Concentrations, seasonal trends, sources, health risk and subchronic toxicity to the respiratory and immune system of PAHs in PM2.5 in Xi'an.

PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) have been proved to be hazardous to health. Previous studies have focused on the distribution and sources of PAHs, whereas there is little knowledge of the damage to organs. Here we sought to investigate the pollution level and seasonal variation characteristics of PAHs in PM2.5 in Xi'an and assess the health risk, to establish a PAHs exposure model, and investigate the toxicological effects of PAHs on the respiratory and immune functions. A sub-chronic exposure model of PAHs was established by inhalation. The pathological changes of lung tissues were observed with a light microscope. Inflammatory reactions in alveolar lavage fluid were determined using the corresponding kit. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with enzyme linked immunosorbent assay (ELISA) kit; the proliferation of lymphocytes in spleen was detected with methyl tetrazolium (MTT); DNA immune damage was determined with DNA gel electrophoresis. The results showed that (1) the total concentration of 16 PAHs ranged from 41.1 to 387 ng/m3, with a mean value of 170 ng/m3, and the concentration of PAHs in PM2.5 was higher in winter than in other seasons. (2) The sources of PAHs in the atmosphere of Xi'an urban area were mainly coal combustion, and the equivalent carcinogenic concentration of PAHs in PM2.5 was 3.9 ng/m3. (3) Foreign body granuloma formation and inflammatory cell damage were observed in the lungs of rats infected with toxin; the levels of reactive oxygen species (ROS) and mobile device assistant (MDA) increased while nitric oxide synthase (NOS) decreased with the increase of dose; the expression levels of IL-6 and IL-8 elevated with the increase of toxin dose, showing an obvious dose-effect relationship; the level of PAHs damage to cells showed a dose-effect relationship. Sub-chronic exposure to PAHs could cause sustained inflammatory injury to the organism. Measures should be taken to counter the problems of PAHs in PM2.5 in Xi'an and relevant health promotion strategies should be developed.

Applications and challenges of low temperature plasma in pharmaceutical field.

Low temperature plasma (LTP) technology has shown an outstanding application value in the pharmaceutical filed in recent ten years. This paper reviews the research advances in LTP, including its effects on enhancing or inhibiting drug activity, its combined use with drugs to treat cancers, its effects on the improvement of drug delivery system, its use in preparation of new inactivated virus vaccines, its use with mass spectrometry for rapid detection of drug quality, and the anti-tumor and sterilization effects of plasma-activated liquids. The paper also analyzes the challenges of LTP in the pharmaceutical filed, hoping to promote related research.

MicroRNA-543 acts as a prognostic marker and promotes the cell proliferation in cervical cancer by BRCA1-interacting protein 1.

Human cervical cancer is one of the most common malignancies worldwide. Recent studies have focused on microRNAs that play crucial roles in cancer development and progression of cervical cancer. In this study, we aimed to analyse the biological function of microRNA-543 in cervical cancer. Samples of human cervical cancer and matched adjacent normal cervical tissues were collected, and expression level of microRNA-543 and the clinical characteristics of cervical cancer were investigated. We found that microRNA-543 expression was significantly elevated in cervical cancer and its aberrant expression levels were positively correlated with tumour size ( p = 0.0315), differentiation ( p = 0.0134), clinical stage ( p = 0.0315) and overall ( p = 0.0426) and disease-free survival ( p = 0.0396) of cervical cancer. Overexpression of microRNA-543 in cancer-derived HeLa and SiHa facilitated cell growth and suppressed cell apoptosis, while down-regulation of microRNA-543 exerted a reverse effect on cell growth and apoptosis. In addition, we demonstrated that BRCA1-interacting protein 1 was directly regulated by microRNA-543 and the restoration of BRCA1-interacting protein 1 expression reversed the effects of microRNA-543 on cell proliferation. Taken together, these findings collectively demonstrate that microRNA-543 exerts its oncogene function by directly targeting BRCA1-interacting protein 1 in cervical cancer, indicating a potential novel potential prognostic biomarker and therapeutic target for cervical cancer.

Uremia-caused changes of ghrelin system in hippocampus may be associated with impaired cognitive function of hippocampus.

PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water-maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment.

Premature senescence and cellular phenotype transformation of mesangial cells induced by TGF-B1.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a polypeptide member of the transforming growth factor ß superfamily of cytokines and performs many cellular functions. Its overexpression may lead to renal fibrosis. AIM: This study planed to investigate the effects of TGF-ß1 on the cell cycle and phenotype of mesangial cells. METHODS: Rat mesangial cells were cultured together with different concentrations (0, 1, 2, 5, and 10 ng/mL) of TGF-ß1 for specified times from 0 min to 72 h. 0 ng/mL TGF-ß1 and 0 min served as controls. Cell cycles were assessed by flow cytometry and α-smooth muscle actin expression (α-SMA) protein expression by western blot analysis. All data were presented as Mean ± SD. Statistical analysis was performed by using one-way analysis of variance and correlation analysis. Results were considered significant at p < 0.05. RESULTS: After 15 min of co-culture with different concentrations of TGF-ß1, the percentage of mesangial cells in G0/G1 phase was significantly elevated compared to the control (p < 0.05). 12 h co-culture induced cell hyperplasia, 24 h co-culture obvious up-regulation of α-SMA (p < 0.01) and one or two cells' myofibroblast phenotype transition, and 36 h co-culture several cells' phenotype transition. Correlation analysis prompted that the TGF-ß1-induced premature aging was time-dependent (p < 0.01). CONCLUSION: TGF-ß1 may induce mesangial cells' premature senescence and myofibroblast-like phenotype transformation time-dependently, which may contribute to the development of early stage of glomerulosclerosis.

[Effects of Qufengtongluo Recipe on expressions of cell cycle regulatory proteins in rat mesangial cells].

OBJECTIVE: To observe the effects of Qufengtongluo Recipe (QFTLR) on the expressions of cell cycle regulatory proteins in rat mesangial cells (MCs) in vitro and investigate the mechanism by which QFTLR inhibits MC proliferation. METHODS: Using the methods of serum pharmacology, we studied the expressions of cell cycle regulatory proteins in rat MCs treated with QFTLR by laser scanning confocal microscope and immunohistochemistry. RESULTS: Compared with the normal control cells, the cells challenged with lipopolysaccharide (LPS) showed significantly enhanced expressions of cyclin D1, CDK2, and P21 (P<0.01) and obviously lowered protein expression of P27 (P<0.01). Treatment of the LPS-challenged cells with QFTLR and benazepril both resulted in significantly attenuated expressions of cyclin D1, CDK2, and P21 and obvious increase of P27 expression (P<0.05 or P<0.01), but QFTLR produced stronger effects than benazepril in regulating of cyclinD1, P21 and P27 protein expressions (P<0.05 or P<0.01). CONCLUSION: QFTLR inhibits rat MC proliferation in vitro possibly by down-regulating the cellular expressions of cyclin D1, CDK2, and P21 and up-regulating the expression of P27 protein.

Therapeutic effect of artemisinin on lupus nephritis mice and its mechanisms.

In this study, we investigated the therapeutic effect of artemisinin (Art) on lupus nephritis mice and its mechanisms by comparing the differences between lupus nephritis (LN) mice given Art and control mice in molecular biology, immunohistochemistry, and histopathology. The results showed that Art could remarkably relieve the symptoms, decrease the level of urine protein/24 h, and alleviate pathological renal lesions. The differences among the four groups in the expression of the NF-κBp65 protein, nuclear factor-κB (NF-κB) activity, and the expression of transforming growth factor-ß1 (TGF-ß1) mRNA in renal tissue suggested that Art can lower the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibit the expression of the NF-κBp65 protein and NF-κB and TGF-ß1 mRNA in the renal tissues of LN mice. These results proved that it is reliable and effective to use Art to treat LN mice, and its therapeutic mechanisms should closely be related to the fact that Art can obviously decrease the serum levels of TNF-α and IL-6 and down-regulate the expression of the NF-κBp65 protein and NF-κB and TGF-ß1 mRNA in renal tissues.

[Qufeng Tongluo decoction inhibits lipopolysaccharide-induced rat mesangial cell proliferation in vitro by suppressing NF-kappaB activation and reducing TGF-beta1 and IL-6 mRNA expressions].

OBJECTIVE: To investigate the effect of Qufeng Tongluo (QFTL) decoction on lipopolysaccharide (LPS)-induced rat mesangial cell proliferation and explore the possible mechanisms underlying the therapeutic effects. METHODS: Thirty-two rats were randomized into normal control, glomerulonephritis model, QFTL treatment and positive control groups, and serum samples were obtained from these groups. Rat mesangial cells with or without LPS exposure were treated with the sera, and the expression of nuclear factor-kappaB (NF-kappaB ) was detected using electrophoretic mobility shift assay (EMSA), and the expressions of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6) mRNAs were detected with RT-PCR. RESULTS: QFTL decoction inhibited the activation of NF-kappaB in LPS-stimulated rat mesangial cells stimulated by LSP, and lowered the expressions of TGF-beta1 and IL-6 mRNA. CONCLUSION: QFTL decoction can inhibit LPS-induced rat mesangial cell proliferation by decreasing the expression of TGF-beta1 and IL-6 mRNA as a result of suppression NF-kappaB activation.

[Effects of Qufeng Tongluo Recipe on proliferation of and TGF-beta1 and IL-6 mRNA expressions in glomerular mesangial cells from rats].

OBJECTIVE: To investigate the effects of Qufeng Tongluo Recipe (QFTLR), a compound of traditional Chinese herbal medicine for dispelling wind and removing obstruction in the meridians, on cell proliferation and expressions of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6) mRNAs induced by lippolysaccharide in glomerular mesangial cells from rats. METHODS: The method of serum pharmacology was used. A total of 32 rats were divided into normal control group, untreated group, QFTLR group and positive control group which also was named Monopril (fosinopril sodium) group. Mesangial proliferative glomerulonephritis was induced by injection of antithymocyte serum in the rats except for the normal control group. Sera of the rats were obtained after corresponding interventions. Lipopolysaccharide-induced proliferation of rat mesangial cells (MCs) cultured in the respective serum-containing media was detected by the method of methyl thiazolyl tetrazolium (MTT) assay, and the expressions of TGF-beta1 and IL-6 mRNAs were analyzed by the method of reverse transcription polymerase chain reaction. RESULTS: Compared with the untreated group, QFTLR showed remarkable inhibitory function on the proliferation of the mesangial cells (P<0.05). The expressions of TGF-beta1 mRNA in mesangial cells were increased in the untreated group, QFTLR group and Monopril group when compared with the normal control group (P<0.01), but the TGF-beta1 mRNA expressions in QFTLR group and in Monopril group were lower than that in the untreated group. The IL-6 mRNA expression could be increased by the LPS stimulation, and it was significantly higher in the other three groups than that in the normal control group, including the untreated group, the Monopril group and the QFTLR group (P<0.01). Compared with the untreated group, the expression of IL-6 mRNA was decreased by QFTLR and Monopril (P<0.01). QFTLR was better than Monopril in inhibiting the proliferation of the mesangial cells and decreasing the expressions of TGF-beta1 and IL-6 mRNAs (P<0.05). CONCLUSION: QFTLR has great inhibitory effect on mesangial cell proliferation and expressions of TGF-beta1 and IL-6 mRNAs, which may be one of its mechanisms in postponing glomerular sclerosis.

Clinical study of Trilogy Detoxicating Therapy combined with routine Western medicine on patients with chronic renal failure.

OBJECTIVE: To investigate the mechanism of Trilogy Detoxicating Therapy in treating patients with chronic renal failure (CRF). METHODS: A total of 142 patients were assigned to the Trilogy Detoxicating Therapy group (the treatment group, 82 patients) and the Western medicine treatment group (the control group, 60 patients). All of the patients were treated with NovoNorm 1 mg and metformin hydrochloride tablets 0.15 g thrice per day for lowering the blood glucose, as well as Perindopril 4 mg twice daily for lowering blood pressure, recombinant human erythropoietin 2 000 U and a hypodermic injection thrice a week for rectifying anemia, 30 days as one course of treatment, and all patients were treated for two courses. Patients in the treatment group were treated with the Trilogy Detoxicating Therapy [dispersing the five-zang organs, expelling toxins through colonic dialysis and skin dialysis fumigation] in addition to the aforementioned drugs. Parameters observed and recorded in the study included renal function [serum creatinine (SCr), blood urea nitrogen (BUN)], blood lipids [triglyceride (TG), total cholesterol (TC), low-density lipoprotein C (LDL-C), high-density lipoprotein C (HDL-C)], plasma total protein (TP), hemoglobin (Hb), serum interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) before and after the treatment. RESULTS: After two courses of treatment, the levels of SCr, BUN, TG, TC, LDL-C, serum IL-6 and TNF-alpha decreased significantly, meanwhile HDL-C increased in the treatment group (P<0.05 or P<0.01). In contrast, no obvious changes of the above mentioned items occurred in the control group. In both groups, the levels of TP and Hb were significantly elevated (P<0.05 or P<0.01), but the changes were more obvious in the treatment group (P<0.01). CONCLUSION: Trilogy Detoxicating Therapy played a therapeutic role on patients with CRF possibly through lowering the levels of blood lipids, serum IL-6 and TNF-alpha.

[Effect of Yishen capsule on serum vascular endothelial growth factor and cell immunity in patients with chronic glomerulonephritis].

OBJECTIVE: To explore the effect of Yishen capsule on the serum vascular endothelial growth factor (VEGF), the cell immunity and the theraphic. METHOD: Serum VEGF and T cell subsets were studied in 30 normal subjects and 83 patients before and after treatment. RESULT: Compare with normal subjects, CD3, CD4, CD4/CD8 were decreased, CD8 and serum VEGF were increased obviously (P <0. 05 or P <0. 01). After three months treatment with YiShen capsule, CD4/CD8 was increased, CD8 and serum VEGF were decreased significantly (P <0.05 or P <0.01). CONCLUSION: Yishen capsule can reduce the proteinuria, increase the function of immunity and improve the clinical symptom of patients with chronic glomerulonephritis, achieved the effects of allevating chronic glomerular sclerosis ultimately.