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1.
Zhonghua Yi Xue Za Zhi ; 100(26): 2032-2035, 2020 Jul 14.
Artigo em Chinês | MEDLINE | ID: mdl-32654448

RESUMO

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide ß(ß-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、ß-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, ß-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) µg/L vs (15.6±5.5) µg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and ß-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, ß-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.


Assuntos
Doenças Ósseas , Mieloma Múltiplo , Fosfatase Ácida , Biomarcadores , Humanos , Inibidores de Proteassoma , Fosfatase Ácida Resistente a Tartarato
2.
Int J Occup Environ Med ; 11(3): 140-147, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32683426

RESUMO

BACKGROUND: The major portion of lead in the body resides in skeletal system. The bone turnover affects the release of lead into the circulation from bones. The bone turnover biomarkers (BTM) in lead-battery workers with long-term exposure to lead have not been explored yet. OBJECTIVE: To evaluate the BTM (formation and resorption) in lead-battery workers with long-term exposure to lead in lead-battery manufacturing plant. METHODS: 176 male lead-exposed workers and 80 matched comparison group were studied. All participants were examined for blood lead levels (BLLs), bone formation biomarkers- serum osteocalcin (OC), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP)-and bone resorption biomarkers-serum pyridinoline (PYD), deoxypyridinoline (DPYD), tartarate-resistant acid phosphatase-5b (TRACP-5b), and urinary hydroxyproline (UHYP). RESULTS: We found a significantly higher bone formation biomarkers such as BALP (p=0.007) and bone resorption biomarkers, eg, PYD (p=0.048), TRCAP-5b (p=0.001), and UHYP (p=0.001) in lead-exposed workers. A significant (p=0.041) negative correlation (ρ ­0.128) was noted between BLLs and OC. A significant positive correlation was noted between BLLs and TRACP-5b (ρ 0.176, p=0.005) and UHYP (ρ 0.258, p=0.004). Serum OC (p=0.040) and UHYP (p=0.015) levels changed significantly with BLL level. Bone resorption biomarkers levels- PYD, TRACP-5b, and BALP-were higher among those with higher BLLs levels. The duration of exposure was significantly associated with BALP (p=0.037), DPYD (p=0.016), TRACP-5b (p=0.001), and UHYP (p=0.002) levels. CONCLUSION: Long-term lead exposure affects the bone turnover.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/fisiologia , Fontes de Energia Elétrica , Chumbo/toxicidade , Exposição Ocupacional/análise , Fosfatase Ácida/sangue , Fosfatase Ácida/metabolismo , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/análise , Reabsorção Óssea/sangue , Estudos de Casos e Controles , Estudos Transversais , Fontes de Energia Elétrica/efeitos adversos , Humanos , Isoenzimas/sangue , Isoenzimas/metabolismo , Chumbo/química , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/diagnóstico , Masculino , Instalações Industriais e de Manufatura , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Osteocalcina/sangue , Local de Trabalho
3.
Top Companion Anim Med ; 38: 100405, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115076

RESUMO

The monitoring of serum prostatic biomarkers during the treatment will help clinicians to know the statement of the response to finasteride in dogs affected by benign prostatic hyperplasia (BPH). The present study was aimed to assess changes in the serum canine prostate-specific esterase (CPSE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, dihydrotestosterone (DHT) and prostate volume evaluation using ultrasonographic examination during the treatment with finasteride in BPH-induced dogs. Twenty dogs were divided into 4 groups (n = 5): BPH + finasteride group, dogs which were induced for BPH and received oral finasteride once daily for 1 month; BPH group, dogs which were induced for BPH and received placebo; finasteride group, normal dogs which received finasteride; and normal group, normal intact dogs which did not receive treatment. Blood sampling and ultrasonography examination were performed on days 0, 14, and 28. The administration of finasteride led to a significant decrease in the concentration of the prostate-specific biomarkers (PSA, CPSE), DHT, testosterone, and the volume of the prostate in BPH + finasteride group compared with the BPH group during 1 month. Interestingly, the PAP concentration did not change in the BPH-induced dogs and in dogs treated with finasteride. It seems that the monitoring of serum PSA and CPSE levels and ultrasonographic examination of the prostate are useful methods for following up the response to finasteride treatment in dogs affected by BPH.


Assuntos
Biomarcadores/sangue , Doenças do Cão/tratamento farmacológico , Finasterida/farmacologia , Hiperplasia Prostática/veterinária , Inibidores de 5-alfa Redutase , Fosfatase Ácida/sangue , Animais , Di-Hidrotestosterona/sangue , Doenças do Cão/sangue , Doenças do Cão/enzimologia , Cães , Esterases/sangue , Estradiol/administração & dosagem , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Testosterona/administração & dosagem , Testosterona/sangue , Ultrassonografia/veterinária
4.
Cancer Immunol Immunother ; 69(4): 641-651, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32016503

RESUMO

Prostate cancer is a candidate for immunotherapy because cancer cells express tissue-specific proteins that can be therapeutic targets. However, immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP) vaccine composed of bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with peptides encoding T cell epitopes from two prostate cancer-associated tumor antigens, prostate stem cell antigen (PSCA), and prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-antigen, stimulator of prostatic adenocarcinoma-specific T cells (SPAS-1). The VLP vaccines induced a mean frequency of antigen-specific IFN-γ secreting CD8 + T cells of 2.9% to PSCA, 9.5% to SPAS-1, 0.03% to PAP-1, and 0.03% to PAP-2 in tumor-bearing TRAMP mice. We treated TRAMP mice at 19-20 weeks of age, when mice have advanced stages of carcinogenesis, with either VLP vaccine, anti-PD1 antibody, or combination immunotherapy. The VLP vaccine alone or in combination with anti-PD1 antibody significantly reduced tumor burden, while anti-PD1 antibody had a modest non-significant therapeutic effect. All treatments significantly increased CD3 + and CD8 + T cell infiltration into tumor tissue compared to control mice, and combination therapy resulted in significantly greater CD3 + and CD8 + T cell infiltration than monotherapy. Reduction in tumor burden in vaccine-treated mice was inversely correlated with CD8 + T cell numbers in tumor tissue. No other immunotherapy has shown efficacy in this animal model of advanced prostate cancer, making bovine papillomavirus VLPs an attractive vaccine technology to test in patients with metastatic prostate cancer.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Proteínas do Capsídeo/imunologia , Proteínas de Neoplasias/imunologia , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Fosfatase Ácida/imunologia , Fosfatase Ácida/metabolismo , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/administração & dosagem , Modelos Animais de Doenças , Epitopos de Linfócito T/imunologia , Proteínas Ligadas por GPI/imunologia , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Camundongos Transgênicos , Neoplasias da Próstata/terapia , Resultado do Tratamento , Vacinação
5.
Ecotoxicol Environ Saf ; 192: 110264, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32035397

RESUMO

Copper (Cu) mining has to address a critical environmental issue related to the disposal of heavy metals and metalloids (HMs). Due to their deleterious effects on living organisms, Cu and arsenic (As) have gained global attention, and thus their monitoring in the environment is an important task. The aims of this study were: 1) to evaluate the alteration of soil enzyme activities (EAs) and soil microbial functional diversity with Cu/As contamination, and 2) to select the most reliable biochemical indicators of Cu/As contamination. A twelve-week soil experiment was performed with four increasing levels of Cu, As, and Cu/As from 150/15 to 1000/100 mg Cu/As kg-1. Soil enzyme activities and soil community-level physiological profile (CLPP) using MicroResp™ were measured during the experiment. Results showed reduced EAs over time with increasing Cu and Cu/As levels. The most Cu-sensitive EAs were dehydrogenase, acid phosphatase, and arylsulfatase, while arginine ammonification might be related to the resilience of soil microbial communities due to its increased activity in the last experimental times. There was no consistent response to As contamination with reduced individual EAs at specific sampling times, being urease the only EA negatively affected by As. MicroResp™ showed reduced carbon (C) substrate utilization with increasing Cu levels indicating a community shift in C acquisition. These results support the use of specific EAs to assess the environmental impact of specific HMs, being also the first assessment of EAs and the use of CLPP (MicroResp™) to study the environmental impact in Cu/As contaminated soils.


Assuntos
Arsênico/farmacologia , Cobre/farmacologia , Microbiologia do Solo , Poluentes do Solo/farmacologia , Fosfatase Ácida/metabolismo , Arilsulfatases/metabolismo , Oxirredutases/metabolismo , Solo/química , Urease/metabolismo
6.
Biosci. j. (Online) ; 36(1): 1-16, jan./feb. 2020. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1049184

RESUMO

The objective of this study was to evaluate the influence of agroforestry systems of different ages (AFS1: one-year old; AFS5: five-years old) on the biological attributes of soil; the following systems were used for comparison: a slash-and-burn (SBF) farming area, Caatinga which has been undergoing regeneration for 6 years (CaR6), and native Caatinga (NCa) in Brazil. Enzyme activity, abundance and composition of arbuscular mycorrhizal fungi (AMF), and production of glomalin-related soil proteins (GRSP) were evaluated at soil depths of 0­0.05 m. AMF species composition in the AFS was more similar to that in the NCa than in the SBF and CaR6 systems. In the rainy season, sporulation was most abundant in the AFS-1, CaR6, and SBF systems, whereas GRSP concentrations were highest in the AFS5 during the dry season. Acid phosphatase and arylsulfatase enzyme activity was lower in the AFS1 soils than in the NCa and SBF soils (rainy period), and levels of ß-glucosidase and fluorescein diacetate hydrolysis in the AFS were equal to or higher than those in the NCa in the dry season but lower in the rainy season. AFS thus appear to promote the maintenance of soil biological quality, and may be more sustainable than SBF farming systems in the Brazilian Caatinga over the long term.


O objetivo do estudo foi avaliar a influência de sistemas agroflorestais (AFS1: um ano de idade; AFS5: cinco anos de idade), nos atributos biológicos do solo usando como referência, uma área de agricultura de corte e queima (SBF), Caatinga em regeneração há 6 anos (CaR6), e Caatinga nativa (NCa), in Brasil. A atividade enzimática, a abundância e composição dos fungos micorrízicos arbusculares (AMF), e a produção de proteína do solo relacionada à glomalina (GRSP) foram avaliados, na profundidade de 0-5 cm do solo. A composição das espécies de AMF nos AFS foi mais semelhante a observada na NCa, do que os sistemas SBF e CaR6. Na estação chuvosa, a esporulação foi mais abundante em AFS-1, CaR6 and SBF quando comparada as outras áreas, enquanto a GRSP apresentou maiores teores no AFS5 no período seco. AFS1 apresentou atividade da fosfatase ácida e arilsulfatase inferiores tanto a NCa quanto a SBF, no período chuvoso. No período seco, a atividade de ß-glicosidase e a hidrólise do diacetato de fluoresceína (FDA) na AFS foram iguais ou superiores a Nca, mas menor no período chuvoso. Verifica-se que os AFS são potenciais para a manutenção da qualidade biológica do solo, podendo, em longo prazo, serem mais sustentáveis que a SBF, em ambiente de Caatinga.


Assuntos
Arilsulfatases , Solo , Fosfatase Ácida , Glicosídeo Hidrolases
7.
Arq. bras. med. vet. zootec. (Online) ; 72(1): 199-207, Jan.-Feb. 2020. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1088910

RESUMO

The target cp1002_RS01850 from Corynebacterium pseudotuberculosis was used to construct a DNA and recombinant subunit vaccine against caseous lymphadenitis. Recombinant protein rCP01850 was expressed in Escherichia coli using pAE vector, and DNA vaccine was engineered with pTARGET vector. BALB/c mice were divided in five groups containing eight animals each, inoculated with: pTARGET/cp01850 as DNA vaccine (G1); rCP01850 plus Al (OH)3 as recombinant subunit vaccine (G2); pTARGET/cp01850 and a boost with rCP01850 plus Al (OH)3 (G3); pTARGET (G4); or Al (OH)3 (G5). Mice were inoculated and blood samples were collected on days 0, 21, and 42 for the analysis of total IgG, IgG1 and IgG2a by ELISA. In each group, five animals were challenged with Mic-6 C. pseudotuberculosis strain, and three were used for cytokine quantification by qPCR. Although no group has been protected by vaccines against lethal challenge, G2 showed an increase in the survival rate after challenge. Significantly higher levels of IL-4, IL-12, IFN-γ, total IgG, IgG1 and IgG2a were also detected for G2, evidencing a mixed Th1/Th2 immunological profile. In conclusion, despite no protection level provided by different vaccinal strategies using cp1002_RS01850 from C. pseudotuberculosis, G2 developed a Th1/Th2 immune response with an increase in survival rate.(AU)


O alvo cp1002_RS01850 de Corynebacterium pseudotuberculosis foi utilizado para construir uma vacina recombinante de subunidade e de DNA contra a linfadenite caseosa. A proteína recombinante rCP01850 foi expressa em Escherichia coli usando o vetor pAE, e a vacina de DNA foi construída com o vetor pTARGET. Camundongos BALB/c foram divididos em grupos de oito animais, inoculados com: pTARGET/cp01850 como vacina de DNA (G1); rCP01850 e Al (OH)3 como vacina recombinante de subunidade (G2); pTARGET/cp01850 e um boost com rCP01850 e Al (OH)3 (G3); pTARGET (G4); ou Al (OH)3 (G5). Os animais foram inoculados e amostras de sangue foram coletadas nos dias 0, 21, e 42 do experimento para a análise de IgG total, IgG1 e IgG2a por ELISA. De cada grupo, cinco animais foram desafiados com a cepa Mic-6 de C. pseudotuberculosis, e três foram usados para a quantificação de citocinas por qPCR. Apesar de nenhum grupo ter sido protegido pelas vacinas testadas contra o desafio letal, G2 apresentou taxa de sobrevida e níveis de IL-4, IL-12, IFN-γ, IgG total, IgG1 e IgG2a significativamente mais altos, evidenciando um perfil imunológico misto Th1/Th2. Conclui-se que apesar das diferentes estratégias vacinais utilizando cp1002_RS01850 de C. pseudotuberculosis não terem sido capazes de gerar proteção, G2 desenvolveu uma resposta Th1/Th2 e elevou a taxa de sobrevida.(AU)


Assuntos
Animais , Camundongos , Fosfatase Ácida , Imunização Secundária/veterinária , Corynebacterium pseudotuberculosis , Linfadenite/imunologia , Proteínas Recombinantes , Hidróxido de Alumínio
8.
Artigo em Inglês | MEDLINE | ID: mdl-31629812

RESUMO

The present report describes a comprehensive study on comparative biochemical characterization of two lysosomal enzymes, acid phosphatase and ß-hexosaminidase in three different strains of Hydra; Hydra vulgaris Ind-Pune, H. vulgaris Naukuchiatal and H. magnipapillata sf-1 (self-feeder-1). Since morphology and habitat of Hydra effect lysosomal enzymes and their response to environmental pollutants, it would be interesting to identify them in different Hydra strains so as to use them as toxicity testing. Preliminary studies revealed a differential expression of acid phosphatase, ß-hexosaminidase and ß-glucuronidase in three Hydra strains. Expression of all three lysosomal enzymes in H. vulgaris Ind-Pune was low in comparison to H. vulgaris Naukuchiatal and H. magnipapillata sf-1, while their expression is comparable in H. vulgaris Naukuchiatal and H. magnipapillata sf-1. The Michaelis-Menten (KM) values for lysosomal ß-hexosaminidase using 4-nitrophenyl N-acetyl-ß-D-glucosaminide as substrate were found to be 1.3 mM, 1.1 mM and 0.8 mM, respectively for H. vulgaris Ind-Pune, H. vulgaris Naukuchiatal and H. magnipapillata sf-1. For acid phosphatase using 4-nitrophenyl-phosphate as substrate, the KM values were 0.38 mM, 1.2 mM and 0.52 mM respectively, for H. vulgaris Ind-Pune, H. vulgaris Naukuchiatal and sf-1 strains. The optimum temperature for ß-hexosaminidase was 60 °C for H. vulgaris Ind-Pune, while 50 °C was observed for H. vulgaris Naukuchiatal and sf-1 strains. The optimum pH for ß-hexosaminidase was found to be 6.0 for H. vulgaris Ind-Pune and H. vulgaris Naukuchiatal, and 5.0 for sf-1. The optimum temperature and pH of acid phosphatase was similar in all three strains, viz., 40 °C and 3.0, respectively. Preliminary localization studies using whole mount in situ hybridization revealed predominant endodermal expression of three enzymes in H. vulgaris Ind-Pune. Our results thus support the conservation of lysosomal hydrolases in Hydra.


Assuntos
Fosfatase Ácida/metabolismo , Hydra/enzimologia , Lisossomos/enzimologia , beta-N-Acetil-Hexosaminidases/metabolismo , Animais , Especificidade da Espécie
9.
Chemosphere ; 239: 124668, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31494325

RESUMO

Nitrite is one of major environmental pollutants that can impact immunological parameters in aquatic organisms. In the present study, we investigated the effects of nitrite exposure on oxidative stress, DNA damage and apoptosis in mud crab (Scylla paramamosain). Mud crab were exposed to 0, 5, 10 and 15 mg L-1 nitrite for 72 h. These data showed that acid phosphatase (ACP) and alkaline phosphatase (ALP) activity significantly decreased in treatments with various concentrations of nitrite (5, 10 and 15 mg L-1) after 24 and 48 h, while the levels of nitric oxide (NO) significantly increased in these treatments. Nitrite exposure could suppress superoxide dismutase (SOD) and catalase (CAT) activity, and increase the formation of malondialdehyde (MDA) after 48 and 72 h of exposure. In addition, nitrite exposure decreased total haemocyte counts after 48 and 72 h of exposure. Cytological damage, DNA damage and apoptosis was observed obviously at 72 h after nitrite exposure. Moreover, nitrite exposure significantly induced the mRNA levels of phosphorylated Jun N-terminal kinases (JNK), and eventually activated p53 signaling and caspase-3. These results indicated that nitrite exposure could induce oxidative stress, which further caused DNA damage and apoptosis in mud crab. Our results will be helpful to understand the mechanism of nitrite toxicity on crustaceans.


Assuntos
Apoptose/efeitos dos fármacos , Braquiúros/efeitos dos fármacos , Dano ao DNA/genética , Nitritos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Braquiúros/genética , Catalase/metabolismo , Hemócitos , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo
10.
Planta ; 251(1): 31, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823013

RESUMO

MAIN CONCLUSION: A high level of the secondary metabolite chicoric acid is produced by intracellular Pi supply and extracellular phosphate limiting in Echinacea purpurea hairy roots. Chicoric acid (CA) is a secondary metabolite which is gained from Echinacea purpurea. It has been found to be one of the most potent HIV integrase inhibitors with antioxidant and anti-inflammatory activities. However, the low-biosynthesis level of this valuable compound becomes an inevitable obstacle limiting further commercialization. Environmental stresses, such as phosphorus (Pi) deficiency, stimulate the synthesis of chemical metabolites, but significantly reduce plant growth and biomass production. To overcome the paradox of dual opposite effect of Pi limitation, we examined the hypothesis that the intracellular Pi supply and phosphate-limiting conditions enhance the total CA production in E. purpurea hairy roots. For this purpose, the coding sequence (CDS) of a purple acid phosphatase gene from Arabidopsis thaliana, AtPAP26, under CaMV-35S promoter was overexpressed in E. purpurea using Agrobacterium rhizogenes strain R15834. The transgenic hairy roots were cultured in a Pi-sufficient condition to increase the cellular phosphate metabolism. A short-term Pi starvation treatment of extracellular phosphate was applied to stimulate genes involved in CA biosynthesis pathway. The overexpression of AtPAP26 gene significantly increased the total APase activity in transgenic hairy roots compared to the non-transgenic roots under Pi-sufficient condition. Also, the transgenic hairy roots showed increase in the level of total and free phosphate, and in root fresh and dry weights compared to the controls. In addition, the phosphate limitation led to significant increase in the expression level of the CA biosynthesis genes. Considering the increase of biomass production in transgenic vs. non-transgenic hairy roots, a 16-fold increase was obtained in the final yield of CA for transgenic E. purpurea roots grown under -P condition compared to +P non-transgenic roots. Our results suggested that the expression of phosphatase genes and phosphate limitation were significantly effective in enhancing the final production yield and large-scale production of desired secondary metabolites in medicinal plant hairy roots.


Assuntos
Fosfatase Ácida/genética , Ácidos Cafeicos/metabolismo , Echinacea/genética , Echinacea/metabolismo , Regulação da Expressão Gênica de Plantas , Fosfatos/metabolismo , Raízes de Plantas/metabolismo , Succinatos/metabolismo , Antioxidantes/metabolismo , Arabidopsis/genética , Biomassa , Vias Biossintéticas/genética , Fósforo/metabolismo , Plantas Geneticamente Modificadas/metabolismo
11.
S Afr Med J ; 110(1): 49-54, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31865943

RESUMO

BACKGROUND: Drug-resistant Acinetobacter species present serious therapeutic and infection control policy challenges globally. Although aminoglycosides have played a crucial role in the treatment of infections with multidrug-resistant (MDR) Acinetobacter spp., recent reports indicate that these bacteria are developing resistance to aminoglycosides around the globe. OBJECTIVES: To determine the association between amikacin resistance and clinical outcomes of patients. The minimum inhibitory concentrations (MICs) of amikacin against Acinetobacter spp. and genes associated with resistance were also investigated. METHODS: Clinical information from 107 patients with Acinetobacter spp. cultured from clinical specimens was recorded during ward rounds at an academic complex hospital in KwaZulu-Natal Province, South Africa, including clinical outcomes, history of antibiotics prescribed and microbiological investigations. The 107 Acinetobacter isolates were investigated for susceptibility to antimicrobial agents in use at local hospitals. Genes related to amikacin resistance (aphA6 and aacA4) were investigated by polymerase chain reaction (PCR) and sequencing. Analysis was performed on the relationship between clinical outcomes and antimicrobial resistance patterns, as well as on the amikacin MICs in resistant isolates (n=6) v. their PCR results. RESULTS: The majority (5/6, 83.3%) of patients with amikacin-resistant Acinetobacter infection were discharged, and 1/6 (16.7%) died. No underlying clinical factors were significantly associated with clinical outcome. Amikacin resistance was observed in 6/107 isolates (5.6%), with MICs of 32 µg/mL (n=3) and ≥64 µg/mL (n=3) for the amikacin-resistant isolates. All 6 of these isolates were also extensively drug-resistant (XDR). The aphA6 gene (797 base pair) was detected in all amikacin-resistant isolates. CONCLUSIONS: Most tested Acinetobacter isolates were susceptible to amikacin, underscoring the crucial role of this antibiotic in the treatment of MDR Acinetobacter spp. in our hospital. The emergence of XDR isolates is of serious concern and necessitates close monitoring and surveillance.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/efeitos dos fármacos , Amicacina/farmacologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Centros Médicos Acadêmicos , Fosfatase Ácida , Acinetobacter/genética , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , DNA Bacteriano/análise , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , África do Sul , Resultado do Tratamento , Adulto Jovem
12.
ACS Appl Mater Interfaces ; 11(50): 47564-47570, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31762263

RESUMO

Enzyme-like activity and efficiency of nanomaterials are strongly controlled by their size, composition, and structure, and hence the structural parameters need to be optimized. Here, we report that two-dimensional Pd nanoplates enclosed by {100}-facets [{100}PdSP@rGO] exhibit substantially enhanced intrinsic oxidase-like activities relative to the {111}-facets ones and Pd nanocubes in catalyzing the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine. By taking ascorbic acid 2-phosphate as the substrate, which transforms to ascorbic acid in the presence of acid phosphatase (ACP), the {100}PdSP@rGO could be used as an efficient nanozyme for colorimetric ACP detection without resorting to destructive H2O2. A good linear relationship from 0.01 to 6.0 mU/mL with a detection limit of 8.3 µU/mL is obtained, which is better than most previously reported ACP assays. Importantly, the excellent assay performance could be successfully applied to ACP determination in serum samples with high accuracy. This study demonstrates that the enzyme-like activity of nanomaterials could be finely tuned simultaneously by controlling their exposed crystal facets and high specific surface area.


Assuntos
Fosfatase Ácida/isolamento & purificação , Técnicas Biossensoriais , Colorimetria , Nanoestruturas/química , Fosfatase Ácida/química , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/química , Materiais Biomiméticos/química , Catálise , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredutases/química
13.
Mycorrhiza ; 29(6): 599-605, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31745622

RESUMO

Arbuscular mycorrhizal (AM) fungi increase phosphate (P) uptake by plants. Organic phosphate comprises 30-80% of total P in most agricultural soils. Some plants can utilize organic phosphate by secreting acid phosphatase (ACP) from their roots, especially under low P conditions. Although secretion of ACP from extraradical hyphae of AM fungi has been reported, the specific factors that affect the secretion of ACP are unknown. The objective of the present study was to investigate whether secretion of ACP from extraradical hyphae is induced by low P conditions. First, specimens of Allium fistulosum were either inoculated with the AM fungus Rhizophagus clarus strain CK001 or remained uninoculated and were grown in soil with 0.5 g P2O5 kg-1 soil or without P fertilization using two-compartment pots. Soil solution was collected using mullite ceramic tubes 45 days after sowing. The soil solution was analyzed for ACP activity by using p-nitrophenylphosphate. Second, Ri T-DNA transformed roots (i.e., hairy roots) of Linum usitatissimum inoculated with R. clarus were grown on solid minimal media with two P levels applied (3 and 30 µM P) using two-compartment Petri dishes under in vitro conditions. Hyphal exudates, extraradical hyphae, and hairy roots were collected and analyzed for ACP activity. ACP activity in the soil solution of the hyphal compartment in the A. fistulosum inoculation treatment was higher without P fertilization than with P fertilization. AM colonization also was higher without P fertilization than with P fertilization. In the in vitro two-compartment culture, ACP activity of hyphal exudates and extraradical hyphae were higher under the 3-µM treatment than under the 30-µM treatment. These findings suggest that the secretion of ACP from the extraradical hyphae of R. clarus into the hyphosphere is promoted under low P conditions.


Assuntos
Micorrizas , Fosfatase Ácida , Hifas , Organofosfatos , Fosfatos , Raízes de Plantas
14.
J Therm Biol ; 85: 102404, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31657746

RESUMO

The red claw crayfish, Cherax quadricarinatus, is an economically important freshwater crustacean that cannot tolerate low temperature, which diminishes survival via unknown mechanisms. Herein, physiological regulation of C. quadricarinatus was investigated following exposure to low temperature stress at 9 ±â€¯2 °C for 4 weeks. Hepatopancreas tissue was tested for nonspecific enzyme activity, histological structure, and transcriptome sequencing analyses. The results showed that the activities of nonspecific enzymes were inhibited following low temperature stress. Ultrastructural observation revealed that the hepatopancreas structure was oxidatively damaged at low temperature, with numerous autophagic vesicles visible. Apoptosis in the hepatopancreas was significantly increased in the cold stress group, indicating diminished function. Transcriptome sequencing identified 2615 differentially expressed genes (DEGs) following low temperature stress, of which 1147 and 1468 were up- and down-regulated, respectively. Functional analysis of DEGs indicated involvement in substance metabolism, antioxidant defences, signal transduction, and immune responses. Therefore, chronic cold stress can suppress metabolism and cause oxidative damage and immune deficiency in crayfish. The findings provide fundamental molecular information for further study of the regulatory mechanisms of cold tolerance in red claw crayfish.


Assuntos
Astacoidea/genética , Temperatura Baixa/efeitos adversos , Hepatopâncreas/metabolismo , Estresse Fisiológico/genética , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Astacoidea/fisiologia , Perfilação da Expressão Gênica , Hepatopâncreas/ultraestrutura , Microscopia Eletrônica de Transmissão , Monofenol Mono-Oxigenase/metabolismo , Muramidase/metabolismo
15.
PLoS Negl Trop Dis ; 13(10): e0007740, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31603908

RESUMO

Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails.


Assuntos
Alcaloides/toxicidade , Frutas/química , Gastrópodes/efeitos dos fármacos , Moluscocidas/toxicidade , Papaveraceae/química , Fenantridinas/toxicidade , Extratos Vegetais/toxicidade , Fosfatase Ácida/efeitos dos fármacos , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Carboxilesterase/efeitos dos fármacos , Carboxilesterase/metabolismo , China , Glutationa Transferase/efeitos dos fármacos , Glutationa Transferase/metabolismo , Inativação Metabólica/efeitos dos fármacos , Fígado/metabolismo , Esquistossomose/prevenção & controle , Esquistossomose/transmissão
16.
Environ Pollut ; 255(Pt 2): 113321, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610515

RESUMO

Ionic liquids (ILs) are extensively used in several chemistry fields. And research about the effects of ILs on soil microbes is needed. In this study, brown soil was exposed to 1-butyl-3-methylimidazolium bromide ([C4mim]Br), 1-hexyl-3-methylimidazolium bromide ([C6mim]Br) and 1-decyl-3-methylimidazolium bromide ([C10mim]Br). The toxicities of the three ILs are evaluated by measuring the soil culturable microbial number, enzyme activity, microbial diversity and, abundance of the ammonia monooxygenase (amoA) genes of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA). Results showed that all tested ILs caused a decrease in culturable microbial abundance. Tested ILs exposure inhibit urease activity and promote acid phosphatase and ß-glucosidase activities. Tested ILs reduced soil microbial diversity and the abundances of AOB-amoA and AOA-amoA genes significantly. After a comparison of the integrated biomarker response (IBR) index, the toxicities of tested ILs to soil microorganisms were as follows: [C10mim]Br > [C6mim]Br > [C4mim]Br. Among all collected biomarkers, the abundance of the AOA-amoA gene was the most sensitive one and was easily affected after ILs exposure.


Assuntos
Archaea/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Boratos/toxicidade , Brometos/toxicidade , Imidazóis/toxicidade , Líquidos Iônicos/toxicidade , Fosfatase Ácida/metabolismo , Amônia/metabolismo , Glucosidases/metabolismo , Oxirredução , Oxirredutases/genética , Filogenia , Solo/química , Microbiologia do Solo , Urease/antagonistas & inibidores
17.
Molecules ; 24(19)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590284

RESUMO

The thiazolidinedione 49 (TD49) is an effective algaecide against harmful algae; however, its potential effects on the immune function of the edible bay scallop are unclear. Therefore, the present work studied the effects of TD49 on the immune response in bay scallop by evaluating activities of acid phosphatase (ACP), alkaline phosphatase (ALP), and superoxide dismutase (SOD), as well as nitric oxide (NO) levels, total protein content, and expression of immune genes (CTL-6, PGRP, PrxV, MT, and Cu/Zn-SOD) at 3-48 h post-exposure (hpe) to TD49. The activities of ACP and ALP significantly increased in TD49-treated groups at 3-24 hpe, whereas NO levels decreased significantly in 0.58 and 0.68 µM of TD49 at 6-24 hpe, after which the level was similar to that in the untreated control. Moreover, SOD activity significantly increased in all three concentration groups at 3-6 hpe, while it decreased at 12 hpe in the 0.68 µM TD49 treatment group. Notably, total protein content increased with TD49 treatment at each time interval. The results revealed that variable effects on the expression of immune-related genes were observed after treatment with TD49. The findings demonstrate that exposure of scallops to TD49 changes immune responses and expression of immune-related genes. We hypothesize that TD49 may disrupt immune system in bay scallop. The current investigation highlights the potential negative effects of using TD49 as an algaecide on marine economic bivalves to control harmful algal blooms in marine environments.


Assuntos
Herbicidas/efeitos adversos , Pectinidae/imunologia , Tiazolidinedionas/efeitos adversos , Fosfatase Ácida/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Herbicidas/química , Imunidade/efeitos dos fármacos , Pectinidae/efeitos dos fármacos , Pectinidae/metabolismo , Frutos do Mar , Superóxido Dismutase/metabolismo , Tiazolidinedionas/química
18.
PLoS One ; 14(9): e0222234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509576

RESUMO

Prostatic acid phosphatase (PAP), which is secreted by prostate, increases in some diseases such as prostate cancer. PAP is also present in the central nervous system. In this study we reveal that α-synuclein (Snca) gene is co-deleted/mutated in PAP null mouse. It is indicated that mice deficient in transmembrane PAP display neurological alterations. By using immunohistochemistry, cerebellar cortical neurons and zone and stripes pattern were studied in Pap-/- ;Snca-/- mouse cerebellum. We show that the Pap-/- ;Snca-/- cerebellar cortex development appears to be normal. Compartmentation genes expression such as zebrin II, HSP25, and P75NTR show the zone and stripe phenotype characteristic of the normal cerebellum. These data indicate that although aggregation of PAP and SNCA causes severe neurodegenerative diseases, PAP -/- with absence of the Snca does not appear to interrupt the cerebellar architecture development and zone and stripe pattern formation. These findings question the physiological and pathological role of SNCA and PAP during cerebellar development or suggest existence of the possible compensatory mechanisms in the absence of these genes.


Assuntos
Fosfatase Ácida/metabolismo , Córtex Cerebelar/metabolismo , alfa-Sinucleína/metabolismo , Fosfatase Ácida/genética , Fosfatase Ácida/fisiologia , Animais , Cerebelo/metabolismo , Expressão Gênica/genética , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Transcriptoma/genética , alfa-Sinucleína/genética , alfa-Sinucleína/fisiologia
19.
Food Funct ; 10(9): 5616-5625, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31432856

RESUMO

A novel osteogenic dodecapeptide peptide (PIE), IEELEEELEAER, was purified from the protein hydrolysate of blue mussels (Mytilus edulis). PIE was identified using a capillary electrophoresis electrospray ionization-quadrupole-time of flight mass spectrometer. PIE showed a good reduction in the bone loss in ovariectomized mice, and it also increased the bone mineral density of the ovariectomized mice. PIE has a high affinity with integrins (PDB: , ). There are 8 and 12 amino acid residues from PIE that interact with integrins and , respectively. PIE accelerates the transformation of G0/G1 phase cells into G2 M phase cells, which promotes the growth of osteoblasts. PIE (100 µg mL-1) can enhance alkaline phosphatase (ALP) activity by 26.48% compared with the control, and it also inhibits the growth of osteoclasts and tartrate resistant acid phosphatase (TRAP) activity. Therefore, PIE may contribute to preventing osteoporosis both in vitro and in vivo.


Assuntos
Mytilus edulis/química , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/administração & dosagem , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Animais , Densidade Óssea , Feminino , Humanos , Integrinas/genética , Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Peptídeos/química , Hidrolisados de Proteína/química , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo
20.
Eur J Med Chem ; 182: 111611, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31445230

RESUMO

Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel therapeutic agents to treat this disease. α-Alkoxy-substituted naphthylmethylphosphonic acid derivatives have been identified previously as molecules that bind with high affinity to PAPs, and docking studies suggest that longer alkyl chains may increase the binding affinities of such compounds. Here, we synthesized several derivatives and tested their inhibitory effect against pig and red kidney bean PAPs. The most potent inhibitor within this series is the octadecyl derivative, which has a Ki value of ∼200 nM. Crystal structures of the dodecyl and octadecyl derivatives bound to red kidney bean PAP show that the length of the alkyl chain influences the ability of the phosphonate group to interact directly with the bimetallic center. These structures represent the first examples of potent inhibitors bound to a PAP that have drug-like properties. This study provides a starting point for the development of much needed new treatments for osteoporosis.


Assuntos
Fosfatase Ácida/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Osteoporose/tratamento farmacológico , Fosfatase Ácida/metabolismo , Animais , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Osteoporose/metabolismo , Phaseolus/enzimologia , Relação Estrutura-Atividade , Suínos
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