The impact of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature terminology in the routine diagnosis of thyroid tumours

Background

Due to the recent proposal of the non‐invasive follicular thyroid neoplasm with papillary‐like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice.

Methods and results

A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically‐treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III‐IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC‐like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1).

Conclusions

In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC‐like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low‐risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

     

Pre‐operative features of non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features: An analysis of their cytological,Gene Expression Classifier and sonographic findings

Objective

To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), as well as any coexisting pathology.

Methods

We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1^st April 2016 and 1^st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in‐house vs outside hospital) and any additional pathology identified in the resection specimen.

Results

The case cohort included 87 nodules diagnosed as NIFTP (size range: 1‐7 cm, mean: 2.5 cm) from 82 patients (age range: 22‐82, mean age: 50.4, M:F—1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non‐calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases.

Conclusions

The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

     

Molecular testing of BRAF,RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy

Objective

Liquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations.

Methods

We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen.

Results

Mutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology.

Conclusions

Mutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.

     

Low‐intensity pulsed ultrasound induced enhanced adipogenesis of adipose‐derived stem cells

Objective

The aim of this study was to investigate effects of low‐intensity pulsed ultrasound (LIPUS) on differentiation of adipose‐derived stem cells (ASCs), in vitro.

Materials and methods

Murine ASCs were treated with LIPUS for either three or five days, immediately after adipogenic induction, or delayed for 2 days. Expression of adipogenic genes PPAR‐γ1, and APN, was examined by real‐time PCR. Immunofluorescence (IF) staining was performed to test for PPAR‐γ at the protein level.

Results

Our data revealed that specific patterns of LIPUS up‐regulated levels of both PPAR‐γ1 and APN mRNA, and PPAR‐γ protein.

Conclusions

In culture medium containing adipogenic reagents, LIPUS enhanced ASC adipogenesis.

     

Character comparison of abdomen‐derived and eyelid‐derived mesenchymal stem cells

Objectives

While most human adipose tissues, such as those located in the abdomen, hip and thigh, are of mesodermal origin, adipose tissues located in the face are of ectodermal origin. The present study has compared stem cell‐related features of abdomen‐derived adult stem cells (A‐ASCs) with those of eyelid‐derived adult stem cells (E‐ASCs).

Materials and methods

Adipose tissue‐derived cells were maintained in DMEM supplemented with 10% FBS. Before passage 6, cells were analysed using FACS, immunocytochemistry and quantitative real time PCR (qRT‐PCR). To examine multi‐differentiational potential, early passage ASCs were cultivated in each of a commercial Stempro^® Differentiation kit.

Results

Unlike fibroblast‐like morphology of A‐ASCs, E‐ASCs had bipolar morphology. Both types of cell exhibited similar surface antigens, and neuronal cell‐related genes and proteins. However, there were differences in mRNA expression levels of CD90 and CD146; neuron‐specific enolase (NSE) and nuclear receptor‐related protein 1 (Nurr1) were different between the two cell types. There was no difference in multi‐differentiational potential between 3 E‐ASCs lines, however, E‐ASCs had higher expression levels of chondrocyte‐related genes compared to A‐ASCs. These cells underwent senescence and maintained normal karyotypes.

Conclusions

Although isolated from similar adipose tissues, both types of cells displayed many contrasting characteristics. Understanding defining phenotypes of such cells is useful for making suitable choices in differing clinical indications.

     

Factors influencing above‐ground and soil seed bank vegetation diversity at different scales in a quasi‐Mediterranean ecosystem

Questions

Are factors influencing plant diversity in a fire‐prone Mediterranean ecosystem of southeast Australia scale‐dependent?

Location

Heathy woodland, Otways region, Victoria, southeast Australia

Methods

We measured patterns of above‐ground and soil seed bank vegetation diversity and associated them with climatic, biotic, edaphic, topographic, spatial and disturbance factors at multiple scales (macro to micro) using linear mixed effect and generalized dissimilarity modelling.

Results

At the macro‐scale, we found species richness above‐ground best described by climatic factors and in the soil seed bank by disturbance factors. At the micro‐scale we found species richness best described above‐ground and in the soil seed bank by disturbance factors, in particular time‐since‐last‐fire. We found variance in macro‐scale β‐diversity (species turnover) best explained above‐ground by climatic and disturbance factors and in the soil seed bank by climatic and biotic factors.

Conclusions

Regional climatic gradients interact with edaphic factors and fire disturbance history at small spatial scales to influence species richness and turnover in the studied ecosystem. Current fire management regimes need to incorporate key climatic–disturbance–diversity interactions to maintain floristic diversity in the studied system.

     

Resistance Training Reduces Skeletal Muscle Work Efficiency in Weight‐Reduced and Non–Weight‐Reduced Subjects

Objective

The objective of this study is to determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight‐reduced and maximal weight subjects.

Methods

This study examined the effects of supervised resistance exercise on skeletal muscle in 14 individuals with overweight and obesity sustaining a 10% or greater weight loss for over 6 months and a phenotypically similar group of 15 subjects who had not reduced weight and were weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x‐ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice‐weekly resistance training.

Results

Non–weight‐reduced subjects were significantly (10%‐20%) stronger before and after the intervention than reduced‐weight subjects and gained significantly more fat‐free mass with a greater decline in percentage of body fat than weight‐reduced subjects. Resistance training resulted in similar significant decreases (~10%) in skeletal muscle work efficiency at low‐level exercise and ~10% to 20% increases in leg strength in both weight‐reduced and non–weight‐reduced subjects.

Conclusions

Resistance training similarly increases muscle strength and decreases efficiency regardless of weight loss history. Increased resistance training could be an effective adjunct to reduced‐weight maintenance therapy.

     

Fluoxetine induces autophagic cell death via eEF2K‐AMPK‐mTOR‐ULK complex axis in triple negative breast cancer

Objectives

Triple negative breast cancer (TNBC) is a complex and intrinsically aggressive tumour with poor prognosis, and the discovery of targeted small‐molecule drugs for TNBC treatment still remains in its infancy. In this study, we aimed to discover a small‐molecule agent for TNBC treatment and illuminate its potential mechanisms.

Materials and methods

Cell viability was detected by using methylthiazoltetrazolium (MTT) assay. Electron microscopy, GFP‐LC3 transfection, monodansylcadaverine staining and apoptosis assay were performed to determine Fluoxetine‐induced autophagy and apoptosis. Western blotting and siRNA transfection were carried out to investigate the mechanisms of Fluoxetine‐induced autophagy. iTRAQ‐based proteomics analysis was used to explore the underlying mechanisms.

Results

We have demonstrated that Fluoxetine had remarkable anti‐proliferative activities and induced autophagic cell death in MDA‐MB‐231 and MDA‐MB‐436 cells. The mechanism for Fluoxetine‐induced autophagic cell death was associated with inhibition of eEF2K and activation of AMPK‐mTOR‐ULK complex axis. Further iTRAQ‐based proteomics and network analyses revealed that Fluoxetine‐induced mechanism was involved in BIRC6, BNIP1, SNAP29 and Bif‐1.

Conclusions

These results demonstrate that Fluoxetine induces apoptosis and autophagic cell death in TNBC, which will hold a promise for the future TNBC therapy.

     

Two‐Year Results of Think Health! ¡Vive Saludable!: A Primary Care Weight‐Management Trial

Objective

Think Health! ¡Vive Saludable! evaluated a moderate‐intensity, lifestyle behavior‐change weight‐loss program in primary care over 2 years of treatment. Final analyses examined weight‐change trajectories by treatment group and attendance.

Methods

Adult primary care patients (n = 261; 84% female; 65% black; 16% Hispanic) were randomly assigned to Basic Plus (moderate intensity; counseling by primary care clinician and a lifestyle coach) or Basic (clinician counseling only). Intention‐to‐treat analyses used all available weight measurements from data collection, treatment, and routine clinical visits. Linear mixed‐effects regression models adjusted for treatment site, gender, and age, and sensitivity analyses evaluated treatment attendance and the impact of loss to follow‐up.

Results

Model‐based estimates for 24‐month mean (95% CI) weight change from baseline were ?1.34 kg (?2.92 to 0.24) in Basic Plus and ?1.16 kg (?2.70 to 0.37) in Basic (net difference ?0.18 kg [?2.38 to 2.03]; P = 0.874). Larger initial weight loss in Basic Plus was attenuated by a ~0.5‐kg rebound at 12 to 16 months. Each additional coaching visit was associated with a 0.37‐kg greater estimated 24‐month weight loss (P = 0.01).

Conclusions

These findings in mostly black and Hispanic female primary care patients suggest that strategies to improve treatment attendance may improve weight loss resulting from moderate‐intensity counseling.

     

2‐(2‐nitrobenzylidene) indolin‐3‐one compound inhibits transmembrane prostate androgen‐induced protein (TMEPAI) expression and cancer cell proliferation

Objectives

The transmembrane prostate androgen‐induced protein (TMEPAI) is aberrantly expressed in many cancer and plays a crucial role in tumourigenesis, which makes it a potential cancer therapeutic target for drug discovery.

Materials and methods

Here, we employed a firefly luciferase reporter driven by the TMEPAI gene promoter to screen for compound capable of inhibiting the expression of TMEPAI, and the effects of TMEPAI inhibitor on cancer cell proliferation were evaluated using the colony formation assay, cell cycle analysis, Ki‐67 immunofluorescence assay and EdU incorporation assay.

Results

2‐(2‐nitrobenzylidene) indolin‐3‐one (JHY‐A007‐50) was identified and shown to effectively inhibit the TMEPAI promoter activity. Further studies revealed that JHY‐A007‐50 specifically inhibited the expression of TMEPAI at both the mRNA and protein levels. Moreover, we found that JHY‐A007‐50 could inhibit cell proliferation and induce cell cycle arrest at the G1 phase. Our results showed that overexpression of TMEPAI decreased the inhibitory effects of JHY‐A007‐50 on cancer cell proliferation, and JHY‐A007‐50 did not affect the cell viability of HeLa cells knocked down of TMEPAI.

Conclusions

Taken together, these results suggest that compound JHY‐A007‐50 mediates the downregulation of TMEPAI expression and inhibits cell proliferation in cancer cells.

     

FBXW7 suppresses epithelial‐mesenchymal transition and chemo‐resistance of non‐small‐cell lung cancer cells by targeting snai1 for ubiquitin‐dependent degradation

Objectives

FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin‐mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear.

Materials and Methods

Immunohistochemical staining and qRT‐PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour‐adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere‐formation assays. Immunofluorescence and co‐immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7.

Results

We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5‐year survival outcomes, and shorter disease‐free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo‐sensitivity and inhibiting Epithelial‐mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression.

Conclusions

FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC

     

Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or Obesity: LIFE‐Moms Prospective Meta‐Analysis

Objective

This study aimed to evaluate the effects of varied lifestyle intervention programs designed to ameliorate excess gestational weight gain (GWG) in pregnant women with overweight or obesity compared with standard care, including effects on pregnancy outcomes.

Methods

Seven clinical centers conducted separate randomized clinical trials to test different lifestyle intervention strategies to modify GWG in diverse populations. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. The results of the separate trials were combined using an individual‐participant data meta‐analysis.

Results

For the 1,150 women randomized, the percent with excess GWG per week was significantly lower in the intervention group compared with the standard care group (61.8% vs. 75.0%; odds ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks' gestation was also lower in the intervention group (8.1 ± 5.2 vs. 9.7 ± 5.4 kg; mean difference: ?1.59 kg [95% CI:?2.18 to ?0.99 kg]). The results from the individual trials were similar. The intervention and standard care groups did not differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight.

Conclusions

Behavioral lifestyle interventions focusing primarily on diet and physical activity among women with overweight and obesity resulted in a significantly lower proportion of women with excess GWG. This modest beneficial effect was consistent across diverse intervention modalities in a large, racially and socioeconomically diverse US population of pregnant women.

     

Weight‐Related Terms Differentially Affect Self‐Efficacy and Perception of Obesity

Objective

Little work has explored the effect of weight‐related terms on treatment initiation; only one study has investigated weight‐related terms and the psychological constructs associated with treatment uptake. The present study examines the effects of four common weight‐related terms on treatment initiation and the moderating effect of weight bias internalization.

Methods

Adult participants with overweight and obesity (n = 436) were recruited online and asked to read three vignettes describing clinical encounters; the weight‐related term (i.e., “weight,” “BMI,” “obesity,” or “fat”) was varied randomly. Participants then reported self‐efficacy, cognitive and emotional illness beliefs about obesity (i.e., illness perception), and interest in a weight loss program.

Results

The term “obesity” resulted in the greatest self‐efficacy and perceived control over obesity. “Fat” resulted in the least illness coherence (i.e., understanding of obesity). Weight bias internalization did not moderate the effect of term on self‐efficacy, nor did it moderate illness perception. No differences in weight loss program enrollment were observed.

Conclusions

Use of the term “obesity” may promote patients’ perceived control and self‐efficacy. Use of “fat” should be avoided. Results suggest that, despite patient and clinician preference for euphemistic weight terms, use of clinical language such as “obesity” may perform better in provider intervention.

     

Old‐growth forests buffer climate‐sensitive bird populations from warming

Aim

Habitat loss and climate change constitute two of the greatest threats to biodiversity worldwide, and theory predicts that these factors may act synergistically to affect population trajectories. Recent evidence indicates that structurally complex old‐growth forest can be cooler than other forest types during spring and summer months, thereby offering potential to buffer populations from negative effects of warming. Old growth may also have higher food and nest‐site availability for certain species, which could have disproportionate fitness benefits as species approach their thermal limits.

Location

Pacific Northwestern United States.

Methods

We predicted that negative effects of climate change on 30‐year population trends of old‐growth‐associated birds should be dampened in landscapes with high proportions of old‐growth forest. We modelled population trends from Breeding Bird Survey data for 13 species as a function of temperature change and proportion old‐growth forest.

Results

We found a significant negative effect of summer warming on only two species. However, in both of these species, this relationship between warming and population decline was not only reduced but reversed, in old‐growth‐dominated landscapes. Across all 13 species, evidence for a buffering effect of old‐growth forest increased with the degree to which species were negatively influenced by summer warming.

Main conclusions

These findings suggest that old‐growth forests may buffer the negative effects of climate change for those species that are most sensitive to temperature increases. Our study highlights a mechanism whereby management strategies to curb degradation and loss of old‐growth forests—in addition to protecting habitat—could enhance biodiversity persistence in the face of climate warming.

     

Loss‐of‐function of miR‐142 by hypermethylation promotes TGF‐β‐mediated tumour growth and metastasis in hepatocellular carcinoma

Objectives

Hypermethylation‐induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA‐142 (miR‐142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR‐142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC).

Methods

Hepatocellular carcinoma tissues and corresponding non‐neoplastic tissues were collected. The expression and function of miR‐142 and TGF‐β in two HCC cell lines were determined. The miRNA‐mRNA network of miR‐142 was analysed in HCC cell lines.

Results

We found that the miR‐142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR‐142 was identified to directly target and inhibit transforming growth factor β (TGF‐β), leading to decreased cell vitality, proliferation, EMT and the ability of pro‐angiogenesis in TGF‐β‐dependent manner. Interestingly, the status of methylation of miR‐142 was analysed and the results found the hypermethylated miR‐142 in tumour patients and cell lines. The treatment of methylation inhibitor 5‐Aza could restore the expression of miR‐142 to suppress the TGF‐β expression, which impaired TGF‐β‐induced tumour growth.

Conclusion

These findings implicated that miR‐142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF‐β‐induced development of hepatocellular carcinoma.

     

Ecological correlates of mammal β‐diversity in Amazonian land‐bridge islands: from small‐ to large‐bodied species

Aim

Mega hydroelectric dams have become one of the main drivers of biodiversity loss in the lowland tropics. In these reservoirs, vertebrate studies have focused on local (α) diversity measures, whereas between‐site (β) diversity remains poorly assessed despite its pivotal importance in understanding how species diversity is structured and maintained. Here, we unravel the patterns and ecological correlates of mammal β‐diversity, including both small (SM) and midsized to large mammal species (LM) across 23 islands and two continuous forest sites within a mega hydroelectric reservoir.

Location

Balbina Hydroelectric Dam, Central Brazilian Amazonia.

Methods

Small mammals were sampled using live and pitfall traps (48,350 trap‐nights), and larger mammals using camera traps (8,160 trap‐nights). β‐diversity was examined for each group using multiplicative diversity decomposition of Hill numbers, which considers the importance of rare, common and dominant species, and tested to what extent those were related to a set of environmental characteristics measured at different spatial scales.

Results

β‐diversity for both mammal groups was higher when considering species presence–absence. When considering species abundance, β‐diversity was significantly higher for SM than for LM assemblages. Habitat variables, such as differences in tree species richness and percentage of old‐growth trees, were strong correlates of β‐diversity for both SMs and LMs. Conversely, β‐diversity was weakly related to patch and landscape characteristics, except for LMs, for which β‐diversity was correlated with differences in island sizes.

Main conclusions

The lower β‐diversity of LMs between smaller islands suggests subtractive homogenization of this group. Although island size plays a major role in structuring mammal α‐diversity in several land‐bridge islands, local vegetation characteristics were additional key factors determining β‐diversity for both mammal groups. Maintaining the integrity of vegetation characteristics and preventing the formation of a large set of small islands within reservoirs should be considered in long‐term management plans in both existing and planned hydropower development in lowland tropical forests.

     

Lifestyle Intervention Decreases Urine Trimethylamine N‐Oxide Levels in Prepubertal Children with Obesity

Objective

Early lifestyle interventions in children with obesity decrease risk of obesity and metabolic disorders during adulthood. This study aimed to identify metabolic signatures associated with lifestyle intervention in urine samples from prepubertal children with obesity.

Methods

Thirty‐four prepubertal children with obesity were studied before and after a 6‐month lifestyle intervention program, and anthropometric, metabolic, and nutritional variables were collected. A nuclear magnetic resonance approach was applied to obtain the metabolomic profile from urine samples. Partial least squares‐discriminant analysis (PLS‐DA) was used to achieve group classification and variable importance on projection (VIP) for biomarker selection.

Results

The intervention reduced caloric intake by 10% (P < 0.05) and BMI standard deviation score by 0.47 SD (P < 0.001). PLS‐DA identified trimethylamine N‐oxide (TMAO, VIP = 2.21) as the metabolite with the highest discrimination properties between groups. Urine TMAO levels were reduced after the intervention (P < 0.05). TMAO is a biomarker of cardiovascular disease risk and is a product of gut microbiota‐dependent metabolism of certain dietary compounds, including choline. Notably, changes in TMAO levels after the intervention did not correlate to differences in choline intake but were inversely associated with fiber intake (P < 0.05).

Conclusions

These results indicate that lifestyle intervention decreases TMAO levels in children with obesity.

     

Effects of simvastatin and rosuvastatin on RAS protein,matrix metalloproteinases and NF‐κB in lung cancer and in normal pulmonary tissues

Objectives

In this study, we have evaluated effects of 24‐hour treatments with simvastatin or rosuvastatin on RAS protein, NF‐κB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery.

Materials and methods

Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5–30 μm ) or rosuvastatin (1.25–30 μm ) and western blot analysis was then performed.

Results

We documented increased expression of proteins, MMP‐2, MMP‐9 and NF‐κB‐p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose‐dependently reduced RAS protein, MMP‐2/9 and NF‐κB‐p65 expression.

Conclusions

In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP‐2/9 and NF‐κB‐p65.