Molecular Recognition of Arginine by Supramolecular Complexation with Calixarene Crown Ether Based on Surface Plasmon Resonance

Arginine plays an important role in cell division and the functioning of the immune system. We describe a novel method by which arginine can be identified using an artificial monolayer based on surface plasmon resonance (SPR). The affinity of arginine binding its recognition molecular was compared to that of lysine. In fabrication of an arginine sensing interface, a calix[4]crown ether monolayer was anchored onto a gold surface and then characterized by Fourier Transform infrared reflection absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The interaction between arginine and its host compound was investigated by SPR. The calix[4]crown ether was found to assemble as a monolayer on the gold surface. Recognition of calix[4]crown monolayer was assessed by the selective binding of arginine. Modification of the SPR chip with the calix[4]crown monolayer provides a reliable and simple experimental platform for investigation of arginine under aqueous conditions

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; Pheterogeneity=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; Pheterogeneity=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; Pheterogeneity=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; Pheterogeneity=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer

Seed Dormancy-Life Form Profile for 358 Species from the Xishuangbanna Seasonal Tropical Rainforest, Yunnan Province, China Compared to World Database

Seed dormancy profiles are available for the major vegetation regions/types on earth. These were constructed using a composite of data from locations within each region. Furthermore, the proportion of species with nondormant (ND) seeds and the five classes of dormancy is available for each life form in each region. Using these data, we asked: will the results be the same if many species from a specific area as opposed to data compiled from many locations are considered? Germination was tested for fresh seeds of 358 species in 95 families from the Xishuangbanna seasonal tropical rainforest (XSTRF): 177 trees, 66 shrubs, 57 vines and 58 herbs. Seeds of 12.3% of the species were ND, and 0.3, 14.8, 60.6, 12.0 and 0% of the species had morphological (MD), morphophysiological (MPD), physiological (PD), physical (PY), and combinational (PY + PD) dormancy, respectively. PD was more important than ND in all life forms, PY was highest in shrubs, MD was not important in any life form and MPD was most common for herb and vines. The seed dormancy profile for XSTRF differs considerably from the composite profile for this vegetation type worldwide, most obviously in ND being much lower and PD much higher in XSTRF

Effects of dietary energy level on antioxidant capability, immune function and rectal microbiota in late gestation donkeys

IntroductionThis study investigated the effects of dietary energy level on the antioxidant capability, immune function, and rectal microbiota in donkey jennets during the last 60 days of gestation.MethodsFifteen pregnant DeZhou donkeys with age of 6.0 ± 0.1 years, body weight of 292 ± 33 kg, parity of 2.7 ± 0.1 parities and similar expected date of confinement (74 ± 4 days) were randomly allocated to three groups and feed three diets: high energy (10.92 MJ/kg, H), medium energy (10.49 MJ/kg, M), and low energy (9.94 MJ/kg, L).Results and DiscussionThe serum activity of catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in group M was significantly higher, whereas the concentrations of malondialdehyde (MDA), interleukin 1 (IL-1), IL-2, and IL-6 were lower than those recorded for groups H and L (p ≤ 0.05). The dietary energy level significantly affected rectal microbial community structure in the jennet donkeys 35 days and 7 days before the parturition (p ≤ 0.05). The abundances of norank_f_norank_o_Coriobacteriales genus was significantly higher (p ≤ 0.05) in group H, and the abundances of norank_f_norank_o_Mollicutes_RF39 and the Candidatus_Saccharimonas were higher in group L (p ≤ 0.05). The abundance of Fibrobacter in group M was significantly increased (p ≤ 0.05). The abundance of norank_f_norank_o_Coriobacteriales was positively correlated with average daily gain (ADG) and tumor necrosis factor-α (TNF-α) concentrations (p ≤ 0.05). The abundance of norank_f_norank_o_Mollicutes_RF39 was positively correlated with IL-2 and IL-6 concentrations. The abundance of Candidatus_Saccharimonas was positively correlated with CAT, T-SOD and GSH-Px activities (p ≤ 0.05). The abundance of Fibrobacter was positively correlated with CAT and T-SOD activities (p ≤ 0.05), but negatively correlated with IL-2 concentration (p ≤ 0.05). In conclusion, an appropriate dietary with an energy content of 10.49 MJ/kg for jennet donkeys during late gestation increased the prenatal antioxidant capacity, reduced inflammatory cytokines, and promoted fetal growth, and these changes were related to diet-induced changes in rectal microbiota compositions

Heparan sulfate promotes TRAIL-induced tumor cell apoptosis

TRAIL (TNF-related apoptosis-inducing ligand) is a potent inducer of tumor cell apoptosis through TRAIL receptors. While it has been previously pursued as a potential anti-tumor therapy, the enthusiasm subsided due to unsuccessful clinical trials and the fact that many tumors are resistant to TRAIL. In this report, we identified heparan sulfate (HS) as an important regulator of TRAIL-induced apoptosis. TRAIL binds HS with high affinity (KD = 73 nM) and HS induces TRAIL to form higher-order oligomers. The HS-binding site of TRAIL is located at the N-terminus of soluble TRAIL, which includes three basic residues. Binding to cell surface HS plays an essential role in promoting the apoptotic activity of TRAIL in both breast cancer and myeloma cells, and this promoting effect can be blocked by heparin, which is commonly administered to cancer patients. We also quantified HS content in several lines of myeloma cells and found that the cell line showing the most resistance to TRAIL has the least expression of HS, which suggests that HS expression in tumor cells could play a role in regulating sensitivity towards TRAIL. We also discovered that death receptor 5 (DR5), TRAIL, and HS can form a ternary complex and that cell surface HS plays an active role in promoting TRAIL-induced cellular internalization of DR5. Combined, our study suggests that TRAIL-HS interactions could play multiple roles in regulating the apoptotic potency of TRAIL and might be an important point of consideration when designing future TRAIL-based anti-tumor therapy

Therapeutic strategies targeting folate receptor α for ovarian cancer

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration

The Role of FGFR1 Gene Amplification as a Poor Prognostic Factor in Squamous Cell Lung Cancer: A Meta-Analysis of Published Data

Objectives. The prognostic factors of the fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) remain controversial. Methods. We conducted a meta-analysis of published studies from 1974 to February 2015. In absence of quality difference between studies of reporting significant and nonsignificant results, the relationship between FGFR1 amplification and clinicopathological parameters in NSCLC was analyzed. And also the combined hazard ratio (HR) and their corresponding 95% confidence interval (CI) were calculated in terms of overall survival. Results. 3178 patients (12 studies) were included in the analysis. It was shown that FGFR1 amplification was significantly more prevalent among male patients (RR 2.03, 95% CI 1.57-2.63) with squamous cell lung cancer (SQCC) (RR 3.49, 95% CI 2.62-4.64) and current smokers (RR 2.63, 95% CI 1.92-3.60). The pooled data also showed that the FGFR1 amplification was a poor prognostic factor in SQCC (HR 1.38, 95% CI 1.07-1.78), Asian patients (HR 1.78, 95% CI 1.22-2.60), and fluorescence in situ hybridization (FISH) method (HR 1.30, 95% CI 1.06-1.58). Conclusions. This meta-analysis strongly suggests that FGFR1 amplification occurs more frequently in male, SQCC and smokers, and it is a risk factor for poor prognosis among Asian patients with SQCC

The effects of weight loss and improved metabolic health status on the risk of non-alcoholic fatty liver disease—results from a prospective cohort in China

BackgroundThe impact of weight loss and/or improved metabolic status on the risk of non-alcoholic fatty liver disease (NAFLD) has yet to be determined.MethodsA total of 35,322 participants without NAFLD were followed. NAFLD risk was compared between consistently metabolically healthy non-obese (MHNO) and non-MHNO who lost weight to become non-obese and/or improved their metabolic health, using Cox proportional hazards and logistic regression models.ResultsFollowing 148,186 person-years, 8,409 participants had onset NAFLD, with an incidence rate of 56.75 (95% CI: 55.57, 57.94) per 1,000 person-years. Metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), and metabolically unhealthy non-obese (MUNO) at baseline were associated with increased NAFLD risk, with hazard ratios of 4.48 (95%CI:4.24, 4.73), 8.85 (95%CI:7.95, 9.84), and 10.70 (95%CI:9.73, 11.78). Weight loss and/or metabolic status improvements could significantly reduce NAFLD risk by 79.46 to 41.46%. Specifically, after weight loss from MHO to MHNO, the reduction in NAFLD risk [OR decreased from 12.01 (95%CI:9.40, 15.35) to 4.14 (95%CI:3.08, 5.57)] was greater than that of the MUNO subgroup whose metabolic status improved to MHNO [OR decreased from 5.53 (95%CI:5.15, 5.94) to 2.71 (95%CI:2.50, 3.93)]. In the MUO subgroup, the group with the greatest risk reduction of NAFLD was the weight and metabolic state both improvement group [MUO to MHNO, OR decreased from 22.74 (95%CI:17.61, 29.37) to 4.67 (95%CI:3.05, 7.16)], followed by the weight loss only group [MUO to MUNO, OR decreased to 6.83 (95%CI:4.87, 9.57)], and finally the group with the least and insignificant risk reduction was the metabolic state improvement group [MUO to MHO, OR decreased to 13.38 (95%CI:9.17,19.53)]. NAFLD risk was negatively correlated with the duration of improvement (p < 0.001).ConclusionIndividuals with non-MHNO were more likely to develop NAFLD than those with consistent MHNO, but metabolic improvements and weight loss can alleviate the risk. Their NAFLD risk was negatively correlated with improvement duration. However, it remained higher than in individuals with consistent MHNO at an average follow-up of 4.2 years