Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers

Objective: To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers.

Methods: Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels.

Results: H3K4me3 was statistically significantly different (p?<?0.05) between the two groups and positively correlated with employment length (r_s?=_?0.267). HP1 was not correlated with employment length (p?=?0.066) but was significantly different between the two groups.

Conclusions: Chronic exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.     

Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome.

Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33?°C or TTM at 36?°C for 24?h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72?h after OHCA. The primary endpoint was neurological outcome.

Results: Median (quartile 1 – quartile 3) tau-A (ng/ml) values were 58 (43–71) versus 51 (43–67), 72 (57–84) versus 71 (59–82) and 76 (61–92) versus 75 (64–89) for good versus unfavourable outcome at 24, 48 and 72?h, respectively (p_group = 0.95). Median tau C (ng/ml) values were 38 (29–50) versus 36 (29–49), 49 (38–58) versus 48 (33–59) and 48 (39–59) versus 48 (36–62) (p_group = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48?h; tau-A: 0.51 and tau-C: 0.51).

Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.     

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction

Context: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes.

Objective: The study examined the early release kinetics of TnTuORF.

Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n?=?31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).

Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18?ng/L versus 27?ng/L; cTnI median: 15?ng/L versus 25?ng/L). TnTuORF showed no variation.

Discussion: We observed a significantly greater increase in cTnI compared with cTnT.

Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.     

Prognostic significance of insulin-like growth factor-I serum levels in acute decompensation of cirrhosis

Context: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown.

Objectives: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis.

Materials and methods: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan–Meier survival probability at 90 days was 94.3% in patients with IGF-I?≥13?ng/mL and 63.2% for patients with IGF-I?<13?ng/mL (p?=?.001).

Discussion and conclusion: IGF-I levels are independently associated with mortality in acute decompensation of cirrhosis.     

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus

Context: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX).

Objectives: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX.

Materials and methods: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina.

Results: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431?ng/ml, p?=?0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX.

Discussion and conclusion: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease.

Trial registration number: NCT01198730 at https://clinicaltrials.gov     

A comparison of HMGB1 concentrations between cerebrospinal fluid and blood in patients with neurological disease

Aims: To determine whether a correlation exists between paired cerebrospinal fluid (CSF) and serum levels of a novel inflammatory biomarker, high-mobility group box 1 (HMGB1), in different neurological conditions.

Methods: HMGB1 was measured in the serum and CSF of 46 neurological patients (18 idiopathic intracranial hypertension [IIH], 18 neurological infection/inflammation [NII] and 10 Rasmussen’s encephalitis [RE]).

Results: Mean serum (±?SD) HMGB1 levels were 1.43?±?0.54, 25.28?±?27.9 and 1.89?±?1.49?ng/ml for the patients with IIH, NII and RE, respectively. Corresponding mean (±?SD) CSF levels were 0.35?±?0.22, 4.48?±?6.56 and 2.24?±?2.35?ng/ml. Both CSF and serum HMGB1 was elevated in NII. Elevated CSF HMGB1 was demonstrated in RE. There was no direct correlation between CSF and serum levels of HMGB1.

Conclusion: Serum HMGB1 cannot be used as a surrogate measure for CSF levels. CSF HMGB1 was elevated in NII and RE, its role as a prognostic/stratification biomarker needs further study.     

Determination of air pollution-related biomarkers of exposure in urine of travellers between Germany and China using liquid chromatographic and liquid chromatographic-mass spectrometric methods: a pilot study

Objective: The influence of different exposures to PM_2.5 (particulate matter with an aerodynamic diameter below 2.5?μm) on the concentrations of biomarkers of exposure and oxidative stress should be investigated. For this purpose, urine samples from individuals travelling from Germany to China were collected and analysed.

Materials: Robust LC and LC-MS/MS methods were established for the determination of biomarkers including 8-hydroxy-2′-deoxyguanosine, malondialdehyde, F_2α-isoprostanes and hydroxylated polycyclic aromatic hydrocarbons. As a pilot study, nine volunteers travelled from Germany (mean daily concentration of PM_2.5: 21?μg/m³) to China (mean daily concentration of PM_2.5: 108?μg/m³). Urine samples were collected before and after the trip.

Results: In samples collected after return to Germany, the median concentrations of oxidative stress biomarkers were observed to be higher than in samples collected before leaving Germany. Decreasing trends were observed in the sequences of samples collected after return in the following weeks. Correlations were found between exposure and oxidative stress biomarkers.

Conclusion: Travellers are ideal models for PM pollution-induced acute health effects study. Exposure to PM pollution can cause oxidative stress and damage.     

Assessment of titanium dioxide nanoparticles toxicity via oral exposure in mice: effect of dose and particle size

Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO₂NPs) according to their doses and particle sizes.

Materials and methods: The effect of five days oral administration of TiO₂NPs (21 and 80?nm) with different doses (50, 250 and 500?mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern.

Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO₂NPS (21?nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations.

Conclusions: Toxicity of TiO₂NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO₂NPs toxicity. More detailed studies are required before the recommendation of TiO₂NP_S as food additives.     

Habitat associations of young Black Grouse Tetrao tetrix broods

Capsule: In the Scottish Highlands, Black Grouse Tetrao tetrix females with young broods selected areas rich in wet flushes, grasses and Sphagnum mosses.

Aims: To identify associations between young Black Grouse broods and habitat characteristics.

Methods: We located brood-rearing Black Grouse females in four areas of moorland-forest mosaic in the Scottish Highlands. Each brood was paired with a random reference location 100?m away. We recorded cover of different habitats and fine-scale vegetation and structure within squares of 1 and 0.25?ha, respectively. Associations between brood occurrence and habitat and vegetation variables were examined at the two scales.

Results: Black Grouse broods were positively associated with wet flushes (1?ha), and with Heather Calluna vulgaris, sedges Carex spp., grasses, Sphagnum mosses and taller vegetation with intermediate levels of height variability (0.25?ha).

Conclusions: This study highlights the importance of wet habitats for young Black Grouse chicks. In addition, relatively tall field-layer vegetation comprising Heather, sedges, grasses over a layer of Sphagnum mosses attracted brood-rearing Black Grouse females. Many management practices associated with peatland restoration, including drain-blocking, Sphagnum re-establishment and the avoidance of burning on deep peat soils, are therefore consistent with favourable habitat management for Black Grouse.     

Improved reliability of the urine lactate concentration under controlled hydration after maximal exercise

Context: Urine lactate may be a novel biomarker of lactate production capacity but its reliability has been unsatisfactory so far.

Objective: To compare the reliability of urine lactate between controlled hydration and no hydration after maximal exercise.

Material and methods: Athletes performed swimming exercise four times: two followed by consumption of 1?L of water and two followed by no water intake. Blood and urine lactate was measured.

Results: The reliability of urine lactate was good and similar to that in blood only after controlled hydration. Blood and urine lactate were correlated under both hydration conditions.

Discussion and conclusion: Controlled hydration after exercise provides satisfactory reliability of urine lactate.     

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome.

Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1?C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians.

Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1?C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p?=?0.012 and p?<?0.001, respectively).

Conclusions: Our work showed a significant association between the -1?C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.     

Neopterin and oxidative stress markers in the diagnosis of extrapulmonary tuberculosis

Background: Extrapulmonary tuberculosis (EPTB) often presents with nonspecific signs and symptoms. Further the paucibacillary nature of extrapulmonary specimens and irregular distribution of bacilli lower the sensitivity of conventional diagnostic methods making EPTB, a diagnostic dilemma.

Objective: To study neopterin, protein carbonyl and malondialdehyde (MDA) in EPTB.

Methods: Sixty nine clinically confirmed cases with an equal number of age and sex matched healthy controls were enrolled. Ziehl–Neelsen staining for acid fast bacilli and culture on Lowenstein–Jensen medium were performed on all the extrapulmonary specimens. Serum neopterin and protein carbonyl levels were estimated using commercial ELISA kits. Malondialdehyde was determined by measuring thiobarbituric acid reactive substances.

Results: Serum neopterin, protein carbonyl and MDA levels were significantly discriminative for cases of EPTB from healthy controls (p?<?0.05). Levels of all the three biomarkers under study significantly differed between culture as well as smear positive and negative cases. A positive correlation between neopterin and protein carbonyl was seen among the cases.

Conclusions: So far few studies have integrated combination of validated host biomarkers for active disease in EPTB. Our study suggests the potential diagnostic role of neopterin, protein carbonyl and MDA in EPTB.     

Salivary protein changes in response to acute stress in medical residents performing advanced clinical simulations: a pilot proteomics study

Context: Quantitative changes of salivary proteins due to acute stress were detected.

Objective: To explore protein markers of stress in saliva of eight medical residents who performed emergency medicine simulations.

Materials and methods: Saliva was collected before the simulations, after the simulations, and following morning upon waking. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), identified by mass spectrometry (MS), and relatively quantified by densitometry.

Results: Salivary alpha-amylase and S–type cystatins significantly increased, while the ～26?kDa and low-molecular weight (MW) (<10?kDa) SDS-PAGE bands exhibited changes after stress.

Discussion and conclusion: Alpha-amylase and cystatins are potential salivary markers of acute stress, but further validation should be performed using larger sample populations.     

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis

Context: Association between inherited variants and the risks of sepsis is controversial.

Objective: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10.

Materials and methods: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls.

Results: Subjects with IL-10 -1082 AA genotypes and IL-6 -174?CC genotype had a higher risk of sepsis and increased mRNA levels.

Conclusion: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.     

Effect of different concentrations of oxygen on expression of sigma 1 receptor and superoxide dismutases in human colon adenocarcinoma cell lines

Context: Tumor cells due to distance from capillary vessels exist in different oxygenation conditions (anoxia, hypoxia, normoxia). Changes in cell oxygenation lead to reactive oxygen species production and oxidative stress. Sigma 1 receptor (Sig1R) is postulated to be stress responding agent and superoxide dismutases (SOD1 and SOD2) are key antioxidant enzymes. It is possible that they participate in tumor cells adaptation to different concentrations of oxygen.

Objective: Evaluation of Sig1R, SOD1, and SOD2 expression in different concentrations of oxygen (1%, 10%, 21%) in colon adenocarcinoma cell lines.

Materials and methods: SW480 (primary adenocarcinoma) and SW620 (metastatic) cell lines were cultured in standard conditions in Dulbecco’s modified Eagle’s medium for 5 days, and next cultured in Hypoxic Chamber in 1% O₂, 10% O₂, 21% O₂. Number of living cells was determined by trypan blue assay. Level of mRNA for Sig1R, SOD1, and SOD2 was determined by standard PCR method. Statistical analysis was conducted using Statistica 10.1 software.

Results: We observed significant changes in expression of Sig1R, SOD1, SOD2 due to different oxygen concentrations. ANOVA analysis revealed significant interactions between studied parameters mainly in hypoxia conditions in SW480 cells and between Sig1R and SOD2 in SW620 cells. It also showed that changes in expression of studied proteins depend significantly on type of the cell line.

Conclusion: Changes of Sig1R and SOD2 expression point to mitochondria as main organelle responsible for survival of tumor cells exposed to hypoxia or oxidative stress. Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen.     

Soluble CD40 ligand in haemodialysis patients: survival impact and cardiovascular prognostic role

Context: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies).

Objective: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up.

Methods: We registered 46?HD patients’ baseline characteristics, mortality and CVE for 108 months.

Results: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality.

Conclusion: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.     

Effect of shoulder stability exercises on hand grip strength in patients with shoulder impingement syndrome

Background: Shoulder impingement syndrome (SIS) is the second most common musculoskeletal condition that causes shoulder pain in the general population. Shoulder girdle muscle imbalance and posterior capsule tightness have been implicated as contributing factors.

Objective: The purpose of this study was to investigate the effect of shoulder stability exercises (SSEs) on hand grip strength in patients with unilateral SIS.

Methods: A total of 16 patients with a mean age of 32?±?9.3?years diagnosed with stage II unilateral SIS participated in this study. A standardized SSE programme was conducted in the clinic under the direct 1-to-1 supervision of a physical therapist thrice weekly for 4?weeks for a total of 12 sessions on the affected and non-affected shoulders. The effect of the SSE programme on isometric hand grip strength was analysed.

Results: A significant difference (p?=?.016) was observed in the hand grip strength of the affected shoulder side before and after the intervention, but no significant difference (p?=?1.0) was found in the hand grip strength of the non-affected shoulder side post-intervention.

Conclusion: The reduction in isometric hand grip strength of the affected shoulder side compared to that of the non-affected shoulder side in the same subject before the intervention shows that SIS significantly affects the hand grip strength of the affected side. SSEs significantly affect the isometric hand grip strength of SIS patients.     

Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren’s Syndrome

Context: Cathepsin S (CTSS) activity is elevated in Sjögren’s Syndrome (SS) patient tears.

Objective: To evaluate longitudinal expression of tear and tissue CTSS activity relative to other disease indicators in Non-Obese Diabetic (NOD) mice.

Methods: CTSS activity was measured in tears and lacrimal glands (LG) from male 1–6?month (M) NOD and 1 and 6?M BALB/c mice. Lymphocytic infiltration was quantified by histopathology, while disease-related proteins (Rab3D, CTSS, collagen 1) were quantified using q-PCR and immunofluorescence.

Results: In NOD LG, lymphocytic infiltration was noted by 2?M and established by 3?M (p?<?0.01). IFN-?, TNF-α, and MHC II expression were increased by 2?M (p?<?0.01). Tear CTSS activity was significantly elevated at 2?M (p?<?0.001) to a maximum of 10.1-fold by 6?M (p?<?0.001). CTSS activity in LG lysates was significantly elevated by 2?M (p?<?0.001) to a maximum of 14-fold by 3?M (p?<?0.001). CTSS and Rab3D immunofluorescence were significantly increased and decreased maximally in LG acini by 3?M and 2?M, respectively. Comparable changes were not detected between 1 and 6?M BALB/c mouse LG, although Collagen 1 was decreased by 6?M in LG of both strains.

Conclusion: Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS.     

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel–Lindau patients

Context: Von Hippel–Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death.

Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.

Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.

Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC.

Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers.     

Inhibitory effect of Tanshinone IIA on inverted formin-2 protects HaCaT cells against oxidative injury via regulating mitochondrial stress

Context: Epidermal cells play an important role in regulating the regeneration of skin after burns and wounds.

Objective: The aim of our study is to explore the role of Tanshinone IIA (Tan IIA) in the apoptosis of epidermal HaCaT cells induced by H₂O₂, with a focus on mitochondrial homeostasis and inverted formin-2 (INF2).

Materials and methods: Cellular viability was determined using the MTT assay, TUNEL staining, western blot analysis and LDH release assay. Adenovirus-loaded INF2 was transfected into HaCaT cells to overexpress INF2 in the presence of Tan IIA treatment. Mitochondrial function was determined using JC-1 staining, mitochondrial ROS staining, immunofluorescence and western blotting.

Results: Oxidative stress promoted the death of HaCaT cells and this effect could be reversed by Tan IIA. At the molecular levels, Tan IIA treatment sustained mitochondrial energy metabolism, repressed mitochondrial ROS generation, stabilized mitochondrial potential, and blocked the mitochondrial apoptotic pathway. Furthermore, we demonstrated that Tan IIA modulated mitochondrial homeostasis via affecting INF2-related mitochondrial stress. Overexpression of INF2 could abolish the protective effects of Tan IIA on HaCaT cells viability and mitochondrial function. Besides, we also reported that Tan IIA regulated INF2 expression via the ERK pathway; inhibition of this pathway abrogated the beneficial effects of Tan IIA on HaCaT cells survival and mitochondrial homeostasis.

Conclusions: Overall, our results indicated that oxidative stress-mediated HaCaT cells apoptosis could be reversed by Tan IIA treatment via reducing INF2-related mitochondrial stress in a manner dependent on the ERK signaling pathway.