Dyslipidemia in diffuse large B-cell lymphoma based on the genetic subtypes: a single-center study of 259 Chinese patients.

Background: Diffuse large B-cell lymphoma (DLBCL) is a kind of highly heterogeneous non-Hodgkin lymphoma, both in clinical and genetic terms. DLBCL is admittedly categorized into six subtypes by genetics, which contain MCD, BN2, EZB, N1, ST2, and A53. Dyslipidemia is relevant to a multitude of solid tumors and has recently been reported to be associated with hematologic malignancies. We aim to present a retrospective study investigating dyslipidemia in DLBCL based on the molecular subtypes. Results: This study concluded that 259 patients with newly diagnosed DLBCL and their biopsy specimens were available for molecular typing. Results show that the incidence of dyslipidemia (87.0%, p <0.001) is higher in the EZB subtype than in others, especially hypertriglyceridemia (78.3%, p = 0.001) in the EZB subtype. Based on the pathological gene-sequencing, patients with BCL2 gene fusion mutation are significantly correlative with hyperlipidemia (76.5%, p = 0.006) and hypertriglyceridemia (88.2%, p = 0.002). Nevertheless, the occurrence of dyslipidemia has no remarkable influence on prognosis. Conclusion: In summary, dyslipidemia correlates with genetic heterogeneity in DLBCL without having a significant influence on survival. This research first connects lipids and genetic subtypes in DLBCL.

Concentration and atmospheric transport of PM2.5-bound polycyclic aromatic hydrocarbons at Mount Tai, China.

Atmospheric PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) pose a major threat to human health. At present, studies on PAHs in the atmosphere have mostly focused on their concentration levels and source apportionment, whereas studies on the vertical transport of PAHs in the atmosphere are limited. However, the vertical transport of PAHs is important for their diffusion near the ground and their long-range transport at higher altitude. In this study, PM2.5 samples were collected simultaneously at the summit and foot of Mount Tai (MTsummit and MTfoot, respectively) from May to June 2017, and the concentrations of 18 PAHs in the samples were determined. The total concentration of PAHs at MTsummit was 2.406 ng m-3, which was well below the pollution levels of domestic cities, whereas that at MTfoot was as high as 9.068 ng m-3, which was within the range of pollution levels in domestic cities. The total carcinogenic risk for both MTsummit and MTfoot was within the potential risk range. Given the source of PAHs and the diurnal variation of the planetary boundary layer, the PAHs showed opposite diurnal trends at MTsummit and MTfoot. Vertical transport was an important source of daytime PAHs at MTsummit, and the vertical transport efficiency of PAHs decreased with an increasing ring number; this may be due to the combined effects of gas-particle partitioning and chemical reactions. Furthermore, PAHs originating in the surrounding high-emission provinces can affect the Mount Tai area via atmospheric trans-regional transport, and the BaP/BeP ratio is a useful indicator of the transport distance of PAHs.

Mitochondrial activity and oxidative stress functions are influenced by the activation of AhR-induced CYP1A1 overexpression in cardiomyocytes.

There is an endemic cardiomyopathy currently occurring in China, termed, Keshan disease (KD). The authors previously compared mitochondrial­associated gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD patients and normal controls, using mitochondria­focused cDNA microarray technology. The results detected an upregulation of the enzyme­associated CYP1A1 gene, (ratios ≥2.0). The aryl hydrocarbon receptor (AhR) regulates the expression of numerous cytochrome P450 (CYP) genes including members of the CYP1 family; CYP1A1 and CYP1A2. Several previous studies have suggested roles for the aryl hydrocarbon receptor (AhR) and the genes that it regulates. An example involves cytochrome P4501A1 (CYP1A1), in the pathogenesis of heart failure, cardiac hypertrophy and other cardiomyopathies. Mitochondria comprise ~30% of the intracellular volume in mammalian cardiomyocytes, and subtle alterations in mitochondria can markedly influence cardiomyopathies. The present study investigated alterations in the activity and functions of mitochondria following AhR­induced overexpression of CYP1A1. AC16 cells were treated with the CYP1A1 inducer 2,3,7,8­tetrachlorodibenzo­p­dioxin (TCDD), and cytotoxicity was then evaluated in MTT assays. Reverse transcription­quantitative polymerase chain reactions, western blot analysis and 7­ethoxyresorufin O­deacylase assays were performed to analyze the mRNA and protein levels, and the enzymatic activity of CYP1A1. Mitochondrial activity and mass were analyzed using an inverted fluorescence microscope and a fluorescence microplate reader. Reactive oxygen species (ROS) activity was analyzed using flow cytometry. The results of the current study demonstrated that TCDD gradually increased mRNA and protein levels of AhR and CYP1A1, in addition to the enzymatic activity. Mitochondrial activity and the quality of mitochondrial membranes were also significantly attenuated, and mitochondrial ROS levels were elevated in the TCDD­induced cardiomyocytes. The results indicate the involvement of the AhR/CYP1A1 signaling pathway in the mechanism of action of TCDD in human cardiomyocytes. The present findings may provide an explanation for myocardial injuries caused by polycyclic aromatic hydrocarbons. The authors conclude that exposure to TCDD results in regulatory alteration to the expression of detoxification genes that ultimately affect the metabolic activation and function of cardiomyocytes.

Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy.

Keshan disease (KD) is an endemic cardiomyopathy. The etiology of KD is selenium deficiency; however, it is not the only one and there is no effective approach to preventing and curing this disease. The aim of the present study was to explore the differences in the role of arachidonic acid (AA) by the cytochrome P450 enzyme between chronic KD (CKD), dilated cardiomyopathy (DCM) and control patients. Reverse transcription-quantitative polymerase chain reaction was used to detect the CYP1A1 and CYP2C19 gene expression levels in 6 CKD patients, 6 DCM and 6 healthy controls. An enzyme-linked immunosorbent assay kit was applied to detect serum protein expression of CYP1A1 and CYP2C19, AA and epoxyeicosatrienoic acids (EETs), and 20-hydroxyeicosatetraenoic acids (20-HETE) in 67 CKD patients, 28 DCM, and 58 controls. The present results showed that the expression levels of CYP1A1 and CYP2C19 genes were significantly upregulated compared with the control group (P<0.01). The expression level of the CYP1A1 protein in the CKD (49.55±35.11 pg/ml) and DCM (46.68 ±13.01 pg/ml) groups were enhanced compared with the control group (44.33±16.76 pg/ml) (P<0.01). The production of the CYP2C19 protein in the CKD (57.52±28.22 pg/ml) and DCM (56.36±11.26 pg/ml) groups was enhanced compared with the control group (51.43±10.76 pg/ml). The concentrations of AA in the CKD (126.27±47.91 ng/ml) and DCM (133.24±58.67 ng/ml) groups were also significantly increased compared to the control (78.16±23.90 ng/ml) (P<0.001). The concentration of 20-HETE in the CKD (198.34±17.22 ng/ml) and DCM (194.46±20.35 ng/ml) groups were also significantly increased compared to the control (130.10±16.10 ng/ml) (P<0.001). The only difference between CKD and DCM was for the expression of the CYP1A1 gene and protein. The maximum concentration of EETs was in the control group (44.37±6.14 pg/ml), and the other two groups were lower than the control group (P<0.001). These findings indicated that AA-derived CYP450 metabolites may have a critical role in the pathogenesis of KD and DCM. Upregulation of the CYP2C19 gene and frequent protein expression may be a protective compensation reaction, while CYP1A1 may aggravate myocardial injury.

[Preparation and transdermal diffusion of flexible nanoliposomes of ginkgolide B].

OBJECTIVE: To prepare flexible nanoliposomes of Ginkgolid B (GB) and study the transdermal diffusion law. METHOD: Flexible nanoliposomes of GB were prepared by film dispersion method, and the shape and particle size of nanoliposomes were analyzed. GB permeation tests in vitro through the skin of rats were performed in modified Franz diffusion cell. The accumulated permeation amounts of GB alcoholic solution, flexible nanoliposomes of GB and ordinary nanoliposomes of GB were compared. RESULT: The average encapsulation percentage, the particle size, and the Zata potential of the flexible nanoliposomes were (89.52 +/- 1.76)%, and was (208.3 +/- 25.49) nm, and was -49.2 mV, respectively. The accumulated permeation amount of flexible nanoliposomes in 8 hours was 189.97 microg x cm(-2), and its transdermal permeability in 8 hours was 23.75 microg x cm(-2) x h(-1). CONCLUSION: The encapsulation percentage of the flexible nanoliposomes is good,and the stability of the GB nanoliposomes is fine. Flexible nanoliposomes can significantly enhance the diffusion rate of GB through the skin of rats.