Methodological Considerations of Electron Spin Resonance Spin Trapping Techniques for Measuring Reactive Oxygen Species generated from metal oxide nanomaterials

Qualitative and quantitative analyses of reactive oxygen species (ROS) generated on the surfaces of nanomaterials are important for understanding their toxicity and toxic mechanisms, which are in turn beneficial for manufacturing more biocompatible nanomaterials in many industrial fields. Electron spin resonance (ESR) is a useful tool for detecting ROS formation. However, using this technique without first considering the physicochemical properties of nanomaterials and proper conditions of the spin trapping agent (such as incubation time) may lead to misinterpretation of the resulting data. In this report, we suggest methodological considerations for ESR as pertains to magnetism, sample preparation and proper incubation time with spin trapping agents. Based on our results, each spin trapping agent should be given the proper incubation time. For nanomaterials having magnetic properties, it is useful to remove these nanomaterials via centrifugation after reacting with spin trapping agents. Sonication for the purpose of sample dispersion and sample light exposure should be controlled during ESR in order to enhance the obtained ROS signal. This report will allow researchers to better design ESR spin trapping applications involving nanomaterials

PI3K-mTOR-S6K Signaling Mediates Neuronal Viability via Collapsin Response Mediator Protein-2 Expression

Collapsin response mediator protein (CRMP)-2 and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway are associated with common physiological functions such as neuronal polarity, axonal outgrowth and synaptic strength, as well as various brain disorders including epilepsy. But, their regulatory and functional links are unclear. Alterations in CRMP-2 expression that lead to its functional changes are implicated in brain disorders such as epilepsy. Here, we investigate whether changes in CRMP-2 expression, possibly regulated by mTOR-related signaling, correlates with neuronal growth and viability. Inhibition of mTOR and/or phosphoinositol-3-kinase (PI3K) led to deceased p-S6K, and p-S6 signals also reduced CRMP-2 expression. These changes corresponded to inhibition of neuronal viability and proliferation in cultured hippocampal HT-22 cells under both basal serum-free and serum- or insulin-induced mTOR pathway-activated conditions. CRMP-2 expression tended to be increased by mTOR activation, indicated by an increase in p-S6/S6 level, in pentylentetrazole (PTZ)-induced epileptic rat hippocampal tissues was also significantly reduced by mTOR inhibition. Knockdown of CRMP-2 by si-RNA reduced the neuronal viability without changes in mTOR signaling, and overexpression of CRMP-2 recovered the glutamate-induced neurotoxicity and decrease of mTOR signaling in HT-22 cells. In conclusion, CRMP-2 protein expression controlled by the PI3K-mTOR-S6K signaling axis exerts its important functional roles in neuronal growth and survival

Serum immunoglobulin fused interferon-α inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 × : 30 µg/kg and 50 × : 150 µg/kg). A slight anti-tumoral effect was observed in all 10 × groups compared to the control. In the 50 × groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-β. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition

2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk

Low dietary inorganic phosphate affects the lung growth of developing mice

Inorganic phosphate (Pi) plays a critical role in diverse cellular functions, and regulating the Pi balance is accomplished by sodium-dependent Pi co-transporter (NPT). Pulmonary NPT has recently been identified in mammalian lungs. However, to date, many of the studies that have involved Pi have mainly focused on its effect on bone and kidney. Therefore, current study was performed to discover the potential effects of low Pi on the lung of developing transgenic mice expressing the renilla/firefly luciferase dual reporter gene. Two-weeks old male mice divided into 2 groups and these groups were fed either a low PI diet or a normal control diet (normal: 0.5% Pi, low: 0.1% Pi) for 4 weeks. After 4 weeks of the diet, all the mice were sacrificed. Their lungs were harvested and analyzed by performing luciferase assay, Western blotting, kinase assay and immunohistochemistry. Our results demonstrate that low Pi affects the lungs of developing mice by disturbing protein translation, the cell cycle and the expression of fibroblast growth factor-2. These results suggest that optimally regulating Pi consumption may be important to maintain health

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated

Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent

Sgs1 and Exo1 Redundantly Inhibit Break-Induced Replication and De Novo Telomere Addition at Broken Chromosome Ends

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5′ to 3′ resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Δ exo1Δ strains, where there is little 5′ to 3′ resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Δ, or exo1Δ cells. In sgs1Δ exo1Δ, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 5′ to 3′ resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5′ to 3′ resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition

Social Determinants of Voice Outcomes: The Configurational Analysis of the Effects of LMX and Peer Relationships

From the perspective of social relationships, this study extends the understanding of employee voice by examining voice outcomes, especially a voicer&rsquo;s influence in their work team. In particular, we explore how two different social relationships, LMX and peer relationship, separately and jointly affect the &lsquo;voice-influence&rsquo; relationship. Drawing on social network theory, we propose that higher LMX and central positions in peer networks (i.e., centrality in the friendship network) strengthen the positive impact of voice on individual influence. From a sample of 128 employees from three firms in South Korea, we found that two types of voice (promotive and prohibitive) are positively related with individual influence. This study also found that LMX strengthened the positive effect of promotive voice on a voicer&rsquo;s influence. Moreover, LMX and peer relationship jointly affect the voice-influence relationship as follows: (1) a voicer with a high LMX-high centrality (in the peer network) is most influential within their team, (2) as for a low LMX-high centrality member, speaking up rather decreases individual influence. These results suggest that voice outcome is not unilateral. Rather, whose voice it is and where a voicer stands may matter more. We discussed the theoretical and practical implications of these findings in employee voice research