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Objective To confirm the role of long noncoding RNA differentiation antagonizing non‐protein coding RNA (DANCR) in chondrocyte inflammatory injury in osteoarthritis (OA) in vitro, as well as its molecular mechanism. Methods Human primary chondrocytes were treated with lipopolysaccharide (LPS) to construct a chondrocyte inflammatory injury in human OA cell model. Gene expression was detected using real‐time quantitative polymerase chain reaction. Cell inflammatory injury was evaluated by Cell Counting Kit‐8 assay, flow cytometry, and enzyme‐linked immunosorbent assay. The interplay between miRNA‐19a‐3p (miR‐19a) and DANCR was validated by dual‐luciferase reporter assay and RNA immunoprecipitation. Results Expression of DANCR was upregulated, and miR‐19a was downregulated in human OA cartilage and LPS‐treated primary chondrocytes in vitro. Moreover, DANCR expression was inversely correlated with miR‐19a in OA patients. LPS reduced cell viability and increased the apoptotic rate and secretion of interleukin (IL)‐1β, IL‐6, IL‐8, as well as tumor necrosis factor (TNF)‐α in primary chondrocyte cells in vitro, suggesting an inflammatory injury model of OA. Functionally, knockdown of DANCR could attenuate LPS‐induced apoptosis and inflammatory response, as evidenced by improved cell viability, and reduced apoptotic rate and products of IL‐1β, IL‐6, IL‐8, and TNF‐α. Notably, DANCR negatively regulated miR‐19a expression, presumably via sponging. Furthermore, miR‐19a deletion eliminated the effect of DANCR knockdown on apoptosis and the inflammatory response of primary chondrocytes under LPS stress. Conclusion Differentiation antagonizing non‐protein coding RNA silencing could protect human chondrocyte cells against LPS‐induced inflammatory injury and apoptosis through targeting miR‐19a, suggesting a vital role of the DANCR/miR‐19a axis in OA., Highlights Expression of DANCR and miR‐19a was upregulated and downregulated in human OA cartilage, respectively.Silencing DANCR alleviated LPS‐induced apoptosis and inflammatory response in primary chondrocytes, which could be counteracted by deleting miR‐19a.DANCR functioned as a sponge for miR‐19a.

OBJECTIVES: Human milk (HM) lipids constitute the primary constituents of HM. Studies are starting to emerge about the lipid components of HM and how they relate to outcomes. We assessed the lipid differences between preterm and term HM and predicted the prospective impacts of these lipids on the development of neonates, especially focused on their immune modulatory and anti-infective effects. METHODS: Using an LC-MS/MS metabolomics strategy, we studied HM samples collected from 113 mothers giving birth prematurely (

Background Studies are beginning to emerge on the important biological effects of the milk lipids exerted on the recipient infant, especially on the premature infants. The aim of this study was to comprehensively describe lipidomic differences between preterm milk of different gestational ages with the term milk over the course of lactation. Methods Breast milk samples were collected from 88 mothers giving birth prematurely and 39 mothers delivering at full-term (FT). Lipid profiles were assessed using an LC-MS/MS metabolomics strategy. Orthogonal partial least-squares discriminant analysis (OPLS-DA) and pathway analysis were subsequently performed. Results The OPLS-DA score plots significantly distinguished the lipids in preterm milk of different gestation ages from their counterparts in term milk. The concentrations of 10 out of 43 lipid subclasses were found to be persistently higher in preterm compared to term milk over the course of lactation; the diacylglycerol (DAG) and a bioactive subclass fatty acid ester of hydroxyl fatty acid (FAHFA) contributed the most to the differences. In terms of individual lipid species, the ten highest substances found in very preterm (VPT) colostrum compared to FT colostrum mainly come from the phosphatidylethanolamine class and the DAG species. Lipid species from the free fatty acid and FAHFA classes were significantly higher in either extremely preterm (EPT) or VPT mature milk (variable importance in projection > 1, P

Breastfeeding has been shown to have a protective effect on the occurrence of necrotizing enterocolitis (NEC), but the mechanism remains unclear. In the context of NEC pathogenesis, many of the protective properties of exosomes on the intestinal epithelial compartment make it an ideal therapeutic target. In the present study, our hypothesis was that intestinal stem cells (ISCs) would be protected from injury by human milk-derived exosomes (HMDEs). Human breast milk was collected, and exosomes were isolated using ExoQuick reagent. Magnetic-activated cell sorting isolation of prominin-1+ ISCs was performed from small intestines of neonatal rat. ISCs were treated with or without H2O2, and HMDEs, an equal volume of HMDE-free milk, or a control solution [phosphate-buffered solution (PBS)] was added, respectively. In the absence of HMDEs, exposure of ISCs to H2O2 led to decreased cell viability. However, addition of HMDEs to ISCs exposed to H2O2 led to significantly increased ISC viability. There was a significant upregulation of mRNA expression of Axin2, c-Myc, and Cyclin D1 genes of the Wnt/β-catenin axis in ISCs treated with HMDEs (6.99 ± 2.34, 4.21 ± 1.68, 6.17 ± 2.22, respectively, P < 0.05 for all), as compared to control. In the presence of carnosic acid (a specific Wnt/β-catenin signaling inhibitor), the cell viability was significantly decreased. Thus, HMDEs protect ISCs from oxidative stress injury in vitro, which were possibly mediated via the Wnt/β-catenin signaling pathway. Our findings indicate that oral administration of HMDEs might be a promising measure in treating NEC or in preventing the development of NEC in high-risk infants when breast milk is not available.

In humans, breast cancer affects a large number of females and causes a high rate of mortality worldwide. Chemokine (C-C motif) ligand 5 (CCL5) is one of the cytokines that is highly correlated to the invasive and metastatic stages of breast cancer. Our previous study has suggested the prognostic value of CCL5 expression in luminal B (HER2−) breast cancer. In this study, CCL5 expression was upregulated or knockdown in a luminal B breast cancer cell line, ZR7530. Further, we elucidated the effects of CCL5 on the differentiation of THP-1 monocytes into M2 macrophages. Overexpression of CCL5 affected THP-1-M2 differentiation and phosphorylation of MEK1/2, ERK1/2, and STAT2 in the cocultivated cell lines. We report that the knockdown of CCR5, a receptor of CCL5 in THP-1, inhibited the effect of ZR7530 in promoting THP-1-M2 differentiation. Furthermore, our data revealed that the inhibition of MEK1/2 and STAT3 in THP-1 cells produced equivalent results similar to those of CCL5 knockdown. In summary, we revealed the role of CCL5 in the polarization of M2 macrophages. Furthermore, we studied its interaction with CCR5 and MEK/STAT3 signaling members. These targets could be used as key regulatory members in human breast cancer therapy.

The celebrated H-theorem of Boltzmann has important physical significance. The H-theorem states that entropy cannot diminish, and that the distribution function f(z, t) must tend towards its equilibrium state. In this paper, using the relationship between solutions of Boltzmann equation and the two-particle Boltzmann equation system, we obtain three forms of Two-Particle Boltzmann H-theorem from the two-particle Boltzmann equation system of BBGGKY hierarchy, and give an application example for the Two-Particle Boltzmann H-theorem. Also, the relation between entropy and the Two-Particle Boltzmann H-theorem is obtained.

The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and ZP4) and has an important role in reproduction. Here we describe a form of infertility with an autosomal recessive mode of inheritance, characterized by abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift mutation in ZP1 in six family members. In vitro studies showed that defective ZP1 proteins and normal ZP3 proteins colocalized throughout the cells and were not expressed at the cell surface, suggesting that the aberrant ZP1 results in the sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the zona pellucida around the oocyte.

Background: Genome-wide association studies identified that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) genetic polymorphisms are related to type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and pioglitazone efficacy in Chinese T2DM patients. Methods: A total of 281 T2DM patients and 111 healthy volunteers were enrolled to identify the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms; 86 patients were randomly selected and given a 12-week pioglitazone treatment (30 mg/day). Fasting plasma glucose, postprandial plasma glucose (PPG), glycated hemoglobin, serum triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-C) were determined before and after pioglitazone treatment. Results: The results showed that the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM in a Chinese population (OR = 2.002, 95% CI 1.170-3.426, p < 0.05; OR = 1.879, 95% CI 1.110-3.182, p < 0.05). The effect of pioglitazone on PPG (p < 0.05), TG (p < 0.01) and HDL-C (p < 0.05) was lower in patients with the rs1470579 AC+CC genotypes than in AA genotype carriers. Its effect on PPG level was also lower in patients with the GT+TT genotypes of rs4402960 than in patients with the GG genotype (p < 0.05). Conclusions: The IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and therapeutic efficacy of pioglitazone in this Chinese population. i 2014 S. Karger AG, Basel

Epilepsy is a chronic neurological illness, in which abnormal electrical activity in the brain causes involuntary changes in body movement, function, sensation, or behavior [1]. The World Health Organization estimates that epilepsy affects approximately 50 million people worldwide. Now‐a‐days, we recognize that genetic factors play an even more important role in the pathogenesis of epilepsy and drug efficacy than previously appreciated [1, 2]. Approximately, every second epileptic patient became resistant to the initial drugs [3]. Why so many epileptic patients show resistance against the antiepileptic drugs (AEDs) is not well‐understood. Some potential mechanisms have been suggested with regard to the targets and transporters of the drugs. The voltage‐gated ion channels are targets of some AEDs; alternations in the composition and functionality of them may lead to resistance in epileptic patients [4, 5]. The overexpression of ATP‐binding cassette (ABC) efflux transporters in the blood‐brain barrier (BBB), causing low‐drug concentration at their target, may be a potential mechanism [6]. Seizures, exposure to some AEDs such as carbamazepine, and genetic factors may influence the expression of transporters [7, 8, 9]. Some ABC transporters such as multidrug resistance 1 (MDR1, p‐glycoprotein, ABCB1), and a group of multidrug resistance proteins (MRPs, ABCCs), have been shown to mediate AEDs in brain [7, 9, 10]. These transporters are expressed in endothelial cells, astrocytes, and neurons of human brain tissues [11]. Therefore, these transporters may influence the efficacy of AEDs. Initial observation of the relationship between ABCB1 3435C>T and drug resistant epilepsy was followed by a number of studies to evaluate the single nucleotide polymorphism (SNP) as a predictor of AED resistance [12, 13]. However, some studies have conversely suggested no association between ABCB1 polymorphisms and the response to AEDs [14, 15]. Leschziner et al. studied a cohort of 503 epilepsy patients and found no evidence to support that ABCB1 common variation influences drug withdrawal outcomes [16]. ABCC2 is one of the ABC efflux transporters, whose role in human brain tissues is not fully understood due to its low expression in normal brain tissues [17]. But some studies found that the expression of ABCC2 was upregulated in the brain tissues of epileptic patients [18, 19]. Moreover, in the ABCC2‐deficient rat model, it is found that ABCC2 is involved in carbamazepine efficacy [20]. Recently, a study found a significant association between ABCC2 V417I polymorphism and reduced oral bioavailability of talinolol [21]. Kin et al. found that the ABCC2 1249G>A, and ABCB1 3435C>T, 1236C>T, 2677G>T/A polymorphisms were not associated with AED resistance in Japanese epileptic patients [22]. The study of Ufer et al. showed that a higher risk of AED failure in ABCC2−24T allele carriers is possible due to upregulation of ABCB1, but the mechanism is unknown [23]. Overall, whether the polymorphisms of these genes are associated with AED resistance is still not clear. To clarify whether ABCC2 and ABCB1 genes are involved in drug resistance epilepsy, we investigated the effects of ABCB1 rs1045642 and ABCC2 rs717620, rs3740066, and rs2273697 polymorphisms on AED resistance in Chinese epileptic patients.

Ginkgo biloba extract (GBE) is one of the most widely used herbal medicines in the world. It is often administered in combination with statins to treat diseases, especially some nervous system disorders. We aimed to investigate the influences of GBE on pharmacokinetics and efficacy of atorvastatin, which are currently unclear. Sixteen volunteers received a single oral dose of 40 mg atorvastatin, followed by a wash-out period of at least 5 days. Then the volunteers took 360 mg GBE daily for 14 days, followed by a single dose of 40 mg atorvastatin. Serial blood samples obtained over a period of 48 h after atorvastatin ingestion were subjected to determination of atorvastatin plasma concentrations and markers of cholesterol synthesis (lathosterol) and cholesterol absorption (sitosterol). With GBE administration, AUC₀₋₄₈, AUC(₀-∞) and C(max) of atorvastatin were reduced by 14.27% (p = 0.005), 10.00% (p = 0.03) and 28.93% (p = 0.002), respectively; Vd/F and CL/F of atorvastatin were increased by 31.95% (p = 0.017) and 6.48% (p = 0.044). After 14 days of treatment, GBE has no significant effects on cholesterol-lowering efficacy of atorvastatin. This study suggests that GBE slightly decreases the plasma atorvastatin concentrations, but has no meaningful effect on the cholesterol-lowering efficacy of atorvastatin.

As a common spectral characterization technique, Raman spectroscopy is widely used and has a specified calibration procedure. Based on laser confocal micro-Raman spectrometer, in this paper, we briefly introduced the principle, configuration and main components of Raman spectrometer. In addition, the calibration procedures were also presented, with an emphasis on the calibration of spectrometer (spectrograph) and that of excitation laser wavelength. On the basis of conventional calibration method, a novel and more accurate method was proposed to obtain the actual excitation wavelength, that is, calibration at the point of Raman shift Δν=0. Using this novel calibration method of excitation wavelength, Raman frequency shift values of sulfur were measured, and compared with the standard values from American Society Testing and Materials (ASTM). As a result, the measured values after calibration were consistent with those ASTM values, which indicated that the calibration method is accurate. Thus, a more reasonable calibration procedure of the laser confocal micro-Raman spectrometer was provided.

Polyalkylene glycols (PAGs) are a type of synthetic lubricants widely used as compressor lubricants, gear oils, hydraulic fluids, and metal working fluids. The PAGs with typical molecular structure can dissolve in water, which makes it a candidate for the base stock of water-based lubricants. Till now, most of the investigations on the water-based lubrication have focussed on the additives. In this work, the potential of PAGs aqueous solutions to replace water as base stocks has been investigated. Four types of PAGs with different molecular weight and their aqueous solutions with different concentrations were studied to reveal their elastohydrodynamic lubrication (EHL) behavior. It has been found that the PAGs solutions can form EHL film like traditional oils. The film-forming capability depends on the viscosity, the pressure–viscosity coefficient, and the molecular weight of PAGs. The results indicate that the PAGs aqueous solution can be employed as base stocks of water-based lubricant.

Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (eGFR) and carotid plaques, stenosis and occlusions, and to assess whether CKD and its severity affect carotid atherosclerosis in a cohort of unselected patients with acute stroke.A total of 249 consecutive patients with acute stroke (ischemic or hemorrhagic) were included in this study and baseline eGFR, carotid intima-media thickness (cIMT), and carotid stenosis were evaluated. The eGFR was calculated using the modified Modification of Diet in Renal Disease equation, which was adjusted for data from Chinese CKD patients. An eGFR rate of60 mL/min/1.73 m was defined as CKD. The cIMT and carotid plaques were detected by carotid ultrasound.CKD, defined as eGFR60 mL/min/1.73 m, was found in 66 individuals (26.50%). Among the 5 subtypes, the level of low-density lipoprotein cholesterol was significantly higher in the moderate and severe stenosis groups compared with the normal, elevated cIMT and mild stenosis groups (P0.01). The value of eGFR gradually decreased with increasing degree of carotid stenosis, and the differences between the groups were statistically significant (P0.01). On linear regression analysis, eGFR was negatively correlated with the degree of carotid stenosis (r=0.03; P0.05). On ordinal logistic regression analysis, eGFR was an independent risk factor associated with carotid atherosclerosis (1.05; 95% confidence interval, 0.47-1.63).There was a significant burden of atherosclerosis among individuals with CKD. CKD is an independent predictor of carotid plaques, stenoses, and occlusions in patients with acute stroke.

Menopause is one of the crucial physiological events during the life of a woman. Transition of menopause status is accompanied by increased risks of various health problems such as osteoporosis. Peripheral blood monocytes can differentiate into osteoclasts and produce cytokines important for osteoclast activity. With quantitative proteomics LC-nano-ESI-MS(E) (where MS(E) is elevated-energy MS), we performed protein expression profiling of peripheral blood monocytes in 42 postmenopausal women with discordant bone mineral density (BMD) levels. Traditional comparative analysis showed proteins encoded by four genes (LOC654188, PPIA, TAGLN2, YWHAB) and three genes (LMNB1, ANXA2P2, ANXA2) were significantly down- and upregulated, respectively, in extremely low- versus high-BMD subjects. To study functionally orchestrating groups of detected proteins in the form of networks, we performed weighted gene coexpression network analysis and gene set enrichment analysis. Weighted gene coexpression network analysis showed that the module including the annexin gene family was most significantly correlated with low BMD, and the lipid-binding related GO terms were enriched in this identified module. Gene set enrichment analysis revealed that two significantly enriched gene sets may be involved in postmenopausal BMD variation by regulating pro-inflammatory cytokines activities. To gain more insights into the proteomics data generated, we performed integrative analyses of the datasets available to us at the genome (DNA level), transcriptome (RNA level), and proteome levels jointly.

Genome-wide association studies identified that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) genetic polymorphisms are related to type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and pioglitazone efficacy in Chinese T2DM patients.A total of 281 T2DM patients and 111 healthy volunteers were enrolled to identify the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms; 86 patients were randomly selected and given a 12-week pioglitazone treatment (30 mg/day). Fasting plasma glucose, postprandial plasma glucose (PPG), glycated hemoglobin, serum triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-C) were determined before and after pioglitazone treatment.The results showed that the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM in a Chinese population (OR = 2.002, 95% CI 1.170-3.426, p0.05; OR = 1.879, 95% CI 1.110-3.182, p0.05). The effect of pioglitazone on PPG (p0.05), TG (p0.01) and HDL-C (p0.05) was lower in patients with the rs1470579 AC+CC genotypes than in AA genotype carriers. Its effect on PPG level was also lower in patients with the GT+TT genotypes of rs4402960 than in patients with the GG genotype (p0.05).The IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2DM and therapeutic efficacy of pioglitazone in this Chinese population.

The second mitochondria‑derived activator of caspases (Smac), an antagonist of the inhibitor of apoptosis protein (IAP), increases chemosensitivity in vitro. Survivin, an IAP family member, mediates cancer cell survival and chemoresistance. The present study investigated the correlation between Smac and survivin expression in primary breast cancer, and the sensitivity to anthracycline during neoadjuvant chemotherapy (NAC). Pre‑treatment biopsies and post‑anthracycline treatment tumor sections were analyzed from 98 cases. Biomarker expression was evaluated by immunohistochemistry in tumor samples from clinical stage II and III anthracycline‑based NAC‑treated breast cancer. A univariate analysis indicated that the estrogen receptor (ER), Smac and survivin were significantly predictive of a pathological complete response (pCR) (P=0.004, 0.001 and 0.037, respectively) in pre‑chemotherapy samples. ER, Smac and survivin expression was also significant for pCR on the multivariate analysis (P=0.001, 0.031 and 0.012, respectively). An inverse association was identified between survivin and Smac expression (r=‑0.217, P=0.032; and r=‑0.335, P=0.003, respectively) prior to and following NAC. The patients with low survivin expression or high Smac expression had significantly longer disease‑free survival (DFS; P=0.012 and P=0.020, respectively) and overall survival (OS; P=0.01 and P=0.033, respectively) compared with the patients with high survivin or low Smac expression. Cox regression analyses demonstrated that survivin, Smac and clinical stage were independent predictors for DFS and OS. The present study indicated the significance of Smac and survivin in determining the breast cancer response to anthracycline‑based chemotherapy, and may permit further stratifying of pre‑chemotherapy patients to undertake more tailored treatments.

Lipofectin-mediated gene transfer was used to introduce plasmid harboring the tyrosine hydroxylase (TH) gene into the striatum of rats with lesions of the nigrostriatal pathway. The rotational asymmetry of Parkinson disease model rat was reduced quickly and significantly, suggesting that plasmid–DNA-transfected brain cells can generate l-dopa locally in the striatum in quantities sufficient to compensate partially for the loss of intrinsic striatal dopaminergic input. Immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) also confirm that striatal cells can express exogenous TH gene. Such in vivo plasmid DNA transfer strategy may be useful in other neurologic disease therapy, especially acute brain insults.

To investigate the influence of peroxisome proliferator-activated receptor γ2 (PPAR-γ2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population. One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled. Among them, 67 type 2 diabetes patients were administered pioglitazone (30 mg/d, po) for 3 months. All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry. Fasting plasma glucose, postprandial plasma glucose, glycated hemoglobin, serum triglyceride, total cholesterol, low-density and high-density lipoprotein-cholesterol were determined. The PPAR-γ2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515, 95% CI 0.268–0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984, 95% CI 1.135–3.469) in a dominant model adjusted for age, gender and BMI. After pioglitazone treatment for 3 months, the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype. The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype. Diabetes risk alleles in PPAR-γ2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.

BACKGROUND β3-Adrenergic receptor (β3-AR) gene is associated with insulin resistance and may affect serum uric acid levels. Our aim was to determine the possible association between β3-AR gene Trp64Arg polymorphism (rs4994) and hyperuricemia in a Chinese male population. METHODS A total of 410 hyperuricemic and 420 normouricemic male subjects were genotyped in this study. The genotypic and allelic frequencies were compared between the two groups. Body mass index (BMI), waist to hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum uric acid, urea nitrogen, creatinine, triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and fasting plasma glucose (FPG) were determined. RESULTS The frequencies of CC genotype and C allele for Trp64Arg polymorphism were higher in hyperuricemic group than in normouricemic group (p

Objectives: To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H 2 O 2 , we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. Materials and methods: The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results: LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50 μmol/L or 100 μmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. Conclusions: LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

AIM: To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. METHODS: Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). RESULTS: Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11-3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44-4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17-0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. CONCLUSION: Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapy treatment for NSCLC patients in Asian population in the future.

The absorption change versus time after switching off the illumination on a polymeric film that contained a bacteriorhodopsin (BR) mutant has been measured. The M-lifetime of this BR mutant is ∼320 s. A pertinent Z-scan was performed to study the BR optical nonlinearity. A physical model with multi-level transitions in the Z-scan was suggested. The minimum saturated light intensity measured at 633 nm is ∼0.9 mW/cm2. A low intensity of 70 μW/cm2 has been used for recording in this film. The change in refraction index Δn633 is −3.0×10−3 and Δn476 is 8.5×10−3 with the intensity all at ∼100 mW/cm2.

Background Mounting clinical and experimental data suggest that the migration of tumor cells into lymph nodes is greatly facilitated by lymphangiogenesis. Vascular endothelial growth factor (VEGF)-C and D have been identified as lymphangiogenic growth factors and play an important role in tumor lymphangiogenesis. The purpose of this study was to investigate the location of lymphangiogenesis driven by tumor-derived VEGF-C/D in breast cancer, and to determine the role of intratumoral and peritumoral lymphatic vessel density (LVD) in lymphangiogenesis in breast cancer. Methods The expression levels of VEGF-C/D were determined by immunohistochemistry, and intratumoral LVD and peritumoral LVD were assessed using immunohistochemistry and the D2-40 antibody in 73 patients with primary breast cancer. The associations of intratumoral LVD and peritumoral LVD with VEGF-C/D expression, clinicopathological features and prognosis were assessed. Results VEGF-C and D expression were significantly higher in breast cancer than benign disease (P P P = 0.005) expression were significantly associated with peritumoral LVD, but not intratumoral LVD. Intratumoral LVD was associated with tumor size (P = 0.01). Peritumoral LVD was significantly associated with lymph node metastasis (LNM; P = 0.005), lymphatic vessel invasion (LVI; P = 0.017) and late tumor,node, metastasis (TNM) stage (P = 0.011). Moreover, peritumoral LVD was an independent risk factor for axillary lymph node metastasis, overall survival and disease-free survival in multivariate analysis. Conclusions This study suggests that tumor-derived VEGF-C/D induce peritumoral lymphangiogenesis, which may be one mechanism that leads to lymphatic invasion and metastatic spread. Peritumoral LVD has potential as an independent prognostic factor in breast cancer patients.