RESUMO
OBJECTIVE: To investigate the association of the haplotypes and genotype combinations of vitamin D receptor (VDR) BsmI (rs1544410), Tru9I (rs757343), ApaI (rs7975232), and TaqI (rs731236) with the susceptibility to elevated blood lead in Chinese Han population. METHODS: According to Diagnostic Criteria of Occupational Chronic Lead Poisoning (GBZ 37-2002) and Occupational Exposure Limits for Hazardous Agents in the Workplace Part 1: Chemical Hazardous Agents (GBZ 2.1-2007), the workers were divided into high-exposure group (lead dust ≥ 0.05 mg/m(3), lead fume ≥ 0.03 mg/m(3)) and low-exposure group based on the concentrations of lead fume and lead dust in the workplace. The high-exposure group was further divided into normal-blood lead subgroup and high-blood lead subgroup. Fasting peripheral venous blood (5 ml) was collected using a heparin tube; genomic DNA was extracted from the peripheral blood cells with a Qiagen kit; single nucleotide polymorphisms were detected by allelic discrimination assay using TaqMan probes (carrying fluorescent dyes); haplotypes were analyzed and compared by Haploview. RESULTS: VDR BsmI, Tru9I, ApaI, and TaqI were in Hardy-Weinberg equilibrium between the normal-blood lead subgroup and high-blood lead subgroup (P > 0.05). Compared with haplotype CCCA which had the highest distribution frequency, haplotypes CCAA and CTCA were the high-risk factors for elevated blood lead (OR = 1.814, 95%CI = 1.055 â¼ 3.119; OR = 1.919, 95%CI = 1.040 â¼ 3.540). Compared with genotype combination CC + CC + CC + AA which had the highest distribution frequency, genotype combination CC + CC + AC + AA was the high-risk factor for elevated blood lead (OR = 2.800, 95%CI = 1.282 â¼ 6.116). CONCLUSION: As for VDR BsmI, Tru9I, ApaI, and TaqI, haplotypes CCAA and CTCA and genotype combination CC + CC + AC + AA are associated with the susceptibility to elevated blood lead.
Assuntos
Chumbo/sangue , Exposição Ocupacional , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adolescente , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: The transplantation of neural stem cells (NSCs) has been accepted as a promising therapeutic strategy for central nervous system disorders. However, the beneficial effect of NSC transplantation upon functional recovery is limited due to the unfavorable microenvironment (niche) at the site of trauma or degenerative disease in the brain. Combination of transplantation of NSCs with neurotrophins may overcome the hurdles of impaired cell survival and neuronal differentiation. MATERIAL/METHODS: In the current study, the neurotrophin-3 (NT-3) gene was transduced into cultured mouse embryonic cortical NSCs via an AAV vector (NSC-NT-3). The effect of NT-3 over-expression on cell proliferation and differentiation in NSCs was observed by immunohistochemistry, cell culture and organotypic hippocampal slice cultures.
RESULTS: The characteristics of self-renewal and multiple differentiation of NSCs were well-preserved. Cells in the NSC-NT-3 group proliferated faster and differentiated into more ß-tubulin III-positive neurons compared to the control group in vitro. Furthermore, cells in the NSC-NT-3 group survived in a significantly higher percentage and undertook neuronal differentiation preferably in organotypic hippocampal slice cultures. CONCLUSIONS: Our results suggest that the transduction of NT-3 into NSCs could effectively promote NSCs survival, proliferation, and neuronal differentiation in vitro without change of the stemness of NSCs. This work also offers evidence to better understand the safety and efficiency of combined treatment with NT-3 and NSCs for the central nervous system disorders.
Assuntos
Diferenciação Celular/fisiologia , Proliferação de Células , Hipocampo/citologia , Células-Tronco Neurais/citologia , Neurotrofina 3/genética , Transdução Genética/métodos , Análise de Variância , Animais , Células Cultivadas , Dependovirus , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos/genética , Imuno-Histoquímica , Camundongos , Células-Tronco Neurais/transplante , Neurotrofina 3/metabolismoRESUMO
OBJECTIVE: To evaluate the potential role of hepatocyte growth factor (HGF) combined with bone marrow mesenchymal stem cells (BMSC) autograft for the treatment of silicosis. METHODS: Bone marrow (100 ml) was aspirated from a severe silicosis patient. BMSCs isolated, purified and cultured in vitro. When BMSC came to 70% confluence at passage 3, the culture medium was added liposomes (lipo2000) and plasmid-HGF (p-HGF) and cultured for 2 d. HGF-MSCSs (5 × 10(7) cells) were resuspended in 50 ml 0.9% sodium chloride (NS) and infused Intravenous drip at 3 consecutive times (once a week). Clinical follow-up were performed before and after treatment: (1) pulmonary high-kV X-ray, chest CT examination; (2) pulmonary function test; (3) determination of serum ceruloplasmin. RESULTS: The symptoms such as coughing, chest tightness disappeared at 12 months after treatment. Pulmonary function tests showed significant changes after treatment: forced vital capacity (FVC) increased from 64.6% to 81.0%, forced expiratory volume in one second (FEV(1.0)) increased from 68.7% to 90.1%, 1 second rate (FEV(1.0)/FVC%) reduced from 111.6% to 107.1%, the maximum mid-expiratory flow (FEF(25%â¼75%) decreased from 100.2% to 94.6%, forced expiratory vital capacity 75% of the moment bit of gas flow (MEF(75%)) increased from 99.2% to 113.5%, forced expiratory vital capacity 50% of the moment bit of gas flow (MEF(50%)) increased from 125.3% to 130.2%, forced expiratory vital capacity 25% of the moment bit of gas flow (MEF(25%)) reduced from 86.9% to 71.7%; serum ceruloplasmin levels decreased from 690 mg/L to 180.6 mg/L; lung high-kV X-ray at 1st review showed that diffuse lung nodules had been absorbed and getting smaller than before treatment; chest CT showed that the distribution and number of small nodules at double lung fields decreased than before treatment. CONCLUSION: HGF combined with BMSC transplantation may have some potential role for the treatment of silicosis patients.
Assuntos
Transplante de Medula Óssea , Fator de Crescimento de Hepatócito/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Silicose/terapia , Adulto , Feminino , Seguimentos , Humanos , Resultado do TratamentoRESUMO
OBJECTIVE: Paraquat (PQ) is associated with high mortality rates in acute poisoning. This study aimed to determine the importance of the alveolar-arterial partial pressure difference (A-aDo2) in the expected consequences of acute PQ poisoning. METHODS: Patients who were hospitalized for PQ poisoning in 2018 were enrolled in this retrospective study. A-aDo2 data were collected. Multivariate analysis was performed using binary logistic regression to determine whether A-aDo2 is an independent risk factor for mortality from PQ. RESULTS: A total of 352 cases were analyzed. The mean PQ dose was 36.84 ± 50.30 mL (0.3-500 mL). There were 185 survivors and 167 non-survivors. The mean A-aDo2 was not significantly correlated between survivors and non-survivors on day 1. However, there were significant differences in A-aDo2 between survivors and non-survivors on days 3, 7, 14, and 21. Increased A-aDo2 values were correlated with an increased mortality rate. The mean A-aDo2 on day 14 showed the most significant difference between survivors and non-survivors. CONCLUSION: Our study suggests that A-aDo2 plays an important role as a reference index, which could be a useful predictor in assessing acute PQ poisoning, especially on the 14th day after onset of poisoning.
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Pulmão , Paraquat , Humanos , Pressão Parcial , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To explore the effects of trichloroethylene (TCE) and its by-products (trichloroacetic acid, TCA; dichloroacetic acid, DCA) on the normal human peripheral blood lymphocyte and the role of DCA in dermatitis medicamentosa- like induced by trichloroethylene (DMLT). METHODS: Lymphocyte was isolated from peripheral venous blood, and cytotoxicity of human lymphocytes treated with different concentrations (0.02 approximately 30.00 mmol/L) of DCA was determined at indicated times (2 h and 4 h) based on the MTS assay. Action of DCA on cell viability, membrane integrity was assessed by neutral red uptake (NRU) assay and lactate dehydrogenase (LDH) release test and measurement of superoxide dismutase (SOD) activity. Fluorescence quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) was employed for detection and quantization of the chemokine receptor CXCR2 and chemokine receptor CXCR3 mRNA in peripheral blood lymphocyte treated with different concentrations of DCA. RESULTS: DCA had a more vital effect on peripheral blood lymphocyte than TCE and TCA. A concentration-dependent release of LDH was observed at 4 h after cells were exposed to different doses of DCA (0.88, 1.75, 3.50 and 7.00 mmol/L) (P < 0.05), and DCA also caused an inhibition of SOD activity in a concentration-dependent manner (P < 0.05). The results of FQ- RT- PCR indicated that CXCR2 and CXCR3 mRNA were all over- expression. At 48 h after the DCA of 0.5 mmol/L and 10.00 mmol/L was used, CXCR2 and CXCR3 mRNA were 10.34, 5.66-fold and 19.43, 8.75-fold of those in the control group (P < 0.01). CONCLUSION: DCA is of a great cytotoxicity and may be one of crucial evocators on DMLT.
Assuntos
Ácido Dicloroacético/toxicidade , Linfócitos/efeitos dos fármacos , Receptores CXCR3/metabolismo , Receptores de Interleucina-8B/metabolismo , Adolescente , Células Cultivadas , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Tricloroetileno/toxicidade , Adulto JovemRESUMO
OBJECTIVE: To investigate the clinical characteristics of acute arsenic poisoning and its influential factors. METHODS: Clinical data of 47 cases of arsenic poisoning were collected and analyzed. Two cases of observation, 40 cases of mild acute poisoning, and 5 severe acute poisoning were investigated in this group. RESULTS: Myocardial enzyme activity was correlated with age and urine arsenic concentrations. Myocardial enzyme, the liver ALT, total bilirubin (TBil) and indirect bilirubin (IBil) were negatively correlated with vomiting frequency, with statistical significance (P < 0.05). Urine arsenic concentration was correlated with vomiting frequency and amount of soup drunk, with statistically significant difference (P < 0.05). Despite no statistical significance in age and amount of soup drunk, the patients with more vomiting or diarrhea had less urine arsenic concentrations, cardiac enzymes and liver enzyme concentration. CONCLUSION: Acute arsenic poisoning can lead to multiple organ damage. The damage is relevant with amount of arsenic intake, vomiting, diarrhea and urinary frequency arsenic concentration. So early use of gastric lavage, vomiting, poison discharges, and adequate application of effective antidote (Na-DMPS) as soon as possible, symptomatic treatment and the reinforced monitoring, are the rescue key for patients with acute arsenic poisoning.
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Intoxicação por Arsênico/fisiopatologia , Contaminação de Alimentos , Doença Aguda , Adolescente , Adulto , Arsênio/urina , Diarreia/induzido quimicamente , Feminino , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Vômito/induzido quimicamente , Adulto JovemRESUMO
OBJECTIVE: To assess the reaction of cytokines induced killer (CIK) cells treatment in hematopoietic injury at different levels on patients with benzene poisoning and seek a novel, safe and effective immunotherapy for benzene poisoning. METHODS: CIK cells were in vitro activated by interleukin-2 (IL-2) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) from the peripheral blood mononuclear cells (PBMC). Thirty-two patients with benzene poisoning were treated with CIK cells. Nineteen patients with mild or moderate benzene poisoning in the control group were treated with VitB4, batilol, leucogen, inosine and stanozolol. The results for treatment of 12 patients with aplastic anemia induced by severe benzene poisoning (the efficacy rate and the case fatality rate) were analyzed. The change of T-lymphocyte subset analyzed by flow cytometry was also observed before and after treatment. RESULTS: For mild or moderate benzene poisoning, the increase of WBC and RLT in CIK group was higher than that in the control group (P < 0.05). The CD(4)/CD(8) levels were significantly increased after CIK treatment. And for severe benzene poisoning, the effective rate of the CIK group was 91.7% and the mortality rate was 0%. CONCLUSION: CIK treatment is safe and effective for hematopoietic injury caused by benzene poisoning. The mechanism may be related with the immune modulation of CIK treatment on immunodeficiency of patients with benzene poisoning.
Assuntos
Benzeno/intoxicação , Células Matadoras Induzidas por Citocinas/imunologia , Imunoterapia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the levels of T cell receptor rearrangement excision DNA circles (TRECs) within peripheral blood from workers exposed to lead, and thereby to evaluate the number of naive T cells and recent thymic output function. METHODS: Quantitative detection of TRECs in peripheral blood mononuclear cells (PBMNC) from 10 cases of workers exposed to lead was performed by real time PCR analysis. 11 workers without exposure to lead served as unexposed controls. In addition, the relationship between TRECs, age, length of service, blood lead, urea lead, blood ZPP and urea delta-ALA was investigated. RESULTS: The mean value of TRECs in workers exposed to lead was (2.44 +/- 1.87)/1000 PBMC, significantly under (5.60 +/- 3.96)/1000 PBMC in unexposed controls. A significant negative correlation was found between the TRECs and urea-ALA. But there was no significant correlation between them after controlling for blood lead, urea lead. CONCLUSION: Lead exposure may damage thymic output naive T cells function. Furthermore, low-level exposure to lead may damage immune system and earlier than expected.
Assuntos
DNA/efeitos dos fármacos , Chumbo/toxicidade , Exposição Ocupacional/efeitos adversos , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/efeitos dos fármacos , Timo/imunologia , Adulto , Rearranjo Gênico do Linfócito T/efeitos dos fármacos , Humanos , Leucócitos Mononucleares , Masculino , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: Efforts have been made by tissue engineers to create a permissive environment for neural regeneration, and to enhance the efficiency of neural stem cell (NSC) transplantation. However, to acquire sufficient number of seed cells on the material appears to be the main obstacle to constructing functional transplantable NSC-biomaterial complexes. A culture system has been optimized in the current study to maintain the specific characteristics of NSCs/neural progenitor cells (NPCs) on the material and achieve sustaining increased multipotent seed cells. METHODS: The PHBHHx film was selected as biomaterial and the surface was firstly modified with NaOH treatment. The NSCs/NPCs isolated from the cerebral cortex of rat embryos were cultured on the treated PHBHHx films in growth medium containing 1%, 5%, and 10% fetal bovine serum (FBS). Then the attachment, survival, proliferation, and differentiation of NSCs/NPCs were assessed. RESULTS: NaOH treatment significantly increased the hydrophilicity of PHBHHx and enhanced NSCs/NPCs attachment. On the treated PHBHHx film, NSCs/NPCs survived well and actively proliferated in the medium containing 1% FBS. After 7-14 days in culture, approximately two-thirds of cells remained as nestin and Sox2 positive NSCs/NPCs. However, in the medium containing 5% and 10% FBS, NSCs/NPCs proliferation was reduced and differentiation, particularly glial differentiation was significantly promoted. CONCLUSION: Growth medium containing low concentration of FBS is favorable for maintaining the characteristics, in terms of self-renewal and multiple differentiation, of NSCs/NPCs on NaOH-treated PHBHHx films. This could be a useful method to construct functional transplantable NSCs/NPCs-biomaterial complex.
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Ácido 3-Hidroxibutírico/química , Materiais Biocompatíveis/química , Caproatos/química , Células-Tronco Neurais/citologia , Animais , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Córtex Cerebral/citologia , Células-Tronco Embrionárias/citologia , Ratos , Soroalbumina Bovina , Hidróxido de Sódio , Propriedades de Superfície , Engenharia TecidualAssuntos
Dermatite Ocupacional/imunologia , Subpopulações de Linfócitos T/imunologia , Tricloroetileno/efeitos adversos , Adolescente , Adulto , Dermatite Ocupacional/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto JovemRESUMO
AIM: To investigate the distribution and clonality of TCR Vß subfamily in peripheral blood from workers exposed to lead, in order to understand the change in T cell immunity of occupational lead-exposed workers. METHODS: The CDR3 of TCR Vß 24 subfamily genes was amplified in peripheral blood mononuclear cells (PBMC) from 6 lead-exposed workers and 6 healthy individuals using RT-PCR, the positive PCR products were further subjected by genescan analysis to identify T cell clonality. RESULTS: All 24 TCR Vß subfamilies were detected in PBMC from 6 healthy individuals which all have polyclonal patterns. Only 1-7 Vß subfamilies could be identified in lead-exposed workers. In detected TCR Vß subfamilies, almost oligoclonal and biclonal patterns which mainly in Vß1 and Vß16. CONCLUSION: The restricted expression and clonal expansion of TCR Vß subfamily have been found in occupational lead-exposed workers, it may have some relationship with lead toxicity damage to the immune function.