Protopanaxadiol-type ginsenoside hydrolases and their application in the preparation of ginsenoside Compound K: a review / 生物工程学报

Ginsenoside Compound K (CK) has anti-cancer and anti-inflammatory pharmacological activities. It has not been isolated from natural ginseng and is mainly prepared by deglycosylation of protopanaxadiol. Compared with the traditional physicochemical preparation methods, the preparation of CK by hydrolysis with protopanaxadiol-type (PPD-type) ginsenoside hydrolases has the advantages of high specificity, environmental-friendliness, high efficiency and high stability. In this review, the PPD-type ginsenoside hydrolases were classified into three categories based on the differences in the glycosyl-linked carbon atoms of the hydrolase action. It was found that most of the hydrolases that could prepare CK were PPD-type ginsenoside hydrolase type Ⅲ. In addition, the applications of hydrolases in the preparation of CK were summarized and evaluated to facilitate large-scale preparation of CK and its development in the food and pharmaceutical industries.

Partial purification, characterization and application of thermoalkaliphilic proteases from Priestia endophytica, Lysinibacillus cresolivorans and Bacillus subtilis isolated from desert soil

Aims@#Thermophilic proteases are important industrial enzymes because they can be used at high temperatures in various bioprocessing schemes. The bacterial population of the Cholistan desert was explored for thermophilic proteases and their industrial applications.@*Methodology and results@#Three bacterial isolates K1, K5 and K7 were found promising protease producers. These isolates were preliminary identified as Bacillus based on morphological characteristics and biochemical tests (positive for catalase, oxidase and citrate tests, and negative for indole and urease tests). The isolates K1, K5 and K7 were further identified as Priestia endophytica, Lysinibacillus cresolivorans and Bacillus subtilis, respectively by phylogenetic analysis. The isolates grew best at 50 °C and P. endophytica (K1), L. cresolivorans (K5) and B. subtilis (K7) produced larger zones of hydrolysis at 37 °C, 45 °C and 50 °C at pH 7, respectively. The optimum temperature where protease activity was maximum was 65 °C for P. endophytica and L. cresolivorans and 55 °C for B. subtilis, and the optimum pH was 9.@*Conclusion, significance and impact of study@#The proteases produced by these isolates were found active at high temperatures (45 °C to 85 °C) and high pH (9-12), which make them industrially important thermoalkaliphilic proteases. These proteases successfully de-haired cow’s skin and de-stained blood from cotton cloth pieces, which are rarely tested applications of these proteases.

Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Alpha-Galactosidase A Levels in Colombian Males with End-Stage Renal Disease: Ten Years of Selective Screening in Dried Blood Spots

Abstract Fabry disease is a metabolic alteration linked to an enzymatic deficiency of Alpha-Galactosidase A, this disorder compromises the sphingolipid metabolism, leading to an accumulation of lysosomal globotriaosylceramide and is inherited in an X-linked recessive way. The diagnostic of this disease, in general, requires the confirmation of below-normal levels of Alpha-Galactosidase A obtained from dried blood spot (DBS) samples, followed by an assessment of the enzyme in leukocytes. We aimed to report the Alpha-Galactosidase A values obtained in Colombian males with end-stage renal disease (ESRD) screened using dried blood spot samples during ten years. This screening was performed with samples sent to the analysis center from 6156 patients between 2006- 2016. All patients with low levels in enzyme activity (compared to the control population) were sent to confirmation through enzyme analysis in isolated leukocytes. 26 males (0.42%) with low levels of Alpha-Galactosidase A were identified (Range 0.0 - 1.14 nmol/ml/hour, cut-off: 1.15), 22 patients were subsequently measured in isolated leukocytes having a confirmation of Fabry disease in 5 patients (0.08% of total male population) (Range: 0.3 -4.7 nmol/mg prot/h). These results are similar to those reported in studies with comparable characteristics being this the first reporting frequency of Fabry disease among Colombian males with end-stage renal disease.

LXYL-P1-2 immobilized on magnetic nanoparticles and its potential application in paclitaxel production

BACKGROUND: LXYL-P1-2 is the first reported glycoside hydrolase that can catalyze the transformation of 7-b-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT) by removing the D-xylosyl group at the C7 position. Successful synthesis of paclitaxel by one-pot method combining the LXYL-P1-2 and 10- deacetylbaccatin III-10-b-O-acetyltransferase (DBAT) using XDT as a precursor, making LXYL-P1-2 a highly promising enzyme for the industrial production of paclitaxel. The aim of this study was to investigate the catalytic potential of LXYL-P1-2 stabilized on magnetic nanoparticles, the surface of which was modified by Ni2+-immobilized cross-linked Fe3O4@Histidine. RESULTS: The diameter of matrix was 20­40 nm. The Km value of the immobilized LXYL-P1-2 catalyzing XDT (0.145 mM) was lower than that of the free enzyme (0.452 mM), and the kcat/Km value of immobilized enzyme (12.952 mM s 1 ) was higher than the free form (8.622 mM s 1 ). The immobilized form maintained 50% of its original activity after 15 cycles of reuse. In addition, the stability of immobilized LXYL-P1-2, maintained 84.67% of its initial activity, improved in comparison with free form after 30 d storage at 4 C. CONCLUSIONS: This investigation not only provides an effective procedure for biocatalytic production of DT, but also gives an insight into the application of magnetic material immobilization technology.

Metaloproteinases da matriz: papel no desenvolvimento das lesões periapicais e modulação após tratamento endodôntico / Matrix metalloproteinases: role in the development of apical periodontitis and modulation after endodontic treatment

Introduction: Apical periodontitis represents a local immune response directed against the progression of microorganisms from the dental pulp to the apical foramen and periapical tissues, which results in bone and dental resorption. The aim of this review is to describe the expression of this group of proteases in apical periodontitis and its modulation during the periapical healing phase following root canal treatment. Literature review: The pathogenesis of apical periodontitis involves degradation of several extracellular matrix components. Matrix metalloproteinases (MMPs) are expressed in response to specific stimuli by resident cells of connective tissue during tissue remodeling and by inflammatory cells that arrive into the surrounding tissues during inflammatory events. MMPs have been reported in apical periodontitis, either experimentally induced or obtained from humans and there is evidence that these enzymes show diff erent expression patterns in granulomas and periapical cysts. Root canal therapy is important for the reduction of periapical inflammation as well as the synthesis of MMPs, especially when using a calcium hydroxide-based dressing. Conclusion: Apical periodontitis show high expression of matrix metalloproteinases and root canal treatment results in less expression of MMPs when compared to untreated apical periodontitis.

Introdução: A lesão periapical representa a resposta imunoinflamatória devido ao aumento do número e progressão de micro-organismos advindos dos canais radiculares contaminados em direção aos tecidos apicais e periapicais, resultando em reabsorção óssea. O objetivo desta revisão será abordar a importância das metaloproteinases da matriz no desenvolvimento das lesões periapicais e sua modulação durante a fase de reparação tecidual depois de instituído o tratamento endodôntico. Revisão da literatura: A patogênese da lesão periapical envolve a degradação progressiva de diversos componentes da matriz extracelular. Dentre as proteases responsáveis pela degradação destes componentes estão as metaloproteinases da matriz (MMPs). Estas proteinases são expressas em resposta a estímulos específicos pelas células residentes do tecido conjuntivo durante o processo de remodelação tecidual e por células inflamatórias que invadem os tecidos durante eventos inflamatórios. As MMPs foram descritas em lesões periapicais experimentais e em humanos e existem evidências de que estas enzimas apresentam padrões de expressões diferentes em granulomas e cistos periapicais. A terapia endodôntica é importante para a redução da inflamação periapical assim como da síntese das MMPs, principalmente quando utilizado um curativo de demora à base de hidróxido de cálcio. Conclusão: As lesões periapicais apresentam alta expressão de metaloproteinases da matriz e o tratamento endodôntico em dentes com lesão periapical resulta em menor expressão de MMPs quando comparado às lesões periapicais não tratadas.

Comparative molecular studies of halophilic bacteria from saline water and soil in the Saudi environment / Estudos moleculares comparativos de bactérias halofílicas de água salina e solo no meio ambiente saudita

Halophilic bacteria are microorganisms that grow optimally in the presence of the very high concentration of sodium chloride. Halophiles are vital sources of various enzymes including hydrolases, which are very stable and catalytically highly efficient at high salt concentration and other extreme conditions such as high temperature, pH and presence of organic solvents. Several hydrolases such as amylases, proteases, and lipases have been obtained from halophilic bacteria and are commonly used for various industrial applications. We initiated a screening to isolate and characterize the halophilic bacteria from the Red Sea, which is one of the saltiest bodies of water in the world. Water and soil samples, collected from the Red Sea coast, Jeddah, Saudi Arabia, were screened for isolation of halophilic bacteria. Ten bacterial isolates were obtained, which were characterized by biochemical tests and 16S rRNA gene sequencing. Hydrolase producing bacteria among the isolates were screened by plate assay on starch and gelatin agar plates for amylase and protease, respectively. Two bacterial isolates i.e. Bacillus glycinifermentans S3 and Enterobacter cloacae W1were found to possess significant amylase and protease activity.

Bactérias halofílicas são microrganismos que crescem de maneira ideal na presença de uma concentração muito alta de cloreto de sódio. Halófilos são fontes vitais de várias enzimas, incluindo hidrolases, que são muito estáveis e cataliticamente altamente eficientes em alta concentração de sal e outras condições extremas, como alta temperatura, pH e presença de solventes orgânicos. Várias hidrolases como amilases, proteases e lipases foram obtidas a partir de bactérias halofílicas e são comumente usadas para várias aplicações industriais. Iniciamos uma triagem para isolar e caracterizar as bactérias halofílicas do Mar Vermelho, que é um dos corpos de água mais salgados do mundo. Amostras de água e solo, coletadas na costa do Mar Vermelho, Jeddah, na Arábia Saudita, foram examinadas quanto ao isolamento de bactérias halofílicas. Foram obtidos dez isolados bacterianos, caracterizados por testes bioquímicos e seqüenciamento do gene 16S rRNA. As bactérias produtoras de hidrolase entre os isolados foram triadas por ensaio em placa em placas de amido e ágar de gelatina para amilase e protease, respectivamente. Verificou-se que dois isolados bacterianos, isto é, Bacillus glycinifermentans S3 e Enterobacter cloacae W1, possuíam significativa atividade de amilase e protease.

Evaluación del daño oxidativo y por metilación del ADN de pintores expuestos ocupacionalmente a solventes orgánicos y pintura / Evaluation of oxidative and methylating DNA damage in painters occupationally exposed to organic solvents and paints

Resumen Introducción. La exposición a solventes orgánicos y pinturas se ha asociado con efectos genotóxicos y mayor riesgo de neoplasias. Sin embargo, aún no se ha caracterizado bien el tipo de daño que esta exposición induce en el ADN humano, ni los mecanismos por los cuales se genera. Uno de los grupos con mayor exposición a dichos solventes y pinturas son los pintores de automóviles del sector informal que trabajan sin adecuadas prácticas de seguridad ocupacional. Objetivo. Determinar el daño oxidativo y por metilación del ADN de linfocitos de pintores de automóviles expuestos a solventes orgánicos y pinturas. Materiales y métodos. Se analizaron linfocitos aislados de sangre periférica de 62 pintores y 62 sujetos no expuestos mediante el ensayo cometa de gran eficiencia acoplado a las enzimas Fpg y AlkA. Las categorías de daño en el ADN evaluadas fueron el daño basal (sin enzimas), el daño oxidativo y el daño por metilación, y el parámetro de medición, el porcentaje de ADN en la cola. Resultados. El porcentaje de ADN en la cola fue mayor en el grupo expuesto con respecto al no expuesto (p<0,05). En el grupo expuesto, dicho porcentaje fue mayor en la categoría de daño oxidativo comparado con la del basal (16,50 Vs. 12,87; p<0,001), en tanto que en el daño por metilación no se encontraron diferencias significativas (14,00 Vs. 12,87; p>0,05). Conclusión. La exposición a solventes orgánicos y pinturas se asoció con el aumento de las lesiones oxidativas del ADN de los linfocitos de pintores de automóviles, tales como la producción de 8-oxo-2'-desoxiguanosina (8-oxodG) y otros productos formamidopirimidina, los cuales se consideran considerablemente mutagénicos.

Abstract Introduction: The exposure to organic solvents and paints has been associated with genotoxicity and a greater risk of neoplasms. However, the type of DNA damage induced in humans by the exposure to these compounds, which would help explain the mechanisms of their genotoxicity, is still not fully characterized. Due to inadequate practices of occupational safety, car painters in the informal sector are a highly exposed group to organic solvents and paints. Objective: To identify the oxidative and methylating damage in the DNA of lymphocytes of car painters exposed to organic solvents and paints. Materials and methods: Isolated peripheral blood lymphocytes from 62 painters and 62 unexposed subjects were analyzed by the modified high-throughput comet assay with the Fpg and AlkA enzymes. The categories used for the evaluation of the DNA damage were basal damage (without enzymes), oxidative and methylating damage. The measurement parameter used to establish the damage was the percentage of DNA in the tail. Results: The percentage of DNA in the tail was higher in the exposed group compared to the unexposed group (p<0.05). In the exposed group, this percentage was higher in the oxidative damage category than the baseline (16.50 vs. 12.87; p<0.001), whereas methylating damage did not show significant differences (14.00 vs. 12.87; p>0.05). Conclusion: In this study, exposure to organic solvents and paints was associated with an increase in oxidative lesions in the DNA of car painters' lymphocytes, such as the production of 8-oxodG and other formamidopyrimidine products which are considered highly mutagenic.

The effects of miR-25 and the potential molecular mechanisms on migration and invasion of triple negative breast cancer / 中华检验医学杂志

Objective To explore the expression of tiny RNA-25 (microRNA-25, miR-25) in the plasma、tissues of triple-negative breast cancer(TNBC) patients and cell lines, to investigate the potential molecular mechanisms of miR-25 on migration and invasion of TNBC. Methods Real-time fluorescent quantitative PCR was used to detect the expression of miR-25 in the plasma of TNBC patients. Linked omics web platform was used to analyse miR-25 level in samples of TNBC and non-TNBC. Real-time fluorescent quantitative PCR was also used to detect the miR-25 level in TNBC cell lines. The wound healing and transwell assay was applied to assess the effects on migration and invasion of TNBC cell lines which transfected with miR-25 inhibitor or the negative control. The luciferase reporter assay was used to validate the relationship between miR-25 and the sphingosine-1-phosphate phosphatase 1 (SGPP1) in HEK293T cell. The wound healing and transwell assay was used to detect the migration and invasion ability of TNBC cell lines when cotransfected with pCMV6-SGPP1 and miR-25. Furthermore, Western blot was performed to detect the SGPP1 level in TNBC cell lines. Results The expression of miR-25 was significantly elevated in the plasma of 86 TNBC patients compared with the healthy controls (P value was 0.031). LinkedOmics web platform analysis showed that miR-25 expression was significantly higher in TNBC samples than in non-TNBC samples with Luminal A or Luminal B (P value was<0.001 and 0.006). The level of miR-25 was also elevated in TNBC cell lines HS578T, HCC1806, MDA-MB-231 and BT549(P value was 0.006, 0.01, 0.029 and 0.046). The MDA-MB-231 and HS578T cells which transfected with miR-25 inhibitor exhibited a significant slower wound healing rate than control (P value was 0.035 and 0.001). At the same time, when transfected with miR-25 inhibitor, MDA-MB-231 and HS578T both exhibited a decreased invasion ability compared with the control group(P value was 0.002 and 0.001). LinkedOmics web platform analysis showed that sphingosine-1-phosphate phosphatase 1 (SGPP1) gene level was negatively correlated with miR-25 in the tissues of TNBC patients (P value was 0.037). The luciferase reporter assay validated that SGPP1 was a directed target of miR-25. The western blot assay indicated that the SGPP1 level was increased in MDA-MB-231 and HS578T after transfection with miR-25 inhibitor. Over-expression of SGPP1 could abrogate the positive effects of miR-25 on migration and invasion when pCMV6-SGPP1 was cotransfected with miR-25 (P value was all 0.002). Conclusions MiR-25 was elevated in both plasma and tissues of TNBC patients and also increased in TNBC cell lines. Transfection of MDA-MB-231 and HS578T cells with miR-25 inhibitor resulted in reduced migration and invasion. Moreover, SGPP1 was identified as a novel target of miR-25. The ability of miR-25 to promote TNBC cell migration and invasion is attributable to its effect on SGPP1 suppression.

Research progress on carbohydrate active enzymes of human microbiome / 华西口腔医学杂志

A massive variety of microorganisms live in and on the human body, especially at oral, skin, vaginal, gastroin-testinal, and respiratory sites. The complicated metabolic activities of microorganisms assist human digestive function and participate in a series of physiological and pathogenetic processes. Carbohydrate-active enzymes (CAZymes) are a series of enzymes that function in degradation, modification, and formation of glycoside bonds. Microbes regulate the physiological and pathogenetic processes of human body by producing various CAZymes to degrade and modify complex carbohydrates and generate signal molecules for further utilization in human cells. Here, we reviewed the mechanisms of complex carbohy-drate metabolism and related microbial CAZymes, especially in digestive tract and oral cavity. We also summarized the rela-tionship between microbial CAZymes and human health, and proposed potential applications.

The expression and clinical significance of ENPP2 in acute myeloid leukemia / 中国医师杂志

Objective To analyze the expression and clinical significance of exonucleotide pyro-phosphatase/phosphodiesterase family member 2 (ENPP2) in acute myeloid leukemia (AML), and to ex-plore its potential molecular mechanism. Methods The expression profiles of ENPP2 in different normal tissues was analyzed with GTEx database. Rstudio and Graphpad were used to analyze ENPP2 expression, genomic mutations and survival curve in data from GEO and TCGA databases, and the signaling pathway as-sociated with ENPP2 expression were further analyzed with GSEA enrichment software. Results In normal tissues, ENPP2 was mainly expressed in fat, brain and uterus;the expression in acute myeloid leukemia tis-sues was higher than that in donors. Only 0. 5％ of patients in 187 TCGA genomic data had gene amplifica-tion, there was no gene mutations and deletions. ENPP2 expression in recurrent AML was significantly high-er than primary patients, and its high expression was associated with poor prognosis. Gene enrichment anal-ysis shows high ENPP2 group isenriched in autoimmune diseases, cytokine receptor activation pathway, and low ENPP2 was enriched in DNA replication, cell cycle pathways. ENPP2 was also involved in the pathway that associated with retinoic acid and glucocorticoids treatment. Conclusions ENPP2 is highly expressed in AML patients and is associated with recurrence and poor prognosis of AML. The main molecular mecha-nism of ENPP2 in AML may be related to autoimmune response and drug treatment response, ENPP2 is a potential therapy target of AML.

Paraoxonase-1 polymorphisms and cerebral ischemic stroke: a pilot study in mexican patients / Caracterización polimórfica de la paraoxonasa-1 en el infarto cerebral aterotrombótico de una poblacion mexicana: estudio piloto

Abstract Background: The serum paraoxonase-1 (PON1) associated to HDL presents two common polymorphisms in the positions 192 and 55. These polymorphisms are considered determinant of the capacity of HDL to protect LDL from their oxidative modification. In this context, the PON1 genotype has been associated with cardiovascular diseases, including stroke. Objective: To determine the allelic and genotypic frequencies of PON1 L55M and Q192R as well as the enzymatic activities of PON1 in subjects with and without atherothrombotic stroke. Methods: There were included 28 people with atherothrombotic stroke and 29 without stroke. The genotyping was carried out by PCR-RFLP and the phenotyping by measurement of the activities of paraoxonase and arylesterase in serum. Results: For the polymorphism Q192R, the allelic frequencies (Q/R) were 0.46/0.54 and 0.48/0.52 (p= 0.843) for the control group and the group with stroke, respectively. While for the polymorphism L55M, the allelic frequencies (L/M) were 0.81/0.19 for the control group, and 0.78/0.22 for the group with stroke (p= 0.610). The activity levels of paraoxonase were not significantly different between the control and stroke groups (450 vs. 348 UI/mL, p= 0.093) While the activity levels of arylesterase were significantly different between the studied groups (90 vs. 70 UI/mL, p= 0.001); however, upon adjustment by multiple linear regression, it was not longer significant. Conclusion: The polymorphisms Q192R and L55M, and the paraoxonase activity of PON1 are not risk factors for atherothrombotic stroke according to the results of this study.

Resumen Introducción: La paraoxonasa-1 (PON1) sérica asociada a las HDL presenta dos polimorfismos comunes en las posiciones 192 y 55. Estos polimorfismos se consideran determinantes para la capacidad de las HDL de proteger a las LDL de su modificación oxidativa. En este contexto, el genotipo de PON1 se ha asociado con enfermedades cerebrovasculares, que incluyen el infarto cerebral. Objetivo: Determinar las frecuencias alélicas y genotípicas de PON1-L55M y PON1- Q192R, así como las actividades enzimáticas de PON1 en sujetos con y sin infarto cerebral aterotrombótico. Métodos: Se incluyeron 28 personas con infarto cerebral aterotrombótico y 29 sin infarto. Las genotipificaciones se realizaron mediante PCR-RFLP y las fenotipificaciones mediante la medición de las actividades paraoxonasa y arilesterasa en suero. Resultados: Para el polimorfismo Q192R, las frecuencias alélicas (Q/R) fueron 0.46/0.54 y 0.48/0.52 (p= 0.843) para el grupo control y el grupo con infarto, respectivamente. Mientras que para el polimorfismo L55M, las frecuencias alélicas (L/M) fueron 0.81/0.19 para el grupo control y 0.78/0.22 para el grupo con infarto (p= 0.610). Los niveles de actividad paraoxonasa no fueron significativamente diferentes entre los grupos control y con infarto (450 vs. 348 Ul/mL, p= 0.093). Mientras que los niveles de actividad arilesterasa fueron significativamente diferentes entre los grupos estudiados (90 vs. 70 Ul/mL, p= 0.001), sin embargo, al ajustarla por regresión lineal múltiple, dejo de ser significativa. Conclusión: Los polimorfismos Q192R y L55M, y la actividad paraoxonasa de la PON1 no son factores de riesgo para el infarto cerebral aterotrombótico en este estudio.

Chemical study on Cassiae Semen processing procedure / 中国中药杂志

References and our previous experiment showed that the contents of glycosides were significantly decreased，while the contents of aglycones were significantly increased after processing of Cassiae Semen.It may be related to its glycosidases or the heating process. In order to investigate the reasons, high performance liquid chromatographic (HPLC) was used to study the effects of these two factors on contents of Cassiae Semen's main chemical components in processing. The results showed that glycoside hydrolases was present in Cassiae Semen and could rapidly hydrolyze glycosides from Cassiae Semen into aglycones in suitable temperature with sufficient water.However，it didn't show effect on contents change of main constituents in the procedure of Cassiae Semen processing.The reason for content decrease of glycosides and content increase of aglycones in processed Cassiae Semen was glycoside bond cracking to produce corresponding aglycone at high temperature.This study further provides basis for further revealing of the processing mechanism of Cassiae Semen.

Research on the relationship between the gene polymorphism of leukotriene A4 hydrolase and the severity of tuberculous meningitis / 中华神经科杂志

Objective To investigate the relationship between rs17525495 locus polymorphism of leukotriene A4 hydrolase (LTA4H) gene and the severity of tuberculous meningitis (TBM). Methods A total of 184 TBM patients from Department of Neurology, the Second Hospital of Hebei Medical University from January 2014 to October 2016 were selected as research subjects. According to the British Medical Research Council criteria, the severity of TBM patients was divided into three stages. The single nucleotide polymorphism rs17525495 of LTA4H gene was sequenced, and the general case data, clinical manifestations and results of lumbar puncture were analyzed. Results There were 91 cases (49.5％) of CC genotypes of rs17525495 locus in LTA4H gene of 184 cases, 75 cases (40.8％) of CT genotypes and 18 cases (9.8％) of TT genotypes. The frequency of allele C was 69.8％ and T was 30.2％. Patients with different genotypes were compared for their severity, clinical manifestations and lumbar puncture results. Among CC patients, the proportion of stage Ⅰ patients(54.9％, 50/91)was higher than that of stage Ⅱ(22.0％, 20/91)and Ⅲ(23.1％, 21/91). Among TT patients, the proportion of patients with stage Ⅱ(8/18)and Ⅲ(8/18)was higher than patients with stageⅠ(2/18)(χ2=15.898,P=0.003). The incidence of headache, fever, nausea and vomiting, neck stiffness, epilepsy and disturbance of consciousness was statistically analyzed. Compared with CC and CT patients, the incidence of fever(TT:13/18,CC:42/91,CT:50/75,χ2=8.932,P=0.011)and neck stiffness(TT:12/18,CC:38/91,CT:46/75,χ2=7.993,P=0.018)was higher in TT patients. Headache, nausea and vomiting, disturbance of consciousness, and the incidence of epilepsy showed no statistically significant difference. And there was no statistically significant difference in lumbar puncture pressure, chloride, protein and glucose between different genotypes. Conclusion TBM patients with mild illness frequently prompt LTA4H gene rs17525495 locus for the CC type;while patients with severe disease prompt TT type.

Draft genome sequence of Streptomyces sp. strain F1, a potential source for glycoside hydrolases isolated from Brazilian soil

ABSTRACT Here, we show the draft genome sequence of Streptomyces sp. F1, a strain isolated from soil with great potential for secretion of hydrolytic enzymes used to deconstruct cellulosic biomass. The draft genome assembly of Streptomyces sp. strain F1 has 69 contigs with a total genome size of 8,142,296 bp and G + C 72.65%. Preliminary genome analysis identified 175 proteins as Carbohydrate-Active Enzymes, being 85 glycoside hydrolases organized in 33 distinct families. This draft genome information provides new insights on the key genes encoding hydrolytic enzymes involved in biomass deconstruction employed by soil bacteria.

Homozygous ectonucleotide pyrophosphatase/phosphodiesterase 1 variants in a girl with hypophosphatemic rickets and literature review / 中华儿科杂志

Objective@#To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants.@*Method@#The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed.@*Result@#Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients.@*Conclusion@#ENPP1 gene mutation was a cause of patient with hypophosphatemic rickets. Comorbid features included generalized arterial calcification of infancy, early onset hearing loss, pseudoxanthoma and ossification of posterior longitudinal ligament. ENPP1 gene testing should be performed on hypophosphatemic rickets patients without PHEX gene variants. Long-term follow up is recommended. The most common types of ENPP1 gene variants were nonsense/splicing variants. The gene c.783C>G was the most common variants in Chinese patients.

Enzymatic potential of heterotrophic bacteria from a neutral copper mine drainage

Abstract Copper mine drainages are restricted environments that have been overlooked as sources of new biocatalysts for bioremediation and organic syntheses. Therefore, this study aimed to determine the enzymatic activities (esterase, epoxide hydrolase and monooxygenase) of 56 heterotrophic bacteria isolated from a neutral copper mine drainage (Sossego Mine, Canaã dos Carajás, Brazil). Hydrolase and monooxygenase activities were detected in 75% and 20% of the evaluated bacteria, respectively. Bacterial strains with good oxidative performance were also evaluated for biotransformation of organic sulfides. Fourteen strains with good enzymatic activity were identified by 16S rRNA gene sequencing, revealing the presence of three genera: Bacillus, Pseudomonas and Stenotrophomonas. The bacterial strains B. megaterium (SO5-4 and SO6-2) and Pseudomonas sp. (SO5-9) efficiently oxidized three different organic sulfides to their corresponding sulfoxides. In conclusion, this study revealed that neutral copper mine drainages are a promising source of biocatalysts for ester hydrolysis and sulfide oxidation/bioremediation. Furthermore, this is a novel biotechnological overview of the heterotrophic bacteria from a copper mine drainage, and this report may support further microbiological monitoring of this type of mine environment.

Research progress of repair enzyme MTH1 and its inhibitors / 中国药理学通报

MTH1 enzyme belongs to the family of Nudix hydro-lases, which can prevent the oxidative damage of nucleic acid by cleaning up oxidized purine nucleotides .Close relationships were found between the activity of MTH 1 and neurodegenerative dis-eases, anti-aging et al.In recent years, MTH1 has been regar-ded as a new promising target for cancer treatment , because it plays an essential role in tumor growth , survival , invasion and metastasis.The transcription and translation , structure, catalyt-ic mechanism, detection and application of MTH1 were de-scribed, as well as various MTH1 inhibitors.

The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics

The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.

Correlation between variants of leukotriene A4 hydrolase gene and risk of ischemic stroke in population of southern Zhejiang Province / 中华神经科杂志

Objective To investigate the correlation between two single nucleotide polymorphisms of the leukotriene A4 hydrolase (LTA4H) gene (rs2660845 and rs2540493) and risk of ischemic stroke in population of southern Zhejiang Province.Methods A total of 300 ischemic stroke patients and 300 healthy controls,recruited from the Department of Neurology,Third Affiliated Hospital of Wenzhou Medical University between September 2010 and June 2013,were enrolled in this study.Two single nucleotide polymorphisms of the LTA4H gene (rs2660845 and rs2540493) were analyzed by polymerase chain reaction and matrix-assisted laser desorption/ionization time of flight,respectively.Sixty-seven patients and thirty controls were randomly selected (complete randomization) and detected the serum leukotriene B4 (LTB4)concentration by ELISA method.Results There was no evidence of association between the two variants of LTA4H gene and the risk of ischemic stroke or its TOAST (Trial of Org 10 172 in acute stroke treatment)subtypes (P ＞ 0.05).Analysis of LTB4 levels revealed that there was no statistically significant difference in serum LTB4 concentration between patients (n =67) and controls (n =30; 0.991 ± 0.305 vs 1.035 ± 0.498 ; P =0.692),and no statistically significant difference in LTB4 concentration was found among the three genotypes of rs2660845 as well (AG genotype vs AA genotype vs GG genotype:0.938 ± 0.269 vs 1.038 ± 0.268 vs 1.043 ± 0.383 ; P =0.401).Conclusion The present study suggests that there is no association between the two polymorphisms in the LTA4H gene and risk of ischemic stroke in population of southern Zhejiang Province.