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Background: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis.Methods: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31).Results: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites.Conclusion: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis.Trial Registration:  This study is registered with ClinicalTrials.gov, number NCT04490447. [ABSTRACT FROM AUTHOR]

Background Studies have reported an association between serum perfluoroalkyl substances (PFASs) and asthma. However, few studies have examined the possible associations between PFASs and the 16-kDa club cell secretory protein (Clara) (CC16) level, a prominent biomarker of asthma, among adolescents. Methods We recruited a total of 231 asthmatic children and 225 non-asthmatic controls in the Genetic and Biomarkers study for Childhood Asthma (GBCA) in northern Taiwan from 2009 to 2010. Structured questionnaires were administered by face-to-face interview. Urine CC16 was determined by an enzyme-link immunoassay kit. Multiple general linear models were employed to examine the associations between PFASs and urinary CC16 levels. Results Asthmatic participants had significantly higher serum PFAS concentrations overall than the healthy controls. After adjusting for confounding factors, urinary CC16 was significantly, negatively associated with PFASs, especially PFOS, PFOA, PFDA and PFNA, and especially among males, as follows: PFOS (β = −0.003, 95% confidence interval [CI]: −0.004, −0.002), PFOA (β = −0.045, 95% CI: −0.086, −0.004), and PFHxA (β = −0.310, 95% CI: −0.455, −0.165) among asthmatic boys, and PFDA (β = −0.126, 95%CI: −0.241, −0.012) and PFNA (β = −0.329, 95% CI: −0.526, −0.132) among non-asthmatic boys. Among girls, PFDA (β = −0.088, 95% CI: −0.172, −0.004), was the only PFAS significantly associated with CC16. Significant interaction effects (p < 0.15) on CC16 levels were found between asthma and PFOS, PFOA, PFBS and PFHxA in all participants. Conclusion Our overall results showed that serum PFASs were significantly, inversely associated with CC16 levels. Associations were stronger among males. [ABSTRACT FROM AUTHOR]

L-3, 4-dihydroxyphenylalanine (L-dopa) is the gold standard for symptomatic treatment of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). In the present study, L-dopa and benserazide were loaded by poly (lactic-co-glycolic acid) microspheres (LBM), which can release levodopa and benserazide in a sustained manner in order to continuous stimulate dopaminergic receptors. We investigated the role of striatal DR1/PKA/P-tau signal transduction in the molecular event underlying LID in the 6-OHDA-lesioned rat model of PD. We found that animals rendered dyskinetic by L-dopa treatment, administration of LBM prevented the severity of AIM score, as well as improvement in motor function. Moreover, we also showed L-dopa elicits profound alterations in the activity of three LID molecular markers, namely (ser396). These modifications are totally prevented by LBM treatment, a similar way to achieve continuous dopaminergic delivery (CDD). In conclusion, our experiments provided evidence that intermittent administration of L-dopa, but not continuous delivery, and (ser396) activation played a critical role in the molecular and behavioural induction of LID in 6-OHDA-lesioned rats. In addition, LBM treatment prevented the development of LID by inhibiting the expression of DR1/PKA/p-tau, as well as PPEB mRNA in dyskintic rats. [ABSTRACT FROM AUTHOR]

Abstract: The nitrate-reducing microbial community in oil reservoirs was examined by PCR using primers to amplify a segment of napA gene encoding for a subunit of the nitrate reductase, and the effects of different organic carbon additions on the nitrate-reducing community were also evaluated. The orders Rhodocyclales and Burkholderiales within Betaproteobacteria and Pseudomonadales within Gammaproteobacteria were recovered in production water of all three oil reservoirs. Amendment of organic acids promoted Enterobacteriales within Gammaproteobacteria and orders of Rhodocyclales, Pseudomonadales, and Burkholderiales, while alkanes favored the Rhizobiaceae family within Alphaproteobacteria and orders of Rhodocyclales and Pseudomonadales. Results indicated that the functional gene napA can be used as a valuable biomarker in analyzing the diversity of nitrate reducers in oil reservoirs. Nitrate-reducing microbial community shifts following the available carbon sources. Information about napA gene in oil reservoirs environment is scarce. This is the first study that combines molecular and culture-dependent approaches to reveal the diversity of the nitrate-reducing microbial community in production water of oil reservoirs by using the napA gene. [Copyright &y& Elsevier]

Background: The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease. Methods: A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ2 test, z test and a multivariate logistic stepwise regression test. Results: We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P < 0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P < 0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis. Conclusions: Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related death worldwide. MicroRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested to be potential biomarkers for cancer diagnosis. The present study was designed to explore whether plasma-derived sEV miRNAs could be utilized as diagnostic biomarkers for differentiating between early-stage small cell lung cancer (SCLC) and early-stage non-small cell lung cancer (NSCLC). We compared the miRNA profiles of plasma-derived sEVs from healthy individuals, patients with early-stage SCLC and patients with early-stage NSCLC. Next-generation sequencing was used to screen for differentially expressed miRNAs (DEMs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the potential functions of these DEMs. Weighted gene coexpression network analysis (WGCNA) was used to identify the different pathology-related miRNA modules. We found that 22 DEMs were significantly different among healthy individuals, patients with early-stage SCLC, and patients with early-stage NSCLC. We selected six representative DEMs for validation by qRT‒PCR, which confirmed that miRNA-483-3p derived from plasma sEVs could be used as a potential biomarker for the diagnosis of early-stage SCLC, miRNA-152-3p and miRNA-1277-5p could be used for the diagnosis of early-stage NSCLC respectively. [ABSTRACT FROM AUTHOR]

Background: Discovery of early-stage biomarkers is a long-sought goal of Alzheimer's disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn't proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology. Results: This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala–Ala–Asn–Cys–Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg−1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice. Conclusions: The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is one of the most common complications in stroke survivors. But, there are still no objective methods to diagnose PSD. This study aims to identify potential biomarkers for diagnosing PSD in middle-aged stroke survivors. Methods: Middle-aged subjects aged 30 to 59 years (92 PSD patients and 89 stroke survivors without depression) were included in this study. Urinary metabolites were detected by gas chromatography-mass spectrometry (GC-MS). Differential urinary metabolites and potential biomarkers were screened by applying statistical analysis. Results: The different urinary metabolic phenotypes between PSD patients and stroke survivors without depression were identified. A total of 12 differential urinary metabolites were accurately identified by using orthogonal partial least-squares-discriminant analysis. After analyzing those 12 differential urinary metabolites by step-wise logistic regression analysis, only seven metabolites (palmitic acid, hydroxylamine, myristic acid, glyceric acid, lactic acid, tyrosine and azelaic acid) were finally selected as potential biomarkers for diagnosing PSD in middle-aged stroke survivors. A panel consisting of these potential biomarkers could effectively diagnose middle-aged PSD patients. Conclusion: Urinary metabolic profiles were different between middle-aged PSD patients and stroke survivors without depression. Our results would be helpful in future for developing an objective method to diagnose PSD in middle-aged stroke survivors. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80–1.21) to 2.76 (95% CI: 1.82–4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1 s: FEV 1 ; forced expiratory flow 25–75%: FEF 25–75 ) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from −0.055 (95%CI: −0.100 to −0.010) for FVC and perfluorooctane sulfonate (PFOS) to −0.223 (95%CI: −0.400 to −0.045) for FEF 25–75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma. [ABSTRACT FROM AUTHOR]

Objective: A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. Methods: Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. Results: Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. Conclusion: K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR- TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. Experimental design: We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Results: Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. Conclusions: This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC. [ABSTRACT FROM AUTHOR]