Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. However, the etiology of this rare disease remains unknown. Serum microRNA (miRNA) profiles have been screened to identify novel biomarkers of prognostic values. Here, we identified serum miRNAs that might play an important role in the pathogenesis of MMD. A genome-wide miRNA array analysis of two pooled serum samples from patients with MMD and controls revealed 94 differentially expressed serum miRNAs, including 50 upregulated and 44 downregulated miRNAs. In an independent MMD cohort, real-time PCR confirmed that miR-106b, miR-130a and miR-126 were significantly upregulated while miR-125a-3p was significantly downregulated in serum. GO analysis showed that the differentially expressed serum miRNAs were enriched in metabolic processes, transcription and signal transduction. Pathway analysis showed that the most enriched pathway was mTOR signaling pathway with 16 potential, functional targets. Finally, we found that 16 and 13 aberrant serum miRNAs coordinately inhibited RNF213 and BRCC3 protein expression at the posttranscriptional level, respectively, resulting in defective angiogenesis and MMD pathogenesis. To our knowledge, this is the first study to identify a serum miRNA signature in MMD. Modulation of the mechanism underlying the role of serum miRNAs in MMD is a potential therapeutic strategy and warrants further investigations.

Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data.

Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex.

Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.

Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke.

We sought to identify serological markers capable of diagnosing preeclampsia (PE). We performed serum peptide analysis (liquid chromatography mass spectrometry) of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used as a training set and the other third as a testing set. Differential serum peptide profiling identified 52 significant serum peptides, and a 19-peptide panel collectively discriminating PE in training sets (n = 21 PE, n = 21 control; specificity = 85.7% and sensitivity = 100%) and testing sets (n = 10 PE, n = 10 control; specificity = 80% and sensitivity = 100%). The panel peptides were derived from 6 different protein precursors: 13 from fibrinogen alpha (FGA), 1 from alpha-1-antitrypsin (A1AT), 1 from apolipoprotein L1 (APO-L1), 1 from inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), 2 from kininogen-1 (KNG1), and 1 from thymosin beta-4 (TMSB4). We concluded that serum peptides can accurately discriminate active PE. Measurement of a 19-peptide panel could be performed quickly and in a quantitative mass spectrometric platform available in clinical laboratories. This serum peptide panel quantification could provide clinical utility in predicting PE or differential diagnosis of PE from confounding chronic hypertension.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a global problem with high mortality. Its pathogenesis is not fully understood. To reveal new serum feature of AECOPD and their potential implications, we have analyzed 180 serum samples, and found that in the serum of AECOPD patients, 4-hydroxy-2-nonenal (4HNE)-protein adducts are dynamically increased as partial pressure of oxygen (PaO2) drops, which is accompanied by progressively decreasing thioredoxin reductase (TrxR1) and thioredoxin (Trx1), as compared with those of healthy people. This phenomenon is unique, because acute hypoxia patients have 1.1-fold or 1.7-fold higher serum TrxR1 or Trx1 activity, respectively, than healthy people, in keeping with low 4HNE level. Moreover, serum 4HNE-protein adducts may form disulfide-linked complexes with high-molecular-weight, the amount of which is significantly increased during AECOPD. Serum 4HNE-protein adducts include 4HNE-Trx1 adduct and 4HNE-TrxR1 adduct, but only the former is significantly increased during AECOPD. Through cell biology, biochemistry and proteomics methods, we have demonstrated that extracellular 4HNE and 4HNE-Trx1 adduct affect human bronchial epithelial cells via different mechanisms. 4HNE-Trx1 adduct may significantly alter the expression of proteins involved mainly in RNA metabolism, but it has no effect on TrxR1/Trx1 expression and cell viability. On the other hand, low levels of 4HNE promote TrxR1/Trx1 expression and cell viability, while high levels of 4HNE inhibit TrxR1/Trx1 expression and cell viability, during which Trx1, at least in part, mediate the 4HNE action. Our data suggest that increasing serum 4HNE and decreasing serum Trx1 in AECOPD patients are closely related to the pathological processes of the disease. This finding also provides a new basis for AECOPD patients to use antioxidant drugs.

Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD.

The latent variable "δ" (for "dementia") uniquely explains dementia severity. Depressive symptoms are independent predictors of δ. We explored 115 serum proteins as potential causal mediators of the effect of depressive symptoms on δ in a large, ethnically diverse, longitudinal cohort. All models were adjusted for age, apolipoprotein E, education, ethnicity, gender, hemoglobin A1c, and homocysteine, and replicated in randomly selected 50% subsets. Alpha1-antitrypsin (A1AT), FAS, Heparin-binding EGF-like Growth Factor (HB-EGF), Insulin-like Growth Factor-1 (IGF-1), Luteinizing Hormone (LH), Macrophage Inflammatory Protein type 1 alpha (MIP-1α), Resitin, S100b, Tissue Inhibitor of Metalloproteinase type 1 (TIMP-1), and Vascular Cell Adhesion Molecule type 1 (VCAM-1) each were partial mediators of depression's association with δ. These proteins may offer targets for the treatment of depression's specific effect on dementia severity and Alzheimer's Disease (AD) conversion risk.

Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated.

Bears do not suffer from osteoporosis during hibernation, which is associated with long-term inactivity, lack of food intake, and cold exposure. However, the mechanisms involved in bone loss prevention have scarcely been elucidated in bears. We investigated the effect of serum from hibernating Japanese black bears (Ursus thibetanus japonicus) on differentiation of peripheral blood mononuclear cells (PBMCs) to osteoclasts (OCs). PBMCs collected from 3 bears were separately cultured with 10% serum of 4 active and 4 hibernating bears (each individual serum type was assessed separately by a bear PBMCs), and differentiation were induced by treatment with macrophage colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). PBMCs that were cultured with the active bear serum containing medium (ABSM) differentiated to multi-nucleated OCs, and were positive for TRAP stain. However, cells supplemented with hibernating bear serum containing medium (HBSM) failed to form OCs, and showed significantly lower TRAP stain (p < 0.001). On the other hand, HBSM induced proliferation of adipose derived mesenchymal stem cells (ADSCs) similarly to ABSM (p > 0.05), indicating no difference on cell growth. It was revealed that osteoclastogenesis of PBMCs is hindered by HBSM, implying an underlying mechanism for the suppressed bone resorption during hibernation in bears. In addition, this study for the first time showed the formation of bears' OCs in-vitro.

Non-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals.

Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now.

Human plasma and serum are widely used matrices in clinical and biological studies. However, different collecting procedures and the coagulation cascade influence concentrations of both proteins and metabolites in these matrices. The effects on metabolite concentration profiles have not been fully characterized.

Vessel proliferation underlies a number of serious pathological conditions. Infantile Hemangioma (IH) is a low-aggressive vascular tumor, interesting as an in vivo model of spontaneous tumor regression. Identifying mechanisms underlying IH spontaneous regression may then help to elucidate vessel-growth control, strongly deregulated in other serious conditions such as sarcoma, melanoma, diabetic retinopathy. The present study was aimed at identifying early regression indicators within hematological parameters. Thirty-four blood samples were collected from IH diagnosed babies (20-months median age), spontaneously regressing with age. Nineteen serum standard blood-tests were carried out using diagnostic reagents; in addition, serum-expression of 27 cytokine/chemokines was measured. Samples were divided in three age-groups, namely ≤ 12, 13 to 24 and >24 months-age, respectively. Red-cells count, Hemoglobin, Hematocrit, Neutrophils, Lymphocytes, MCP-1 and MIP-1beta were significantly different in the three age-groups, according to one-way ANOVA analysis. The same parameters showed a significant Pearson-correlation with age, supporting the direct link of age with IH-regression. ROC analysis showed that red-cells count, Hemoglobin, Hematocrit, MCP-1 and MIP-1beta levels significantly discriminate IH in the proliferating-phase from IH in the regressing-phase. Such data indicate for the first time that standard hematological tests and cytokine serum-expression values may effectively discriminate proliferating- from regressing-IH, unrevealing early regression signs, and demonstrate that standard blood-tests may have novel unsuspected diagnostic/prognostic relevance in altered vessel-growth conditions.

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion.

Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; 2) Albuminuric DKD cases: T2DM patients with urinary albumin excretion (UAE) ≥30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; 3) Diabetic controls: T2DM patients with UAE <30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; and 4) Non-diabetic controls: individuals without T2DM. Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04-83.16) vs. albuminuric cases 57.16 (42.24-67.38), diabetic controls 57.28 (42.08-70.47) and non-diabetic controls 44.54 (41.44-53.32) ng/mL; p<0.001]. Urinary progranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30-16.08) vs. 20.94 (12.35-30.22); diabetic controls 14.06 (9.88-20.82) and non-diabetic controls 13.51 (7.94-24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; p<0.001) and interleukin-6 (r = 0.37; p<0.001) and a negative correlation with eGFR (r = -0.22; p = 0.023). Urinary progranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.

End-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN.

Placental-specific protein 1 (PLAC1) is an X-linked trophoblast gene that is re-expressed in several malignancies, including breast cancer, and is therefore a potential biomarker to follow disease onset and progression. Sera from 117 preoperative/pretreatment breast cancer patients and 51 control subjects, including those with fibrocystic disease, were analyzed for the presence of PLAC1 protein as well as its expression by IHC in tumor biopsies in a subset of subjects. Serum PLAC1 levels exceeded the mean plus one standard deviation (mean+SD) of the level in control subjects in 67% of subjects with ductal carcinoma in situ (DCIS), 67% with HER2+ tumors, 73% with triple-negative cancer and 73% with ER+/PR+ tumors. Greater sensitivity was achieved using the mean+2 SD of control PLAC1 serum values, where the false positive rate was 3% and was exceeded by 38%, 40%, 60% and 43% of subjects with DCIS, HER2+, TNBC and ER+/PR+/HER2- tumors. PLAC1 was detected in 97% of tumor biopsies, but did not correlate quantitatively with serum levels. There was no significant correlation of serum PLAC1 levels with race, age at diagnosis, body mass index (BMI) or the presence of metastatic disease. It remains to be determined whether PLAC1 serum levels can serve as a diagnostic biomarker for the presence or recurrence of disease post-surgery and/or therapy.

Progranulin (PGRN) is secreted by adipose tissue and has been linked to obesity, insulin resistance and type 2 diabetes mellitus. There is evidence that a high fat diet increases PGRN expression in rodent adipose tissue. In humans, the relationship between diet composition and concentration of PGRN is still unknown.