Crystal structure of 1-methyl-3-[2,2,2-tri-fluoro-1-(1-methyl-1H-indol-3-yl)-1-phenyl-eth-yl]-1H-indole.

The title compound, C26H21F3N2, was prepared by the palladium-catalysed reaction of (2,2,2-tri-fluoro-eth-yl)benzene with 1-methyl-1H-indole. The dihedral angle between the planes of the indole-ring systems is 52.13 (6)° and the N-methyl groups point away from each other. Three short intra-molecular C-H⋯F contacts are observed.

[Effect of methylation modification on the expression of Cosmc gene in peripheral B lymphocyte of IgA nephropathy patients].

OBJECTIVE: To investigate the effect of methylation modification on the mRNA expression of Cosmc gene in peripheral B lymphocytes from IgA nephropathy (IgAN). METHODS: Biopsy identified 22 cases of IgAN patients and 20 cases of normal control were included. Peripheral B lymphocytes were isolated and were cultured with RPMI1640 medium, with LPS (12.5 microg/mL) as well as demethylation agent (5-AZA 0.1 micromol/L, 0.5 micromol/ L and 1.0 micromol/L) for 72 hours, respectively. Expression level of Cosmc gene was measured using real-time PCR. RESULTS: The mRNA expression level of Cosmc gene in IgAN patients was significantly lower than that of control (P<0.05). The Cosmc gene expression level increased dramatically after RPMI1640 treatment (P<0.05), however, LPS could apparently reverse this effect (P<0.05). De-methylation modification up regulated the Cosmc gene expression significantly (P<0.05). CONCLUSION: De-methylation modification could effectively reverse the repressed Comsc gene mRNA expression caused by external suppressors.

[Sources Analysis and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in the PM2.5 Fraction of Fugitive Dust in Nanchang City].

In order to understand the sources and health risks of polycyclic aromatic hydrocarbons in the PM2.5 fraction of road dust and soil dust in Nanchang city, PM2.5 samples were collected by a resuspension sampler and the concentrations of sixteen polycyclic aromatic hydrocarbons (PAHs) were detected. The results showed that the ΣPAHs of the road dust ranged from 48.85 to 166.16 µg·kg-1, with a mean of (114.22±39.95) µg·kg-1. The ΣPAHs of the soil dust ranged from 31.05 to 62.92 µg·kg-1 with a mean of (40.79±9.39) µg·kg-1. The PAHs in the PM2.5 fraction of fugitive dust were mainly composed of 4-5 rings. The results of the principal component analysis and multiple linear regression analysis indicated that the PAHs in PM2.5 samples of road dust mainly originated from motor vehicle emissions, coal sources, and oil leakage, with contribution rates of 51.7% and 48.3%, respectively. For children and adult males, the carcinogenic risk values of PAHs in different exposure pathways followed the order dermal contact > ingestion > inhalation, while those for adult females followed the order ingestion > dermal contact > inhalation. For all exposure pathways, the carcinogenic risks of the PAHs to adults were higher than those to children. For all populations, the total carcinogenic risk values of the PAHs were lower than the US EPA recommended carcinogenic risk threshold of 10-6, indicating no carcinogenic risk.

External suppression causes the low expression of the Cosmc gene in IgA nephropathy.

OBJECTIVE: IgA(1) aberrant O-glycosylation is one of the main pathogeneses of IgA nephropathy (IgAN), and the core I beta3-Gal-T-specific molecular chaperone (Cosmc) mRNA expression of IgAN patients was significantly decreased. This study tried to clarify whether the down-regulation was a result of genetic disorders or external suppressions. METHOD: Sixty-five IgAN patients, 23 non-IgAN glomerulonephritis patients and 21 normal controls were recruited. Genomic DNA was extracted and the Cosmc gene was PCR amplified and directly sequenced. Peripheral B lymphocytes of IgAN patients and normal controls were isolated, and cultured with RPMI-1640 alone or with lipopolysaccharide (LPS) for 72 h. The Cosmc mRNA expression levels at baseline, after RPMI culture or RPMI + LPS treatment were measured by real-time RT-PCR. RESULTS: (1) The whole coding frame region of the Cosmc gene was successfully amplified and directly sequenced. Four single nucleotide polymorphisms were detected in two IgAN patients. Two were missense mutations and the others were silent mutations. However, they are different from each other, and unrelated to expression levels; (2) the baseline Cosmc mRNA expression in IgAN patients was significantly lower than normal controls (Ct(COSMC/GAPDH) 1.29 +/- 0.08 versus 1.20 +/- 0.01, 31% of normal controls); (3) the Cosmc mRNA expression level of IgAN patients was remarkably increased after the RPMI culture (1.22 +/- 0.12 versus 1.29 +/- 0.08, 219% of the baseline level), while not in normal controls and (4) treatment with LPS (culture with RPMI + LPS) could strongly inhibit the expression of Cosmc mRNA (1.25 +/- 0.01 versus 1.22 +/- 0.12, 61% of the RPMI treatment group). CONCLUSION: No common Cosmc gene mutation was detected. Significantly increased Cosmc expression was observed in plasma-free culture, while LPS could significantly inhibit it, which suggested that it might not be genetic disorders but external suppression that causes the low Cosmc mRNA expression in IgAN.

Silencing of NAC1 Expression Induces Cancer Cells Oxidative Stress in Hypoxia and Potentiates the Therapeutic Activity of Elesclomol.

In order to survive under conditions of low oxygen, cancer cells can undergo a metabolic switch to glycolysis and suppress mitochondrial respiration in order to reduce oxygen consumption and prevent excessive amounts of reactive oxygen species (ROS) production. Nucleus accumbens-1 (NAC1), a nuclear protein of the BTB/POZ gene family, has pivotal roles in cancer development. Here, we identified that NAC1-PDK3 axis as necessary for suppression of mitochondrial function, oxygen consumption, and more harmful ROS generation and protects cancer cells from apoptosis in hypoxia. We show that NAC1 mediates suppression of mitochondrial function in hypoxia through inducing expression of pyruvate dehydrogenase kinase 3 (PDK3) by HIF-1α at the transcriptional level, thereby inactivating pyruvate dehydrogenase and attenuating mitochondrial respiration. Re-expression of PDK3 in NAC1 absent cells rescued cells from hypoxia-induced metabolic stress and restored the activity of glycolysis in a xenograft mouse model, and demonstrated that silencing of NAC1 expression can enhance the antitumor efficacy of elesclomol, a pro-oxidative agent. Our findings reveal a novel mechanism by which NAC1 facilitates oxidative stress resistance during cancer progression, and chemo-resistance in cancer therapy.

[Inflammatoin, oxidative stress and carbonyl stress in uremic patients].

OBJECTIVE: To evaluate the states of inflammation, oxidative stress and carbonyl stress in uremic patients and analyze their relationships. METHODS: One hundred and twenty-eight cases were divided into 6 groups: non-dialysis uremia group (n=25), peritoneal dialysis group (n=19), hemophan(Hem) membrane dialysis group (n=25), polyamide (PS) membrane dialysis group (n=25), diabetes with normal renal function group (n= 23) and normal control group (n=11). Spectrophotometry and immune turbidimetry were used to measure the serum SOD, VitC, VitE, MDA and total carbonyl compounds (TCC) levels. RESULTS: Compared with non-uremia groups, the uremia groups had lower serum SOD, VitE and VitC levels, but higher CRP, MDA and TCC levels (P < 0.01). The peritoneal dialysis group had higher SOD, VitC, VitE levels in comparison with the Hem group, but did not differ from PS group in those levels (P > 0.05). The MDA and TCC levels in the peritoneal dialysis group were lower than those in the two hemodialysis groups, but there were no significant differences in CRP level between the groups. Compared with Hem group, the PS group had higher VitC, VitE levels, higher TCC clearance, and the same SOD, MDA, CRP and pre-dialysis TCC levels. When the variables were analyzed with TCC, the results of multi-variate regression showed that the standardized coefficients were MDA (0.727, P < 0.01), CRP (0.370, P < 0.01), SOD (0.192, P < 0.05), VitC (-0.153, P < 0.01), VitE (0.054, P = 0.30) respectively. CONCLUSION: Uremic patients are in inflammatory, oxidative-stress and carbonyl-stress states. Inflammation and oxidative stress are probably the important mechanism of carbonyl stress. It is not yet clear whether dialysis methods can influence uremic inflammatory, oxidative-stress or carbonyl-stress state.

[Characteristics and Source Apportionment of Metals in the Dustfall of Quanzhou City].

Concentrations of 23 metal elements in the dustfall collected from different functional areas of Quanzhou City, China, were determined. Several methods were applied to assess the enrichment degree, pollution level and potential ecological risk of the above elements. The sources of the above elements were analyzed based on the multivariate statistical analysis combining Pb and Sr isotopic tracing technology. The results showed that the concentrations of metals in the dustfall presented significant spatial difference. The results of enrichment factor and geo-accumulation index indicated that Cd, Hg, Zn, Ca, Pb, Cu, Ni and Sr showed relatively higher enrichment degree and pollution level. The results of ecological risk index showed that the comprehensive ecological risk of heavy metals was very high in the dustfall of all functional areas with the sequence of industrial area>heavy traffic area >commercial area >residential area >scenic area >agricultural area. Cd and Hg showed extremely high potential ecological risk, and they contributed 95.56% to the comprehensive potential ecological risk index. The multivariate statistical analysis demonstrated that the elements of V, Fe, Ba, Bi, Ni, Sr, Pb, Cs, Sc, Zn, Cd were mainly from industrial and vehicle emissions; Th, U, Rb, Y, Ti were mainly derived from soil dust; Li, Mn, Cu, Hg, Cr, Co, Ca were mainly from coal combustion. The contribution ranges of parent soil, coal combustion and vehicle emission to the Pb in the dustfall were 29.41%-64.00%, 22.53%-60.48% and 3.13%-13.47%, respectively, as calculated by a ternary hybrid model; The plots of 87Sr/86Sr vs 1/Sr showed that Sr in the dustfall was dominated by coal combustion and vehicle emission.

[Epidemiology of cardiovascular risk in Chinese chronic kidney disease patients].

OBJECTIVE: To identify the risk factors associated with cardiovascular disease (CVD) in Chinese chronic kidney disease (CKD) patients. METHODS: As part of a multicenter Chinese cohort study, the clinical data associated with CVD of 1239 patients with CKD (stage 2 - 5) hospitalized in 7 grade 3A hospitals distributed in 5 regions of China 2002 - 2003 were collected. Logistic regression model was used to analyze the association between CVD and the demographic variables, lifestyle, medical history, medication, physical examination, and laboratory variables. RESULTS: (1) Increase of serum C-reactive protein (CRP, cut off > 10 mg/L) was an independent risk factor for development of coronary artery disease (CAD) (OR 2.13; 95% confidence interval [CI], 1.32 - 3.43). 21.5% of the patients in this group showed a value of CRP > 10 mg/L. (2) Being female, anemia, and systolic hypertension were the major determinants of the development of left ventricular hypertrophy (OR 2.99, CI 2.09 - 4.26; OR 2.66, CI 1.19 - 3.57; and OR 1.02, CI 1.00 to -1.02). 54.2% of the patients in this group had their systolic pressure controlled under 140mmHg, and only 15% of the patients in this group had their hemoglobin remain at the level >or= 110 g/L. (3) There was a significant interaction between the calcium-phosphate product and congestive heart failure (CHF) (OR 1.023, CI 1.01 - 1.03). 25.9% of the patients in this cohort had their calcium-phosphate product >or= 55. (4) Hypoalbuminemia (OR 6.01, CI 1.25 - 28.96) and diastolic hypertension (OR 1.05, CI 1.00 - 1.09) played major role in determining cerebrovascular accidents (CVA). In these cohort the prevalence of hypoalbuminemia was 37.3%. (5) Diabetes was associated with CAD (OR 2.34), CHF (OR 1.97), and CVA (OR 4.40), although its prevalence was lower in Chinese CKD patients (20%). Age was the risk factors of CAD (OR 1.04) and CVA (OR 1.22). Hypertension was associated with LVH (OR 1.016), CHF (OR 1.02), and CVA (OR 1.04). CONCLUSION: CKD is associated with nontraditional risk factors for the development of CVD, including chronic inflammation, malnutrition and calcium-phosphate disorders. Particular care must be taken to give optimal treatment for the most important CVD risk factors active in Chinese CKD patients, e.g. anemia and hypertension.

[Cardiovascular disease in Chinese chronic renal insufficiency patients-epidemiology survey].

OBJECTIVE: Cardiovascular (CV) disease (CVD) is the single most important cause of death among Chinese dialysis patients, accounting for 51% of overall mortality. The study was performed to investigate the prevalence and the spectrum of CVD in Chinese chronic kidney disease (CKD) patients. METHODS: The multicenter Chinese cohort study examined 1239 CKD patients from 7 main medical centers (distributed in 5 regions of China) who were hospitalized between 2002 and 2003. RESULTS: (1) The most prevalent pathological form of CVD was left ventricular (LV) hypertrophy (LVH), accounting for 58.5% of total patients. The prevalence of coronary artery disease (CAD), congestive heart failure (CHF), and cerebrovascular accidents (CVA) was 16.5%, 27.7% and 5.6%, separately. (2) The cohort with minor renal dysfunction (stage 2-3) had higher prevalence of CAD (5.9%) and CVA (1.0%) compared with general population in the same regions. Up to 41.2% of minor CKD patients were complicated with LVH, and 13.8% of them had clinical evidence of CHF. The prevalence of CAD, LVH and CHF increased as glomerular filtration decline. (3) The prevalence of CAD (20.0%) was much lower and the prevalence of CVA (5.4%) was higher in Chinese dialysis patients than that in American dialysis population. There was significant geographical variations in CAD prevalence, but it was not different between genders. CONCLUSION: The CV risk is significantly increased in patients with CKD. Even minor CKD has a major impact on the CV risk. The prevalence of CAD in Chinese dialysis patients is markedly lower than that in American dialysis population.

[Effect of high glucose on the expression of fibronectin and plasminogen activator inhibitor-1 in human peritoneal mesothelial cells].

OBJECTIVE: To evaluate the effect of high glucose on the expression of fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) in human peritoneal mesothelial cells (HPMC). METHODS: The cultured HPMC were exposed to the culture medium containing different concentrations of glucose (1.5%, 2.5%, 4.25%) for 6, 12, 24, 48 hours, and normal culture medium was used as control. FN and PAI-1 in supernatant were detected by enzyme-linked immunoassay(ELISA). RESULTS: The glucose at 1. 5%, 2.5%, 4.25% resulted in a time- and concentration-dependent increase in FN expression in HPMC(P < 0.05). The glucose at 2.5%, 4.25% increased PAI-1 expression in HPMC (P < 0.05), and the effect was time- and concentration-dependent. PAI-1 expression was not affected by 1.5% glucose (P > 0.05). CONCLUSION: High glucose increases the expression of FN and PAI-1 in HPMC, thus playing a part in the progression of peritoneal fibrosis.

Spontaneous retroperitoneal hemorrhage after hemodialysis involving anticoagulant agents.

In this paper, we described the symptoms and treatment of a patient with diabetic nephropathy accompanied by spontaneous retroperitoneal hemorrhage after hemodialysis. An elderly female patient with diabetic nephropathy presented with severe pain, numbness, and an increasing swelling in the left hip and left thigh after six sessions of hemodialysis involving the use of an antiplatelet drug and an anticoagulant agent. Her hemoglobin decreased to 46 g/L. An abdominal ultrasound showed a hematoma in the left retroperitoneal space, and computed tomography (CT) findings revealed a 6 cm × 8 cm × 10 cm hematoma in the left psoas muscle. After aggressive supportive therapy [the administration of packed red blood cell transfusion, carbazochrome sodium sulfonate injection, and continuous venovenous hemofiltration (CVVH)], the patient's vital signs stabilized and her hemoglobin increased to 86 g/L. Repeat CT showed that the hematoma had been partially absorbed after two weeks. Eventually, the patient was discharged with stable vital signs. Physicians should be aware of the possibility of spontaneous retroperitoneal hemorrhage, particularly in patients with diabetic nephropathy undergoing hemodialysis involving the use of anticoagulant agents.