MiR-375 impairs breast cancer cell stemness by targeting the KLF5/G6PD signaling axis.

Recurrence of breast cancer may be due to the presence of breast cancer stem cells (BCSC). Abnormal tumor cell growth is closely associated with increased reactive oxygen species (ROS) and disruption of redox homeostasis, and BCSCs exhibit low levels of ROS. The detailed mechanism between the low levels of ROS in BCSCs and their maintenance of stemness characteristics has not been reported. A growing number of studies have shown that tumor development is often accompanied by metabolic reprogramming, which is an important hallmark of tumor cells. As the first rate-limiting enzyme of pentose phosphate pathway (PPP), the expression of G6PD is precisely regulated in tumor cells, and there is a certain correlation between PPP and BCSCs. MiR-375 has been shown to inhibit stem cell-like properties in breast cancer, but the exact mechanism is not clear. Here, KLF5, as a transcription factor, was identified to bind to the promoter of G6PD to promote its expression, whereas miR-375 inhibited the expression of KLF5 by binding to the 3'UTR region of KLF5 mRNA and thus reduced the expression of G6PD expression, inhibits PPP to reduce NADPH, and increases ROS levels in breast cancer cells, thereby weakening breast cancer cell stemness. Our study reveals the specific mechanism by which miR-375 targets the KLF5/G6PD signaling axis to diminish the stemness of breast cancer cells, providing a therapeutic strategy against BCSCs.

Trends of Blood Lead Levels in US Pregnant Women: The National Health and Nutrition Examination Survey (2001-2018).

Objectives: This study investigates the trends of blood lead levels in US pregnant women based on the National Health and Nutrition Examination Survey from 2001 to 2018. Methods: A total of 1,230 pregnant women were included in this study. The weighted logistic regression was applied to analyze the association between sociodemographic characteristics with high blood levels. We computed the blood lead levels for each survey period from 2001-2002 to 2017-2018. Moreover, we used the adjusted linear regression model to investigate the time-related change in blood lead level. The odds ratio (OR) with a 95% confidence interval (CI) was calculated accordingly. Results: The mean blood lead was 0.73 ± 0.03 ug/dL, and high blood lead was observed in 2.53% of individuals. The Mexican Americans were more associated with high blood lead than the non-Hispanic white (OR, 1.072; 95% CI, 1.032-1.112). The mean blood lead level has decreased from 0.97 ug/dL in 2001-2002 to 0.46 ug/dL in 2013-2014. Afterward, a slight increase was observed with the mean blood lead of 0.55 ug/dL in 2015-2016 and 0.53 ug/dL in 2017-2018. In the adjusted linear regression model, each year's increase would lead to a 0.029 ug/dL decrease in blood lead (P < 0.001). However, no significant change was observed in the 2017-2018 cycle compared with 2009-2010 (P = 0.218). Conclusion: This study summarized the trend of blood lead levels in US pregnant women over 2001-2018. Continued effort is still required to control lead sources better and protect this population from lead exposure.

Short Term Usage of Omega-3 Polyunsaturated Fatty Acids Ameliorate Lipopolysaccharide-Induced Inflammatory Response and Oxidative Stress in the Neonatal Rat Hippocampal Tissue.

Objective: To investigate the effect of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on lipopolysaccharide (LPS)-induced inflammatory response and oxidative stress in neonatal rat brain. Methods: Ninety-six 3-day-old Sprague Dawley rats were divided into four groups: control (saline/saline), LPS/ω-3, LPS/ω-6, and LPS/saline (n = 24/group). All rats, except those in the control group, were intraperitoneally challenged once with LPS (0.6 mg/kg) and were treated with ω-3 PUFAs, ω-6 PUFAs, or saline at 15 mL/kg for 1 or 5 consecutive days beginning on the day of LPS-challenge. Rats in the control group underwent the same procedures and received saline (vehicle). After 1 or 5 days of treatment, 12 rats from each group were sacrificed and their hippocampuses were collected. The expression of inflammation-related genes as well as the levels of oxidative stress markers in hippocampal tissues were determined. Results: After 1 or 5 days of treatment, the expression of toll-like receptor 4 and multiple proinflammatory cytokines were significantly decreased in the LPS/ω-3 group compared with those in the LPS/saline group. The activities of superoxide dismutase and glutathione (GSH) were significantly elevated, whereas amounts of malondialdehyde and oxidized glutathione (GSSG) and the ratio of GSSG/GSH were remarkably lowered in the LPS/ω-3 group compared with those in the LPS/saline group after 1 day of treatment. Opposite effects were observed in the LPS/ω-6 group. Conclusion: ω-3 PUFAs may protect rat brain tissue against LPS-induced inflammatory response and oxidative stress.

The Mediating Role of Cognitive Emotion Regulation in BIS/BAS Sensitivities, Depression, and Anxiety Among Community-Dwelling Older Adults in China.

BACKGROUND: The behavioral inhibition system (BIS) and behavioral activation system (BAS), which primarily underlie emotions and behaviors, are associated with depression and anxiety. However, the reasons behind these associations require further exploration. OBJECTIVE: This study aims to examine the mediating effects of cognitive emotion regulation between BIS/BAS and depression/anxiety among community-dwelling elderly Chinese. METHODS: A cross-sectional survey was conducted with a sample of 836 elderly individuals. Structural equation modeling was used to determine relationships among BIS/BAS, cognitive emotion regulation, and depression/anxiety. RESULTS: Participants reporting higher BIS sensitivity were more likely to use maladaptive cognitive emotion regulation strategies, which were in turn associated with higher rates of depression and anxiety. BAS sensitivity was more likely to lead to adaptive cognitive emotion regulation strategies, which resulted in lower levels of depression and anxiety. CONCLUSION: Our findings suggest that incorporating emotional regulation in interventions targeting BIS/BAS sensitivities may enhance the accuracy and efficiency of these treatments for depression and anxiety.

Expression of flotillin-2 in human non-small cell lung cancer and its correlation with tumor progression and patient survival.

INTRODUCTION: Recent studies have revealed that flotillin-2 (FLOT2) played important roles in cancer progression. The aim of this study was to investigate the clinicopathologic and prognostic significance of FLOT2 expression in human non-small cell lung cancer (NSCLC). METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect FLOT2 mRNA expression in lung cancer cell lines, normal bronchial epithelial cells, 24 pairs of NSCLC tissues and matched adjacent non-tumor tissues. Immunohistochemistry (IHC) was performed to examine FLOT2 protein expression in paraffin-embedded tissues from 90 NSCLC patients. Statistical analyses were performed to evaluate the clinicopathological significance of FLOT2 expression. RESULTS: FLOT2 mRNA expression was evidently up-regulated in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues. In the 90 cases of tested NSCLC samples, FLOT2 protein level was positively correlated with tumor stage, and lymph node metastasis. Patients with high FLOT2 expression had shorter overall survival compared with the low FLOT2 expression group. Univariate and multivariate analyses indicated that high FLOT2 expression was an independent poor prognostic factor for NSCLC patients. CONCLUSIONS: Our findings provided that high FLOT2 expression was associated with poor outcomes in NSCLC patients, and FLOT2 could be a potential prognostic biomarker for lung cancer progression.

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival.

INTRODUCTION: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). CONCLUSIONS: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.

Down-regulation of long non-coding RNA LET is associated with poor prognosis in gastric cancer.

INTRODUCTION: Long non-coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although down-regulation of lncRNA LET in several cancers has been studied, its role in gastric cancer remains unknown. The aim of our study was to investigate the expression, and clinical significance of lncRNA LET in gastric cancer. METHODS: The expression of lncRNA LET was detected by quantitative real-time PCR (qRT-PCR) in pairs of tumor tissues and adjacent non-tumor tissues of 93 gastric cancer patients. Then, we analyzed the potential relationship between lncRNA LET expression levels in tumor tissues and clinicopathological features of gastric cancer, and clinical outcome. RESULTS: We found that lncRNA LET expression was markedly down-regulated in tumor tissues compared with adjacent non-tumor tissues, and associated with depth of invasion, lymph node metastasis, distant metastasis, and TNM stage. Kaplan-Meier analysis showed that patients with low lncRNA LET expression had a poor overall survival than those with high lncRNA LET expression. Moreover, univariate and multivariate analyses showed that low lncRNA LET expression was an independent poor prognostic factor for gastric cancer patients. CONCLUSIONS: Our data provided the first evidence that lncRNA LET might be a novel prognostic indicator in gastric cancer and might be a potential target for diagnosis and gene therapy.