Relationship between serum MBL,HRG,IL-23/IL-17 inflammatory axis and cerebral vasospasm and prognosis in patients with aneurysmal subarachnoid hemorrhage after interventional embolization / 国际检验医学杂志

Objective To investigate the relationship between serum mannan binding lectin(MBL),histi-dine rich glycoprotein(HRG),interleukin(IL)-23/IL-17 inflammatory axis and cerebral vasospasm(CVS)and prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH)after interventional emboliza-tion.Methods A total of 195 patients with aSAH who underwent interventional embolization treatment in the hospital from March 2019 to February 2022 were selected and were divided into no CVS group(126 cases),mild CVS group(18 cases),moderate CVS group(39 cases),and severe CVS group(12 cases)according to the occurrence and severity of CVS detected by digital subtraction angiography at the 4th postoperative day.The levels of serum MBL,HRG,IL-23 and IL-17 among the four groups before and 3 d after surgery were compared.The patients were followed up for 6 months and divided into good prognosis group(137 cases)and poor prognosis group(58 cases)according to their prognosis.Factors influencing poor prognosis in aSAH pa-tients were analyzed by multivariate Logistic regression model.The predictive value of serum MBL,HRG,IL-23,IL-17 levels and their combined application models for poor prognosis in patients with aSAH was analyzed by receiver operating characteristic(ROC)curve.Results The incidence rate of CVS after interventional em-bolization was 35.38%in 195 patients with aSAH.3 d after surgery,the serum levels of MBL,IL-23 and IL-17 in the mild,moderate,and severe CVS groups were higher than those in the no CVS group,those in the severe CVS group were higher than those in the moderate CVS group,those in the moderate CVS group were higher than those in the mild CVS group(P<0.05).The serum HRG levels in the mild,moderate,and severe CVS groups were lower than those in the non CVS group,those in the severe CVS group were lower than those in the moderate CVS group,those in the moderate CVS group were lower than those in the mild CVS group(P<0.05).3 d after surgery,the levels of serum MBL,IL-23 and IL-17 in the four groups were higher than that before surgery,while the levels of serum HRG were lower than that before surgery(P<0.05).The pro-portions of patients with aneurysm diameter≥6 mm,number of aneurysms>1,surgery time>24 h,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,and serum levels of MBL,IL-23,and IL-17 on the 3rd day after sur-gery in the good prognosis group were lower than those in the poor prognosis group,and serum HRG levels at 3 d after surgery in the good prognosis group were higher than that in the poor prognosis group(P<0.05).Multivariate Logistic regression analysis showed that aneurysm diameter≥6 mm,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,elevated serum levels of MBL,IL-23,and IL-17 and decreased HRG level at 3 d after sur-gery were independent risk factors for poor prognosis in aSAH patients(P<0.05).ROC results showed that serum levels of MBL,HRG,IL-23,and IL-17 at 3 d after surgery had certain predictive power for poor progno-sis in patients with aSAH.The predictive model with the combined application of four indicators had relatively high efficiency(the area under the curve was 0.853).Conclusion Elevated levels of MBL,IL-23,IL-17,and decreased HRG levels in aSAH patients after interventional embolization could increase the risk of CVS and are associated with poor prognosis in aSAH patients after interventional embolization.The above indicators have a certain predictive power for poor prognosis in aSAH patients.

Correlation between psychiatric symptoms and semi-essential amino acid levels in patients with schizophrenia / 西安交通大学学报(医学版)

【Objective】 To elucidate the possible role of arginine and histidine in the pathogenesis of schizophrenia by exploring the serum levels of semi-essential amino acids (arginine and histidine) in patients with schizophrenia and their correlation with psychiatric symptoms. 【Methods】 We selected 72 inpatients with schizophrenia admitted to The First Affiliated Hospital of Xi’an Jiaotong University from March 2021 to October 2022 and 72 healthy volunteers enrolled in Yanta Community during the same period as the research subjects. Serum arginine and histidine levels were measured in patients with schizophrenia and healthy controls using serum liquid chromatography-mass spectrometry (LC-MS). We used the Positive and Negative Symptom Scale (PANSS) to evaluate the mental symptoms of patients with schizophrenia and analyzed the correlation of serum arginine and histidine levels with disease course, frequency of onset, and PANSS score. 【Results】 The levels of serum arginine (P<0.001) and histidine (P=0.011) in the schizophrenia group were significantly lower than those in the control group. The levels of serum arginine and histidine were significantly negatively correlated with the frequency of onset (rs=-0.410, rs=-0.262), total score of PANSS (rs=-0.298, rs=-0.256), positive factors (rs=-0.299, rs=-0.234) and cognitive impairment factors (rs=-0.251, rs=-0.296). In addition, serum arginine levels had significantly negative correlation with anxiety and depression factors (rs=-0.269, P<0.05). 【Conclusion】 The serum levels of arginine and histidine in patients with schizophrenia are significantly lower than those in healthy individuals, and are negatively correlated with overall mental symptoms, severity of positive symptoms and cognitive impairment. The severity of anxiety and depression symptoms is negatively correlated with arginine levels. The detection of serum arginine and histidine can provide reference for the diagnosis and assessment of the severity of schizophrenia in the future.

Biological threats to global malaria elimination II Deletion in the malaria rapid diagnostic test target Plasmodium falciparum histidine-rich protein 2/3 genes / 中国血吸虫病防治杂志

The global malaria epidemic is still severe. Because of simple procedures, rapid detection and accuracy results, rapid diagnostic test (RDT) has become the most important and the most widely used diagnostic tool for malaria prevention and control. However, deletions in the RDT target Plasmodium falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes may cause false-negative results of RDT, which has been included as one of the four biological threats to global malaria elimination. This article reviews the applications of RDT in the global malaria diagnosis, analyzes the threats and challenges caused by Pfhrp2/3 gene deletion, proposes methods for monitoring Pfhrp2/3 gene deletion, and summarizes the causes and countermeasures of negative RDT detections, so as to provide insights into consolidation of malaria elimination achievements in China and contributions to global malaria elimination.

Development and verification of pre-column derivatization reverse phase-high performance liquid chromatography for determination of Glycine and Histidine content in recombinant proteins / 中国生物制品学杂志

@#Objective To develop and verify a pre-column derivatization reverse phase-high performance liquid chromatography(RP-HPLC) method for determination of Glycine and Histidine content in recombinant proteins.Methods AccQ Tag-C 18(3.9 mm × 150 mm,4 μm) column was used as chromatographic column,6-aminoquinolyl-N-hydroxysccinimidyl carbamate(AQC) was used as pre-column derivatization reagent,while α-aminobutyric acid as internal standard.AccQTag Eluent A solution,acetonitrile solution and high-purity water were used as mobile phases.The UV detection wavelength was 248 nm,injection volume was 10 μL,flow rate was 1.0 mL/min,and column temperature was 37 ℃.The contents of Glycine and Histidine in samples were determined by the internal standard method,and the specificity,linearity,detection limit,quantitative limit,precision,accuracy and stability of the method were verified.Results The developed method effectively separated Glycine,Histidine and internal standard α-aminobutyric acid with high specificity.The standard curves of Glycine in the range of 2.25～11.25 μg/mL and Histidine in the range of 72.85～364.24 μg/mL showed good linearity,each correlation coefficient(R~2) 0.99.The detection limits were 2.25 μg/mL for Glycine and 18.21 μg/mL for Histidine.The quantitative limits were 4.69 μg/mL for Glycine and 32.86 μg/mL for Histidine.The relative standard deviation(RSD) of 6 replicates with the same concentration of Glycine and Histidine were 4.6% and 5.0%,and the RSD of recovery rate in intermediate precision test was 6.9% and 2.0%,respectively.The content of Glycine was close to the quantitative limit,and the average recoveries of high,medium and low concentrations of samples were within 75.9%～111.7%;The recoveries of Histidine ranged from 88.9% to 97.3%.The RSD of Glycine content and Histidine content was 7.7% and 3.3% respectively at 0,12,18,24,30 and 48 h in the same sample.Conclusion The pre-column derivatization RP-HPLC method has accurate and reliable results with high precision,which might be used for quality control of Glycine and Histidine content in recombinant proteins.

Quantitative determination of endogenous histamine and histidine in biological matrices by double adsorption based on HPLC-MS/MS / 中国药科大学学报

@#An innovative approach to quantitatively analyze the histamine and its precursor histidine simultaneously in biological matrices was established for the first time based on double adsorption combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).The internal standard was 2-dihydroxybenzoic acid (DHB).The plasma and brain tissue homogenate was protein precipitated with 3-fold acetonitrile, and the supernatant was then sampled for injection analysis.The chromatographic separation of the target components was achieved on an amino chromatography column (ODS-SPXBridge? Amide).Gradient elution was carried out with the mobile phase consisting of solvent A (0.1% formic acid and 1mmol/L ammonium formate in water) and solvent B (acetonitrile).Mass spectrometry was employed for quantitative analysis with ESI ion source in multiple reaction monitoring (MRM) mode.In order to improve the specificity and accuracy, activated carbon and calcite were used for the double adsorption of biological matrices for the first time.The adsorbed matrix was then used for methodology validation.The results showed that histamine and histidine were linear in the quantitative range (correlation coefficient r ≥ 0.999).Accuracy, precision, extraction recovery, matrix effect and stability all met the requirements of biological sample analysis.All results suggested that the present method could not only be efficiently and reliably used for simultaneous quantitative analysis of histamine and histidine in biological samples, but also provide reference for the detection of other endogenous substances.

Research progress of histidine-based tumor-targeting drug delivery systems / 药学学报

As a basic amino acid, histidine has a pKa close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

Roles of Histidine Kinases and Histidine Phosphatases in Cancer / 中国肺癌杂志

Phosphorylation is the most common and important post-translational modification of proteins, which plays an important role in the regulation of cell proliferation, differentiation, development and metabolism, and is closely related to the tumorigenesis and metastasis of cancer. Protein kinases and phosphatases generally regulate protein phosphorylation levels as a pair of opposite acting enzymes. Protein phosphorylation in eukaryotes occurs mainly in serine, threonine, and tyrosine residues, and their roles in tumorigenesis and development have been extensively studied. But the roles on histidine phosphorylation is less known due to the immature mass spectrometry and enrichment techniques. In recent years, with the rapid development of related technologies and the discovery of new histidine phosphatases, researchers have paid more attention to the roles of histidine phosphorylation in tumors. Therefore, we aim to review the roles of histidine kinases and phosphatases in tumor.
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Comparison between the effects of bretschneiders htk solution and cold blood cardioplegia on systemic endothelial functions in patients who undergo coronary artery bypass surgery: a prospective randomized and controlled trial

Abstract Objective: To investigate the effects of Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia on systemic endothelial functions. Methods: A total of 50 patients who underwent isolated coronary artery bypass surgery between March 2018 and May 2018 were randomly divided into two groups - group 1 (Bretschneider's HTK solution, n=25) and group 2 (cold blood cardioplegia, n=25). Data related to the indicators of endothelial dysfunction were recorded. Flow-mediated dilation was measured together with the assessment of the values of endothelin-1, von Willebrand factor, and asymmetric dimethylarginine to identify endothelial dysfunction. Then, the two groups were compared regarding these values. Results: The most significant result of our study was that the endothelin-1 level was significantly higher in group 2 than in group 1 (P<0.001). The value of flow-mediated dilation was found to increase to a lesser degree on the postoperative days compared to the value at the day of admission in group 1 (P=0.002 and P=0.030, respectively). Conclusion: Cardiopulmonary bypass leads to endothelial dysfunction. Our results revealed that Bretschneider's HTK solution causes less severe endothelial injury than cold blood cardioplegia.

Tumor microenvironment responsive biomimetic nanoparticles for photodynamic tumor therapy / 药学学报

Inspired by the coordination effects between imidazole and metal ions in hemoglobin, biomimetic nanoparticles were constructed for photodynamic tumor therapy. The photosensitizer of protoporphyrin IX (PpIX) was modified with histidine, which could be self-assembled with Zn2+ to obtain the biomimetic nanoparticles (NPs). Under the conditions of high glutathione and low pH, the biomimetic nanoparticles could be degraded and released for enhanced photodynamic tumor therapy. The structures of NPs were characterized by dynamic light scattering (DLS), UV-visible spectrophotometer (UV-Vis), fluorescence microscope and transmission electron microscope (TEM). The reactive oxygen species (ROS) production ability of NPs was measured by singlet oxygen sensor green (SOSG) test kit. Mouse breast cancer cell lines (4T1 cells) were employed to investigate the subcellular organelle distribution and cytotoxicity of NPs. These results confirmed that NPs possessed a good dispersibility and stability with a uniform structure and particle size at 165 nm. Moreover, MTT assay and live/dead cell staining assay demonstrated that NPs could inhibit the proliferation of 4T1 cells and exhibit a good biocompatability. This research would promote the construction of intelligent biomedicine for tumor precision therapy.

Assessment of fragile histidine triad expression in ameloblastoma, odontogenic keratocyst and dentigerous cyst

Background: FHIT (Fragile histidine triad) a member of tumor suppressor family, has been extensively studied in many solid tumors including head and neck squamous cell carcinoma. Among all head and neck cyst and tumors odontogenic lesions account approximately 3%-9%. The molecular pathogenesis of these lesions is less explored. Defects in cell cycle regulators and tumor suppressor genes could result in the development of odontogenic cyst and tumors. Hence, we aimed to determine the significant role of a tumor suppressor gene FHIT in most commonly occurring odontogenic lesions mainly ameloblastoma, odontogenic keratocyst and dentigerous cyst. Subjects and Methods: Immunohistochemical analysis of FHIT was done in ameloblastoma, odontogenic keratocyst, dentigerous cyst and dental follicle. Interpretation of the stained slides were done using standard scoring criteria by two pathologist. The results were subjected for statistical analysis. Results: Expression of FHIT varied among the groups, with highest negative expression in ameloblastoma 44.4% followed by odontogenic keratocyst 14% and 100%positive expression was seen in dentigerous cyst. The expression levels between the groups were statistically insignificant. Conclusion: The varied expression or negative expression of FHIT could be considered as an indicator for aggressive behavior and transformation of preneoplastic/cystic epithelium.

Values of the leukocyte count, D-dimer, histidine decarboxylase and intestinal fatty acid binding protein for diagnosing acute intestinal obstruction / 国际外科学杂志

Objective To investigate the clinical values of the leukocyte count,D-dimer,histidine decarboxylase (HDC) and intestinal fatty acid binding protein (I-FABP) for diagnosing acute intestinal obstruction.Methods Sixty patients who treated in China-Japan Union Hospital of Jilin University from January 2017 to January 2018 were collected prospectively,and were divided into strangulated intestinal obstruction (STR-IO) group (n =20),simple intestinal obstruction (SIM-IO) group (n =20) and peritonitis group (n =20).Twenty healthy volunteers were collected as control group.Automatic blood cell analyzer was used to detecting the leukocyte count.The concentration of plasma D-dimer was detected by immune turbidimetry method.The concentration of serum HDC and I-FABP were measured by enzyme linked immunosorbent assay (ELISA) method.Compared the above indicators of four groups of samples.The measurement data are expressed as mean ± standard deviation (Mean ± SD).Tamhane's T2 and Dunnett's T3 methods were used to comparison between groups.Estimation of receiver operating characteristic curve(ROC) and area under curve (AUC) used logistic regressive model.Results The leukocyte count in control group,SIM-IO group,peritonitis group,and STR-IO group were (6.97 ± 1.68) × 109/L,(8.24 ± 2.78) × 109/L,(11.33 ±4.75) × 109/L,and(12.53 ± 5.96) × 109/L respectively.STR-IO group and peritonitis group were significantly higher than those of control group(F =12.74,P =0.01),but there was no significant difference between SIM-IO group and control group(P ＞ 0.05).The concentration of plasma D-dimer in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.44± 0.30) μg/ml,(1.17 ± 0.67) μg/ml,(1.20 ± 0.72) μg/ml,and (1.67 ± 0.67) μg/ml respectively.The concentration of D-dimer in STR-IO group was significantly higher than those of control group (F =57.08,P =0.00),and there was no significant difference among other group (P ＞ 0.05).The concentration of serum HDC in control group,SIM-IO group,peritonitis group,and STR-IO group were (5.51 ±4.30) ng/ml,(14.33 ± 3.71) ng/ml,(11.53 ± 4.67) ng/ml,and (35.65 ± 21.15) ng/ml respectively.The concentration of HDC in STR-IO group was significantly higher than those of other three groups (F =39.03,P =0.00).The concentration of serum I-FABP in control group,SIM-IO group,peritonitis group,and STR-IO group were (0.20 ± 0.06) ng/m],(0.31 ± 0.17) ng/ml,(0.22 ±0.03)ng/ml,and (0.81 ±0.56) ng/ml respectively.The concentration of I-FABP in STR-IO group was significantly higher than those of other three groups (F =23.07,P =0.01).The AUC of HDC,I-FABP,D-dimer,and leukocyte count were 0.998,0.868,0.730,and 0.704 respactively.Conclusion Leukocyte count,D-dimer,and HDC or I-FABP combined detection may be a more effective index for diagnosing acute intestinal obstruction.

Inhibidores de histidina decarboxilasa atenúan la actividad proangiogénica de células de Leydig tumorales: ¿Potencial terapia neoadyuvante para el tratamiento de leydigiomas? / Histidine decarboxylase inhibitors attenuate the pro angiogenic activity of Leydig tumor cells: Potential neoadjuvant therapy for the treatment of leydigiomas?

Resumen Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.

ABSTRACT Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.

Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization / 中华流行病学杂志

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.

Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization / 中华流行病学杂志

Objective To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization.Methods A total of 73 patients with cervical squamous cell carcinoma (SCC),113 patients with cervical intraepithelial neoplasia (CIN Ⅰ,n =45;CIN Ⅱ/Ⅲ,n=68) and 60 women with normal cervix (NC) were included in the study.Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2,respectively.The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP).Kruskal-Wallis H test,x2 test,trend x2 test and Spearman correlation analysis were conducted with software SPSS 20.0.The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model.Results With the deterioration of cervical lesion,the methylation rates of FHIT gene CpG island (x2=18.64,P＜0.001;trendx2=18.08,P＜0.001) increased gradually,while the expression levels of FHIT mRNA (H=27.32,P＜0.001;trendx2=12.65,P＜0.001) and protein (H=47.10,P＜0.001;trendx2=29.79,P＜0.001) decreased gradually.There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226,P＜0.001).The levels of MeCP2 mRNA (H=26.19,P＜0.001;trend x2=11.81,P=0.001) and protein (H=69.02,P＜ 0.001;trend x2 =47.44,P＜ 0.001) increased gradually with the aggravation of cervical lesions.There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254,P＜0.001).Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213,P=0.001).The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression,the CpG island methylation of FHIT and mRNA and protein expression in CIN Ⅱ/Ⅲ group,and among high MeCP2 mRNA and protein expression,the CpG island methylation of FHIT and low mRNA and protein expression in SCC group.Conclusion High expression of MeCP2 mRNA and protein,the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis,and there might be a synergistic effect on cervical carcinogenesis.

Evaluation of silybum marinaum efficacy on University of Wisconsin and histidine-tryptophan-ketoglutarate solutions latter the damage of the perfused liver

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.

Histamine production by Enterobacter aerogenes in chub mackerel (Scomber japonicus) at various storage temperatures

Abstract Growth of Enterobacter aerogenes and accumulation of histamine in chub mackerel (Scomber japonicus) were investigated through measuring bacterial count, histidine decarboxylase (HDC) activity and histamine content in fish samples stored at various temperatures from 4 to 37 °C. Results showed that bacterial count and HDC activity rapidly increased in chub mackerel inoculated with E. aerogenes at storage temperature above 20 °C and reached the highest values (8.64 log CFU/g and 31.68 U/g) at 37 °C. Meanwhile, fish samples stored at 25 and 37 °C for 18 h, formed histamine at above 50 mg/100 g of the potential hazard level. In contrast, bacterial growth and histamine formation were controlled for 36 h by cold storage at low temperature (4 °C). Therefore, strict temperature control was necessary for preservation and processing of chub mackerel in order to assure this marine fish safety.

Terminal Deoxynucleotidyl Transferase Amplification Based DNA-Copper Nanoclusters Sensor for Detection of L-Histidine / 分析化学

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

Terminal Deoxynucleotidyl Transferase Amplification Based DNA-Copper Nanoclusters Sensor for Detection of L-Histidine / 分析化学

A terminal deoxynucleotidyl transferase ( TdT ) amplification based DNA-copper nanoclusters (CuNCs) sensor was developed for detection of L-histidine ( L-His). Single strand DNA containing poly-thymine ( T) sequences were synthesized by TdT in the presence of dTTP. In blank control, poly-T sequences worked as templates of CuNCs due to the affinity between thymine and copper ions( II) . Fluorescence intensity was enhanced when CuNCs formed with reducing agents. In the presence of L-His, the imidazolyl group of L-His worked as a chelating agent that formed L-His-Cu2+ chelated complex. Thus less copper ions were induced in poly-T sequences, and less CuNCs were obtained to produce week fluorescence signals. A good linear correlation was obtained between fluorescence change and the logarithm of the L-His concentration over the range of 5. 0 ×10-9-5. 0 ×10-4 mol/L. The detection limit was estimated as 3. 4 ×10-9 mol/L. And the recoveries were 97. 4%-104. 6% for the actual urine samples. Compared with other methods of synthetic CuNCs, this method allowed to specifically determining L-histidine without template or labeling, which showed good potential in biomedical and clinical analysis.

Recombinant IFN-α-IL-18 increases level of histamine produced by chicken lymphocyte and activate NF-κB p65 activity / 中国免疫学杂志

Objective:To discuss the effects of recombinant IFN-α-IL-18 fusion protein on chicken lymphocyte histamine induced and the NF-κB p65 activation and nucleo-cytoplasmic transport.Methods: The healthy chickens blood was sterile adopted with anticoagulant,then separation of the chicken peripheral blood lymphocyte and divided into 10 groups:The yeast expression and purification protein IFN-α-IL-18,IL-18,IFN-α were added with 250 ng/ml,500 ng/ml and 1 000 ng/ml respectively while the control was only added RPMI1640 with 3 repetitions for each group.Then the histidine decarboxylase activity,histamine,IFN-γ,PI3K,MAPK and NF-κB p65 in cell nucleus were detected.Results: The recombinant IFN-α-IL-18 and IL-18 could significantly promote the activity of histidine decarboxylase (P<0.01),increase the contents of histamine (P<0.01),induce IFN-γ (P<0.01),improve the contents of PI3K (P<0.01) and the NF-κB p65 levels in nucleus (P<0.01),and the higher concentration of IFN-α had a similar effect to lymphocytes.The effects of IFN-α-IL-18,IL-18 and IFN-α on MAPK was acratia.Conclusion: IFN-α-IL-18 and IL-18 can stimulate chicken peripheral blood lymphocyte populations increased histamine contents significantly and promote the induction of IFN-γ.IFN-α-IL-18,IL-18 and IFN-α increase PI3K expression in lymphocyte associated with the NF-κB activation and NF-κB p65 nucleo-cytoplasmic transport.The study built foundation for the function of IFN-α-IL-18 and the exploration of the mechanism of controlling epidemic diseases.

Storage effect and transplant outcomes of University of Wisconsin preservation solution and histidine-tryptophan-ketoglutarate preservation solution on liver allografts: a Meta-analysis / 中华消化外科杂志

Objective To systematically evaluate the storage effect and transplant outcomes of University of Wisconsin (UW) preservation solution and histidine-tryptophan-ketoglutarate (HTK) preservation solution on liver allografts.Methods Literatures were researched using PubMed,Embase (1980-),Ovid Medline (1948-),The Cochrane Library,Wanfang database,VIP database from the database establishement to October 2015 with the key words including organ preservation,storage solutions,Histidine-tryptophan-ketoglutarate or HTK,custodial,bretschneider,University of Wisconsin,UW solution,viaspan,cardiosol,belzer solution,hepatic transplantation,liver transplantation,viscera transplantation,liver grafts,hepatic grafts,liver allografts,hepatic allografts,器官移植,器官保存液,UW,HTK,肝移植and比较.Two reviewers independently screened literatures,extracted data and assessed the risk of bias.All the patients using UW and HTK preservation solutions were respectively allocated into the UW group and HTK group.Count data were represented as the odds ratio (OR) and measurement data were represented as the standardized mean difference (SMD) and 95％ confidence interval (CI).The heterogeneity of the studies was analyzed using the I2 test.Results Eleven literatures were retrieved,and the total sample size were 34 475 patients including 25 248 in the UW group and 9 227 in the HTK group.The results of Meta analysis showed that there were no statistically significant differences in the primary transplants nonfunction,retransplant rate and 1-year grafts overall survival rate between the 2 groups (OR =1.18,0.84,0.97,1.02,95％ CI:0.55-2.57,0.47-1.50,0.66-1.42,0.66-1.58,P ＞0.05).There were also no statistically significant differences in the levels of alanine transaminase (ALT),aspartate transaminase (AST),total bilirubin (TBil) at postoperative day 1 between the 2 groups (SMD =-0.19,-O.30,0.30,95％ CI:-0.62-0.23,-0.70-0.10,-0.01-0.61,P ＞0.05).There were no statistically significant differences in the postoperative prothrombin time(PT) and alkaline phosphatase(ALP) between the 2 groups (P ＞0.05) and in the incidence of postoperative biliary complications between the 2 groups (OR =1.49,95％ CI:0.97-2.30,P ＞ 0.05).Conclusion There is similar storage effect between UW and HTK preservation solutions on liver allografts,and no difference in the transplant outcomes.