Leukocyte telomere length mediates the association between cadmium exposure and cognitive function in US older adults.

BACKGROUND: Long-term exposure to cadmium-polluted environments may lead to shortened leukocyte telomere length and cognitive decline. This study aims to investigate (1) the associations among blood cadmium levels, leukocyte telomere length, and cognitive function, and (2) the mediating role of leukocyte telomere length between blood cadmium levels and cognitive function among older adults in the United States. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cadmium exposure level was assessed by measuring cadmium levels in blood samples. Leukocyte telomere length was measured by quantitative polymerase chain reaction, and cognitive function was measured by the digit symbol substitution test (DSST). RESULTS: A total of 2185 older adults aged over 60 were included in this study, comprising 1109 (49.65%) males. Elevated blood cadmium levels were significantly associated with the risk of a decline in cognitive function (ß = - 2.842, p = 0.018). Shorter leukocyte telomere lengths were significantly associated with a higher risk of a decline in cognitive function (ß = 4.144, p = 0.020). The total indirect effect on the blood cadmium level and cognitive function via leukocyte telomere length was - 0.218 (p = 0.012). The mediation effect was estimated to be 0.218/2.084 × 100% = 10.46%. CONCLUSION: The findings suggest that cadmium exposure may increase the risk of cognitive impairment by causing shortened leukocyte telomere length.

A novel molecular mechanism mediated by circCCDC134 regulates non-small cell lung cancer progression.

BACKGROUND: Circular RNA (circRNA) plays a crucial role in non-small cell lung cancer (NSCLC) progression. However, the role of circCCDC134 in NSCLC is still largely unknown. METHODS: Quantitative real-time PCR was utilized for measuring circCCDC134, microRNA (miR)-625-5p and nuclear factor of activated T cell 5 (NFAT5) expression. Cell functions were evaluated by colony formation, EdU, transwell, and wound healing assays and flow cytometry. Glucose consumption, lactate production, and ATP level were determined to analyze cell glycolysis. Western blot analysis was used to detect protein expression. Animal experiments were performed to assess the effect of circCCDC134 on NSCLC tumor growth. RNA interaction was evaluated by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from the serum of NSCLC patients and healthy normal controls. RESULTS: Highly expressed circCCDC134 was found in NSCLC tissues and cells, as well as in the serum exosomes of NSCLC patients. Downregulated circCCDC134 restrained NSCLC cell growth, metastasis and glycolysis. CircCCDC134 sponged miR-625-5p to regulate NFAT5. MiR-625-5p inhibitor abolished the regulation of circCCDC134 knockdown on NSCLC progression, and NFAT5 overexpression eliminated the effects of miR-625-5p on NSCLC cell behaviors. CircCCDC134 knockdown also inhibited NSCLC tumor growth. CONCLUSION: Our study revealed that circCCDC134 was involved in regulating NSCLC progression through the miR-625-5p/NFAT5 pathway, confirming that circCCDC134 might function as the diagnostic and therapeutic target for NSCLC.

Ginsenoside Rg1 suppresses paraquat-induced epithelial cell senescence by enhancing autophagy in an ATG12-dependent manner.

Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ-induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ-poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ-induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ-induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3-MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ-induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning-induced pulmonary fibrosis.

Improvement of Cerebral Ischemia-Reperfusion Injury via Regulation of Apoptosis by Exosomes Derived from BDNF-Overexpressing HEK293.

Brain-derived neurotrophic factor (BDNF) provides neuroprotective effects towards therapeutic cerebral ischemia-reperfusion (I/R) injury. This view has been proposed by more and more evidence. However, due to the lack of permeability of the blood-brain barrier (BBB) as well as the brief half-life in serum, clinical application is not widespread. To study the participation of exosomes containing BDNF in I/R, we isolated exosomes from BDNF-overexpressing HEK293. The protective outcomes of exosomes in hypoxia/reoxygenation (H/R) experiments were determined by the use of SY-5Y cells. Exosome-BDNF therapy restrained H/R-induced apoptosis by inhibition of the reducing levels of oxidative stress and calcium ions in the cells while maintaining stable levels of mitochondrial membrane potential in brain cells damaged by I/R. We then constructed a cerebral I/R injury model using SD rats to find the function of BDNF in exosome-mediated neuroprotection. The in vivo experiments conducted established that exosomes from BDNF-overexpressing HEK293 cells improved cerebral I/R injury by concealing neuronal apoptosis. Findings gained demonstrated that BDNF is a part of preventing cerebral I/R injury due to exosome mediation by regulating the cellular internal environment and inhibiting apoptosis.

[Nicotine regulates large conductance ca2+ activated K+ channels in rat coronary arterial smooth muscle cells].

OBJECTIVE: The present study was to explore signaling mechanisms underlying nicotine-induced inhibition of large-conductance calcium-activated potassium channels (BK(Ca)). METHODS: 8 week male Wistar rats were divided randomly into saline group and nicotine group and received respectively injection with saline or nicotine (Sigma, Shanghai, China) at 2 mg/(kg x d) for 21 days. Coronary vascular smooth muscle cells were dissociated enzymatically. Dissociated smooth muscle cells were interfered with CPT-cAMP (100 micromol/L) or forskolin (10 micromol/L). The signal channel open dwell-time (To), close dwell-time (Tc) and open probability (Po) were recorded. RESULTS: CPT-cAMP or forskolin significantly prolonged To, shorten Tc and increased Po in saline group (P < 0.01). But in nicotine group To, Tc and Po did not been changed. CONCLUSION: This phenomenon may serve as a physiological mechanism that nicotine inhibits BK(Ca) channel activity to increase via cAMP/PKA-dependent pathway.