Blood glucose mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.

OBJECT: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum. METHOD: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis. RESULT: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al. CONCLUSION: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function.

Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway.

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.

Up-regulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration, and invasion by inactivating the CTNNB1-mediated Notch signaling pathway.

Osteosarcoma (OS) is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults. The present study aims at exploring the regulatory effect of microRNA-340 (miR-340) on OS cell proliferation, invasion, migration, and apoptosis via regulating the Notch signaling pathway by targeting ß-catenin (cadherin-associated protein) 1 (CTNNB1). OS tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected. Cells were allocated to different groups. In situ hybridization was performed to determine the positive rate of miR-340 expression while immunohistochemistry was used to determine that of CTNNB1 and B-cell lymphoma 2 (Bcl-2). We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.

Effects of MicroRNA-206 on Osteosarcoma Cell Proliferation, Apoptosis, Migration and Invasion by Targeting ANXA2 Through the AKT Signaling Pathway.

BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting. The cultured OS cells were divided into 6 groups: a blank group, negative control (NC) group, miR-206 mimic group, miR-206 inhibitor group, si-ANXA2 group and miR-206 inhibitor + si-ANXA2 group. Cell cycle and apoptosis were assessed by flow cytometry, cell migration was examined with a wound-healing assay, and cell invasion was assessed with a Transwell assay. Pearson correlation analysis was used to determine the correlation between ANXA2 mRNA expression and miR-206 expression in OS. RESULTS: OS tissues exhibited increased mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-2; decreased miR-206 expression; and decreased Bax mRNA and protein expression. ANXA2 mRNA expression was strongly negatively correlated with miR-206 expression in OS. ANXA2 was found to be a miR-206 target gene. In the miR-206 mimic group and the si-ANXA2 group, the mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-1 decreased markedly, cell proliferation was inhibited, apoptosis was promoted, higher cell growth in G1 phase and decreased growth in S phase was detected, and decreased cell migration and invasion were observed compared with those in the blank group. CONCLUSION: The current results demonstrate that miR-206 overexpression inhibits OS cell proliferation, migration and invasion and promotes apoptosis through targeting ANXA2 by blocking the AKT signaling pathway.

[Correlation of serum omentin-1 and chemerin with gestational diabetes mellitus].

OBJECTIVE: To investigate the relationship of serum omentin-1 and chemerin with gestational diabetes mellitus (GDM). METHODS: Serum levels of omentin-1 chemerin, glycolipids biochemical index, inflammation index, fasting insulin (FINS), and insulin resistance indexes (HOMA-IR) were determined in 85 women with GDM and 85 pregnant women with normal glucose tolerance (NGT). RESULTS: BMI, FPG, hs-CRP, blood lipids, blood glucose, FINS, HOMA-IR and serum chemerin level were all significantly higher while serum omentin-1 significantly lower in GDM group than in NGT group (P<0.05). In both groups, serum omentin-1 level was significantly lower and serum chemerin was significantly higher in obese subjects than in the non-obese subjects (P<0.05). Obesity before delivery and/or HOMA-IR ≥2 was associated with a significantly decreased serum omentin-1 level; serum chemerin increased significantly in obese women before delivery but was not associated with HOMA-IR. Serum omentin-1 level was positively correlated with HDL but inversely with BMI (at pregnancy and before delivery), FPG, FINS and HOMA-IR; Chemerin was positively correlated with TC, TG, hs-CRP and FPG; serum omentin-1 and chemerin levels were not significant correlated (P=0.301). In women with GDM, BMI at pregnancy, TG, FPG, and FINS were all independent factors affecting serum omentin-1; TG, LDL, and hs-CRP were independent factors affecting serum chemerin. CONCLUSION: An decreased serum omentin-1 can be indicative of glucose and lipid metabolism disorder and insulin resistance, and an increased serum chemerin level indicates hyperlipidemia and chronic inflammation in pregnant women. Both of the adipokines are closed associated with GDM and probably participate in the occurrence and development of GDM.

[Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats].

OBJECTIVE: To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in Sprague-Dawley (SD) rats. METHODS: Thirty-two male SD rats were randomly and equally divided into 4 groups: control group and high-, middle-, and low-dose exposure groups. The rats in high-, middle-, and low-dose exposure groups were fed with the feed mixed with AlCl(3) (120.0, 12.0, and 1.2 mg/kg, respectively), while the rats in control group were fed conventionally. After 6 months of feeding, brain aluminum levels were determined by inductively coupled plasma mass spectrometry; Morris water maze was employed to test the learning and memory abilities; the expression and content of BDNF in brain tissue were measured by Western blot and enzyme-linked immuno sorbent assay (ELISA). RESULTS: The high- and middle-dose exposure groups had significantly higher brain aluminum levels than the control group (P<0.05). The Morris water maze test showed that the high- and middle-dose exposure groups had significantly prolonged escape latency (P<0.05), significantly prolonged time taken to first reach the target quadrant (P<0.01), and significantly decreased number of platform crossings and time spent in the target quadrant (P<0.05), as compared with the control group. The Western blot and ELISA showed that the expression and content of BDNF in brain tissue decreased as the dose of AlCl(3) increased, and they were significantly lower in the high- and middle-dose exposure groups than in the control group (P<0.05). CONCLUSION: Chronic aluminum exposure (12.0 and 120.0 mg/kg) can lead to cognitive dysfunction in rats, and the decreased expression of BDNF may be one of the mechanisms of learning and memory deficits induced by aluminum.

Trefoil factor 1 gene alternations and expression in colorectal carcinomas.

AIMS AND BACKGROUND: Aberrant expression of the trefoil factor family (TFF) has been recognized to be involved in the development and/or progression of various solid tumors. Increased trefoil factor 1 (TFF1) expression is found associated with tumor progression in some tumors, and TFF1 missense mutations have been detected in gastric cancer. The aim of the study was to analyze TFF1 alternations and expression in colorectal carcinoma and their correlation with cancer progression and pathological aspects. METHODS: TFF1 mutations were detected in colorectal carcinomas by DNA sequencing. TFF1 mRNA and protein levels in subsets of the primary tumors were determined using quantitative reverse transcription polymerase chain reaction and immunohistochemistry analyses. The serum level of TFF1 was also detected by enzyme-linked immunosorbent assay for patients with colorectal carcinoma. RESULTS: Five variants were detected in the 5'-untranslation region and intron 1 of TFF1. TFF1 expression was increased in colorectal carcinoma compared to paired distal colonic mucosa. Immunohistochemistry in primary colorectal carcinoma showed no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, cancer differentiation, stage and lymph node metastasis. However, serum TFF1 levels were significantly elevated in patients with colorectal carcinoma compared to healthy individuals. CONCLUSIONS: The results indicate that TFF1 missense mutations seem to be a rare event in colorectal carcinogenesis. Serum TFF1 may be a potential useful marker for patients with colorectal carcinoma.

Aluminium-maltolate-induced impairment of learning, memory and hippocampal long-term potentiation in rats.

Recently, aluminium (Al) has been proposed to be one of the environmental factors responsible for cause Alzheimer's disease (AD). However, the relationship between Al and AD is controversial. To investigate the effects of subchronic Aluminium-maltolate (Al (mal)(3)) exposure on the behavioral, electrophysiological functions. Forty Sprague-Dawley (SD) rats were randomly distributed into five groups. Over two months, rats in the saline group received daily intraperitoneal (i.p.) injections 0.9% saline, rats in the maltolate group received 7.56 mg/kg maltolate, and rats in the 0.27, 0.54, 1.08 mg/kg Al (mal)(3) groups received i.p. administrations of these three doses, respectively. Neural behavior was assessed in Morris water maze. Long-term potentiation (LTP) in hippocampus was recorded. Al content in the neocortex was determined using a graphite furnace atomic absorption spectrophotometer. Our studies indicate that subchronic Al (mal)(3) exposure significantly impaired spatial learning and memory abilities, suppressed the LTP in the CA1 hippocampal area, and elevated Al levels in cerebral cortex in a dose-dependent fashion. In conclusion, low doses of Al (mal)(3) can still lead to dramatic Al accumulation in the brain, severely impair learning and memory capacities, and hippocampal LTP.