Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines

RON receptor tyrosine kinase is a transmembrane protein directly involved in suppression of inflammation and its aberrant expression linked to cancers and metastasis. Efforts to block deregulated RON signaling in tumors using small molecule kinase inhibitors or antibodies have been complicated by the presence of unknown number/types of isoforms of RON, which, despite being structurally similar, localize differently and mediate varied functions. Current study was designed to identify the splice variants of RON transcripts formed by skipping of sequences between exons 9 and 14 for better understanding of isoform specific RON signaling in cancers. PCR amplification and bi-directional sequencing of a 901 bp cDNA sequence located between exons 9 to 14 of RON from lung cancer cell lines revealed the presence of two splicing variants formed by skipping of exons 11 and 11–13. Each of these transcripts was found in more than one cell line. Expressed sequence tag (EST) database search indicated that the splicing variant lacking exons 11–13 was a novel one. Here we conclude that the splice variants of RON lacking exon 11 and exons 11–13 were detected in several lung cancer cell lines. Novel variant formed by skipping exons 11–13, the sequence of which code for transmembrane region, is predicted to code for a truncated isoform that may be secreted out. Tumors may antagonize the ligand dependent anti-inflammatory function of wild-type RON by secreting out the ligand binding isoforms

Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects

Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m2) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05), insulin (r = −0.230, p < 0.01) and HOMA-IR (r = −0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01), insulin (r = −0.248, p < 0.01), HOMA-IR (r = −0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r2 = −0.17, p < 0.05) and in children (r2 = −0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r2 = −0.78, p < 0.05). Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population

SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects

Background: Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population. Methods: Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected. Results: Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016). Conclusions: SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin

Favorable Changes in Fasting Glucose in a 6-month Self-Monitored Lifestyle Modification Programme Inversely Affects Spexin Levels in Females with Prediabetes

Spexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body-weight regulatory functions, we aimed to determine whether lifestyle intervention programs on weight loss and fasting glucose (FG) improvement among people with impaired glucose regulation also alter levels of circulating SPX. A total of 160 Saudi adult males and females with prediabetes were randomly selected from a larger cohort (N = 294) who underwent a 6-month lifestyle modification program to improve their glycemic status. Participants were split into two groups based on differences in glucose levels post-intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured at baseline and after 6 months. Changes in SPX was significant only in the improved group [baseline: median (Q1\u2013Q3) of 164 pg/ml (136\u2013227) vs follow-up: 176 pg/ml (146\u2013285); p &lt; 0.01]. When stratified by sex, the significant increase was observed only in females [159 pg/ml (127\u2013252) vs 182.5 (152,369.1); p &lt; 0.01]. Furthermore, SPX levels showed a significant inverse association with FG (\u3b2 = 120.22, p = 0.003) even after adjustment with age and BMI, again only in females. Circulating SPX levels increase over time in people with prediabetes, particularly women who responded favorably in a 6-month lifestyle intervention program. Whether an unknown mechanism regulating the sexual disparity seen in SPX levels post-intervention exists should be further investigated using a larger sample size

Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18\u201322) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in \u2013vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and \u2013vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women

Pitfalls in the measurement of muscle mass: a need for a reference standard

Background All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. Methods Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face‐to‐face meetings were organized for the whole group to make amendments and discuss further recommendations. Results A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X‐ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. Conclusions Based on the feasibility, accuracy, safety, and low cost, dual energy X‐ray absorptiometry can be considered as the reference standard for measuring muscle mass

Vanhemmuus - yksi elämän vaativimpia tehtäviä : opas 0-3 kk ikäisen lapsen vanhemmille

Vanhemmuuden käsite ja odotukset ovat muuttuneet viimeisen sadan vuoden aikana. Painetta vanhemmuudelle luovat niin yhteiskuntapolitiikka kuin työelämäkin. Vanhemmat ovat entistä enemmän huolissaan omasta kelpoisuudestaan vanhempana. Myös huoli omasta jaksamisesta vanhempana on yleistä. Toimeentulo, työn vaatimukset ja vanhempien oma terveys huolestuttavat ja kuormittavat nykyvanhempia. Suuri osa vanhemmista tarvitsee tukea vanhemmuuteensa. Tukea kaivataan muun muassa konkreettisiin asioihin kuten lapsen kasvatukseen ja perushoitoon. Tämän opinnäytetyön tavoitteena oli tukea vanhempia heidän vanhemmuudessaan ja arjessaan lapsen kanssa. Opinnäytetyön tarkoituksena oli luoda terveyskasvatusmateriaali verkkoon Naantalin terveyskeskukselle. Terveyskasvatusmateriaali on tarkoitettu tueksi vastasyntyneen vauvan vanhemmille sekä tiedon lähteeksi. Materiaali julkaistaan verkko-oppaana, jolloin se on helposti saatavilla ja päivitettävissä. Oppaassa on kustakin aiheesta pieni alustus sekä linkkejä, jotka johdattavat vanhemmat lisätiedon äärelle. Opinnäytetyömme on menetelmältään toiminnallinen ja se on toteutettu yhteistyössä Naantalin terveyskeskuksen kanssa. Opinnäytetyö kuuluu Turun ammattikorkeakoulun ”Terveesti tulevaisuuteen” – hankkeeseen, joka on osa Turun ammattikorkeakoulun lakisääteistä tutkimus-, kehitys- ja innovaatiotoimintaa (TKI). Opinnäytetyömme toteutettiin kahdessa osassa. Ensimmäisen osan tuotos eli verkko-opas pohjautuu kirjallisuuskatsaukseen sekä Naantalin terveyskeskuksen lastenneuvolan terveydenhoitajien toiveisiin. Tarkoituksena on ollut tuottaa luotettavaa ja ajankohtaista tietoa vastasyntyneen vauvan tuomista iloista ja haasteista vanhempien tarpeet huomioiden. Kirjallisuuskatsauksessa on käsitelty vanhemmuutta ja sen tuomia haasteita. Erikseen on perehdytty siihen, millaista tukea äidit ja isät omilla tahoillaan kaipaavat. Lisäksi on paneuduttu siihen, miten neuvola ja yksittäinen terveydenhoitaja voivat tukea vanhempia näissä asioissa. Tavoitteena on, että terveydenhoitajat pystyvät hyödyntämään valmista opasta omassa ohjaustyössään vauvaperheiden parissa. Tavoitteena on, että vanhemmat saavat tukea vanhemmuuteensa sekä arjen apuvälineitä ja lisätietoa haluamistaan asioista luotettavaksi todettujen verkkosivujen kautta. Opinnäytetyön toisessa osassa tehtiin ammatillinen posteri mainostamaan verkko-opasta.The concept and expectations of parenthood have changed over the last hundred years. Parents are faced with pressures from society as well as working life. Even more than before, parents are concerned by their capabilities as parents, and coping as a parent is a common worry. Parents of today are concerned and burdened by issues of livelihood, work and health. Most parents need support with parenting. Among other things, support is needed in concrete matters such as child rearing and basic care. The object of this thesis was to support parents with parenting and with everyday life with their child. The purpose of the thesis was to create online health education material for Naantali Health Station. The intention of the health education material was to support parents of a newborn child and to provide information. The material will be released as an online guide which makes it easily available and easy to update. Each subject includes a brief introduction and links to additional information. The methods of our thesis are functional, and the thesis has been carried out in collaboration with Naantali Health Station. The thesis is part of the “Terveesti tulevaisuuten” project of Turku University of Applied Sciences. The project is part of the university’s statutory research, development and innovation operations (RDI). Our thesis was carried out in two parts. The product of the first part, i.e. the online guide, is based on the literature review and the wishes of the public health nurses of the Naantali child health clinic. The purpose has been to produce reliable and up-to-date information about the joys and challenges of having a newborn baby, taking the needs of parents into consideration. The literature review deals with parenthood and its challenges. Focus has been placed on what kind of support both mothers and fathers need seperately. In addition, we have examined how a child health clinic and an individual public health nurse can support parents in these matters. The aim is that public health nurses can utilise the finalised guide in their guidance work with families with infants. In addition, the guide is meant to help parents with parenting, and to provide every-day tools as well as reliable web information. In the second part of our thesis, a professional poster was made to advertise the online guide

Vitamin D and cardiovascular risk among adults with obesity: A systematic review and meta-analysis

Background: Obesity is a risk factor for both vitamin D deficiency and cardiovascular disease. A link between vitamin D status optimisation and improved cardiometabolic profile among adults with obesity could inform public health initiatives. Methods: PubMed, Embase and Web of Science were searched for interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors (anthropometric measures, lipid profile, blood pressure, glucose tolerance) among nondiabetic adults with obesity. Results: Seventeen publications reporting results from 11 different studies were included. Number of participants ranged from 34 to 1179 subjects. Duration was between 6 weeks and 4 years. Vitamin D was administered as a supplement in ten studies (1000 IU daily to 120 000 IU fortnightly). In one study, participants were advised to increase sunlight exposure and dietary vitamin D intake. The random and fixed-effects meta-analysis showed that vitamin D significantly increased systolic blood pressure and LDL-C levels. The fixed-effects model also indicated a significant decrease in triglyceride levels, which was not evident using the random-effects model. Caution should be given to these results given the small number of studies used and the high heterogeneity between studies for the two latter outcomes. Additionally, a subset of eligible studies with compatible data presentation was included in the meta-analysis. Conclusion: This systematic review highlights a paucity of interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors among otherwise healthy adults with obesity. Large-scale studies at pharmacologically relevant doses and with sufficient duration are warranted. © 2015 Stichting European Society for Clinical Investigation Journal Foundation