Acacetin blocks kv1.3 channels and inhibits human T cell activation.

BACKGROUNDS/AIMS: Acacetin, a natural flavonoid compound, has been proven to exert anti-inflammatory and immunomodulatory effects. Kv1.3 channels, highly expressed in human T cells, are attractive therapeutic targets to treat inflammatory and immunological disorders. The present study was designed to characterize the inhibition of Kv1.3 channels by Acacetin in human T cells and examine its role in T cell activation. METHODS: Whole-cell patch-clamp was applied to record the Kv1.3 and KCa currents in human T cells; Western blot was used to detect Kv1.3 expression as well as NFAT1 and NF-κB activity; Fluo-4, CCK-8 and an ELISA kit were used to measure Ca(2+) influx, proliferation, and IL-2 secretion, respectively. RESULTS: Acacetin decreased the Kv1.3 current, accelerated the decay rate and negatively shifted the steady-state inactivation curves in a concentration-dependent manner. The IC50 values at +40 mV for peak and the current at end of pulse were 21.09 ± 2.75 and 3.63 ± 0.25 µmol/L, respectively. Treatment with Acacetin for 24 h significantly inhibited Kv1.3 protein expression. Additionally, paralleling Kv1.3 inhibition, Acacetin also inhibited Ca(2+) influx, the Ca(2+)-activated transcription factors NFAT1, NF-κB p65/p50 activity, and proliferation as well as IL-2 production. Small interfering RNA against Kv1.3 reduced the inhibitory effect of Acacetin on IL-2 secretion. CONCLUSIONS: Acacetin blocks the Kv1.3 channel and inhibits human T cell activation. This action most likely contributes to its immunomodulatory and anti-inflammatory actions.

Enrichment of MTHFR 677 T in a Chinese long-lived cohort and its association with lipid modulation.

BACKGROUND: Variants in the Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but the findings remain mixed. Herein, we sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China. METHODS: Genotyping of MTHFR C677T was undertaken in 516 long-lived inhabitants (aged 90 and older, long-lived group, LG) and 493 healthy controls (aged 60-75, non-long-lived group, non-LG) recruited from Bama area. Correlation between MTHFR genotypes and lipids was then evaluated. RESULTS: T allele and TT genotype were significantly more prevalent in LG (P=0.001 and 0.002, respectively), especially in females, than in non-LG. No difference in the tested lipid measures among MTHFR C677T genotypes was observed in LG, non-LG and total population (P>0.05 for all). However, female but not male T carriers exhibited higher TC and LDL-C levels than did T noncarriers in the total population and in LG after stratification by sex (P<0.05 for each). These differences did not however remain through further subdivision by hyperlipidemia and normolipidemia. CONCLUSION: The higher prevalence of MTHFR 677 T genotypes and its modest unfavorable impact on lipids in Bama long-lived individuals may imply an existence of other protective genotypes which require further determination.

Blocking of the human ether-à-go-go-related gene channel by imatinib mesylate.

Imatinib mesylate (IM), a widely prescribed powerful tyrosine kinase inhibitor, has been associated with increased risk of heart failure and is known to induce cell apoptosis and death in isolated cardiomyocytes. In addition to acquired long QT syndrome, pharmacological inhibition of human ether-à-go-go-related gene (HERG) channel has been reported to involve in apoptosis. The present study was undertaken to characterize the biophysical properties of IM on HERG and the molecular determinants of HERG blockade using mutant channels (Y652A and F656A). Wild type (WT) and mutant HERG channels were expressed in HEK-293 cells and Xenopus oocytes and the currents (I(HERG)) were measured using patch-clamp and two-microelectrode voltage-clamp techniques. IM inhibited WT I(HERG) in a concentration-dependent manner with an IC(50) of 19.51±2.50 µmol/L and 44.76±1.54 µmol/L in HEK-293 cells and Xenopus oocytes, respectively. The IM-induced inhibition of WT I(HERG) followed a voltage- and time-dependent manner. The blockade was enhanced by further activation of currents, which were in accordance with an open-channel blockade. The V(1/2) for steady-state activation shifted from -15.48±1.21 to -26.66±2.98 mV (p<0.05, n=6). The inactivation kinetics and voltage dependence of steady-state inactivation of the WT HERG channel were not significantly altered by IM. Two S6 domain mutants, F652A and Y656A, attenuated IM-induced inhibition of WT I(HERG). Therefore, IM preferentially blocked the open HERG channel through F652 and Y656, providing a molecular mechanism for the cardiac side effects during the clinical administration of IM.

[The dose-response relationship of chrysotile asbestos exposure and lung cancer in cohort study].

OBJECTIVE: To clarify the dose-response relationship between asbestos dust exposure and lung cancer incidence in chrysotile asbestos miners by fixed cohort study and to investigate the incidence rates of lung cancer in exposure to different concentrations of asbestos dust. METHODS: A retrospective cohort study was conducted in 1932 asbestos miners who registered from January 1, 1981 to December 31, 1988, had worked for at least 1 year, and had no obvious cardiopulmonary diseases; the cohort study began in July 2009 and covered a time span of 29 years (1981 - 2009). The personal information, occupational history, disease history, and health data of these miners were recorded, and the monitoring data on dust concentrations in the mine over the years were collected. The dose-response relationship between asbestos dust concentration and lung cancer incidence was established by the method of life table; a regression equation was fitted to predict the excess incidence rates of lung cancer under the conditions of different working years and dust concentrations. RESULTS: A significant dose-response relationship was observed between cumulative exposure (Ce) and cumulative probability (Px) of lung cancer incidence, and the smokers hada higher Px than nonsmokers. When Ce was less than 2000 mg/m(3)·each year, Px reached 6.58/10000; when Ce was not less than 2000 mg/m(3)·and less than 3000 mg/m(3)·each year, Px reached 91.72/10000; when Ce was more than 5000 mg/m(3)·each year, Px was as high as 141.02/10000. The three models were fitted to obtain the optimal regression equation: Px = -0.0004Ce(2) + 0.0052Ce - 0.0011 (r(2) = 0.9387). In the workshop of asbestos mine in this study, the average dust concentration was 85 times higher than the limit in 2009, so the excess incidence rate of lung cancer was 112.598/10000 if the miners worked under this condition for 40 years, according to the equation. CONCLUSION: There is a significant dose-response relationship between cumulative asbestos exposure and lung cancer incidence in chrysotile asbestos miners. The risk for lung cancer rises as asbestos exposure increases.

High expression of p300 is linked to aggressive features and poor prognosis of nasopharyngeal carcinoma.

BACKGROUND: Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood. METHODS: In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model. RESULTS: Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036). CONCLUSIONS: Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.

Microsomal triglyceride transfer protein gene -493G/T polymorphism and its association with serum lipid levels in Bama Zhuang long-living families in China.

BACKGROUND: The -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China. METHODS: The MTP -493G/T was genotyped by PCR-restriction fragment length polymorphism in 391 Bama Zhuang long-lived families (BLF, n = 1467, age 56.60 ± 29.43 years) and four control groups recruited from Bama and out-of-Bama area with or without a familial history of exceptional longevity: Bama non-long-lived families (BNLF, n = 586, age 44.81 ± 26.83 years), Bama non-Zhuang long-lived families (BNZLF, n = 444, age 52.09 ± 31.91 years), Pingguo long-lived families (PLF, n = 658, age 50.83 ± 30.30 years), and Pingguo non-long-lived families (PNLF, n = 539, age 38.74 ± 24.69 years). Correlation analyses between genotypes and serum lipid levels and longevity were then performed. RESULTS: No particularly favorable lipoprotein and clinical phenotypes were seen in BLF as compared to general families in the same area. Instead, the levels of total cholesterol (TC), TG, LDL-C, and the prevalence of dyslipidemia were significantly higher in the three Bama families as compared to the two non-Bama families (P < 0.01 for all). There were no differences in the allelic and genotypic frequencies among the tested cohorts (P > 0.05 for all), but the TT genotype tended to enrich in the three long-lived cohorts from both areas. In addition, the individuals harboring TT genotype exhibited lower LDL-C and TC levels in the overall populations and Bama populations with a region- and sex-specific pattern. Multiple linear regression analyses unraveled that LDL-C levels were correlated with genotypes in Bama combined population, BNLF, and the total population (P < 0.05 for each) but not in Pingguo populations; TC and HDL-C levels were correlated with genotypes in Bama combined population and BLF, respectively (P < 0.05 for each). CONCLUSIONS: MTP -493G/T polymorphism may play an important role in fashioning the serum lipid profiles of Bama populations, despite no direct association between MTP -493G/T and longevity was detected.

NOVA1 promotes SMN2 exon 7 splicing by binding the UCAC motif and increases SMN protein expression.

Spinal muscular atrophy (SMA) is a rare hereditary neuromuscular disease with a high lethality rate in infants. Variants in the homologous genes survival of motor neuron (SMN)1 and SMN2 have been reported to be SMA pathogenic factors. Previous studies showed that a high inclusion rate of SMN2 exon 7 increased SMN expression, which in turn reduced the severity of SMA. The inclusion rate of SMN2 exon 7 was higher in neural tissues than in non-neural tissues. Neuro-oncological ventral antigen (NOVA) is a splicing factor that is specifically and highly expressed in neurons. It plays a key role in nervous system development and in the induction of nervous system diseases. However, it remains unclear whether this splicing factor affects SMA. In this study, we analyzed the inclusion of SMN2 exon 7 in different tissues in a mouse model of SMA (genotype smn-/-SMN22tg/0) and littermate controls (genotype smn+/-SMN22tg/0). We found that inclusion level of SMN2 exon 7 was high in the brain and spinal cord tissue, and that NOVA1 was also highly expressed in nervous system tissues. In addition, SMN2 exon 7 and NOVA1 were expressed synchronously in the central nervous system. We further investigated the effects of NOVA1 on disease and found that the number of neurons in the anterior horn of spinal cord decreased in the mouse model of SMA during postnatal days 1-7, and that NOVA1 expression levels in motor neurons decreased simultaneously as spinal muscular atrophy developed. We also found that in vitro expression of NOVA1 increased the inclusion of SMN2 exon 7 and expression of the SMN2 protein in the U87MG cell line, whereas the opposite was observed when NOVA1 was knocked down. Finally, point mutation and RNA pull-down showed that the UCAC motif in SMN2 exon 7 plays a critical role in NOVA1 binding and promoting the inclusion of exon 7. Moreover, CA was more essential for the inclusion of exon 7 than the order of Y residues in the motif. Collectively, these findings indicate that NOVA1 interacts with the UCAC motif in exon 7 of SMN2, thereby enhancing inclusion of exon 7 in SMN2, which in turn increases expression of the SMN protein.

[Relationship between the mutation of leptin receptor gene and tumorigenesis of breast cancer].

OBJECTIVE: The aim of this study was to investigate the relationship of the mutations of leptin receptor gene exon 4, exon 6, exon9, and exon20 with the tumorigenesis of breast cancer. METHODS: Genomic DNA was extracted from breast cancer tissues of 155 patients, benign lesions of 56 patients and normal tissues and blood samples from 100 health control subjects. The leptin receptor genes were assayed with polymerase chain reaction (PCR) amplification and direct sequence analysis. RESULTS: Nucleotide substitutions no mutations were found at exon 4, and nucleotide substitutions occurred at codon 1029 in exon 9, no significant difference among the three groups (P = 0.574). The nucleotide substitutions at codon 668 in exon 6 resulted in Gln223Arg polymorphisms. The occurring frequencies of GG, GA, AA in breast cancer, breast benign lesions tissues and health tissues control group were 70.9% and 17.4%, 12.3%; 80.4%, 14.3% and 5.4%; and 81.0%, 16.0%, and 3.0%, respectively. Alleles of G and A in the three groups were 79.1% and 20.8%, 87.5% and 12.5%, and 89.0% and 11.0%, respectively. Compared the Gln223Arg genotype with the three allele groups, there were significant differences (χ(2) = 16.11, P < 0.005 and χ(2) = 11.41, P < 0.01), respectively. The nucleotide substitutions at codon 3057 in exon 20 resulted in Pro1019Pro polymorphisms. The occurrence frequencies of GG, GA, AA in the breast cancer, benign disease and health control groups were 11.6%, 30.3% and 56.1%; 32.1%, 44.0% and 28.5%; and 32.0%, 45.0% And 23.0%, respectively. Alleles of G and A in the three groups were 26.8% and 73.2%, 51.8% and 48.2%, and 54.5% and 45.5%, respectively. There are significant differences among the three groups (χ(2) = 6.56, P < 0.03 and χ(2) = 5.45, P < 0.05), respectively. Nucleotide substitutions occurred at relatively high frequencies at exon 6 and exon 20 in obese and overweight breast cancer patients compared with those in normal weight breast cancer patients, there were significant differences (P < 0.05 and P < 0.01). CONCLUSIONS: Our findings show that there is no relationship between the variations of leptin receptor gene exon 9 and tumorigenesis of breast cancer. The variation rate of leptin receptor gene exon 6 and exon 20 are significantly increased in the obese and overweight breast cancer patients.

[Radiometric calibration of LCTF-based multispectral area CCD camera].

Multispectral area CCD camera based on liquid crystal tunable filter (LCTF) is a new spectral imaging system, which could record image of one wavelength on the area CCD by utilizing electrically controlled birefringence of liquid-crystal and interference principle of polarized light. Because of the special working principle of LCTF and frame transfer area CCD, the existing radiometric calibration method can not meet the precision need of remote sensing application if it is used for LCTF-camera. An improved radiometric calibration method is proposed, in which the camera performance test and calibration experiment are carried out relying on the devices of integrating sphere and standard detector, and the absolute calibration coefficient is calculated via correcting frame transfer smear and improving data process algorithm. Then the validity of the laboratory calibration coefficient is checked by a field validation experiment. Experimental result indicates that the calibration coefficient is valid, and the radiation information on the ground could be accurately inverted from the calibrated image data. With the resolution of radiometric calibration of LCTF-camera and the improvement of calibration precision, the application field of the image data acquired by the camera would be extended effectively.

Derivatives of (phenylsulfonamido-methyl)nicotine and (phenylsulfonamido-methyl)thiazole as novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitors: synthesis and biological activities in vitro.

AIM: To design and synthese a novel class of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors, featuring the (phenylsulfonamido-methyl)pyridine and (phenylsulfonamido-methyl)thiazole framework. METHODS: Our initial lead 4-(phenylsulfonamido-methyl)benzamides were modified. Inhibition of human and mouse 11beta-HSD1 enzymatic activities by the new compounds was determined by a scintillation proximity assay (SPA) using microsomes containing 11beta-HSD1. RESULTS: Sixteen new compounds (6a-6h, 7a-7h) were designed, synthesized and bioassayed. In dose-response studies, several compounds showed strong inhibitory activities with IC50 values at nanomolar or low nanomolar concentrations. Structure-activity relationships are also discussed with respect to molecular docking results. CONCLUSION: This study provides two promising new templates for 11beta-HSD1 inhibitors.

Stem cells based transplantation for cardiovascular diseases in China.

Stem cells based therapy has been a realistic option for cardiovascular diseases. Since 1990s, Chinese researchers and doctors have been starting to seek for optimal stem cells sources, effective methods of stem cells proliferation and differentiation with traditional Chinese medicine and clinical application of stem cells based transplantation for cardiovascular diseases. This review will summarize the investigation of stem cells in the field of cardiovascular diseases in China.

[Expression and clinical significance of nuclear matrix protein 22 and cytokeratin 18 in transitional cell carcinoma of the bladder].

OBJECTIVE: To evaluate the expression and clinical significance of urinary nuclear matrix protein (NMP22) and cytokeratin 18 (CK18) for transitional cell carcinoma of the bladder. METHODS: Urinary NMP22 and CK18 levels of 293 patients with transitional cell carcinoma of the bladder, 400 patients with non-transitional cell carcinoma of the bladder, and 105 bladder benign disease were analysed by enzyme-linked-immunosorbent assay (ELISA). RESULTS: The levels of urinary NMP22 and CK18 in the patients with transitional cell carcinoma of the bladder (M = 17.3 U/ml, M(CK18) = 484.2 U/L) were significantly higher than those in the non-transitional cell carcinoma of the bladder (M = 6.8 U/ml, M(CK18) = 156.0 U/L) and the benign disease group (M(NMP22) = 2.3 U/ml, M(CK18) = 66.6 U/L) (P < 0.001). The sensitivity and specificity of urinary NMP22 and CK18 were 79.2%, 88.6% and 78.2%, 82.9%, respectively, for transitional cell carcinoma of the bladder before any treatment. The joint sensitivity of the two markers was 91.7%. The NMP22 and CK18 levels were significantly lower in the recovered patients after surgical operation (P < 0.01), while in patients with recurrence or metastasis the levels of the markers were significantly higher (P < 0.01). There was a significant relationship between NMP22 and CK18, (r = 0.689, P < 0.01). The levels of urinary nmp22 and CK18 were significantly different among pathological grade G1, G2, G3, and stage Ta, T1, T2, T3 (P < 0.01). CONCLUSION: NMP22 and CK18 are useful tumor marker for diagnosis of transitional cell carcinoma of the bladder and for monitoring the state of illness. The joint use of the two markers can improve the sensitivity of cancer detection. NMP22 and CK18 may become a new class of tumor markers, and to be the basis for development of a new assay with an increased efficacy for the detection and treatment of bladder cancer.

[Two new anthropometric panels of respirator fit test for Chinese adult workers].

OBJECTIVE: To develop two new respirator fit test panels using data from anthropometric survey of Chinese adult workers: bivariate panel and principal component analysis (PCA) panel for meeting the requirements of respirator fit design and testing and evaluate the applicability of the two different fit test panels for current Chinese workers. METHODS: An anthropometric database based upon anthropometric data of current Chinese workers was used for panel design. The bivariate panel was based upon the bivariate distribution of the face length and face width measurements, and the PCA panel was developed using principal components analysis of 10 stable facial dimensions (minimum frontal breadth, face width, bigonial breadth, face length, interpupillary distance, head breadth, nose protrusion, nose breadth, nasal root breadth, subnasale-sellion length). The distribution of Chinese workers across the panels was used to analyze the panels' applicability for Chinese workers. RESULTS: The bivariate panel and PCA panel developed in this study consisted of 10 cells and 8 cells respectively, covered 96.9% (male 95.4%, female 98.4%) and 96.5% (male 95.1%, female 98.1%) of the current Chinese workers, respectively. The distribution of workers across both panels was uniform. Each cell contained 4.6% - 21.7% of the population in the bivariate panel and 10.4% - 14.6% of the population in the PCA panel. The LANL full-face piece respirator fit test panel covered only 70.9% of the Chinese workers, It was thought to be no longer adequate for the Chinese adult workers. CONCLUSION: New respirator fit test panels based on updated anthropometric database and distributions specific to Chinese workers may be more beneficial for applications in China.

[Measurement and analysis of human head-face dimensions].

OBJECTIVE: To probe into the physical changes on the head and face of Chinese adults, find the representative indexes and provide references for head-face products design especially in the field of labor protection. METHODS: The ISO7250-1996 and GB/T5703-99 Basic Human Body Measurements for Technological Design was used. Twenty items of head-face referential parameters and 4 items of body indexes (height, weight, waist circumference and buttock circumference) were measured by using sliding caliper, spreading caliper and pupillometer. The populations were sampled by age, gender and region and their influences on the head and face dimensions were statistically analyzed. By studying the relationship between these parameters with correlation and cluster analysis, the representative indexes of head and face dimensions were concluded. RESULTS: 3000 objectives (2026 men and 974 women) were involved in this survey. The results enunciated that the values of the items in male were larger than those in female. For example, the mean values of face length, face width, jaw width, lip length and nose protrusion were 117.0, 147.6, 118.5, 51.7, 18.7 mm for male and 109.7, 140.1, 114.5, 49.3, 17.7 mm for female. The regional disparity and obesity were significant factors. The sizes of head and face of north-eastern population were significantly bigger than those of south-western population except of maximum length of head, the length of lip and face configuration length. The sizes of head and face of obesity population were significantly bigger than those of non-obesity population (P < 0.01). By the cluster analysis, five representative indexes (face length, face width, jaw width, lip length and nose protrusion) were obtained. Further correction analysis suggested that these indexes could well represent the head-face dimensions. CONCLUSION: The influence of gender, region and obesity on the head-face dimensions is significant. The age is not a significant influential factor. Five representative indexes (face length, face width, jaw width, lip length and nose protrusion) are obtained to provide foundation in the standard design of head-face products.

[Mortality analyses for tungsten miners].

OBJECTIVE: To investigate the mortality from main causes of death in 6 tungsten miners and explore the effects of cumulative dust exposure on standardized mortality ratios (SMRs) from main causes. METHODS: A cohort of 18027 workers registered in the employment record from 6 tungsten mines located in Hunan and Jiangxi province and working for at least 1 year was identified for this study. SMRs were calculated based on Chinese national mortality. Trend analysis was used to analyze the effect of cumulative dust exposure on SMRs of main causes of death. RESULTS: The cohort was followed up from 1972 to 2003 with an accumulative of 470 722.21 person-years. A total of 6135 workers died, and the mortality was 13.03 per thousand. Cardiovascular disease, respiratory disease, malignant neoplasm and pulmonary tuberculosis accounted for 79.32% of all death. The mortalities of all-causes, pneumoconiosis, pulmonary tuberculosis, nasopharyngeal carcinoma, infectious disease, respiratory disease, cardiovascular disease and liver cancer were found to be significantly higher than the national average level. Positive dose-response relationship between SMRs and cumulative dust exposure was observed in all-causes, pneumoconiosis, pulmonary tuberculosis, respiratory disease, cardiovascular disease (P < 0.01). CONCLUSION: The mortality from main causes of death for the dust-exposed workers are higher than that for non dust-exposed workers. Positive dose-response relationships are observed between cumulative dust exposure and SMRs from all-causes, respiratory disease (including silicosis), pulmonary tuberculosis and cardiovascular disease.

[Effect of humidity and temperature on filter and gravimetric measurement of ambient particulate matter in a balance room].

OBJECTIVE: To assess the effects of the alteration of humidity and (or) temperature on weight of filters without and with ambient particulate matter in a balance room. METHODS: The mass of blank dust sampling filters were weighed under (18 +/- 1) degrees C and (28 +/- 1) degrees C respectively, with the humidity varying from 35% relative humidity (RH) to 100% RH in a balance room. Then the blank filters were divided into two groups and were used to sample total dust and respirable dust. After sampling, the loaded filters were re-weighed under above conditions and the mass difference before and after the sampling were compared and analyzed. RESULTS: The vibration of the average mass of filters varied from 0.10 to 0.13 mg and from 0.06 to 0.09 mg under the temperatures of (18 +/- 1) degrees C and (28 +/- 1) degrees C respectively; When both the temperature and humidity changed, it varied from 0.12 to 0.16 mg. The deviation of average mass difference ranged from 0.07 to 0.10 mg and from 0.04 to 0.08 mg under the two temperatures mentioned above; When both the temperature and humidity changed, it varied from 0.09 to 0.14 mg. The average mass of blank filters and loaded filters were all positively correlated with the change of humidity (P < 0.01). No effects of humidity on the average mass difference of the loaded filters were observed. The average mass differences of loaded filters and blank filters under (18 +/- 1) degrees C were significantly higher than that under (28 +/- 1) degrees C (P < 0.01) when humidity was not changed. CONCLUSION: The alteration of humidity and (or) temperature in a balance room attributes to the deviation of the measurement of the mass of filters and thus affects the gravimetric measurements of ambient particulate matter.

The Role and Molecular Mechanism of Long Nocoding RNA-MEG3 in the Pathogenesis of Preeclampsia.

A growing body of evidence suggests that the dysregulation of long noncoding RNA is increasingly linked to many human diseases. Maternally expressed gene 3 ( MEG3) is one such gene thought to be affected. In the placenta of patients with preeclampsia, there is reduced expression of MEG3; however, its role and the mechanism involved are not clear. Therefore, we examined the expression of MEG3, epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin), and TGF-ß/smad signaling pathway genes ( TGF-ß1, smad3, and smad7) in the placental tissues of 20 patients with preeclampsia and 20 healthy patients. We further observed the impact of MEG3 on the invasion and migration functions of human trophoblast cells and the effects on EMT and TGF-ß/smad signaling pathways in an Human trophoblast cell-8 (HTR-8)Vneo cell line. The expression of MEG3 was lower in tissues from patients with preeclampsia having an EMT decline, as well as a messenger RNA expression of smad7. The expression of TGF-ß1 and smad3 were higher in patients with preeclampsia. In HTR-8/SVneo cells with overexpressed MEG3, the invasion and migration functions were enhanced and accompanied by higher EMT and a significantly increased expression of smad7. Our data indicate that MEG3 is closely associated with the pathogenesis of preeclampsia and thus associated with changes in the EMT of placental trophoblast cells. These results indicate that MEG3 regulation of trophoblast cell EMT via the TGF-ß pathway inhibitor smad7 may be the molecular mechanism involved in the pathogenesis of preeclampsia.

[The diagnosis and monitoring of transitional cell cancer of the urinary tract through nuclear matrix protein 22].

OBJECTIVE: To evaluate the urinary nuclear matrix protein (NMP22) as an adjuvant diagnostic index for transitional cell carcinoma of urinary tract and monitoring the state of disease. METHODS: Urinary samples were collected from 262 patients with transitional cell carcinoma, 198 non-transitional cell carcinoma of the urinary tract and 65 patients with benign diseases. Urinary NMP22 concentration was determined through enzyme linked immunosorbent assay (ELISA). RESULTS: The urinary NMP22 concentration had significant difference among the three groups (Kruskal Wallis, chi(2) = 197.17 P < 0.001). The detection sensitivity and specificity of urinary NMP22 to transitional cell carcinoma were 71.37% and 87.69% respectively. The NMP22 concentration showed significant difference among three groups divided according to the pathological grade (Kruskal-Wallis test, chi(2) = 34.06 P < 0.01). The NMP22 concentration was significant lower in the recovery patients after the operation than the peoples of pre-operation and recurrence (Kruskal-Wallis test, chi(2) = 37.53, P < 0.001). CONCLUSION: MP22 is a helpful tumor marker for the diagnosis of transitional cell carcinoma and monitoring the state of illness with increased efficacy.

Mineralocorticoid Receptor Deficiency in T Cells Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction Through Modulating T-Cell Activation.

Although antagonists of mineralocorticoid receptor (MR) have been widely used to treat heart failure, the underlying mechanisms are incompletely understood. Recent reports show that T cells play important roles in pathologic cardiac hypertrophy and heart failure. However, it is unclear whether and how MR functions in T cells under these pathologic conditions. We found that MR antagonist suppressed abdominal aortic constriction-induced cardiac hypertrophy and decreased the accumulation and activation of CD4+ and CD8+ T cells in mouse heart. T-cell MR knockout mice manifested suppressed cardiac hypertrophy, fibrosis, and dysfunction compared with littermate control mice after abdominal aortic constriction. T-cell MR knockout mice had less cardiac inflammatory response, which was illustrated by decreased accumulation of myeloid cells and reduced expression of inflammatory cytokines. Less amounts and activation of T cells were observed in the heart of T-cell MR knockout mice after abdominal aortic constriction. In vitro studies showed that both MR antagonism and deficiency repressed activation of T cells, whereas MR overexpression elevated activation of T cells. These results demonstrated that MR blockade in T cells protected against abdominal aortic constriction-induced cardiac hypertrophy and dysfunction. Mechanistically, MR directly regulated T-cell activation and modulated cardiac inflammation. Targeting MR in T cells specifically may be a feasible strategy for more effective treatment of pathologic cardiac hypertrophy and heart failure.

[Effectiveness and safety of recombinant human interleukin-11 in the treatment of chemotherapy-induced thrombocytopenia].

OBJECTIVE: To investigate the effectiveness and safety of domestically produced recombinant human interleukin 11 (rhIL-11) for the treatment of chemotherapy- induced thrombocytopenia. METHODS: A total of 32 solid cancer patients who developed chemotherapy-induced thrombocytopenia ( _70 x 10(9)/L) after the first cycle of chemotherapy was studied by self-cross control. The patients were given subcutaneous injection of rhIL-11 (25 microg x kg(-1) x d(-1)) for 7 to 14 consecutive days or until platelet count > or = 100 x 10(9)/L during the second cycle of chemotherapy using the identical regimen as in the first cycle. RESULTS: The mean platelet count of the patients after rhIL-11 treatment was higher at different time points during the second cycle of chemotherapy than that during the first cycle of chemotherapy with the mean platelet count of (110.2 +/- 53.5) x 10(9)/L in the first cycle of chemotherapy versus (55.6 +/- 46.8) x 10(9)/L in the second cycle of chemotherapy (P < 0. 01). Patients with platelet count < or = 50 x 10(9)/L was 4/32 (12.5%) in the first cycle of chemotherapy and 12/32 (37.5%) in the second cycle of chemotherapy (P < 0.01). The time recovery to the normal platelet count was 2 - 18 days (median 5 days) in the first cycle of chemotherapy versus 5 - 27 days (median 12 days) in the second cycle of chemotherapy (P < 0.01). The case/frequency of the platelet transfusion was 2/2 in the first cycle of chemotherapy, while it was 7/9 in the second cycle of chemotherapy (P < 0.01). The major adverse reactions relative to rhIL-11 treatment were fatigue, myalgia/arthralgia, ache, headache, palpitation, edema and fever, most of which could be relieved automatically without any specific treament. However, some 3 grade side effects such as fatigue, myalgia/arthralgia and headache needed proper medication. CONCLUSION: rhIL-11 is safe and effective for chemotherapy-induced thrombocytopenia with mild and manageable side effects.