Monoamine oxidase B inhibits epithelial-mesenchymal transition and trigger apoptosis via targeting ERK1/2 signaling pathway in head and neck squamous cell carcinoma.

BACKGROUND: Monoamine oxidase B (MAOB), a flavin monoamine oxidase, regulates biogenic and xenobiotic amine oxidative deaminization. We demonstrate MAOB expression in head and neck epithelium and its biological importance in head and neck squamous cell carcinoma (HNSCC) development. METHODS: First, we found a possible MAOB downregulation in HNSCC using bioinformatic analysis. Second, we validated MAOB expression changes in vitro and assessed its tumorigenicity in HNSCC. Finally, preclinical xenograft models further confirmed our findings. RESULTS: Results proved that MAOB was significantly reduced in HNSCC tissues and cell lines. By comparing MAOB localization in patient specimens, we found that epithelial basal cells express MAOB and that it changes throughout HNSCC development. We observed that MAOB overexpression inhibited HNSCC cell malignancy via lentiviral transfection. We additionally discovered that selegiline partly counter-regulated MAOB overexpression-induced phenotypes in HNSCC cells. CONCLUSIONS: We found that MAOB is a potent biomarker and a unique and essential indication of HNSCC carcinogenesis.

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure.

AIM: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure. BACKGROUND: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure. OBJECTIVES: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated. METHODS: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats. RESULTS: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group. CONCLUSION: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Multi-omics data reveals the disturbance of glycerophospholipid metabolism caused by disordered gut microbiota in depressed mice.

INTRODUCTION: Although researchers have done intensive research on depression, its pathogenesis is still not fully explained. More and more evidence suggests that gut microbiota is closely related to the onset of depression; but its specific functional ways are not clearly identified. OBJECTIVES: The purpose of our work was to find out how the gut microbiota was involved in the onset of depression, and to identify the potential ways to link the gut and brain in mice with depressive-like behaviors (DLB). METHODS: We used the chronic restraint stress (CRS)-induced depression model here. Gut microbiota compositions in fecal samples, lipid metabolism (in fecal, serum and hippocampus samples) and neurotransmitters in hippocampus samples were detected. RESULTS: We found that the 7 of 13 differential genera that significantly correlated with DLB belonged to phylum Firmicutes. The differential lipid metabolites in fecal samples mainly belonged to glycerophospholipids (GP) and fatty acids (FA) metabolism, and three important "metabolite type-bacterial taxa" correlated pairs were identified: "FA/GP-Firmicutes", "FA/GP-Akkermansia", and "FA/GP-Bifidobacterium". The key differential lipid metabolites significantly correlated with DLB mainly belonged to FA and GP, and the DLB-related metagenomic genes were consistently enriched in GP metabolism and FA metabolism. Three significantly changed short-chain fatty acids (SCFAs) were significantly correlated with the majority of differential genera. Meanwhile, we found that the differential lipid metabolites in serum and hippocampus samples were mainly mapped into the GP metabolism, and there were four differential neurotransmitters from the tryptophan pathway in hippocampus samples. CONCLUSION: Together, our findings could provide novel insights into the role of "microbiota-gut-brain" (MGB) axis in depression, and indicate that the gut microbiota might have a vital role in the onset of DLB by affecting the peripheral/central GP metabolism and tryptophan pathway. The "Firmicutes-SCFAs-GP metabolism-Tryptophan pathway" might be a possible way to link the gut and brain in depressed mice.

Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder.

Objective: Increasing evidence shows a close relationship between gut microbiota and major depressive disorder (MDD), but the specific mechanisms remain unknown. This study was conducted to explore differential gut microbiota compositions related to the severity of MDD. Methods: Healthy controls (HC) (n = 131) and MDD patients (n = 130) were included. MDD patients with Hamilton Depression Rating Scale (HDRS) score <25 and ≥25 were assigned into moderate (n = 72) and severe (n = 58) MDD groups, respectively. Univariate and multivariate analyses were used to analyze the gut microbiota compositions at the genus level. Results: Thirty-six and 27 differential genera were identified in moderate and severe MDD patients, respectively. The differential genera in moderate and severe MDD patients mainly belonged to three (Firmicutes, Actinobacteriota, and Bacteroidota) and two phyla (Firmicutes and Bacteroidota), respectively. One specific covarying network from phylum Actinobacteriota was identified in moderate MDD patients. In addition, five genera (Collinsella, Eggerthella, Alistipes, Faecalibacterium, and Flavonifractor) from the shared differential genera by two MDD groups had a fair efficacy in diagnosing MDD from HC (AUC = 0.786). Conclusions: Our results were helpful for further exploring the role of gut microbiota in the pathogenesis of depression and developing objective diagnostic methods for MDD.

miRNA-29 aggravates myocardial infarction via inhibiting the PI3K/mTOR/HIF1α/VEGF pathway.

INTRODUCTION: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. METHODS: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. RESULTS: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. CONCLUSIONS: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.

miRNA-29a inhibits atherosclerotic plaque formation by mediating macrophage autophagy via PI3K/AKT/mTOR pathway.

BACKGROUND: miR-29a plays a vital role in AS, but the relationship between the miR-29a-targeted PI3K signaling pathway and AS remains unclear. Therefore, this study was carried out. METHODS: Gene expression profiles from the GEO database containing AS samples were analyzed. ApoE-/- mice and RAW264.7 cells were treated with miR-29a negative control (NC), miR-29a mimic and miR-29a inhibitor to establish the AS model. Then MOVAT staining, TEM, Western blotting, and immunofluorescence staining were adopted for testing target proteins. RESULTS: DEGs were identified from GSE137578, GSE132651, GSE113969, GSE43292, and GSE97210 datasets. It was found that there were targeted binding sites between miR-29a and PIK3CA. Besides, GO and KEGG analysis demonstrated that autophagy was an enriched pathway in AS. Later, PPI network was depicted, and hub genes were then determined. The results revealed that miR-29a suppressed the areas of plaques and lesional macrophages, but had no impact on VSMCs. TEM results showed the organelles pyknosis of lesional macrophages damaged morphological changes. Furthermore, miR-29a amplified the M2-like macrophages but suppressed the polarization of M1-like macrophages in atherosclerotic plaques. According to mouse and RAW 264.7 cell experiments, miR-29a significantly inhibited the protein expressions of PI3K, p-PI3K, p-AKT, and p-mTOR, which were consistent with the increased expressions of autophagy-related proteins, Beclin 1 and LC3II. However, the miR-29a suppression exhibited the contrary results. CONCLUSION: MiR-29a elevation induces the increase of autophagy by down-regulating the PI3K/AKT/mTOR pathway in the progression of AS, indicating that miR-29a is a novel therapeutic strategy for AS.

Inhibiting effect of miR-29 on proliferation and migration of uterine leiomyoma via the STAT3 signaling pathway.

AIM: Uterine leiomyoma is the most common benign tumor of female genitalia, and the incidence is rising gradually. This study explores the mechanism of miR-29 and STAT3 signaling pathways on uterine leiomyoma. METHODS: GSE64763 and GSE5244 datasets were downloaded. Enrichment analyses were performed in GSE64763. PPI network was constructed, and the significant module was identified. Uterine leiomyoma cell lines were divided into NC, miR-29 mimic, anti-NC, and miR-29 inhibitor groups. Plate clone formation and Transwell assays detected the proliferation, invasion, and migration of cells. The expression levels of STAT3, proliferation, EMT, invasion-associated proteins were determined by Western blotting. RESULTS: Differently expressed genes were mainly enriched in positive regulation of cell migration and gene expression, cell proliferation. Through GSEA, JAK-STAT is a significantly correlated enrichment pathway. A Venn diagram was drawn to identify the common miRNA (miR-29-3p). miR-29 inhibitors promoted protein expression of STAT-3, Cyclin D1, and c-Myc compared with the anti-NC control (P < 0.01), and miR-29 inhibitors promoted cell proliferation in uterine leiomyoma cells (P < 0.05). Furthermore, miR-29 inhibitors promoted the protein expression of MMP-2 and MMP-9 (P < 0.01), and EMT promoting proteins N-cadherin, snail, vimentin, and Transwell assay showed that miR-29 inhibitors promoted cell migration in uterine leiomyoma (P < 0.01). CONCLUSIONS: High expression of miR-29 could inhibit cell proliferation, invasion, and metastasis in uterine leiomyoma, which might be related to the inhibition of the STAT3 signaling pathway, and could provide a novel target for the treatment of uterine leiomyoma.

Suppression of ADAM8 attenuates angiotensin II-induced cardiac fibrosis and endothelial-mesenchymal transition via inhibiting TGF-ß1/Smad2/Smad3 pathways.

Endothelial-to-mesenchymal transition (EndMT) is involved in cardiac fibrosis induced by angiotensin II (Ang II). A disintegrin and metalloproteinase 8 (ADAM8), a member of ADAMs family, participates in cell adhesion, proteolysis and various signaling. However, its effects on the development of cardiac fibrosis remain completely unknown. This study aimed to reveal whether ADAM8 aggravates cardiac fibrosis induced by Ang II in vivo and in vitro. The C57BL/6J mice or cardiac endothelial cells were subjected to Ang II infusion to induce fibrosis. The results showed that systolic blood pressure and diastolic blood pressure were significantly increased under Ang II infusion, and ADAM8 was up-regulated. ADAM8 inhibition attenuated Ang II-induced cardiac dysfunction. ADAM8 knockdown suppressed Ang II-induced cardiac fibrosis as evidenced by the down-regulation of CTGF, collagen I, and collagen III. In addition, the endothelial marker (VE-cadherin) was decreased, whilst mesenchymal markers (α-SMA and FSP1) were increased following Ang II infusion. However, ADAM8 repression inhibited Ang II-induced EndMT. Moreover, ADAM8 silencing repressed the activation of TGF-ß1/Smad2/Smad3 pathways. Consistent with the results in vivo, we also found the inhibitory effects of ADAM8 inhibition on EndMT in vitro. All data suggest that ADAM8 promotes Ang II-induced cardiac fibrosis and EndMT via activating TGF-ß1/Smad2/Smad3 pathways.

Treatment challenges in patients with early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery: A case report.

INTRODUCTION: Early acute massive pulmonary thrombosis embolism (PTE) after lung cancer surgery is one of the most fatal surgical complications. It is often accompanied by shock and hypotension, with high mortality rate. Due to surgical wounds, patients with early acute massive PTE after lung cancer surgery have a high risk of thrombolytic bleeding, which renders treatment more challenging and there is currently no standard protocol on how to safely and effectively treat these patients in the clinic. PATIENT CONCERNS: A 66-year-old woman after video-assisted thoracoscopic surgery for lung cancer, experienced sudden severe dyspnea, shock and hypotension with high D-Dimer, changed electrocardiogram (ECG), right ventricular dilatation, severe tricuspid regurgitation, and raised pulmonary arterial pressure on ultrasonic cardiogram (UCG), thromboses found on Ultrasonography of lower extremity vein. DIAGNOSIS: Because of her clinical manifestations and results of bedside auxiliary examinations, the patient was finally diagnosed with acute high-risk PTE after lung cancer surgery. INTERVENTIONS: 1.5 hours after onset of symptoms, thrombolysis using a continuous micropump infusion of 20,000 units/kg urokinase into the peripheral vein for 2 hours was initiated for this patient. OUTCOMES: The patient died of massive hemorrhage after thrombolysis. LESSONS: Treatment for patients with early acute PTE after lung cancer surgery is challenging due to a high risk of thrombolytic bleeding at the surgical site. Real-time monitoring of vital signs during thrombolysis and catheter-directed thrombolysis are recommended for these patients, in order to use the minimum drug dosage for quick curative effects and a low risk of bleeding.

[Relationship between perirenal adipose tissue neuropeptide Y and insulin resistance in nutritional transition model].

OBJECTIVE: To observe the changes of neuropeptide Y(NPY) expression in perirenal adipose tissue and its relationship with insulin resistance in the nutritional transition models of refeeding after calorie restriction. METHODS: SPF Male SD rats, aged 8 weeks, were randomly divided into normal chow group and refeeding with normal chow after calorie restriction for 4 weeks group. NPY gene expression in perirenal adipose tissue were detected by real-time quantitative PCR at the end of 4 and 12 weeks, along with fasting plasma glucose, fasting serum lisulin, free fatty acids and average glucose infusion rate(GIR_(60-120)) of hyperinsulinemic-euglycemic clamp test for 60-120 minutes. NPY gene mRNA expression in perirenal adipose tissue was detected by real-time quantitative PCR. And the relationship between NPY gene expression and insulin resistance was detected by Spearman correlation analysis. RESULTS: The expression level of NPY gene in perirenal adipose tissue in caloric restriction for 4 weeks group was significantly increased by calorie restriction(P<0. 01). After refeeding, the expression level of NPY gene in refeeding with normal group was still slightly increased, which was significantly higher than that in normal group at the end of the experiment(P<0. 01). The levels of fasting plasma glucose and fasting insulin in caloric restriction for 4 weeks group decreased slightly, GIR_(60-120) increased slightly, but there were no statistical differences compared with normal group(P>0. 05), but free fatty acid levels increased significantly(P<0. 01). After refeeding, the levels of fasting insulin, free fatty acid in refeeding with normal group increased significantly, GIR_(60-120) decreased evidently(P<0. 01), but the changes of fasting blood glucose were not obvious. The result of stepwise regression showed that the expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120) and fasting insulin, with R values of-0. 816 and 0. 789 respectively(R~2=0. 892, P<0. 01). The result of correlation analysis showed that in the 4-week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_( 60-120)、fasting insulin and free fatty acid, with R values of-0. 765, 0. 716 and 0. 657 respectively(P<0. 01). In the 12 week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120), fasting insulin and free fatty acid, with R values of-0. 853, 0. 622 and 0. 608 respectively(P<0. 01). CONCLUSION: The mRNA expression of NPY gene in perirenal adipose tissue was closely related to indicators of insulin resistance. It is an important factor affecting insulin sensitivity.

Sequential Whole Exome Sequencing Reveals Somatic Mutations Associated with Platinum Response in NSCLC.

PURPOSE: Resistance is one of the main limitations of successful platinum treatment in non-small-cell lung cancer (NSCLC) patients. In this study, we aimed to identify somatic mutations associated with platinum response. PATIENTS AND METHODS: A total of 57 patients who received platinum-based chemotherapy only and 13 patients who received neoadjuvant chemotherapy (NAC) were enrolled. Somatic mutations were obtained from targeted and whole exome sequencing (WES). RESULTS: Somatic mutations in a total of 225 genes were observed. Nonsynonymous variants in EGFR, TTN, TP53 and KRAS, and copy number variations (SCNVs) in chromosome 8q24.3 and 22q11.21 were identified to be associated with platinum response. Based on these mutations, the mutational signature associated with the failure of DNA double-strand break and calcium signaling pathways were identified to be associated with platinum response. Besides, we observed a decrease in tumor mutational burden after chemotherapy. We also evaluated the mutation spectrum consistency between cell-free DNA (cfDNA) and tissue DNA. Somatic mutations detected in cfDNA were consistent with that in tDNA, which indicated that plasma might be used for somatic mutation detection. CONCLUSION: These results support that somatic mutations can affect platinum drug response and provide potential clinical biomarkers for NSCLC treatment.

Current and emerging treatment options for lung cancer in patients with pre-existing connective tissue disease.

An association between connective tissue disease (CTD) and lung cancer has been claimed in accumulating studies. However, the management of lung cancer with CTD is challenging because the pre-existing CTDs have proved to be significant risk factors for treatment-related toxicity, resulting in poor survival. In this review, we summarize the available information related to the treatment for lung cancer with CTD, discuss risk factors for treatment-related toxicities and management recommendations, which attempts to approach lung cancer with comorbid CTD systematically. Preliminary data show that: i) limited studies have focused on the effect of traditional therapeutic modalities, such as surgical treatment and chemotherapy; ii) with the development of the modern radiation techniques, radiotherapy would be well tolerated in this challenging clinical situation, but a cautious decision should be made for patients with CTD associated interstitial lung disease (ILD); iii) for patients with inactive CTD, immunotherapy was shown to have excellent local control with acceptable toxicity; iv) little information is available on the effects of tyrosine kinase inhibitors because of acute exacerbation (AE) of ILD risks; v) antiangiogenic therapy might be useful in preventing the progression in both lung cancer and CTD without increasing the AE-ILD risk; vi) Nintedanib would be a potentially promising novel therapy since it has recently been developed with promising results for both lung cancer and CTD-ILD. Further large-scale, randomized, controlled studies are still required to develop better therapeutic management for patients with lung cancer and pre-existing CTD.

[Effect of resveratrol on body composition in adult catch-up growth rats and its mechanism].

OBJECTIVE: To observe the effects of resveratrol on body composition in adult catch-up growth rats and to explore the possible mechanism. METHODS: Eight-week-old male SD rats were randomly divided into 6 groups: normal controls for 4 weeks (NC4) group, caloric restriction for 4 weeks (R4) group, calorie restriction meanwhile resveratrol treatment for 4 weeks (R4E) group, normal controls for 12 weeks (NC12) group, catch-up growth (CUG) group and catch-up growth meanwhile resveratrol treatment for 8 weeks (CUGE) group. At the end of the four-week and twelve-week experimental period, the body weight, muscle and fat content of trunk and whole body, the ratio of trunk to whole body fat were detected, and at the end of twelve-week experimental period, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue, and the expression of PPARγ in epididymal adipose tissue were detected. RESULTS: Compared with NC12 group, the fat content of trunk and whole body and trunk to whole body fat ratio in CUG group were increased significantly, along with the expression of PPARγ in epididymal adipose tissue was increased significantly (P＜0.05), while the muscle content of trunk and whole body, the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUG group were decreased significantly compared with NC12 group (P＜0.05 or P＜0.01); compared with CUG group, oral administration of resveratrol distinctly reduced the body fat content and trunk to whole body fat ratio in the CUGE groups, and the expression of PPARγ in epididymal adipose tissue of CUGE group was also significantly decreased (P＜0.05). Meanwhile, the muscle content and the expression of SIRT1 in skeletal muscle and epididymal adipose tissue in CUGE group were significantly increased compared with the CUG group (P＜0.05). CONCLUSION: Resveratrol can decrease body fat content, increase muscle content and improve abdominal fat accumulation in adult catch-up growth rats, and its mechanism may be associated with increasing SIRT1 expression in skeletal muscle and visceral adipose tissue, decreasing PPARγ expression in visceral adipose tissue.

A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family.

PURPOSE: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

A Robust Signature Based on Autophagy-Associated LncRNAs for Predicting Prognosis in Lung Adenocarcinoma.

OBJECTIVE: To construct a predictive signature based on autophagy-associated lncRNAs for predicting prognosis in lung adenocarcinoma (LUAD). Materials and Methods. Differentially expressed autophagy genes (DEAGs) and differentially expressed lncRNAs (DElncRNAs) were screened between normal and LUAD samples at thresholds of ∣log2Fold Change∣ > 1 and P value < 0.05. Univariate Cox regression analysis was conducted to identify overall survival- (OS-) associated DElncRNAs. The total cohort was randomly divided into a training group (n = 229) and a validation group (n = 229) and a validation group (. RESULTS: A total of 30 DEAGs and 2997 DElncRNAs were identified between 497 LUAD tissues and 54 normal tissues; however, only 1183 DElncRNAs were related to the 30 DEAGs. A signature consisting of 13 DElncRNAs was built to predict OS in lung adenocarcinoma, and the survival analysis indicated a significant OS advantage of the low-risk group over the high-risk group in the training group, with a 5-year OS AUC of 0.854. In the validation group, survival analysis also indicated a significantly favorable OS for the low-risk group over the high-risk group, with a 5-year OS AUC of 0.737. Univariate and multivariate Cox regression analyses indicated that only positive surgical margin (vs negative surgical margin) and high-risk group (vs low-risk group) based on the predictive signature were independent risk factors predictive of overall mortality in LUAD. CONCLUSIONS: This study investigated the association between autophagy-associated lncRNAs and prognosis in LUAD and built a robust predictive signature of 13 lncRNAs to predict OS.

Correction: Dietary cholesterol intake and stroke risk: a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.23933.].

Dietary cholesterol intake and stroke risk: a meta-analysis.

Background/Objectives: The association between dietary cholesterol and stroke risk has remained controversial over the past two decades. The aim of this meta-analysis was to assess the relationship between dietary cholesterol and stroke risk. Results: Seven prospective studies including 269,777 non-overlapping individuals (4,604 strokes) were included. The combined RR of stroke for higher cholesterol intake (> 300 mg/day) was 0.98 (95% CI, 0.90-1.07), and the combined RR of stroke for higher cholesterol intake (> 300 mg/day) in females (age of ≥ 60 years or body mass index of ≥ 24 kg/m2) was 1.18 (95% CI, 1.02-1.36). Materials and Methods: The PubMed, Medline, Embase, Web of Knowledge, and Google Scholar databases were searched. Relevant studies were identified by searching these online databases through September 2017. The relative risk (RR) and 95% confidence interval (CI) were used to investigate the strength of the association. Conclusions: Higher cholesterol intake has no association with the overall stroke risk. Age and body mass index affect the relationship between dietary cholesterol intake and stroke risk. However, the association between higher dietary cholesterol and stroke risk in males remains unclear.

Biomarkers identified for prostate cancer patients through genome-scale screening.

Prostate cancer is a threat to men and usually occurs in aged males. Though prostate specific antigen level and Gleason score are utilized for evaluation of the prostate cancer in clinic, the biomarkers for this malignancy have not been widely recognized. Furthermore, the outcome varies across individuals receiving comparable treatment regimens and the underlying mechanism is still unclear. We supposed that genetic feature may be responsible for, at least in part, this process and conducted a two-cohort study to compare the genetic difference in tumorous and normal tissues of prostate cancer patients. The Gene Expression Omnibus dataset were used and a total of 41 genes were found significantly differently expressed in tumor tissues as compared with normal prostate tissues. Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and clinical association analysis. MIR1908 was also found decreased expression level in prostate cancer whose target genes were found expressing in both prostate tumor and normal tissues. These results indicated that these potential biomarkers deserve attention in prostate cancer patients and the underlying mechanism should be further investigated.

Can dietary saturated fat be beneficial in prevention of stroke risk? A meta-analysis.

We conducted a meta-analysis to summarize available evidence regarding the relation between saturated fatty acid (SFA) intake and stroke risk. We searched multiple electronic databases through February 2016. Log relative risks (RRs) with 95 % confidence intervals (CIs) of the highest versus the lowest for cohort studies were weighed by the inverse variance method to obtain combined RRs. 15 prospective studies including 476,569 individuals and 11,074 strokes were included. Higher SFA intake was associated with reduced overall stroke risk [RR = 0.89 (95 % CI 0.82-0.96)] and fatal stroke risk [RR = 0.75 (95 % CI 0.59-0.94)]. Subgroup analysis indicated that higher SFA intake was associated with reduced stroke risks for East-Asians [RR = 0.79 (95 % CI 0.69-0.90)], for dose <25 g/day [RR = 0.81 (95 % CI 0.71-0.92)], for males [RR = 0.85 (95 % CI 0.75-0.96)], and for individuals with body mass index (BMI) <24 [RR = 0.75 (95 % CI 0.65-0.87)], but not for non East-Asians, females, and individuals with dose ≥25 g/day and BMI ≥24. This meta-analysis reveals that higher SFA intake is inversely associated with risk of stroke morbidity and mortality with race, sex, and BMI as key factors influencing this risk. There seems to be a threshold of SFA intake for inverse relation of SFA intake with stroke. However, the stroke-reducing or -increasing effects for specific subtypes and specific food sources of SFA can be concealed. Functions of specific subtypes of SFA (e.g. lignoceric acid) and specific food sources of SFA (i.e. plant vs. animal) in relation to stroke need to be clarified in further studies.

Monounsaturated Fatty Acid Intake and Stroke Risk: A Meta-analysis of Prospective Cohort Studies.

BACKGROUND: We performed a meta-analysis aiming to clarify the relationship between monounsaturated fatty acid (MUFA) intake and stroke risk. METHODS: Relevant studies were identified by searching relevant databases through January 2016. We included cohort studies that reported relative risks (RRs) with 95% confidence intervals (CIs) for the association between MUFA intake and stroke risk. A random-effects model was used to derive composite RR estimates for stroke. RESULTS: Ten prospective cohort studies including 314,511 nonoverlapping individuals and 5827 strokes were included. Higher MUFA intake was not associated with risk of overall stroke (RR = .86 [95% CI, .74-1.00]) and risk of ischemic stroke (RR = .92 [95% CI, .79-1.08]), but was associated with a reduced risk of hemorrhagic stroke (RR = .68 [95% CI, .49-.96]). In subgroup analyses, higher MUFA intake was associated with a reduced risk of stroke for a follow-up duration of 14 years or more (RR = .77 [95% CI, .68-.87]), for males (RR = .79 [95% CI, .69-.91]), for 24-hour recall (RR = .74 [95% CI, .63-.86]), and for a quality score of more than 8 stars (RR = .78 [95% CI, .61-.98]). CONCLUSIONS: There is no significant evidence for concluding that dietary MUFA is associated with a reduced risk of overall stroke. However, higher MUFA intake seems to be associated with a reduced risk of hem orrhagic stroke but not ischemic stroke. Duration of MUFA intake and sex are considered as factors affecting the relationship between MUFA intake and stroke risk. Further studies are needed to evaluate the relationship between specific food sources of MUFA (i.e., plant versus animal) and stroke risk.