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1.

Introduction

In spite of advances in antibiotics, urinary tract infection (UTI) is still among the most common reasons for antibiotic medication worldwide. Persicaria capitata (Buch.-Ham. ex D. Don) H.Gross (P. capitata) is a herbal medicine used by the Miao people in China to treat UTI. However studies of its mechanism are challenging, owing to the complexity of P. capitata with multiple constituents acting on multiple metabolic pathways.

Objective

The objective of this study was to explore the working mechanism of P. capitata on urinary tract infection.

Methods

Relinqing® granule, which is solely made from aqueous extracts of the whole P. capitata plant, was used in this study. Urine metabolomics based on gas chromatography-mass spectroscopy was employed to assess the metabolic changes caused by administration of Relinqing® granule in a UTI mouse model. Female specific-pathogen-free Kunming mice were divided into control group (mock infection, saline treatment), model group (E.coli infection, saline treatment), Relinqing® group (E.coli infection, Relinqing® granule treatment), ciprofloxacin group (E.coli infection, ciprofloxacin treatment), and sham-Relinqing® group (no surgery, Relinqing® granule treatment).

Results

The results showed that after the treatments, urine levels of itaconic acid in Relinqing® group increased by 4.9 fold and 11.3 fold compared with model and ciprofloxacin groups respectively. Itaconic acid is an endogenous antibacterial metabolite produced by macrophages, which also functions as a checkpoint for metabolic reprogramming of macrophage.

Conclusion

Our findings suggest that this herbal medicine can cure urinary tract infection through modulation of immune system.
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2.

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.
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3.

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.
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4.

Introduction

The human gut microbes and their metabolites are involved in multiple host metabolic pathways. Dysbiosis in the gut microbiota and altered metabolite profiles were reported in diseased state. In a region like Assam, where 12.4% of the populations are tribal population, evaluating the influence of ethnicity on gut microbiota and metabolites has become important to further differentiate it from the diseased state.

Objective

To study the influence of ethnicity on fecal metabolite profile and their association with the gut microbiota composition.

Methods

In this study, we determined the untargeted fecal metabolites from five ethnic groups of Assam (Tai-Aiton, Bodo, Karbi, Tea-tribe and Tai-Phake) using GC–MS and compared them among the tribes for common and unique metabolites. Metabolites of microbial origin were related with the available metagenomic data on gut bacterial profiles of the same ethnic groups and functional analysis were carried out based on HMDB.

Results

The core fecal metabolite profile of the Tea-tribe contained aniline, benzoate and acetaldehyde. PLS-DA based on the metabolites suggested that the individuals grouped based on their ethnicity. PCA plot of the data on bacterial abundance at the level of genus indicated clustering of individuals based on ethnicity. Positive correlations were observed between propionic acid and the genus Clostridium (R?=?0.43 and p?=?0.03), butyric acid and the genus Lactobacillus (R?=?0.45 and p?=?0.024), acetic acid and the genus Bacteroides (R?=?0.63 and p?=?0.001) and methane and the genus Escherichia (R?=?0.58 and p?=?0.002).

Conclusion

Results of this study indicated that ethnicity influences both gut bacterial profile and their metabolites.
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5.

Background

After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population.

Methods

Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2.

Results

A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR?=?2.924, P?=?2.3E?06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR?=?0.08033, P?=?2.11E?09) and dominant models (OR?=?0.05359, P?=?4.15E?11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR?=?20.05, P?=?2.74 E?12) and recessive models (OR?=?22.24, P?=?6.811E?10).

Conclusions

Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.
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6.

Background

We describe coagulase-negative staphylococci (CoNS) isolates collected from ducklings exhibiting tremor in South Korea over the period of 2010 to 2011. Screening of antimicrobial susceptibility and analysis of SCCmec elements of CoNS were also investigated.

Results

Staphylococcus cohnii was the most frequent staphylococcus (9 isolates) and S. sciuri (4 isolates), S. lentus (3 isolate), S. simulans (1 isolate) and S. epidermidis (1 isolate) were also detected. Among the 15 antimicrobials tested in this study, resistance against oxacillin (15 isolates, 83.3%) was most frequently observed, but only one isolate (SNUDS-1) possessed mecA. This isolate was shown to possess SCCmec type III; the type 3 ccr complex and the class A mec complex.

Conclusions

Based on these results, isolate SNUDS-1 was shown to possess SCCmec type III; the type 3 ccr complex and the class A mec complex. Although the SCCmec type III is not predominant in human, MR-CoNS (Methicillin resistance Coagulase-negative staphylococci) in food animals should be monitored to prevent the dissemination of antimicrobial resistance genes and resistant pathogens to the community.
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7.

Background

The rupture of a brain aneurysm causes bleeding in the subarachnoid space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a South Indian population.

Methods

The study was performed on 200 subjects with aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic discrimination assay. Statistical software R.3.0.11 was used to statistically analyze the data and a p value <?0.05 was considered as statistically significant.

Results

We found a significant association with the risk of aSAH in ε3/ ε4 genetic model (OR?=?1.91, 95% CI?=?1.16–3.14, p?=?0.01). However, in the other genetic models and allele frequency, there was no significant association with the risk of aSAH. In subtyping, we found a significant association of ε2 allele frequency with posterior communicating artery (PCOM) aneurysm (OR?=?3.59, 95% CI?=?1.11–11.64, p?=?0.03).

Conclusion

Our results suggest that APOE polymorphism has an influence on the risk of aSAH in this South Indian population, specifically in the PCOM subtype.
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8.

Background

Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.

Methods

The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.

Results

Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04–1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06–1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01–2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05–1.78, P?=?0.018).

Conclusion

The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.
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9.

Background

The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed.

Results

A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P?<?0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r?=?0.59, P?<?0.05), Ki-67 antigen expression (r?=?0.43; P?<?0.0005), TUNEL-positive cells (r?=?0.62, P?<?0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r?=?0.57, P?<?0.05).

Conclusion

Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans.
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10.
11.

Background

Current guidelines recommend a single inhaler maintenance and reliever therapy (SMART) regimen for moderate to severe asthma. However, evidence for the inhaled corticosteroid plus fast-onset-acting β2-agonist (ICS/FABA) as reliever therapy in management of intermittent and mild asthma patients is lacking.

Objective

To systematically explore efficacy and safety of the proof-of-concept of the ICS plus FABA regimen in a single inhaler as reliever therapy across children and adults with intermittent and mild persistent asthma.

Methods

We searched online bibliographic databases for randomized controlled trials (RCTs) involving the as-needed use of ICS/FABA as monotherapy in intermittent or mild asthma patients. The primary outcomes were exacerbations and the hazard ratio (HR) of the time to first exacerbation.

Results

Six RCTs (n?=?1300) met the inclusion criteria. Compared with the as-needed FABA regimen, the as-needed use of ICS/FABA as monotherapy statistically reduced exacerbations (RR?=?0.56, P?=?0.001). Compared with regular ICS regimen, the as-needed ICS/FABA therapy had slightly higher risk of exacerbations (RR?=?1.39, P?=?0.011). The HR for time to first exacerbations in the ICS/FABA regimen was significant lower when compared with FABA regimen (HR?=?0.52, P?=?0.002) but had no difference when compared with ICS regimen (HR?=?1.30, P?=?0.286). The corticosteroid exposure in the daily ICS regimen was 2- to 5-fold compared with as-needed use of ICS/FABA regimen.

Conclusions

Our analysis shows that the ICS/FABA as a symptom-driven therapy may be a promising alternative regimen for the patients with intermittent or mild asthma, but it needs further real-world RCTs to confirm these findings.
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12.

Background

Salmonella spp. have been isolated from a wide range of wild animals. Opportunistic wild carnivores such as red foxes (Vulpes vulpes) and badgers (Meles meles) may act as environmental indicators or as potential sources of salmonellosis in humans. The present study characterizes Salmonella spp. isolated from the intestinal contents of hunted or dead red foxes (n?=?509) and badgers (n?=?17) in northern Italy.

Findings

Thirty-one strains of Salmonella belonging to 3 Salmonella enterica subspecies were isolated. Fourteen different serovars of S. enterica subsp. enterica were identified, among which were serovars often associated with human illness.

Conclusions

Wild opportunistic predators can influence the probability of infection of both domestic animals and humans through active shedding of the pathogen to the environment. The epidemiological role of wild carnivores in the spread of salmonellosis needs to be further studied.
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13.

Background

There is conflicting evidence regarding the benefit of adjunctive corticosteroid therapy in patients with Mycoplasma pneumoniae pneumonia. We hypothesised that corticosteroid therapy could reduce mortality and length of stay (LOS) in such patients.

Methods

Adult patients with M. pneumoniae pneumonia from January 2010 to December 2013 were identified from the Japanese Diagnosis Procedure Combination inpatient database. The effects of low-dose and high-dose corticosteroid therapies on mortality, LOS, drug costs and hyperglycaemia requiring insulin treatment were evaluated using propensity score analyses.

Results

Eligible patients (n?=?2228) from 630 hospitals were divided into no-corticosteroid (n?=?1829), low-dose corticosteroid (n?=?267) and high-dose corticosteroid (n?=?132) groups. The propensity score-matched pairs were generated from no-corticoid and low-dose corticoid groups (251 pairs), or no-corticoid and high-dose corticosteroid groups (120 pairs). Adjunctive corticosteroid therapy did not decrease 30-day mortality. In addition, both low-dose and high-dose corticosteroid therapies were associated with increases in LOS. Furthermore, hyperglycaemia requiring insulin treatment and drug cost increased with corticosteroid use.

Conclusions

Adjunctive treatment with low-dose or high-dose corticosteroids may not be beneficial in M. pneumoniae pneumonia.
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14.

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.
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15.

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.
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16.

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.
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17.

Background

Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.

Methods

We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.

Results

Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z?=???8.635, p?<?0.001) and peritumoral (median 113.53 vs. 82.48; Z?=???3.741, p?<?0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z?=???0.817,p?=?0.414) and peritumoral (median 402.56 vs. 390.84; Z?=???1.138,p?=?0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z?=???2.009, p?=?0.045) and peritumoral areas(median 63.31 vs. 98.48; Z?=???2.469, p?=?0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR?=?0.297; 95% CI, 0.109–0.810, p?=?0.018) and overall survival (HR?=?0.078; 95% CI, 0.010–0.598, p?=?0.014).

Conclusions

NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.
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18.

Objectives

To develop a versatile Trichoderma reesei (teleomorph Hypocrea jecorina) expression system for the high-purity production of heterologous proteins.

Results

The versatile T. reesei expression system is based on xyn1 and xyn2 promoters, A824V transition in XYRI, and a bicomponent carbon source strategy. Red fluorescent protein gene rfp and alkaline endoglucanase EGV gene egv3 from Humicola insolens were used as reporter genes to test our versatile expression system

Conclusions

The versatile T. reesei expression system can be applied to produce heterologous proteins with high purity and high yield.
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19.

Objectives

A Neissaria bacterial pilus sugar, bacillosamine, was synthesized and, for the first time, used as a probe to screen a single-chain variable fragment (scFv).

Results

Four Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria sicca and Neisseria subflava, and two negative controls, Streptococcus pneumoniae and Escherichia coli, were tested through ELISA, immunostaining and gold nanoparticle immunological assay. All results indicated that the selected scFv is feasible for the specific detection of Neisseria species via the recognition of bacillosamine.

Conclusions

The recombinant scFv could detect Neisseria strains at 106 CFU/ml.
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20.

Background

The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.

Methods

Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.

Results

At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).

Conclusions

Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.
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