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Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions involved in vasodilation, inflammation, oxidative stress, cardioprotection and neuroprotection. It has been demonstrated that intravenous and volatile anesthetics (such as propofol, ketamine, midazolam, isoflurane, sevoflurane, and desflurane, etc.) modulate NO production through multiple mechanisms that may influence physiological and pathophysiological processes. This review focuses on the effects of different anesthetics on NO/NOS regulation in different disease conditions. Possible cellular mechanisms and intermediate role of NO/NOS in anesthetic-mediated organ protection are also discussed. It would be interesting to clarify the impact of anesthetics on NO/NOS regulation. This review gives an overview of the effects of different anesthetics on NO/NOS regulation and function in different physiologic and pathophysiologic states., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Sialyllactose is a key human milk oligosaccharide and consists of sialic acid (SA) bound to a lactose molecule. Breastfed infants have increased accumulation of ganglioside-bound SA compared with formula-fed infants., Objective: This study aimed to determine whether different isomers of sialyllactose enrich brain SA and modulate the microbiome of developing neonatal piglets., Methods: Day-old pigs were randomly allocated to 6 diets (control, 2 or 4 g 3'-sialyllactose/L, 2 or 4 g 6'-sialyllactose/L, or 2 g polydextrose/L + 2 g galacto-oligosaccharides/L; n = 9) and fed 3 times/d for 21 d. Pigs were killed, and the left hemisphere of the brain was dissected into cerebrum, cerebellum, corpus callosum, and hippocampus regions. SA was determined by using a modified periodic acid-resorcinol reaction. Microbial composition of the intestinal digesta was analyzed with the use of 16S ribosomal DNA Illumina sequencing., Results: Dietary sialyllactose did not affect feed intake, growth, or fecal consistency. Ganglioside-bound SA in the corpus callosum of pigs fed 2 g 3'-sialyllactose or 6'-sialyllactose/L increased by 15% in comparison with control pigs. Similarly, ganglioside-bound SA in the cerebellum of pigs fed 4 g 3'-sialyllactose/L increased by 10% in comparison with control pigs. Significant (P < 0.05, Adonis Test) microbiome differences were observed in the proximal and distal colons of piglets fed control compared with 4-g 6'-sialyllactose/L formulas. Differences were attributed to an increase in bacterial taxa belonging to species Collinsella aerofaciens (phylum Actinobacteria), genera Ruminococcus and Faecalibacterium (phylum Firmicutes), and genus Prevotella (phylum Bacteroidetes) (Wald test, P < 0.05, DeSeq2) compared with piglets fed the control diet. Taxa belonging to families Enterobacteriaceae and Enterococcaceae (phylum Proteobacteria), as well as taxa belonging to family Lachnospiraceae and order Lactobacillales (phylum Firmicutes), were 2.3- and 4-fold lower, respectively, in 6'-sialyllactose-fed piglets than in controls., Conclusions: Supplementation of formula with 3'- or 6'-sialyllactose can enrich ganglioside SA in the brain and modulate gut-associated microbiota in neonatal pigs. We propose 2 potential routes by which sialyllactose may positively affect the neonate: serving as a source of SA for neurologic development and promoting beneficial microbiota., (© 2016 American Society for Nutrition.)

Background: Human chromosome 9q33.3 is one of the most important loci for pathophysiological stresses with complex genetic traits. We hypothesized that the common single-nucleotide polymorphisms on this region may affect non-small-cell lung cancer risk., Methods: We genotyped 43 single-nucleotide polymorphisms that span 13 genes on 9q33.3 in two independent cohorts: the discovery study including 485 cases and 532 controls (North China) and the replicative study including 1063 cases and 1247 controls (South China). Both of the discovery cohort and the replicative cohort were included in the combined study., Results: In the discovery study, we identified a potential protective locus rs10118570 in mitogen-activated protein kinase associated protein 1 with a lower population attributable risk under logistical regression adjusted by age, gender, smoking, and drinking status (adjusted odds ratio [OR] 0.26, 95% confidence interval [CI] 0.10-0.71, p = 1.138 × 10 for genotype GG in lung squamous cell carcinoma). This protective quality increased in a dose-dependent manner as genotype GG decreased (ptrend = 9.675 × 10). Replicative and combined studies showed consistent association for this genotype (replicative: adjusted OR 0.36, 95% CI 0.20-0.66, p = 6.109 × 10, ptrend = 7.386 × 10; combined: adjusted OR 0.33, 95% CI 0.18-0.55, p = 1.259 × 10, ptrend = 7.725 × 10)., Conclusion: We concluded that mitogen-activated protein kinase associated protein 1 rs10118570 may be an important protective factor for developing better management strategies in lung squamous cell carcinoma.

Background: Glucose-regulated protein 78 (GRP78) is involved in not only the progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78 affects survival among patients with NSCLC treated with platinum-based chemotherapy., Methods: Blood samples of patients with advanced NSCLC (IIIB/IV) were maintained in our specimen bank between 2001 and 2006. Genomic DNA was genotyped for rs430397. Associations between rs430397 and platinum-based treatment response, overall survival (OS), NSCLC-related survival, progression-free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC tissues were tested by real-time polymerase chain reaction and immunohistochemistry., Results: The AA genotype is significantly associated with platinum-based chemoresistance (P = .019) and NSCLC-related death (P = .022). OS, NSCLC-related survival, and PFS of the AA genotype group are decreased compared with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group showed a higher prevalence of early NSCLC relapses than the AG and GG group (P = .030). In addition, the AA genotype showed a significantly increased risk for OS (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group. Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78 RNA and protein expression compared with those carrying GG at rs430397., Conclusions: The rs430397 AA genotype of GRP78 is associated with reduced survival and higher prevalence of early relapses in patients with advanced NSCLC treated with platinum-based chemotherapy.

Nitric oxide (NO) is a free radical gas that has been shown to be produced by nitric oxide synthase (NOS) in different cell types and recognized to act as a neurotransmitter or neuromodulator in the nervous system. NOS isoforms are expressed and/or can be induced in the related structures of trigeminal nerve system, in which the regulation of NOS biosynthesis at different levels of gene expression may allow for a fine control of NO production. Several lines of evidence suggest that NO may play a role through multiple mechanisms in orofacial pain processing. This report will review the latest evidence for the role of NO involved in orofacial pain and the potential cellular mechanisms are also discussed., (Copyright © 2011 Elsevier Inc. All rights reserved.)