Novel 532-nm Q-switched Nd: YAG laser for the treatment of melasma and rejuvenation: a prospective, randomized controlled comparison with 1,064-nm Q-switched Nd: YAG laser.

BACKGROUND: Melasma is a common pigmentary and photoaging disorder. Although various treatments, including 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd: YAG) laser toning, are available for melasma, results are often unsatisfactory. OBJECTIVE: We aimed to determine the efficacy and safety of 532-nm QS-Nd: YAG laser (shortwave toning) in patients with melasma and facial rejuvenation. METHODS: Fifty-two patients were recruited to receive either 1,064-nm QS-Nd: YAG laser or 532-nm QS-Nd: YAG laser every 2 weeks for 8 sessions and a 2-month follow-up visit in a randomized controlled double-blinded study. The primary outcome measure was the Melasma Area and Severity Index (MASI) score. Dermoscope and high-frequency ultrasound (HFUS) were used to assess the improvement of melasma and photoaging. RESULTS: 532-nm QS-Nd: YAG laser achieved significantly higher improvement in the MASI score (P = 0.000). The Dermoscopic melasma score (DMS) displayed significant change and confirmed the improvement. HFUS showed a significant decrease in the thickness of the subepidermal low-echogenic band (SLEB) and increases in dermal thickness and dermal density in both groups (P = 0.000 for all). The rate of very satisfied responses was significantly higher in the 532-nm laser group (P = 0.001). There was no significant difference in the visual analog scale pain assessment score (P = 0.248) and recurrence rate (P = 0.734) between the two groups. CONCLUSION: 532-nm QS-Nd: YAG laser (shortwave toning) proved to be an effective and safe treatment for melasma and rejuvenation. Shortwave toning was significantly better for pigmentation clearance, while 1,064-nm laser showed better improvement in skin rejuvenation.

The role of estrogen receptors (ERs)-Notch pathway in thyroid toxicity induced by Di-2-ethylhexyl phthalate (DEHP) exposure: Population data and in vitro studies.

BACKGROUND: This study aimed to assess the exposure level and risk of Di-2-ethylhexyl Phthalate (DEHP) among adults in Jilin Province, China, clarify the impact of DEHP on human thyroid function, and to explore the role of estrogen receptors (ERs)-Notch signaling pathway in the effect of DEHP metabolites on thyroid hormones based on population data and in vitro experiments. METHODS: 312 adults participated in this study. Urinary DEHP metabolites were determined by high performance liquid chromatography coupled to a tandem mass spectrometer (HPLC-MS/MS). Two pharmacokinetic models were used to evaluate the estimated daily intake (EDI) and hazard quotient (HQ) of the adults. Multiple linear regression and mediating effect models were used to evaluate the target associations. In cell experiments, thyroid follicular epithelial (Nthy-ori3-1) cells were exposed to mono (2-ethylhexyl) phthalate (MEHP) for testing. The inhibitions of ERα and Notch pathway were conducted by siRNA and Notch pathway inhibitor DAPT. RESULTS: The detection rate of five DEHP metabolites was 97.1∼100.0%. The HQ value of 0.3% of adults was higher than 1. The levels of urinary DEHP metabolites were significantly correlated with thyrotropin (TSH), thyrotropin-releasing hormone (TRH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3) and free thyroxine (FT4) and gene (estrogen receptor α (ERα), Notch1, Dll4) levels. The ERα-Notch pathway played a mediating role in the association between DEHP metabolite levels and FT4. The cell results showed, the levels of FT3 and FT4 in cell supernatant decreased after MEHP exposure, and the downward trend was reversed after ERα and notch pathways were inhibited, notch pathway genes also decreased after ERα inhibition. CONCLUSION: Adults in the Jilin Province of China were widely exposed to DEHP. ERs-Notch pathway played an important role in the effect of DEHP metabolites on thyroid hormones.

ATR induces hepatic lipid metabolism disorder in rats by activating IRE1α/XBP1 signaling pathway.

Atrazine (ATR) is a widely used herbicide and due to its persistence in environment and bioaccumulation, it can cause harmful impacts on human health. ATR exposure can lead to disorders of lipid metabolism in the liver, but its underlying mechanism is still unclear. 40 eight-week-old rats were given different doses of ATR (0, 0.5, 5 and 50 mg/kg/d) for 90 days. The liver tissue and serum were collected for histological observation and biochemical analysis. The levels of lipid and oxidative stress were assessed using colorimetry. Changes in MMP and ROS of liver cells were observed through flow cytometry. The expression of mRNA and protein was detected using Real-Time PCR and western blot. The results showed that TC and HDL-C levels in both the liver and serum were increased in the ATR-treated groups. The levels of MDA were accumulated, while the levels of SOD and GSH were depleted in the liver with ATR exposure. The expression of liver lipid metabolism related genes (SCD1, DGAT2, ACC1, PPARγ) was elevated. The liver ERS was activated and the gene expression of IRE1α/XBP1 signal pathway and GRP78, GRP94 in the liver was increased. There was a correlation between the levels of ERS and the levels of lipid metabolism. These results suggested that ATR can activate ERS and promote the expression of IRE1α/XBP1 signaling pathway, and further lead to lipid metabolism disorders in rat liver. This study can provide valuable insights as a reference for the prevention and control of hazards associated with agricultural residues.

Di-(2-ethylhexyl) phthalate (DEHP) promoted hepatic lipid accumulation by activating Notch signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) can induce hepatic lipid metabolism disorders, while the molecular mechanism still remain unknown. We aim to explore the underlying mechanism of Notch signaling pathway on hepatic lipid accumulation induced by DEHP/MEHP. A total of 40 male wistar rats were exposed to DEHP (0, 5, 50, and 500 mg/kg/d) for 8 weeks, BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100, and 200 µM) for 24 h. About 50 µM DAPT and 100 µg/mL Aspirin were used to inhibit Notch pathway and prevent inflammation, respectively. Real-Time PCR was performed to detect the mRNA expression, western blot and immunofluorescence were used to detect the protein expression. Lipids and inflammatory factors levels were determined by commercial kits. The results showed that DEHP/MEHP promoted the expression of Notch pathway molecules and lipids accumulation in rat livers/BRL-3A cells. The up-regulated Notch receptors were correlated with the TG levels in the rat liver. MEHP increased the levels of IL-8 and IL-1ß. The lipids levels were reduced after anti-inflammation. The inhibition of Notch pathway reversed the elevation of inflammation and lipid accumulation caused by MEHP. In conclusion, this study demonstrated that DEHP/MEHP led to lipid accumulation in hepatocytes by up-regulating Notch pathway and the inflammation might play a key role in the process.

Di(2-ethylhexyl) phthalate induced thyroid toxicity via endoplasmic reticulum stress: In vivo and in vitro study.

Di(2-ethylhexyl) phthalate (DEHP) could induce thyroid injury but the mechanism was unclear. This study combined in vivo and in vitro experiments to clarify the mechanism. In vivo, the offspring of Sprague Dawley rats were gavaged with different doses of DEHP (5, 50, and 250 mg/[kg⋅d]) from in utero to 12 weeks-old. Transcriptome sequencing was used to detect the mRNA expression profile of the offspring's thyroids. Differentially expressed genes were identified, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In vitro, Nthy-ori 3-1 cells were exposed to DEHP's metabolite mono (2-ethylhexyl) phthalate (MEHP) to verify the pathway we found by KEGG analysis. The results indicated that DEHP could disorder the thyroid hormones. Compared with the offspring in control group, the mRNA levels of 656 genes were upregulated in the offspring exposed to 50 mg/(kg⋅d) DEHP. The upregulated genes were enriched in the pathway of "protein processing in the endoplasmic reticulum (ER)." It indicated that the ER stress might play significant role in the thyroid toxicity induced by DEHP. In vitro, the mitochondrial membrane potential (ΔΨm) level of cells was decreased while the reactive oxygen species level was increased after MEHP exposure. MEHP increased the intracellular Ca2+ level and induced ER stress. After ER stress was inhibited by the 4-phenylbutyric acid, the thyroid toxicity caused by MEHP was alleviated. Taken together, our results indicated that DEHP could induce thyroid toxicity by activating ER stress.

Effect of Di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-thyroid axis in adolescent rat.

Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which results in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms underlying DEHP disrupting the function of the HPTA. DEHP was administered to Wistar rats by gavage at 0, 5, 50, and 500 mg/kg/day for consecutive 28 days and then the rats were sacrificed within 24 h following the last dose. The hormone levels of HPTA were quantified with radioimmunoassay and enzyme-linked immunosorbent assay, the protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, and the expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. The low dose of DEHP increased the body weights of rats. Serum levels of T3, T4, FT3 and FT4 as well as protein and mRNA levels of TSHR decreased in rats treated with 50 mg/kg or 500 mg/kg DEHP compared with those of controls. Although the protein levels of TRH in the hypothalamus or protein and mRNA levels of TRHR in pituitary were up-regulated, serum levels of TSH did not change statistically in rats treated with DEHP. Therefore, DEHP can produce thyroid toxicity and may interfere with the secretion of pituitary TSH. In conclusion, DEHP could interfere with the balance of HPTA of adolescent rats, and disturb the homeostasis of thyroid related hormones and the expression levels of receptors.

MEHP promotes liver fibrosis by down-regulating STAT5A in BRL-3A hepatocytes.

OBJECTIVE: As an environmental endocrine disruptor, mono-2-ethylhexyl phthalate (MEHP) can interfere with liver metabolism and lead to liver diseases. We aimed to investigate the role of MEHP in liver fibrosis and its molecular mechanism. METHODS: BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 µM) for 24 h. STAT5A gene was overexpressed by lentivirus transfection. The reactive oxygen species (ROS) was tested by the flow cytometer. The malondialdehyde (MDA), glutathione peroxidase (GSH-PX), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected by commercial kits. Real-Time PCR and Western blot were performed to test the relative mRNA and proteins levels, respectively. RESULTS: MEHP exposure significantly induced oxidative damage in BRL-3A cells, which inhibited the expression of STAT5A and promoted the expression of fibrosis related proteins MMP2, MMP9, TIMP2 and CTGF. After over-expression of STAT5A gene in BRL-3A cells, the elevated expression levels of CTGF, MMP2, MMP9 and TIMP2 induced by MEHP exposure were significantly reversed. CONCLUSION: This study demonstrated that MEHP exposure inhibited the expression of STAT5A by causing oxidative damage in BRL-3A hepatocytes, thus accelerating the expression of key molecules in fibrosis and promoting the occurrence of liver fibrosis.

Adverse effects of PM2.5 on cardiovascular diseases.

As an air pollutant, fine particulate matter with a diameter ≤ 2.5 µm (PM2.5) can enter the body through the respiratory tract and cause adverse cardiovascular effects. Here, the effects of PM2.5 on atherosclerosis, hypertension, arrhythmia, myocardial infarction are summarized from the perspective researches of human epidemiology, animal, cell and molecule. The results of this review should be proved useful as a scientific basis for the prevention and treatment of cardiovascular disease caused by PM2.5.

The associations of urinary DEHP metabolite levels, serum thyroid hormones, and thyroid-related genes among the adolescent students from China: a cross-sectional study.

Our study aimed to investigate the associations between DEHP exposure and serum thyroid hormone levels in 347 adolescents and young adults. We measured DEHP metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-carboxymethyl)hexyl phthalate (MCMHP) in their urine. Total thyroxine (TT4), total triiodothyronine, free triiodothyronine, free thyroxine (FT4), thyroid-stimulating hormone and the mRNA levels of thyroid peroxidase (TPO), thyroglobulin (TG), sodium iodide symporter (NIS), thyroid transcription factor 1 (TTF-1), and paired box gene 8 (PAX-8) in serum were measured. The results of statistical analysis showed that urinary DEHP metabolites were generally negatively associated with TT4 levels in serum. In the males, the FT4 levels showed positive associations with urinary MEHP, MECPP, MCMHP, and ∑DEHP. The mRNA level of TG was significantly positively correlated with the levels of MECPP, MCMHP, and ∑DEHP, while the levels of TTF-1 and PAX-8 mRNA were significantly positively correlated with the levels of DEHP metabolites. Taken together, DEHP may affect the synthesis of TG by altering the normal transcription of TTF-1 and PAX-8, leading to decreased TT4 levels in Chinese adolescents.

DNA methylation of JAK3/STAT5/PPARγ regulated the changes of lipid levels induced by di (2-ethylhexyl) phthalate and high-fat diet in adolescent rats.

Di (2-ethylhexyl) phthalate (DEHP) and high-fat diet (HFD) could induce lipid metabolic disorder. This study was undertaken to identify the effect of DNA methylation of JAK3/STAT5/PPARγ on lipid metabolic disorder induced by DEHP and HFD. Wistar rats were divided into a normal diet (ND) group and HFD group. Each diet group treated with DEHP (0, 5, 50, 500 mg/kg/d) for 8 weeks' gavage. The DNA-methylated levels of PPARγ, JAK3, STAT5a, and STAT5b in rats' livers and adipose were analyzed with MethylTarget. The lipid levels of rats' livers and adipose were detected with ELISA. Results showed in ND group that the DNA methylation levels of PPARγ, JAK3 in livers, and STAT5b in adipose were lower in 500 mg/kg/d group than the control. And the level of total cholesterol (TC) in adipose was higher in 500 mg/kg/d group than the control. In HFD group, the DNA methylation level of JAK3 was the lowest in livers and the highest in adipose in 50 mg/kg/d group. And the level of TC in livers was the lowest in 50 mg/kg/d group. In the 500 mg/kg/d group, the DNA methylation level of STAT5b was lower in livers and higher in adipose in HFD group than that in ND group. And the levels of TC in livers were lower in HFD group than those in ND group. Therefore, DNA methylation of JAK3/STAT5/PPARγ regulated the changes in lipid levels induced by DEHP and HFD in adolescent rats.

Influencing factors of coexistence PreDM and PreHTN in occupational population of state grid corporation of Chinese.

BACKGROUND: Early intervention of coexisting prediabetes (PreDM) and prehypertension (PreHTN) has great significance for the prevention and treatment of cardiovascular diseases. Therefore, the influencing factors of the coexisting PreDM and PreHTN has been widely concerned by human beings. The State Grid Corporation occupational population as a special group, who are often exposed to a certain amount of voltage. Earlier studies have shown that exposure to a certain level of voltage can cause cardiovascular disease. The aim of the present study was to explore the risk factors of coexisting PreDM and PreHTN, and to provide theoretical basis for early intervention. METHODS: A stratified random sampling method was used to randomly select Occupational population from the five power supply regions of China in 2012 for questionnaire surveys and clinical examinations. Respondents were divided into Normal blood glucose group, PreDM group, Diabetes group, Normal blood pressure group, PreHTN group, Hypertension group. RESULTS: The prevalence of coexisting PreDM and PreHTN in the study population was 1.9%. The binary Logistic regression results showed that region, gender, age, BMI, triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were the effects of factor coexisting PreDM and PreHTN. CONCLUSION: It is important to pay attention to the early stage of hypertension and diabetes, control the transition from PreHTN and PreDM to hypertension and diabetes, and improve the health of Power Supply Enterprise Population.

Effects of di (2-ethylhexyl) phthalate and high-fat diet on lipid metabolism in rats by JAK2/STAT5.

Exposure to di (2-ethylhexyl) phthalate (DEHP) induces lipid metabolism disorder and high-fat diet (HD) may have joint effects with DEHP. We aim to clarify the role of JAK2/STAT5 pathway in the process and reveal the effects of HD on the toxicity of DEHP. Wistar rats (160 animals) were fed with HD or normal diet (ND) respectively and exposed to DEHP 0, 5, 50, and 500 mg/kg/day for 8 weeks. Lipid levels, as well as the morphology of liver and adipose, mRNA levels, and protein levels of JAK2, STAT5A, STAT5B, FAS, ap2, and PDK4 were detected. The results showed that DEHP exposure leads to increased weight gain. The JAK2/STAT5 pathway was activated in adipose after DEHP exposure and promoted the expression of FAS, ap2, and PDK4 in ND rats. While in the liver, JAK2 was inhibited, and lipid synthesis and accumulation were increased. However, rats exposed to DEHP in combination with HD showed a complete disorder of lipid metabolism. Therefore, we conclude that DEHP affects lipid metabolism through regulating the JAK2/STAT5 pathway and promotes adipogenesis and lipid accumulation. High-fat diet may have a joint effect with DEHP on lipid metabolism disorder.

Correction to: Effects of di (2-ethylhexyl) phthalate and high-fat diet on lipid metabolism in rats by JAK2/STAT5.

We found an error in the materials and methods section. Since our team used two methodsfor anesthesia in rats and the anesthesia method used in this paper was 3.5% chloralhydrate anesthesia, we mistakenly wrote the anesthetic as 3% sodium pentobarbital.

Mono-2-ethylhexyl phthalate (MEHP) promoted lipid accumulation via JAK2/STAT5 and aggravated oxidative stress in BRL-3A cells.

Mono-2-ethylhexyl phthalate (MEHP), as the major metabolite of Di-(2-ethylhexyl) phthalate (DEHP), can induce lipid accumulation in hepatocytes and further leads to non-alcoholic fatty liver disease (NAFLD), while the underlying mechanism is unclear. We aim to clarify the effects of JAK2/STAT5 pathway on lipid accumulation induced by MEHP and the role of oxidation stress in NAFLD. BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 µM) for 24 h and 48 h. Then the lipid droplets in cells were observed by Oil-Red-O staining and quantified by isopropyl alcohol. The levels of TG, SOD, TBARS, AST and ALT were all detected by commercial kits. RT-PCR was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by JAK2/STAT5 pathway genes and lipid metabolism-related genes. As a result, MEHP promoted the lipid synthesis and accumulation in BRL-3A cells. MEHP down-regulated the expression and inhibited the activation of JAK2/STAT5. Moreover, the lipid metabolism-related kinases levels were elevated after MEHP exposure. In addition, the SOD levels were gradually decreased and the TBARS levels were increased in MEHP-treated groups. The lipid metabolism-related proteins levels were correlated with the oxidation stress levels. Furthermore, the ALT and AST levels were elevated after MEHP exposure. Therefore, we concluded that MEHP led to lipid accumulation through inhibiting JAK2/STAT5 pathway, resulted in damaging liver parenchyma and NAFLD by aggravating oxidation stress.

Urinary levels of phthalate metabolites and their association with lifestyle behaviors in Chinese adolescents and young adults.

BACKGROUND: Adolescence and young adulthood are critical periods of human growth and development. Phthalates are environmental endocrine disruptors, and their health hazards in adolescents and young adults cannot be ignored. This study was undertaken to assess phthalate exposure and determine the associations between lifestyle behaviors and phthalate metabolite levels in Chinese adolescents and young adults. METHODS: Four hundred and seventy-eight adolescents and young adults aged 16-20 years were included in this study. The levels of mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-carboxmethyl)-hexyl phthalate (MCMHP) in the subjects' urine were measured by high-performance liquid chromatography-tandem mass spectrometry. The estimated daily intake (EDI) and hazard index (HI) of phthalates were calculated based on urinary metabolite levels. Relevant information on the subjects was collected via questionnaires. The associations between phthalate metabolite levels and lifestyle behaviors were examined using the independent-sample t-test, Mann-Whitney test and multiple linear regression. RESULTS: In this study, the detection rates of all seven metabolites were >98%. The highest median metabolite concentration was MBP, which was 43.00 µg/L (33.11 µg/g creatinine). The highest median EDI was for di-(2-ethylhexyl) phthalate (DEHP), which was 2.40 µg/kg-bw/day (volume-based) and 1.51 µg/kg-bw/day (creatinine-based). 2.7% (volume-based) and 1.0% (creatinine-based) of the subjects showed excessive HITDI (HI of the tolerable daily intake) values, which indicated the cumulative risk of anti-androgenic effects. Furthermore, factors significantly associated with phthalate metabolite levels included the use of plastic food packages (DEHP metabolites), physical exercise (MEOHP), the frequency of fast food consumption (MBP), and the frequency of skin care cosmetics and color cosmetics use (MEP). CONCLUSION: Our results suggest that Chinese adolescents and young adults are widely exposed to phthalates and their metabolite levels are influenced by lifestyle behaviors.

Effects of Different Components of PM2.5 on the Expression Levels of NF-κB Family Gene mRNA and Inflammatory Molecules in Human Macrophage.

Background: Studies have found that exposure to fine particulate matter with sizes below 2.5 µm (PM2.5) might cause inflammation response via the NF-κB pathway. To date, only a few studies have focused on the toxicity of different components of PM2.5. We aimed to explore the effects of PM2.5 with different components on the expression levels of NF-κB family gene mRNA and inflammatory molecules in human macrophages. Methods: Human monocytic cell line THP-1-derived macrophages were exposed to water-soluble (W-PM2.5), fat-soluble (F-PM2.5), and insoluble (I-PM2.5) PM2.5. The cell survival rate was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of inflammatory molecules were determined by enzyme-linked immunosorbent assay (ELISA), and the relative mRNA levels of the NF-κB family gene were determined by real time PCR. Results: PM2.5 could decrease the cell viability. After exposure to W-PM2.5, the levels of interleukins (IL)-1ß and IL-12 p70 significantly increased. After exposure to F-PM2.5, the levels of IL-12 p70 significantly increased. The levels of IL-12 p70 and TNF-α after exposure to I-PM2.5 were significantly higher than that in W- and F-PM2.5 treatment groups. The levels of IL-8, C reactive protein (CRP), and cyclooxygenase (COX)-2 increased only after exposure to I-PM2.5. F-PM2.5 increased the mRNA levels of NF-κB genes, especially NF-κB1 and RelA. Conclusions: PM2.5 can decrease the cell survival rate and up-regulate the expression of NF-κB family gene mRNA and inflammatory molecules. The main toxic components of PM2.5 related to inflammatory response in macrophages were the I-PM2.5.

Over-expression of nuclear factor-κB family genes and inflammatory molecules is related to chronic obstructive pulmonary disease.

Background: Nuclear factor-κB (NF-κB) signaling plays essential roles in inflammatory responses. However, whether the expression levels of NF-κB family genes affect inflammatory responses is unclear. Moreover, little is known regarding the association between NF-κB family genes expression and the pathogenesis of chronic obstructive pulmonary disease (COPD). The present study was undertaken to assess the relationship between the expression levels of NF-κB family genes mRNA and of inflammatory markers relevant to COPD pathogenesis. Methods: A total of 186 unrelated patients with acute exacerbations of COPD and 180 healthy controls were recruited. Total RNA was extracted from the peripheral fasting blood of each subject using trizol reagent. The mRNA levels of NF-κB family genes (NF-κB1, NF-κB2 and c-REL) were measured by real-time quantitative polymerase chain reaction. The serum levels of cyclooxygenase-2 (COX-2), C-reactive protein, interleukin (IL)-1ß, IL-6, IL-8, IL-12 and tumor necrosis factor-α were measured with enzyme-linked immunosorbent assay kits. Results: The relative mRNA levels of the NF-κB family genes and the levels of inflammatory molecules were significantly higher in the COPD group than in the control group after adjustment for smoking. The IL-1ß, IL-8 and COX-2 levels were significantly lower in the NF-κB2 under-expression subgroup as compared to the NF-κB2 over-expression subgroup. The COX-2 level was significantly lower (P < 0.05) in the c-REL under-expression subgroup as compared to the c-REL over-expression subgroup. Conclusion: NF-κB2 over-expression was associated with IL-1ß, IL-8 and COX-2 levels, whereas c-REL overexpression was associated with COX-2 level. Over-expression of both NF-κB2 and c-REL was found to be related to COPD.

Effect of Atmospheric PM2.5 on Expression Levels of NF-κB Genes and Inflammatory Cytokines Regulated by NF-κB in Human Macrophage.

Exposure to PM2.5 induces systemic inflammation, and the NF-κB signaling pathway plays an important role in the inflammation process. We aim to clarify whether the expression of NF-κB gene family affects inflammation caused by PM2.5. Human monocytic cells (THP-1) were induced to differentiate into macrophages using phorbol myristate acetate. The macrophages were then treated with 100, 200, and 400 µg/ml of PM2.5 for 12, 24, and 48 h, respectively. Then, we determined the survival rate of macrophages through the MTT assay. The TNF-α and CRP levels in the cell culture medium were measured through enzyme-linked immunosorbent assay. The NF-κB1, NF-κB2, RelA, RelB, and Rel mRNA levels in macrophages were measured with reverse transcriptase-polymerase chain reaction. As a consequence, the survival rate of macrophages decreased with increasing PM2.5 exposure time and dose. The TNF-α levels in PM2.5-treated groups were lower as compared with the control group and in contrast to the NF-κB mRNA levels at all exposure times. The TNF-α level in the 400-µg/ml group and the NF-κB1, NF-κB2, RelB, and Rel mRNA levels in all PM2.5-treated groups were found to be higher at 24 h than at 12 h. Furthermore, the TNF-α, CRP, and NF-κB2 mRNA levels in the group treated with 400 µg/ml PM2.5 were higher at 48 h that at 12 and 24 h. On the other hand, the NF-κB1, RelA, RelB, and Rel mRNA levels in all PM2.5-treated groups were lower as compared to levels of TNF-α, CRP, and NF-κB2 mRNA. The levels of NF-κB genes and inflammatory cytokines demonstrated different correlations at different exposure times. Therefore, we conclude that PM2.5 reduces the survival rate of macrophages. As macrophages are exposed to PM2.5, the NF-κB gene family expression is increased, which subsequently affects inflammatory factor levels.

Di-(2-ethylhexyl)-phthalate induces glucose metabolic disorder in adolescent rats.

As a plasticizer, di-(2-ethylhexyl)-phthalate (DEHP) is widely added in various commercial products. Some researchers had suggested that DEHP has adverse effects on the glucose metabolism, but the mechanisms remain unclear. Adolescent Wistar rats were divided into four groups and administered DEHP by gavage at 0, 5, 50, and 500 mg kg-1 d-1 for 28 days. ELISA was used to quantify the serum insulin and leptin levels; RT-PCR, immunohistochemistry, and Western blot were used to detect the mRNA and protein expressions of Janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3), leptin receptor (Ob-R), and insulin receptor (IR) in liver and pancreas In comparison to the control group, the DEHP-treated rats showed the following: (1) higher organ coefficient of liver; (2) higher fasting blood glucose levels, higher fasting serum insulin and leptin levels, higher insulin resistance index homeostasis model assessment; (3) lower protein levels of Ob-R and IR in the liver and pancreas; (4) higher protein levels of JAK2 and STAT3 in the liver; and (5) higher protein and mRNA levels of SOCS3 in the liver and pancreas. Exposure to DEHP induced glucose metabolic disorder in the adolescent rats, and the mechanism is that DEHP may interfere with the JAK2/STAT3/SOCS3 pathway, regulated the sensitivity of the insulin receptor and leptin receptor.