Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains unclear.Additionally,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase.We examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these associations.Methods:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included.IF1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year visit.Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations.Mediation analyses were conducted to examine whether apoA-I mediated these associations.Mixedeffect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA.Results:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly mediates this association.Additionally,this study finds that baseline concentrations of IF1 can predict future changes in PA.However,further research is needed to fully understand the mechanisms underlying these observations.

Multi-Compartment SCFA Quantification in Human

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

Protein-S-100-beta is increased in patients with decompensated cirrhosis admitted to ICU

Background Hepatic encephalopathy(HE)is highly prevalent in patients with liver diseases.The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation.However,some data suggest altered functioning of the blood–brain barrier(BBB).Assessing BBB function is challenging in clinical practice and at the bedside.Protein-S-100 Beta(PS100-Beta)could be a useful peripheral marker of BBB permeability in HE.This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit(ICU)with decompensated cirrhosis with and without overt HE.Methods We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement.Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded.Overt HE was defined as West-Haven grades 2 to 4.The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes.After ICU discharge,the patients were followed for at least 3 months for the occurrence of overt HE.Adverse outcomes(liver transplantation or death)were collected.The ability of PS100-Beta–in combination with other factors–to predict overt HE was evaluated in a multivariate analysis using logistic regression.Likelihood ratios were used to determine the effects and calculate odds ratios(OR).Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test.Results A total of 194 ICU patients and 207 outpatients were included in the study.Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients([0.15±0.01]mg/L vs.[0.08±0]mg/L,P<0.001).ICU patients with overt HE had higher levels of PS100-Beta([0.19±0.03]mg/L)compared with the ICU patients without overt HE([0.13±0.01]mg/L)(P=0.003).PS100-Beta levels did not differ in outpatients with F 0–3 compared to F 4 fibrosis(P=0.670).PS100-Beta values were correlated with Child-Pugh score(P<0.001),Model for End-Stage Liver Disease(MELD)score(P=0.004),C-reactive protein(P<0.001),ammonemia(P<0.001),and chronic liver failure consortium(CLIF-C)organ failure(P<0.001)and CLIF-C acute-on-chronic(P=0.038)scores,but not with leukocytes(P=0.053),procalcitonin(PCT)(P=0.107),or the lymphocyte-to-neutrophil ratio in ICU patients(P=0.522).In a multivariate model including age,ammonemia,PS100-Beta,PCT,MELD,presence of transjugular portosystemic shunt,and sodium level,the diagnostic performance was 0.765 for the diagnosis of overt HE.Patients with a PS100-Beta level<0.12 mg/L had a better overall survival(P=0.019)and a better survival without liver transplantation(P=0.013).Conclusions Serum levels of PS100-Beta are elevated in ICU patients with decompensated cirrhosis,and even more so in those displaying overt HE,and the levels are correlated with outcome.This suggests an increase in the permeability of the BBB in these patients.

Relationships between mucinous gastric carcinoma, MUC2 expression and survival

AIM:To investigate the expression of the four secreted gel-forming mucins(MUC2,MUCSAC,MUCSB and MUC6)in a series of gastric carcinomas,classified according Laurén's,Mulligan's,WHO and Goseki's classifications,with special attention to all the different components(major and minor)present in tumors and to follow up clinical data.METHODS:Expression of MUC2,MUC5AC,MUC5B and MUC6 was investigated using immunohistochemistry and in situ hybridization.RESULTS:Expression of secreted gel-forming mucins in gastric carcinoma was particularly complex,each mucin being not restricted to any histopathological type even considering all components(major and minor)present in a given tumor.There was a worst survival in patients with a higher content of mucus(GosekiⅡorⅣ)and high positive MUC2 expression.CONCLUSION:Complexity of mucin gene expression patterns in gastric cancer may reflect a precise state of differentiation at the cell level not recognized in used morphologic classification systems.High expression of MUC2 was nevertheless associated with mucinous subtype of the WHO classification and with groupⅡof Goseki's classification identified by the major component of a particular tumor.The quantity and quality of mucus were related to survival.

Inflammatory status in chronic renal failure: The role of homocysteinemia and pro-inflammatory cytokines

AIM： To evaluate determinants of infammatory mark-ers in chronic renal failure patients according to the level of glomerular fltration rate. METHODS： One hundred ffty four patients （Age： 44 ± 06 years; male/female： 66/88） with chronic renal fail-ure （CRF） were divided into 6 groups according to the National Kidney Foundation （NKF） classification. They included 28 primary stage renal failure patients （CRF 1）, 28 moderate stage renal failure patients （CRF 2）,28 severe stage renal failure patients （CRF 3）, 18 end-stage renal failure patients （CRF 4）, 40 hemodialysis （HD） patients, and 12 peritoneal dialysis （PD） patients. Tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, interleukin-6 （IL-6） and C-reactive protein （CRP） were analyzed by immunosorbent assay kit （ELISA） （Cayman Chemical’s ACETM EIA kit）. Immunoassay methods were used for total homocysteine （tHcy） （fuorescence polarization immunoanalysis HPLC, PerkinEmer 200 series）, transferrin （MININEPHTM human transferin kit： ZK070.R）, ferritin （ADVIA Centaur ） and fbrinogen analysis （ACL 200）. Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.RESULTS： Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD （16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P 〈 0.001） and PD （14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P 〈 0.001）. IL-1β levels were increased in HD （9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P 〈 0.001） and CRF 4 （7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P 〈 0.001） patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD （32.27 ± 12.08 μmol/L） and PD （28.37 ± 4.98 μmol/L） patients compared to the other groups of CRF （P 〈 0.001）. The serum CRP level was signifcantly increased in HD （18.17 ± 6.38 mg/L） and PD （17.97 ± 4.85 mg/L） patients compared to the other groups of CRF patients （P 〈 0.001）. The plasma fbrinogen level was more elevated in HD （6.86 ± 1.06 g/L） and CRF 4 （6.05 ± 0.57 g/L） than in the other groups （ P 〈 0.001）. Furthermore; the ferritin level was higher in HD （169.90 ± 62.16 ng/mL） and PD （90.08 ± 22.09 ng/mL） pa-tients compared to the other groups of CRF （P 〈 0.001）. The serum transferrin value was signifcantly decreased especially in PD （1.78 ± 0.21 g/L） compared to the oth-er groups （P 〈 0.001）. We found a negative correlation between glomerular fltration rate （GFR）, TNF-α levels （ r = -0.75, P 〈 0.001）, and tHcy levels （ r = -0.68, P 〈 0.001）. We observed a positive correlation between GFR and transferrin levels （ r = 0.60, P 〈 0.001）. CONCLUSION： CRF was associated with elevated in-flammatory markers. The inflammation was observed at the severe stage of CRF and increases with progres-sion of renal failure.

Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma

AIM: To assess the predictive value of the insulinlike growth factor 2 (Igf2) methylation profile for the occurrence of Hepatocellular Carcinoma (HCC) in hepatitis C (HCV) cirrhosis. METHODS: Patients with: (1) biopsy-proven compensated HCV cirrhosis; (2) available baseline frozen liver sample; (3) absence of detectable HCC; (4) regular screening for HCC; (5) informed consent for genetic analysis were studied. After DNA extraction from liver samples and bisulfite treatment, unbiased PCR and DHPLC analysis were performed for methylation analysis at the Igf2 locus. The predictive value of the Igf2 methylation profile for HCC wasassessed by Kaplan-Meier and Cox methods. RESULTS: Among 94 included patients, 20 developed an HCC during follow-up (6.9 ± 3.2 years). The methylation profile was hypomethylated, intermediate and hypermethylated in 13, 64 and 17 cases, respectively. In univariate analysis, two baseline parameters were associated with the occurrence of HCC: age (P = 0.01) and prothrombin (P = 0.04). The test of linear tendency between the three ordered levels of Igf2 methylation and probability of HCC occurrence was significant (Log Rank, P = 0.043; Breslow, P = 0.037; Tarone-Ware, P = 0.039). CONCLUSION: These results suggest that hypomethylation at the Igf2 locus in the liver could be predictive for HCC occurrence in HCV cirrhosis.

Real-time in situ magnetic measurement of the intracellular biodegradation of iron oxide nanoparticles in a stem cell-spheroid tissue model

The use of magnetic nanoparticles in nanomedicine keeps expanding and,for most applications,the nanoparticles are internalized in cells then left within,bringing the need for accurate,fast,and easy to handle methodologies to assess their behavior in the cellular environment.Herein,a benchtop-size magnetic sensor is introduced to provide real-time precise measurement of nanoparticle magnetism within living cells.The values obtained with the sensor,of cells loaded with different doses of magnetic nanoparticles,are first compared to conventional vibrating sample magnetometry(VSM),and a strong correlation remarkably validates the use of the magnetic sensor as magnetometer to determine the nanoparticle cellular uptake.The sensor is then used to monitor the progressive intracellular degradation of the nanoparticles,over days.Importantly,this real-time in situ measure is performed on a stem cell-spheroid tissue model and can run continuously on a same spheroid,with cells kept alive within.Besides,such continuous magnetic measurement of cell magnetism at the tissue scale does not impact either tissue formation,vibility,or stem cell function,including differentiation and extracellular matrix production.

尿钙和先兆子痫的病例对照研究

Objective: The aim of this study was to compare calciuria of preeclamptic cases to normotensive controls among pregnant women hospitalized in the French West Indies obstetrics department. Study design: This case-control study included 47 preeclamptic women and 50 controls. The main outcome was 24 h urinary calcium excretion rate. Serum levels of creatinine, calcium and uric acid were also analyzed. A logistic regression analysis has been performed to investigate the relationship between hypocalciuria and preeclampsia after having taken into account prognostic preeclampsia factors and pertinent clinical criteria. Results: Women with preeclampsia had significantly lower calciuria than normotensive patients (1.5 mmol/24 h ± 1.0 versus 6.0mmol/24 h ± 4.2, p = 0.0001). After taking into account gestational age at hospitalization, body mass index and nulliparity, hypocalciuria was significantly associated with preeclampsia (ORa = 21.74; 95% CI, 6.9- 66.7). The diagnosis value of a calciuria less than 2.1 mmol/24 h is interesting because of its negative predictive value (97% ), but its positive predictive value is weak (42% ). Conclusion: In our population, preeclamptic women had a calciuria significantly lower than controls.

PHProteomicDB:A Module for Two-dimensional Gel Electrophoresis Database Creation on Personal Web Sites

PHProteomicDB is a PHP-written module to help researchers in proteomics to share two-dimenslonal gel electrophoresis data using personal web sites. No technical or PHP knowledge is necessary except a few basics about web site management. PHProteomicDB has a user-friendly administration interface to enter and update data. It creates web pages on the fly displaying gel characteristics, gel pictures, and numbered gel spots with their related identifications pointing to their reference pages in protein databanks. The module is freely available at http：//www.huvec.com/index.php3？rub=Download.

上海人群面肩肱型肌营养不良症相关位点的D4Z4多态性(英文)

目的对上海人群4q35位点D4Z4重复序列进行研究,分析D4Z4的多态性。方法191名正常上海人的基因组DNA经EcoRⅠ/B1nⅠ双酶水解后,应用脉冲场凝胶电泳及Southern印迹测定其染色体4q35位点的D4Z4片段长度,并对短的D4Z4片段用KpnⅠ酶进行部分酶切以计数其D4Z4串联重复序列数。结果在191名正常上海人群中,有17人(占8.9%)携带短的D4Z4片段,其长度在22～34kb之间;其中16人携带的短D4Z4片段位于4q35位点,1人携带的短D4Z4片段为4q35→10q26。结论面肩肱型肌营养不良症的发病虽与4q35位点D4Z4片段的串联重复序列数减少有关,但上海人群中携带4q35位点短的D4Z4片段个体的比例明显高于西方人群,提示其他因素可能也参与面肩肱型肌营养不良症的发病。