Association of the live microbe intake from foods with all-cause and cardiovascular disease-specific mortality: a prospective cohort study.

BACKGROUND: Live dietary microbes have been hypothesized to promoting human health. However, there has been lacking perceptions to crystallize nexus between consumption of foods with live microbes and mortality. OBJECTIVE: To investigate the association of consumption of foods with medium to high amounts of live microbes with all-cause, cancer-specific, and cardiovascular disease (CVD)-specific mortality. METHODS: The data were obtained from the National Health and Nutrition Examination Survey 1999-2018 at baseline linked to the 2019 National Death Index records. Based on consumption of foods that were categorized as either having medium or high microbial content (MedHi foods), participants were classified into three groups. Kaplan-Meier survival curves and multivariable Cox regression models were used to estimate the association of consumption of MedHi foods with mortality. Population-attributable fractions (PAFs) of consumption of MedHi foods in relation to mortality risk were also estimated. RESULTS: A total of 35,299 adults aged ≥ 20 years were included in this study. During a median follow-up of 9.67 years, compared with adults in G1, those in G3 had 16% (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.77-0.90) reduced risk of all-cause mortality, and 23% (HR, 0.77; 95% CI, 0.67-0.89) reduced risk of CVD-specific mortality. The PAF of high (G3) vs. intermediate or low consumption of MedHi foods (G1 + G2) with all-cause and CVD-specific mortality was 3.4% and 4.3%, respectively. CONCLUSIONS: Consumption of foods with higher microbial concentrations is associated with a reduced risk of all-cause and CVD-specific mortality in US adults.

Association of physical activity and dietary inflammatory index with overweight/obesity in US adults: NHANES 2007-2018.

BACKGROUND: Overweight and obesity lead to a range of noncommunicable diseases (NCDs), such as type 2 diabetes, cardiovascular disease, and stroke. Physical activity (PA) is an important lifestyle behavior for controlling body weight. Dietary inflammatory index (DII), which is associated with systemic inflammatory markers, is used to evaluate the potential of dietary inflammation. This is the first study to investigate the independent and joint associations of PA and DII with the risk of overweight/obesity among US adults. METHODS: Participants and data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, which is designed to examine the health and nutritional status of the non-institutionalized US population by a complex, multi-stage, probability sampling design. RESULTS: A total of 10723 US adults were selected. Physically active participants had lower overweight/obesity risk (total-time PA: OR = 0.756, 95% CI: 0.669-0.855; leisure-time PA: OR = 0.723, 95% CI: 0.643-0.813; and walk/bicycle-time PA: OR = 0.748, 95% CI: 0.639-0.875); however, those with work-time PA showed no significant association between PA and overweight/obesity. Compared with participants in the lowest DII group (Q1), those in the other three groups had high risks of overweight/obesity (Q2: OR = 1.218, 95% CI: 1.054-1.409; Q3: OR = 1.452, 95% CI: 1.245-1.693; Q4: OR = 1.763, 95% CI: 1.495-2.079). In joint analyses, PA was not eligible for reducing risks of weight/obesity if far more pro-inflammatory diet (Q4 of DII = 2.949-5.502) was taken in (total-time PA: OR = 1.725, 95% CI: 1.420-2.097; leisure-time PA: OR = 1.627, 95% CI: 1.258-2.105; walk/bicycle-time PA: OR = 1.583, 95% CI: 1.074-2.332; and work-time PA: OR = 1.919, 95% CI: 1.493-2.467). CONCLUSIONS: More leisure-time PA and walk/bicycle-time PA are associated with lower risk of overweight/obesity, and higher DII is associated with higher risk of overweight/obesity. In addition, higher DII impacts overweight/obesity substantially: once the DII score reached Q4, there is still risks of overweight/obesity even if PA is performed.

MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma.

MiR-204-5p, as a tumour suppressor, has been found in several cancers. However, whether miR-204-5p is involved in papillary thyroid carcinoma (PTC) has not yet been investigated. In this study, we identified miR-204-5p as a down-regulated miRNA in PTC tissues, unveiling that the levels of miR-204-5p in serum of patients with PTC were linked to PTC risk, and that the expression in patients concomitant with both PTC and benign lesions was much lower than that in patients only with PTC. Furthermore, we documented that miR-204-5p inhibited proliferation, migration, invasion, and cell cycle progression and triggered apoptosis of PTC cells via cell biology experiments. Finally, we identified that AP1S2 was a target of miR-204-5p using RNA-seq, iTRAQ, and bioinformatics prediction. Overall, miR-204-5p functions as a suppressor for PTC pathogenesis via the miR-204-5p/AP1S2 axis.

C1QA, C1QB, and GZMB are novel prognostic biomarkers of skin cutaneous melanoma relating tumor microenvironment.

Skin cutaneous melanoma (SKCM) is the most lethal form of skin cancers owing to high invasiveness and high metastatic potential. Tumor microenvironment (TME) provides powerful evidences for discerning SKCM, raising the prospect to identify biomarkers of SKCM. Based on the transcriptome profiles of patients with SKCM and the corresponding clinical information from The Cancer Genome Atlas (TCGA), we used ESTIMATE algorithm to calculate ImmuneScore and StromalScore and identified the TME-Related differentially expressed genes (DEGs), than the intersected TME-Related DEGs were used for subsequent functional enrichment analysis. Protein-protein interaction (PPI) analysis was used to identify the functionality-related DEGs and univariate Cox regression analysis was used to identify the survival-related DEGs. Furthermore, SKCM-related DEGs were identified based on two Gene Expression Omnibus (GEO) datasets. Finally, we intersected functionality-related DEGs, survival-related DEGs, and SKCM-related DEGs, ascertaining that six DEGs (CCL4, CXCL10, CCL5, GZMB, C1QA, and C1QB) function as core TME-related genes (CTRGs). Significant differences of GZMB, C1QA, and C1QB expressions were found in gender and clinicopathologic staging of SKCM. High levels of GZMB, C1QA, and C1QB expressions were associated with favorable prognosis. Gene set enrichment analysis (GSEA) showed that cell-cell interaction, cell behavior, and intracellular signaling transduction may be mainly involved in both C1QA, C1QB and GZMB expressions and metabolism of phospholipid and amino acid, transcription, and translation may be implicated in low GZMB expressions. C1QA, C1QB, and GZMB are novel SKCM-relating CTRGs, providing promising immune-related prognostic biomarkers for SKCM.

Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension.

BACKGROUND: Hypertension, as one of the most common chronic diseases, is a major public health issue. Previous studies have shown that there are miRNAs differentially expressed in hypertensive patients. In addition, hypertension is closely related to endothelial dysfunction, and miRNAs have been identified as important molecular mediators for endothelial function. Therefore, it is necessary to identify specific miRNAs related to hypertension and explore their molecular mechanism in the progression of hypertension. METHODS: We investigated the association of circulating levels of miR-3656 with hypertension. Furthermore, in-vitro studies were performed to investigate its possible mechanisms for hypertension in that the direct target genes of miR-3656 were confirmed using dual-luciferase reporter assay; moreover, the effects of miR-3656 on proliferation, migration, apoptosis, and microvascular rarefaction of HUVECs were investigated using MTS kit, wound-healing assay, FITC Annexin V apoptosis detection kit, and tube formation assay, correspondingly. RESULTS: Circulating miR-3656 was upregulated in patients with hypertension. MiR-3656 suppressed the proliferation, migration, and angiogenesis of HUVECs, but promoted the apoptosis of HUVECs. In addition, eNOS and ADAMTS13 were direct target genes of miR-3656, and overexpression of eNOS and ADAMTS13 abolished the effect of miR-3656 on HUVECs. CONCLUSION: MiR-3656 is a potential biomarker for hypertension. MiR-3656 is involved in endothelial cellular injury implicated in hypertension by targeting eNOS and ADAMTS13.

Down-regulated FST expression is involved in the poor prognosis of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is more commonly associated with young patients, featuring high histological grade, visceral metastasis, and distant recurrence. Follistatin (FST) is a secreted extracellular regulatory protein that antagonizes TGF-ß superfamily such as activin and TGF-ß related superfamily such as bone morphogenetic protein (BMP). The implication of FST in the proliferation, angiogenesis, and metastasis of solid tumors documents good or poor outcome of patients with BC. However, the role of FST in TNBC remains unclear. METHODS: Data of 935 patients with breast cancer (BC) were extracted from TCGA. Case-control study, Kaplan-Meier, uni-multivariate COX, and ROC curve were utilized to investigate the relationship between FST expression and the clinical characteristics and prognosis of BC. Functional studies were used to analyze the effect of FST expression on proliferation, apoptosis, migration, and invasion of TNBC cell lines. Bioinformatic methods such as volcanoplot, GO annd KEGG enrichment, and protein-protein interactions (PPI) analyses were conducted to further confirm the different roles of FST in the apoptotic pathways among mesenchymal and mesenchymal stem-like cells of TNBC. RESULTS: Data from TCGA showed that low FST expression correlated with poor prognosis (for univariate analysis, HR = 0.47, 95% CI: 0.27-0.82, p = 0.008; for multivariate analysis, HR = 0.40, 95% CI: 0.21-0.75, p = 0.004). Low FST expression provided high predicted value of poor prognosis in TNBC amongst BCs. FST knockdown promoted the proliferation, migration and invasion of BT549 and HS578T cell lines. FST inhibited the apoptosis of mesenchymal cells by targeting BMP7. CONCLUSIONS: Low FST expression is associated with poor prognosis of patients with TNBC. FST expressions exhibit the anisotropic roles of apoptosis between mesenchymal and mesenchymal stem-like cells but promote the proliferation, migration, invasion in both of two subtypes of TNBC in vitro. FST may be a subtype-heterogeneous biomarker for monitoring the progress of TNBC.

OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein-1 inhibitor T-5224.

Previous studies have shown that expression of activator protein-1 (AP-1) family is significantly elevated in triple-negative breast cancer (TNBC), compared with that in other breast cancer subtypes. Here we investigated the anti-tumor effect and mechanism of T-5224, an inhibitor of c-Fos/AP-1, on TNBC. We identified that T-5224 inhibited the proliferation, migration, and invasion of TNBC cells and resulted in an increase in apoptosis. Furthermore, we found that OLFML2A is a key regulatory protein acting downstream of AP-1 and is involved in T-5224-targeted AP-1 action. Multiple clinical databases online have identified that high OLFML2A level is associated with poor prognosis in TNBC patients. In summary, our experimental and bioinformatic studies indicated that OLFML2A is necessary for AP-1-overexpressing TNBC. These findings demonstrate that AP-1-overexpressing TNBC dependent on OLFML2A, and targeting both AP-1 and OLFML2A through T-5224 may be a synergistic therapeutic strategy for this clinically challenging subset of breast cancer.

Association between ATM rs1801516 polymorphism and cancer susceptibility: a meta-analysis involving 12,879 cases and 18,054 controls.

BACKGROUND: Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis. METHODS: Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk. RESULTS: A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG + GA: OR = 0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR = 1.00, 95% CI, 0.90-1.11; AA vs GG: OR = 0.89, 95% CI, 0.75-1.06; GA vs GG: OR = 1.01, 95% CI, 0.91-1.13; GG + AA vs GA: OR = 1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG + GA: OR = 0.79, 95% CI, 0.65-0.96, P = 0.017; AA vs GG: OR = 0.79, 95% CI, 0.65-0.96, P = 0.017), South American (AA+GA vs GG: OR = 2.15, 95% CI, 1.37-3.38, P = 0.001; GA vs GG: OR = 2.19, 95% CI, 1.38-3.47, P = 0.001; GG + AA vs GA: OR = 0.46, 95% CI, 0.29-0.72, P = 0.001), and Asian (AA vs GG + GA: OR = 7.45, 95% CI, 1.31-42.46, P = 0.024; AA vs GG: OR = 7.40, 95% CI, 1.30-42.19, P = 0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR = 0.76, 95% CI, 0.59-0.98, P = 0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR = 0.68, 95% CI, 0.47-0.98, P = 0.039). CONCLUSIONS: ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.

Entire Peroxidation Reaction System of Myeloperoxidase Correlates with Progressive Low-Density Lipoprotein Modifications via Reactive Aldehydes in Atherosclerotic Patients with Hypertension.

BACKGROUND/AIMS: Reactive oxygen species (ROS) contribute to the dysfunction of serum lipoproteins, which triggers lipid metabolism abnormalities in the development of atherosclerosis and hypertension. Myeloperoxidase (MPO) is involved in ROS modifications, triggering lipid peroxidation and aldehyde formation. However, the relationship between the entirety of the MPO reaction system and oxidative modification of serum lipoproteins in atherosclerotic patients with hypertension remains unclear. METHODS: We measured MPO activity (peroxidation and chlorination), 4-hydroxynonenal-modified low-density lipoprotein (HNE-LDL), malondialdehyde-modified low-density lipoprotein (MDA-LDL), H2O2, reduced glutathione (GSH), and oxidized glutathione (GSSG) using a corresponding commercial kit in atherosclerotic patients with hypertension and healthy participants. We used Spearman's correlation analysis to investigate the correlation between MPO activity and the levels of these oxidative and anti-oxidative stress-related indices and performed response surface regression to investigate the relationship between the MPO reaction system and the levels of HNE-LDL, MDA-LDL, and the GSH/GSSG ratio. RESULTS: Our results showed no association between the levels of MPO peroxidation activity, MPO chlorination activity, H2O2, and Cl- and those of HNE-LDL, MDA-LDL, GSH, and GSSG, and the GSH/GSSG ratio in healthy participants. In addition, no effects of the peroxidation reaction system of MPO (PRSM) and the chlorination reaction system of MPO (CRSM) on GSH/GSSG were found in this investigation. However, we found that the PRSM rather than the CRSM correlated with progressive low-density lipoprotein (LDL) modifications by HNE-LDL and MDA-LDL in atherosclerotic patients with hypertension. CONCLUSION: The PRSM rather than the CRSM correlated with progressive LDL modifications via reactive aldehydes in atherosclerotic patients with hypertension. Further investigation is warranted to evaluate whether the PRSM may serve as a potential index for monitoring LDL function in atherosclerosis and hypertension.

Classified status of smoking and quitting has different associations with dyslipidemia in residents in northeast China.

BACKGROUND: Various smoking status and high prevalence of dyslipidemia in residents exist in northeast China. However, associations of dyslipidemia with smoking status remain unclear. METHODS: A total of 17,114 participants selected by a multistage stratified cluster random sampling design were enrolled from a cross-sectional study conducted in northeast China. Associations of dyslipidemia with smoking/quitting status (smoking amount, smoking duration, and quitting duration) were investigated using multiple logistic regression. RESULTS: Prevalence (39.2%) of dyslipidemia existed in residents in northeast China. Smoking amount was associated with dyslipidemia (1-10 cigarettes daily: OR = 1.19, 95% CI: 1.08-1.32; 11-20 cigarettes daily: OR = 1.29, 95% CI: 1.16-1.42; and over 20 cigarettes daily: OR = 1.51, 95% CI: 1.25-1.83). Smoking duration was associated with dyslipidemia risk (6-10 years: OR = 1.75, 95% CI: 1.51-2.03; 11-15 years: OR = 1.85, 95% CI: 1.51-2.26; and ≥15 years: OR = 1.12, 95% CI: 1.02-1.23). Quitting duration (1-5 years) was associated with dyslipidemia (OR = 1.26, 95% CI: 1.07-1.48); however, we found no statistically significant associations between dyslipidemia and quitting duration (over 6 years). CONCLUSIONS: Dyslipidemia risk is positively associated with smoking/quitting status. Smoking amount and smoking duration may co-determine dyslipidemia risk, and quitting duration (>6 years) is necessary for reducing dyslipidemia risk.