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.     

Propeptide big-endothelin,N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study

Context: The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF).

Objectives: We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP).

Methods: Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years).

Results: Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF.

Discussion: The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF.

Conclusions: Big-ET-1improves risk stratification in patients referred for coronary angiography.     

Review of biomarkers to assess the effects of switching from cigarettes to modified risk tobacco products

Context: One approach to reducing the harm caused by cigarette smoking, at both individual and population level, is to develop, assess and commercialize modified risk alternatives that adult smokers can switch to. Studies to demonstrate the exposure and risk reduction potential of such products generally involve the measuring of biomarkers, of both exposure and effect, sampled in various biological matrices.

Objective: In this review, we detail the pros and cons for using several biomarkers as indicators of effects of changing from conventional cigarettes to modified risk products.

Materials and methods: English language publications between 2008 and 2017 were retrieved from PubMed using the same search criteria for each of the 25 assessed biomarkers. Nine exclusion criteria were applied to exclude non-relevant publications.

Results: A total of 8876 articles were retrieved (of which 7476 were excluded according to the exclusion criteria). The literature indicates that not all assessed biomarkers return to baseline levels following smoking cessation during the study periods but that nine had potential for use in medium to long-term studies.

Discussion and conclusion: In clinical studies, it is important to choose biomarkers that show the biological effect of cessation within the duration of the study.     

Micronuclei as a marker for medical screening of subjects continuously occupationally exposed to low doses of ionizing radiation

Context: Genotoxicity assays are widely employed in human biomonitoring studies to assess genetic damage inflicted by genotoxic agents.

Objective: Evaluation of micronuclei (MN) as a screening marker of occupational ionizing radiation (IR) exposure.

Materials and methods: Using micronucleus test, peripheral blood lymphocytes (PBL) of 402 control and exposed subjects were screened for genetic damage.

Results: The mean frequencies of micronucleus test parameters were significantly higher in exposed persons. Increase of micronucleus yield with duration of exposure (DOE) by 0.303MN/year was revealed.

Discussion and conclusion: The obtained data encourage us to consider MN as valuable markers for preventive medical screening of occupationally exposed groups.     

The effect of chronic exposure to extremely low-frequency electromagnetic fields on sleep quality,stress, depression and anxiety

Exposure to extremely low-frequency electromagnetic fields (ELF-EMF) is inevitable in some industries. There are concerns about the possible effects of this exposure. The present study aimed to investigate the effect of chronic exposure to extremely low-frequency electromagnetic fields on sleep quality, stress, depression and anxiety among power plant workers.

In this cross-sectional study, 132 power plant workers were included as the exposed group and 143 other workers were included as the unexposed group. The intensity of ELF-EMF at work stations was measured by using the IEEE Std C95.3.1 standard and then the time weighted average was calculated. Sleep quality, stress, depression and anxiety were measured by using the Pittsburgh Sleep Quality Index Questionnaire; and the Depression, Anxiety and Stress Scale.

The workers in the exposed group experienced significantly poorer sleep quality than the unexposed group. Depression was also more severe in the exposed group than the unexposed group (P = 0.039). Increased exposure to ELF-EMF had a direct and significant relation with increased stress, depression, and anxiety. Sleep quality in technicians with the highest exposure was significantly lower than the other groups.

This study suggests that long-term occupational exposure to ELF-EMF may lead to depression, stress, anxiety and poor sleep quality.     

Limited dispersal and geographic barriers cause population differentiation and structuring in Begonia maxwelliana at both large and small scales

Background: Genetic divergence is one of the key processes in speciation. In the Begoniaceae, genetic divergence caused by limited gene flow may explain its high species diversity and endemicity. This hypothesis has been supported by past genetic work but there is a lack of empirical studies on the causes of limited gene flow.

Aim: To identify the causes of limited gene flow in Begonia.

Methods: We examined the genetic structure among the populations of Begonia maxwelliana at the macro- and micro-spatial scales using microsatellites, measured seed dispersal range and observed flowering phenology.

Results: Population differentiation and structuring were detected at both the macro- and micro-scales. Dispersal range was short, and all populations showed similar reproductive behaviour.

Conclusions: The strong population differentiation and structuring among the populations studied imply that they are evolutionarily significant units and possible candidates for speciation. Geographical barriers and limited seed dispersal restrict gene flow in the populations, and these factors may be responsible for the rapid speciation and large diversity in the family.     

Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

Emerging MS-based platforms for the characterization of tumor-derived exosomes isolated from human biofluids: challenges and promises of MudPIT

Introduction: Exosomes are small extracellular vesicles of endosomal origin that are produced and released by several type of cells. These vesicles contain different macromolecules: proteins, mRNA, miRNA, mitochondrial DNA, and lipids. Exosomes play an important role in cell-to-cell communication, also promoting cancer progression.

Areas covered: Various proteomic approaches have been applied to study exosomes isolated from different human biofluids in search of possible cancer biomarkers. The results of these studies are reported, and pros and cons of each employed technique are described. Gel-free and gel-based mass spectrometry systems are discussed, giving particular emphasis on the innovative multidimensional protein identification technology (MudPIT).

Expert commentary: Proteomic studies on exosomes as candidate cancer biomarkers from urine and other body fluids in cancer have shown the potential of MS-based techniques. In particular, MudPIT is a promising tool to be applied in clinical proteomics of cancer.     

Quantification of 1-hydroxypyrene, 1- and 2-hydroxynaphthalene, 3-hydroxybenzo[a]pyrene and 6-hydroxynitropyrene by HPLC-MS/MS in human urine as exposure biomarkers for environmental and occupational surveys

Context: Several urinary PAHs metabolites can be detected by HPLC-MS/MS for individual exposure assessment.

Objective: Quantitation of urinary metabolites of four PAHs, selected on the basis of their significance, with reduced costs and high sensitivity.

Materials and methods: HPLC-MS/MS was used and pure standards and isotope-labeled internal analogs of the analytes. Two hundred samples were tested after enzymatic hydrolysis.

Results: Accuracy was higher than 90% and variability lower than 19%; LODs permit to measure 1-hydroxypyrene, 1 and 2-hydroxynaphthalene in all subjects, 6-hydroxynitropyrene in the 65% and 3-hydroxybenzo[a]pyrene in the 70%.

Discussion and conclusion: The method is suitable both for occupational and for environmental studies. This is the first paper reporting urinary levels of 6-hydroxynitropyrene in European subjects, nonoccupationally exposed to nitro-PAHs.     

A proposed explanation for thunderstorm asthma and leukemia risk near high-voltage power lines: a supported hypothesis

Thunderstorm asthma and increased childhood leukemia risk near high-voltage power lines (HVPL) are occurrences whose mechanism of effect is not fully understood.

This paper proposes and discusses a key similarity: both thunderstorms and HVPL generate a high enough electrical field in the environment to ionize nearby air and air-borne particles.

I argue that the repeatedly demonstrated acute asthma response to pollen-laden air during thunderstorms is largely due to ionization of air-borne allergens, which adhere more readily and in greater quantity in the lungs than non-ionized particles. If these bind to mucous or phagocytic cells, it would enhance immune response. A rapid temperature drop and high ozone also seem to be drivers of thunderstorm asthma.

This causal nexus provides strong support for the parallel situation of prolonged exposure to ionized particles near HVPL and an increased rate of childhood leukemia. Here, it is proposed that upwind carcinogens are ionized when passing HVPL and then residential and business areas. Published evidence for most steps are presented, but have not previously been published as a coherent whole, nor has it been suggested that the inhaled ionized micro-particle explanation for acute asthma may also explain development of childhood leukemia over time.

The demonstrated series of events leading to increased deposition and retention of ionized particles in airways provides support for explaining both adverse health outcomes: acute thunderstorm asthma and increased risk of childhood leukemia near HVPL. Further support for this explanation of both outcomes is provided by effects of on-going proximity to highways.     

The relationship of single-strand breaks in DNA to breast cancer risk and to tissue concentrations of oestrogens

Context: Clinical study of breast cancer patients in Chicago, IL, USA.

Objective: Ascertain the utility of measurements of single-strand breaks (SSB) in DNA for assessment of breast cancer risk.

Methods: Fine-needle aspirates of the breast, SSB by nick translation, percent breast density (PBD), Gail model risk, cumulative methylation index (CMI), enzymes of DNA repair and tissue antioxidants.

Results: DNA repair enzymes and 4-hydroxyestradiol were negatively associated with SSB; CMI and PBD were positively associated.

Conclusions: Quantitative measurement of SSBs by this procedure indicates the relative number of SSBs and is related to promoter methylation, antioxidant availability and percent breast density.     

Circulating microparticles in cardiovascular disease: going on stage!

Context: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In spite of the fact that treatments are based on risk calculators which in turn are based on population characteristics, it is well known that these methods have definite levels of uncertainty. Recently, more precise diagnostic or predictive methods have been developed based on indicators of vascular and/or cardiac damage in order to supplement this risk evaluation.

Objective: In this review, we describe the main discoveries leading to the idea of using circulating microparticles as a promising and complementary tool in the evaluation of cardiovascular risk.

Methods: A Medline search for the terms cardiovascular diseases, microparticles, miRNAs, diagnosis, prognosis, biomarkers and microvesicles was performed.

Results: We found (i) nine articles, which were relevant to forming the idea of using microparticles as biomarkers in CVDs, and (ii) 15 and 12 experimental clinical studies which describe their potential in primary and secondary CVD prevention, respectively.

Conclusions: The levels of circulating microparticles have been associated with cardiovascular damage in asymptomatic patients as well as in patients who suffered a cardiovascular event, becoming promising diagnostics or prediction biomarkers in recent years.     

The effects of nifedipine on respiratory mechanics investigated by theend-inflation occlusion method in the rat

Context: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle.

Objective: To investigate possible effects of nifedipine on respiratory mechanics in the rat.

Methods: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine.

Results: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells.

Conclusion: Should these results be further confirmed by human investigations, a possible role of nifedipine in pharmacological respiratory system’s diseases treatment may be suggested.     

Lipoprotein-associated phospholipase A2, and subsequent cardiovascular events and mortality among patients with coronary heart disease

Objective: The objective of this study is to evaluate the relevance of Lp-PLA₂ to risk prediction among coronary heart disease (CHD) patients.

Methods: Lp-PLA₂ activity was measured in 2538 CHD patients included in the Bezafibrate Infarction Prevention (BIP) study.

Results: Adjusting for patient characteristics and traditional risk factors, 1 standard deviation of Lp-PLA₂ was associated with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.00–1.25) for mortality and 1.03 (0.93–1.14) for cardiovascular events. Lp-PLA₂ did not significantly improve model discrimination, or calibration nor result in noteworthy reclassification.

Conclusions: Our results do not support added value of Lp-PLA₂ for predicting cardiovascular events or mortality among CHD patients beyond traditional risk factor.     

Biomarker discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric acid ratio in urine and plasma as potential markers

Context: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable.

Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.

Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.

Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.

Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis.     

Matrix metalloproteinase multiplex screening identifies increased MMP-2 urine concentrations in women predicted to develop preeclampsia

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.

Objective: The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development.

Methods: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA).

Results: Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population.

Conclusion: Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population.     

Blood markers of inflammation and endothelial dysfunction in cardioembolic stroke: systematic review and meta-analysis

Context: Various processes including inflammation and endothelial dysfunction have been implicated in the pathogenesis of cardioembolic (CE) strokes.

Objective: To review the evidence and investigate the association between immune-inflammatory biomarkers and CE strokes versus other stroke subtypes.

Methods: We systematically reviewed the literature (sources: MEDLINE, web-based register http://stroke-biomarkers.com, reference lists) with quality assessment and meta-analysis of selected articles.

Results: The most consistent association was found between C-reactive protein (CRP) and CE strokes when compared to other stroke subtypes (standardized mean difference 0.223 (0.116, 0.343); p?<?0.001)

Conclusions: Our findings confirm a possible association between selected inflammatory biomarkers and CE stroke.     

JNK pathway in osteoarthritis: pathological and therapeutic aspects

Context: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway.

Objective: In this study, we have reviewed the recent updates on the association of JNK pathway with OA.

Methods: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OA

Results: JNK has been shown by scientific studies to be activated (phosphorylated) in OA that can play a key role in the cartilage destruction. Activation of JNK causes the phosphorylation of c-Jun that causes decreased proteoglycan synthesis and enhanced production of matrix metalloproteinase 13 (MMP-13). Overproduction of MMP-13 by chondrocytes plays a central role in cartilage degeneration in OA. Thus, targeting JNK pathway might be a promising therapeutic application for the prevention and treatment of OA. A number of JNK-inhibitors have been used in vitro and in vivo studies; however, not yet been translated into human use.

Conclusions: This review study indicates that JNK pathway plays an important role in development and progression of OA, and targeting the JNK pathway might be a potential approach for the treatment of OA in future.     

Prediction of Alzheimer’s disease with serum lipid levels in Asian individuals: a meta-analysis

Background: The serum lipid profile has become a routine clinical test and used as an important predictor for Alzheimer’s disease (AD), although its predictive value remains undetermined.

Objective: To evaluate the role of serum lipid levels in predicting the risk of AD.

Methods: Meta-analyses were conducted using Comprehensive Meta-analyses (CMA) software to investigate the association between four conventional serum lipid profile parameters and the risk of AD, focused on samples from Asian.

Results: In total, 3423 AD patients and 6127 healthy participants were involved. The results demonstrated that AD patients showed higher LDL-C and TC levels (SMD?=?0.27, 95% CI: 0.04–0.51, p?=?0.02 for LDL-C; SMD?=?0.25, 95% CI: 0.05–0.46, p?=?0.02 for TC) compared with those of healthy controls. People with higher LDL-C and/or TC levels had an increased risk of AD (OR?=?1.64, 95% CI: 1.07–2.51 for LDL-C and OR?=?1.58, 95% CI: 1.10–2.92 for TC).

Conclusions: This study provided evidence that serum LDL-C and TC levels were associated with the risk of AD in Asian individuals. The routine lipid profile may be useful for AD diagnosis, monitoring and treatment.     

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.

Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n?=?30,193, age = 60.2?±?11.5?year).

Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p?<?0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p?<?0.001).

Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.