Quercetin-loaded nanoparticles enhance cytotoxicity and antioxidant activity on C6 glioma cells

Erdemir, Aysegul/0000-0002-6099-4903; Mansuroglu, Banu/0000-0001-8440-9118;WOS: 000524166500001PubMed: 32192406Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items. the dietary phytochemical quercetin prevents tumor proliferation and is a potent therapeutic cancer agent. the purpose of this study was to synthesize and characterize quercetin-loaded poly(lactic-co-glycolic acid) nanoparticles (Qu(1)NP, Qu(2)NP, and Qu(3)NP) with different size and encapsulation properties and to evaluate their in vitro activity on C6 glioma cells. Nanoparticles were synthesized by single emulsion solvent evaporation method. Then, particle size, zeta potential, polydispersity index and encapsulation efficiency of nanoparticles were determined. Particle size of Qu(1)NP, Qu(2)NP, and Qu(3)NPs were determined as 215.2 +/- 6.2, 282.3 +/- 7.9, and 584.5 +/- 15.2 nm respectively. Treating C6 glioma cells with all nanoparticle formulations effectively inhibited the cell proliferation. Qu(1)NPs were showed the lowest IC50 value in 48 h with 29.9 mu g/ml and achieved higher cellular uptake among other nanoparticles and Qu. Additionally, 48-h treatment with Qu(1)NPs significantly decreased MDA level (14.90 nmol/mu g protein) on C6 glioma cells which is related to reduced oxidative stress in cells. Findings of this study revealed that quercetin's cellular uptake and anti-oxidant activity is improved by small-sized Qu(1)NPs in C6 glioma cells.Research Foundation of Yildiz Technical UniversityYildiz Technical University [FKG-2017-3067]This work was supported by the Research Foundation of Yildiz Technical University under Grant [FKG-2017-3067]

Comparison of long-latency reflex and mixed nerve silent period responses in various hypokinetic movement disorders = A hosszú latenciájú reflexválaszoknak és a kevert idegek csendes periódusainak összehasonlítása különböző hipokinetikus mozgási rendellenességekben

Background and purpose – Long-latency reflex and mixed nerve silent period responses are electrophysiological methods to study the sensorimotor functions of the central nervous system. Here we aimed to study longlatency reflexes and mixed nerve silent period responses in different types of hypokinetic movement disorders in order to find an electrophysiological landmark to distinguish them. Methods – We included 39 patients with idiopathic Parkinson’s disease (IPD), 12 patients with multiple system atrophy (MSA), 10 patients with corticobasal syndrome (CBS), 5 patients with progressive supranuclear palsy (PSP) and 26 healthy participants. We recorded the segmental reflex, the long-latency reflexes and the mixed nerve silent period responses for each participant. Results – C reflex, long-latency reflex-I and long-latency reflex-III responses were not obtained in any patients with PSP. Long-latency reflex amplitude/ F amplitude ratio was significantly lower in patients with IPD and PSP compared to healthy individuals (p=0.036, p=0.006 respectively). The mixed nerve silent period end latencies were significantly longer in IPD, MSA, CBS groups compared to the healthy individuals (p=0.026, p=0.050, p=0.008 respectively). Conclusion – We suggest that recording long-latency reflex, particularly C reflex responses may provide promising results in distinction of CBS and MSA from PSP. Prospective studies with clinical findings and brainstem reflexes may offer more information. = Háttér és cél – A hosszú latenciájú reflexválaszoknak és a kevert idegek csendes periódusainak elektrofiziológiai módszerekkel való vizsgálata lehetôvé teszi a központi ideg rendszer szenzomotoros funkcióinak tanulmányozását. Jelen vizsgálatunk célja a hosszú latenciájú reflexválaszok és a kevert idegek csendes periódusainak összehasonlí - tása volt különbözô hipokinetikus mozgási rendelle nes sé - gekben, annak érdekében, hogy olyan elektrofiziológiai jeleket ta lál junk, amelyek alkalmasak megkülönböz te - tésükre. Módszerek – 39 idiopathiás Parkinson-kórban (IPD), 12 mul tiszisztémás atrófiában (MSA), 10 corticobasalis szind - rómában (CBS), 5 progresszív szupranukleáris paresisben (PSP) szenvedô beteget és 26 egészséges kontrollszemélyt vontunk be a vizsgálatba. Min den résztvevô esetében rögzítettük a szegmentális reflexet, a hosszú latenciájú reflexeket és a kevert idegek csendes periódusait. Eredmények – C-reflex-, hosszú latenciájú reflex-I- és hosszú latenciájú reflex-III-válaszokat nem kaptunk PSPben szenvedô betegeknél. A hosszú latenciájú reflex - amplitúdó/F-amplitúdó arány szignifikánsan alacsonyabb volt az IPD- és a PSP-bete geknél, mint az egészséges kont - rollszemélyek nél (p=0,036, p=0,006). A kevert idegek csendes perió du sának végén je lent kezô latenciák szignifikánsan hosszabbak voltak az IPD-, az MSA- és a CBScsoportokban, mint az egészséges kont roll személyeknél (p=0,026, p=0,050, p=0,008). Következtetés – Véleményünk szerint a hosszú latenciájú ref lexválaszok, különösen a C-reflex-válaszok rögzítése ígé retes eszköz lehet a CBS és az MSA PSP-tôl való megkülönböztetésében. A klinikai leleteket és az agytörzsi reflex válaszokat egyaránt tartalmazó, prospektív vizsgálatok további információt nyújthatnak

Mentalis muscle related reflexes

The mentalis muscle (MM) arises from the incisive fossa of the mandible, raises and protrudes the lower lip. Here, we aim to characterize responses obtained from MM by supraorbital and median electrical as well as auditory stimuli in a group of 16 healthy volunteers who did not have clinical palmomental reflex. Reflex activities were recorded from the MM and orbicularis oculi (O.oc) after supraorbital and median electrical as well as auditory stimuli. Response rates over MM were consistent after each stimulus, however, mean latencies of MM response were longer than O.oc responses by all stimulation modalities. Shapes and amplitudes of responses from O.oc and MM were similar. Based on our findings, we may say that MM motoneurons have connections with trigeminal, vestibulocochlear and lemniscal pathways similar to other facial muscles and electrophysiological recording of MM responses after electrical and auditory stimulation is possible in healthy subjects

Comparative evaluation of hesperetin loaded nanoparticles for anticancer activity against C6 glioma cancer cells

WOS: 000457571200002PubMed ID: 30688095The aim of this study was to evaluate anti-cancer properties of hesperetin (Hsp) and hesperetin-loaded poly(lactic-co-glycolic acid) nanoparticles (HspNPs) for glioblastoma treatment. Nanoparticles prepared by single emulsion method had a size of less than 300nm with 70.7 +/- 3.9% reaction yield and 26.4 +/- 1.1% Hsp loading capacity. Treatment of C6 glioma cells with HspNPs for 24 and 48 h resulted in dose- and time-dependent decrease in cell viability, with approximate IC50 of 28 and 21 mu g/mL, respectively (p = .036 for 24 h, p = .025 for 48 h). The percentage of PCNA positive cells decreased to 20% and 10%, respectively, for Hsp- and HspNP-treated cells at concentration of 100 mu g/mL. Treatment with increasing concentrations of HspNPs (25, 50, 75 and 100 mu g/mL) resulted in 9.1-, 7-, 12.5- and 12.7-fold in increase in apoptotic cell number. Optimum doses of Hsp and HspNPs were found to increase oxidative damage in C6 glioma cells. MDA levels, an indicator of lipid peroxidation, were found to be significantly elevated at 75 and 100 mu g/mL exposure concentration of HspNPs with (p = .002) and (p = .018), respectively for 48-h treatment. The results obtained with this study showed biocompatible polymeric nanoparticle systems has great advantages to enhance anti-cancer activity and poor solubility of therapeutic agents. Overall our findings suggest that Hsp-loaded PLGA nanoparticle systems showed significant anti-cancer activity and HspNPs could be used as promising novel anti-cancer agent

Neurological Level in Spinal Cord Injury: Comparison Between ASIA Standards and Transcranial Magnetic Stimulation

Objective: The aim of the present study was to compare the findings of neurological examination performed according to the American Spinal Injury Association (ASIA) Standards with Motor Evoked Potentials (MEPs) obtained from paravertebral muscles of complete traumatic spinal cord injured (SCI) patients by using Transcranial Magnetic Stimulation (TMS)

Bronchopulmonary dysplasia and wnt pathway-associated single nucleotide polymorphisms.

AIM: Genetic variants contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to evaluate the association of 45 SNPs with BPD susceptibility in a Turkish premature infant cohort. METHODS: Infants with gestational age <32 weeks were included. Patients were divided into BPD or no-BPD groups according to oxygen need at 28 days of life, and stratified according to the severity of BPD. We genotyped 45 SNPs, previously identified as BPD risk factors, in 192 infants. RESULTS: A total of eight SNPs were associated with BPD risk at allele level, two of which (rs4883955 on KLF12 and rs9953270 on CHST9) were also associated at the genotype level. Functional relationship maps suggested an interaction between five of these genes, converging on WNT5A, a member of the WNT pathway known to be implicated in BPD pathogenesis. Dysfunctional CHST9 and KLF12 variants may contribute to BPD pathogenesis through an interaction with WNT5A. CONCLUSIONS: We suggest investigating the role of SNPs on different genes which are in relation with the Wnt pathway in BPD pathogenesis. We identified eight SNPs as risk factors for BPD in this study. In-silico functional maps show an interaction of the genes harboring these SNPs with the WNT pathway, supporting its role in BPD pathogenesis. TRIAL REGISTRATION: NCT03467828. IMPACT: It is known that genetic factors may contribute to the development of BPD in preterm infants. Further studies are required to identify specific genes that play a role in the BPD pathway to evaluate them as a target for therapeutic interventions. Our study shows an association of BPD predisposition with certain polymorphisms on MBL2, NFKBIA, CEP170, MAGI2, and VEGFA genes at allele level and polymorphisms on CHST9 and KLF12 genes at both allele and genotype level. In-silico functional mapping shows a functional relationship of these five genes with WNT5A, suggesting that Wnt pathway disruption may play a role in BPD pathogenesis

Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration.Peer reviewe

Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging

Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration. Mihaylova et al. show that short-term fasting promotes intestinal stem and progenitor cell function in young and aged mice by inducing a robust fatty acid oxidation (FAO) program. PPARδ agonists emulate these effects, showing that fatty acid metabolism has positive effects on young and old ISCs.National Institutes of Health (U.S.) (Grant R00 AG045144)National Institutes of Health (U.S.) (Grant R01CA211184)National Institutes of Health (U.S.) (Grant R01CA034992)National Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (K99 Pathway to Independence award K99AG054760