Roles of NPAS2 in circadian rhythm and disease.

NPAS2, a circadian rhythm gene encoding the neuronal PAS domain protein 2 (NPAS2), has received widespread attention because of its complex functions in cells and diverse roles in disease progression, especially tumorigenesis. NPAS2 binds with DNA at E-box sequences and forms heterodimers with another circadian protein, brain and muscle ARNT-like protein 1 (BMAL1). Nucleotide variations of the NPAS2 gene have been shown to influence the overall survival and risk of death of cancer patients, and differential expression of NPAS2 has been linked to patient outcomes in breast cancer, lung cancer, non-Hodgkin's lymphoma, and other diseases. Here, we review the latest advances in our understanding of NPAS2 with the aim of drawing attention to its potential clinical applications and prospects.

Level of reduced glutathione and oxidized glutathione in a mouse bone cell line MC3T3-E1 cells exposed to fluoride / 中国地方病学杂志

Objective To observe the level of reduced glutathione(GSH) and oxidized glutathione(GSSG)in a mouse bone cell line MC3T3-E1 cells exposed to fluoride.Methods MTT method was used to detect cell viability of M C3T3-E1 cells exposed to varying concentrations and periods of fluoride [F-concentration:0(control),0.5,1.0,2.0,4.0,8.0,12.0,20.0 mg/L; F-periods:1,2,4 and 10 days].The Xevo TQ MS was employed to test the levels of GSH,GSSG and glutamine (Gln).Results The MC3T3-E1 cell viability was significantly higher in the 2 mg/L group(0.57 ± 0.05) 1 day after the exposure compared to the respective control(0.49 ± 0.03,P ＜0.01); conversely,cell viability was markedly lower in the 8 mg/L(0.49 ± 0.07) and 12 mg/L(0.47 ± 0.09)groups 4 days after the exposure in comparison to the control(0.63 ± 0.06,P ＜ 0.05 or P ＜ 0.01).The cell viability in the 8 mg/L group(1.52 ± 0.29) 10 days after the exposure was significantly higher than that in the control group (0.86 ± 0.23,P ＜ 0.01),however,the value in the 20.0 mg/L group (0.54 ± 0.07) was significantly lower(P ＜0.01).The level of cell GSH decreased significantly in the 20 mg/L groups 2 days[(13.92 ± 4.63)μmol/L]and 10 days [(0.53 ± 0.30)μmol/L]after exposure compared to the respective comtrols [(26.42 ± 3.67),(24.85 ± 5.68)μmol/L,all P ＜ 0.01].The level of cell GSSG markedly increased in the 2 mg/L group 2 days [(1.12 ± 0.62)μ mol/L]and the 8 mg/L group 4 days [(2.13 ± 0.62)μ mol/L]after exposure compared to the controls[(0.55 ± 0.22),(1.46 ± 0.46)μmol/L,all P ＜ 0.05].The similar change was observed in the 8 mg/L group[(2.97 ± 1.30)μmol/L] 10 days after exposure compared to the control [(1.35 ± 0.50)μmol/L,P ＜ 0.05].The level of Glndecreased significantly in the 2 mg/L group[ (62.80 ± 17.4l)μ mol/L] 4 days and in the 8 and 20 mg/L groups 10 days[ (122.26 ± 19.51), (19.38 ± 8.11)μmol/L] after exposure compared to the controls [ (83.28 ±14.32), ( 147.15± 16.95) μmol/L , all P ＜ 0.05 or P ＜ 0.01 ]. Conclusions Fluoride exposure can significantly promote the changes of GSH, GSSG and Gln levels in the osteoblast, thus affecting the intracellular redox equilibrium.

Randomized-controlled study on anti-inflammation and safety of three drugs after Nd : YAG laser posterior capsulotomy / 中华实验眼科杂志

Background Nd: YAG laser posterior capsulotomy is an important way for after cataract.Usually the patient will use glucocorticoid eye drops to treat the anterior chamber inflammation after operation,but there is potential risk of elevating intraocular pressure (IOP).Objective This study was to compare the clinical effectiveness and safety of loteprednol etabonate ophthalmic suspension,tobramycin+ dexamethasone eye drops and fluorometholone eye drops following Nd: YAG laser posterior capsulotomy.Methods A randomized-controlled clinical trail was performed.One hundrcd and seventy-onc cycs of 127 paticnts who received Nd: YAG laser posterior capsulotomy for after cataract were randomly divided into four groups.Loteprednol etabonate ophthalmic suspension,fluorometholone eye drops,tobramycin+dexamethasone eye drops and systane eye drops was topically administered respectively in the four groups after laser posterior capsulotomy and 6 times per day for 5 days.IOP was measured with Goldmann tomometer 1 hour before operation and 1 hour,1 day,3 days and 7 days after operation.The ocular anterior segment inflammatory response was examined under the slit lamp and scored based on the Peizeng criteria.Written informed consent was obtained from each patient before any relevant medical procedure.Results The IOP was (18.2 ±4.7),(20.1 ±5.7),(18.7±5.5),(19.0 ±4.1),(19.5 ±3.5) mmHg in various time points in the loteprednol etabonate group; (18.7 ±5.3),(20.9±5.7),(21.3±4.5),(21.0±4.9),(22.5±6.5) mmHg in the fluorometholone eye drops group ; (17.9± 6.3),(20.3 ± 6.1),(23.0 ± 3.7),(24.7 ± 4.9),(24.5 ± 6.5) mmHg in the tobramycin +dexamethasone group and(18.4±6.3),(20.7±3.7),(22.7±6.5),(19.6±4.8),(18.5±3.5) mmHg in the systane group,showing a significant difference among the 4 groups (Fgroup =3.876,P =0.023).With the time lapse,the IOP was gradually reduced in the loteprednol etabonate group and systane group,but that in the fluorometholone group and tobramycin+dexamethasone group was elevated,showing a significant difference among them (Ftime =3.801,P =0.031).No any ocular and systemic adverse effect was found in various groups.The percentage of grade 1 and 2 of aqueous inflammatory cells was lower in the loteprednol etabonate group and tobramycin+dexamethasone group than the fluorometholone group and fluorometholone group and systane group(H =8.276,P =0.012).The percentage of Ⅰgrade of aqueous flare was 8％ in the loteprednol etabonate group,22％ in the fluorometholone group,18％ in the tobramycin+dexamethasone group and 30％ in the systane group,with a significant difference among them (H=9.305,P=0.000).Conclusions The use of corticosteroid eye drops can relieve the inflammatory response of ocular anterior chamber after Nd: YAG laser posterior capsulotomy.Loteprednol etabonate ophthalmic suspension has a better anti-inflammatory effect and less influence on IOP.

Immunoglobulin binding protein gene and protein expression in femur tissue of fluorosis rats / 中国地方病学杂志

Objective To observe the protein and gene expression of immunoglobulin binding protein (BiP) in the femur of fluoride-treated rats, and preliminarily study the possible role of endoplasmic reticulum stress in the pathogenesis of skeletal fluorosis. Methods Sixty Wistar rats were divided into 4 groups according to body weight, n =15. The control and low-calcium groups were fed with normal diet(0.79％ calcium) and low-calcium diet(0.063％ calcium), respectively, and both drank tap water(fluoride concentrations ＜ 1 mg/L). High-fluoride and coexpesure to low-calcium groups were fed with conventional feed (0.79％ calcium) and low-calcium diet (0.063％ calcium), respectively, and both drank tap water containing sodium fluoride (sodium fluoride concentration of 221 mg/L). During experimental period, rats were measured body weight once a week with a stand diet and water available ad libitum. The experiment lasted for 12 weeks. The immunohistochemical and reverse transcription polymerase chain reaction(RT-PCR) techniques were used to detect the protein and gene expression of BiP in the femur of fluoride-treated rats and control subjects. Results The bone mineral contents of high fluoride, lowcalcium and coexposure groups[(0.131 ± 0019), (0.097 ± 0.011 ), (0.083 ± 0.007)g/cm] were lower than those of the control group[(0.159 ± 0.029)g/cm, all P ＜ 0.05]; the bone mineral density of low calcium and coexpesure to fluoride group[(0.243 ± 0.018), (0.223 ± 0.022)g/cm2] was lower than that of the control group[(0.296 ± 0.046)g/cm2, all P ＜ 0.05]. The immunohistochemical staining showed that the anti-BiP antibody positive osteoblasts were significantly increased in the low calcium diet and coexposure to fluoride groups than that in the control, and coexposure to fluoride elevated the positive cells than that in only low calcium diet group. The mRNA expression of osteopontin(OPN) and osteocalcin(OCN) in coexposure to fluoride with low-calcium group(1.36 ± 0.20, 1.31 ±0.11 ) was higher than that of the control groups (0.82 ± 0.16, 0.85 ± 0.15, all P ＜ 0.05) ; moreover, OPN expression significantly increased in this group than that of the only high fluoride group (0.97 ± 0.29, P ＜ 0.05). The mRNA expression of BiP in the low calcium and coposure to fluoride group (1.38 ± 0.24,1.35 ± 0.12) was significantly higher than that of the control group ( 1.14 ± 0.06, all P ＜ 0.05 ). Conclusions Higher fluoride or coexposure to low calcium diet stimulates the gene and protein expression in rat femur BiP, indicating that varying degrees of endoplasmic reticulum stress is likely involved in the pathogenesis of rat skeletal fluorosis.