samples had been previously morphologically identified as rusty-necklaced partridge were genetically identified as hybrids through Bayesian analysis using STRUCTURE analysis.These hybrids exhibited a mosaic of alleles that were derived from both parental lineages.However,chukar partridges did not present the genotype of the rusty-necklaced partridge.Thus,our findings demonstrate that the hybridization between the 2 species was the result of asymmetrical introgression,with gene flow occurring only from the chukar partridge to the rusty-necklaced partridge.In addition,we also note the high linkage disequilibrium in populations of the rusty-necklaced partridge.These results indicate that although unidirectional introgression did not reduce genetic diversity of the Alectoris partridges,it affected the balance of gene flow between populations.The data from microsatellite DNA prompted our concern about the genetic integrity of the rusty-necklaced partridge.展开更多
基金funded by grants from Instituto de Salud Carlos III (Grant No. DTS15/00201 and DTS17/00081)Junta de Andalucía (Grant No. PIN-0474-2016)
文摘Pancreatic ductal adenocarcinoma(PDAC)has one of the highest mortality rates among all cancer types.Its delayed diagnosis precludes curative resection,thus most of the current therapies against PDAC are based on chemo-and radiotherapy.Unfortunately,these strategies are insufficient to improve its poor prognosis.Despite the advances made in chemotherapy(e.g.nab-paclitaxel and gemcitabine),many patients with PDAC are unable to benefit from them due to the rapid development of drug resistance.Currently,more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins,mucins,NF-κB,RAS and CXCR4.Moreover,drug resistance in PDAC is thought to be mediated by the modulation of miRNAs(e.g.miRNA-21,miRNA-145 and miRNA-155),which regulate genes that participate in cell proliferation,invasion and metastasis.Finally,cancer stem cells are intimately related to drug resistance in PDAC due to their ability to overexpress ABC genes-involved in drug transport-,and enzymes such as aldehyde dehydrogenases-implicated in cellular drug metabolism-and poly(ADP-ribose)polymerases-involved in drug-induced DNA damage repair.Understanding the mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with PDAC.
文摘To show the risks and harm caused by the occupational exposure to the benzene, toluene, ethylbenzene and xylenes compounds (BTEX), the working conditions of 113 persons employed at gas stations in the cities of Riach?o do Jacuipe, Feira de Santana and Salvador in the state of Bahia, Brazil were investigated by experts who correlated protection measures required by law and those applied to the workers. Data collection was performed by help of a questionnaire and non-participant observation record. The age groups of the workers in the three cities surveyed were between 18 to 25 years (30.08%) and 26 to 33 years (34.51%) of the total. The study revealed an association between occupational habits of workers at gas stations and the prevalence of symptoms due to the exposure to the BTEX compounds. Regarding the use of Personal Protective Equipment (PPE) most workers wear boots. The data show that these workers reported symptoms such as headache, rhinitis, leg pain, drowsiness, cough, fatigue, insomnia, tremors and palpitations. These disorders are related back to previous exposure to BTEX compounds which is associated with inadequate occupational habits of the workers which potentiate chemical contamination in their respective environment.
文摘Objective: To evaluate the toxicological and psychotropic properties of Calotropis(C.) procera. Methods: C. procera leaves and root-bark aqueous extracts were evaluated for their toxic and behavioral effects using adult mice. Toxicity studies were carried out using Organisation for Economic Cooperation and Development guidelines 423 and 407 for acute and subacute evaluation. Behavioral studies were performed using traction test, fireplace test, hole-board test and forced-swimming test to evaluate the sedative, anxiety and depressive-like activities of the extracts. Results: Very low acute toxicity was observed in mice that received both leaves and rootbark extracts. The subacute test showed some morphological, biochemical and hematological changes in the treated groups. Behavioral assessment demonstrated anxiety effects on mice for C. procera leaf extract(400 mg/kg of body weight). Conclusions: The acute use of C. procera(leaves and root-barks) aqueous extracts could be considered as low toxic. However, their repeated uses could have harmful effect on some organs. Likewise, a single dose up to 400 mg/kg body weight of these extracts produce no sedative or depressive-like effect, but they possess possible dose dependent anxiety effect. Yet, more studies are necessary to relate these results to the chemical profile of the plant extracts.
基金Junta de Andalucia,No.PC-0498-2017 and No.PC-0549-2017.
文摘Pancreatic cancer(PC)continues to pose a major clinical challenge.There has been little improvement in patient survival over the past few decades,and it is projected to become the second leading cause of cancer mortality by 2030.The dismal 5-year survival rate of less than 10%after the diagnosis is attributable to the lack of early symptoms,the absence of specific biomarkers for an early diagnosis,and the inadequacy of available chemotherapies.Most patients are diagnosed when the disease has already metastasized and cannot be treated.Cancer interception is vital,actively intervening in the malignization process before the development of a full-blown advanced tumor.An early diagnosis of PC has a dramatic impact on the survival of patients,and improved techniques are urgently needed to detect and evaluate this disease at an early stage.It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position;however,liquid biopsies are readily available and can provide useful information for the diagnosis,prognosis,stratification,and follow-up of patients with PC and for the design of individually tailored treatments.The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates,proteins,cell-free nucleic acids,circulating tumor cells,metabo-lome compounds,exosomes,and platelets in blood as potential biomarkers for PC,focusing on their clinical relevance and potential for improving patient outcomes.
文摘Nocardiosis diagnosis is a major challenge. The clinical features and radiological findings are nonspecific. Traditionally, Nocardia identification is based on colonial and microscopical morphology and biochemical tests. However, molecular biology techniques allow a better characterization of species and biotypes. PCR-RFLP of the 65-kDa heat shock protein (HSP) gene provides a rapid, sensitive, and time and labor-efficient method for this proposal. Using this technique, six of eight isolates tested were identified as Nocardia asteroides type VI. PCR-RFLP of the 65-kDa HSP gene could be very useful for determining the incidence of this pathogen in different population groups and its association with susceptibility/resistance profiles to the drugs of choice for treatment. This work is the first molecular detection of Nocardia species in Cuba.
基金supported by the Plan Nacional de Investigación Científca,Desarrollo e Innovación Tecnológica(I+D+I)Instituto de Salud Carlos III-Health Research Funding(FONDOS FEDER)(PI051968,PI1102042 and PI1600871)Maria C.Rico is funded by Redes temáticas de Investigación cooperativa RETIC(Red SAMID RD12/0026/0015)and the Mapfre Foundation.
文摘Objectives To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1(ISM1)and obesity-related phenotypes in a population of Spanish children and to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.Methods The study population is a sub-cohort of the PUBMEP research project,consisting of a cross-sectional population of 119 pubertal children with overweight(17 boys,19 girls),obesity(20 boys,25 girls),and normal weight(17 boys,21 girls).All subjects were classified into experimental groups according to their sex,obesity,and insulin resistance(IR)status.They were counted anthropometry,glucose and lipid metabolism,inflammation and cardiovascular biomarkers as well as isthmin-1(ISM1)serum levels.This population was intended as a discovery population to elucidate the relationship between obesity and ISM1 levels in children.Furthermore,the study population had blood whole-genome DNA methylation examined,allowing deepening into the obesity–ISM1 molecular relationship.Results Higher serum ISM1 levels were observed in boys with obesity than in normal weight(P=0.004)and overweight(P=0.007)boys.ISM1 serum levels were positively associated with body mass index(BMI)Z-score(P=0.005)and fat mass(P=0.058)and negatively associated with myeloperoxidase(MPO)(P=0.043)in boys.Although we did not find associations between ISM1 serum levels and metabolic outcomes in girls,which may indicate a putative sexual dimorphism,fat mass was positively associated in all children,including boys and girls(P=0.011).DNA methylation levels in two-enhancer-related CpG sites of ISM1(cg03304641 and cg14269097)were associated with serum levels of ISM1 in children.Conclusions ISM1 is associated with obesity in boys at the pubertal stage,elucidating how this protein might be of special relevance as a new biomarker of obesity in children.Further studies including a longitudinal design during puberty are needed.
文摘Vascular smooth muscle cells（VSMCs） are the major component of vascular wall which are often stretched and compressed by pounding intravascular pressure.These mechanical signals are usually transformed to electrical signals by the opening or closing of ion channels in VSNCs and endothelial cells.Intravascular pressure causes a graded membrane potential depolarization of the VSMCs and leads to vasoconstriction（i.e.,myogenic response）,independent of the vascular endothelium. Although the important role of cation channels including L-type Ca<sup>2+</sup> channels,K<sup>+</sup> channels,and TRP channels in the regulation of vascular tone has been well established the functional roles played by Cl<sup>-</sup> channels in the regulation of the membrane potential and vascular tone remain essentially obscure. Recent emerging evidence implicates very important roles of Cl<sup>-</sup> channels in vascular function ranging from the control of membrane potential equilibrium, vascular contraction and relaxation to the regulation of intracellular pH,cell volume homeostasis,cell proliferation,migration,and apoptosis.
基金supported by the“Excellence Initiative—Research University”program at the Nicolaus Copernicus UniversityK.P.is supported by the subsidy from the Polish Ministry of Science and Higher Education for the research on the SARS-CoV-2 and a grant from the National Science Center UMO-2017/27/B/NZ6/02488C.S.v.B.is supported by grant GM103554 from the National Institutes of Health.
文摘In a recent paper in Science,Bruchez et al.1 provide new insights how host cells can fight virus infection.They show that an MHC class II transactivator(CIITA)—which normally operates as part of the interferon(IFN)-stimulated immune response—is also involved in an antiviral response,beyond its well-known function of antigen presentation.
文摘Paclitaxel （PTX）, one of the most effective cytotoxins for the treatment of breast and lung cancer, is limited by its severe side effects and low tumor selectivity. In this work hollow-poly（4-vinylpyridine） （hollow-p4VP） nanoparticles （NPs） have been used for the first time to generate PTX@p4VP NPs, employing a novel technique in which a gold core in the center of the NP is further oxidized to produce the hollow structure into which PTX molecules can be incorporated. The hollow-p4VP NPs exhibit good physicochemical properties and displayed excellent biocompatibility when tested on blood （no hemolysis） and cell cultures （no cytotoxicity）. Interestingly, PTX@p4VP NPs significantly increased PTX cytotoxicity in human lung （A-549） and breast （MCF-7） cancer cells with a significant reduction of PTX ICs0 （from 5.9 to 3.6 nM in A-549 and from 13.75 to 4.71 nM in MCF-7）. In addition, PTX@p4VP caused a decrease in volume of A-549 and MCF-7 multicellular tumor spheroids （MTS）, an in vitro system that mimics in vivo tumors, in comparison to free PTX. This increased antitumoral activity is accompanied by efficient cell internalization and increased apoptosis, especially in lung cancer MTS. Our results offer the first evidence that hollow- p4VP NPs can improve the antitumoral activity of PTX. This system can be used as a new nanoplatform to overcome the limitations of current breast and lung cancer treatments.
基金supported by the National Natural Science Foundation of China(Nos.39870140,30470242 and 30530130).
文摘The rusty-necklaced partridge(Alectoris magna)and the chukar partridge(Alectoris chukar)are the most common gamebirds in northern China.Previous comparisons of mitochondrial DNA(mtDNA)have revealed an introgression phenomenon between 2 species of partridge in the Liupan Mountain region of China.mtDNA is maternally inherited,making it difficult to determine the origin of parental genes.We assessed the genetic variation and gene flow between these 2 species of partridges using 8 microsatellite loci as neutral diagnostic markers in 171 samples from the hybrid zone.Our data revealed an extensive divergence of genetic structure between populations of rusty-necklaced partridges and chukar partridges.In this study,we found that 19 samples had been previously morphologically identified as rusty-necklaced partridge were genetically identified as hybrids through Bayesian analysis using STRUCTURE analysis.These hybrids exhibited a mosaic of alleles that were derived from both parental lineages.However,chukar partridges did not present the genotype of the rusty-necklaced partridge.Thus,our findings demonstrate that the hybridization between the 2 species was the result of asymmetrical introgression,with gene flow occurring only from the chukar partridge to the rusty-necklaced partridge.In addition,we also note the high linkage disequilibrium in populations of the rusty-necklaced partridge.These results indicate that although unidirectional introgression did not reduce genetic diversity of the Alectoris partridges,it affected the balance of gene flow between populations.The data from microsatellite DNA prompted our concern about the genetic integrity of the rusty-necklaced partridge.
