Polystyrene nanoplastics induce vascular stenosis via regulation of the PIWI-interacting RNA expression profile.

Nanoplastics (NPs) have become common worldwide and attracted increasing attention due to their serious toxic effects. Owing to their higher surface area and volume ratios and ability to easily enter tissues, NPs impose more serious toxic effects than microplastics. However, the effect of NP exposure on vascular stenosis remains unclear. To measure the effects of polystyrene NP (PS-NP) exposure on vascular toxicity, we conducted analyses of blood biochemical parameters, pathological histology, high-throughput sequencing, and bioinformatics. Red fluorescent PS-NPs (100 nm) were effectively uptake by mouse vascular arterial tissue. The uptake of PS-NPs resulted in vascular toxicity, including alterations in lipid metabolism and thickening of the arterial wall. Based on PIWI-interacting RNA (piRNA) sequencing, 1547 and 132 differentially expressed piRNAs (DEpiRNAs) were detected in the PS-NP treatment group after 180 and 30 days, including 787 and 86 upregulated and 760 and 46 downregulated compared with the control group, respectively. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the target genes of DEpiRNAs were mostly involved in cell growth and cell motility-related signaling, such as the MAPK signaling pathway. This is the first study to highlight the alteration in piRNA levels in mouse vascular arterial tissue after PS-NP exposure. This study adds to the knowledge regarding the regulatory mechanism of pathological changes induced by PS-NP exposure.

A novel tiRNA-Glu-CTC induces nanoplastics accelerated vascular smooth muscle cell phenotypic switching and vascular injury through mitochondrial damage.

Nanoplastics pose several health hazards, especially vascular toxicity. Transfer RNA-derived small RNAs (tsRNAs) are novel noncoding RNAs associated with different pathological processes. However, their biological roles and mechanisms in aberrant vascular smooth muscle cell (VSMC) plasticity and vascular injury are unclear. This study investigated the potent effects of tsRNAs on vascular injury induced by short- and long-term exposure to polystyrene nanoplastics (PS-NPs). Mice were exposed to PS-NPs (100 nm) at different doses (10-100 µg/mL) for 30 or 180 days. High-throughput sequencing was used to analyze tsRNA expression patterns in arterial tissues obtained from an in vivo model. Additionally, quantitative real-time polymerase chain reaction, fluorescent in situ hybridization assays, and dual-luciferase reporter assays were performed to measure the expression and impact of tiRNA-Glu-CTC on VSMCs exposed to PS-NPs. Short-term (≥50 µg/mL, moderate concentration) and long-term (≥10 µg/mL, low concentration) PS-NP exposure induced vascular injury in vivo. Cellular experiments showed that the moderate concentration of PS-NPs induced VSMC phenotypic switching, whereas a high concentration of PS-NPs (100 µg/mL) promoted VSMC apoptosis. PS-NP induced severe mitochondrial damage in VSMCs, including overexpression of reactive oxygen species, accumulation of mutated mtDNA, and dysregulation of genes related to mitochondrial synthesis and division. Compared with the control group, 13 upregulated and 12 downregulated tRNA-derived stress-induced RNAs (tiRNAs) were observed in the long-term PS-NP (50 µg/mL) exposure group. Bioinformatics analysis indicated that differentially expressed tiRNAs targeted genes that were involved in vascular smooth muscle contraction and calcium signaling pathways. Interestingly, tiRNA-Glu-CTC was overexpressed in vivo and in vitro following PS-NP exposure. Functionally, the tiRNA-Glu-CTC inhibitor mitigated VSMC phenotypic switching and mitochondrial damage induced by PS-NP exposure, whereas tiRNA-Glu-CTC mimics had the opposite effect. Mechanistically, tiRNA-Glu-CTC mimics induced VSMC phenotypic switching by downregulating Cacna1f expression. PS-NP exposure promoted VSMC phenotypic switching and vascular injury by targeting the tiRNA-Glu-CTC/Cacna1f axis.

Effects of seed size and bract of Ceratoides arborescens on germination and seedling growth under drought stress.

Drought is a crucial factor affecting seed germination and seedling growth of desert plants. In the study, we examined the effects of seed size (large, small) and bract (without bracts, with bracts) on seed germination and seedling growth of Ceratoides arborescens, a perennial super xerophyte semi-shrub, under different drought levels (0, 100, 200, 300 and 400 g·L-1 PEG6000). The results showed that drought stress significantly inhibited seed germination and reduced shoot length of seedlings. Under the 100 and 200 g·L-1 PEG6000 stress conditions, root length of seedlings were significantly increased, whereas it was significantly reduced under the 300 and 400 g·L-1 PEG6000 stress intensities. The presence of bract significantly reduced seed germination percentage by 12%, germination index by 50.5%, and shoot length by 20.8%, but increased root length by 6.3%. Seed size did not affect seed germination index. Compared with small seeds, germination percentage of large seeds was 3% higher, shoot length and root length of seedlings were 20.5% and 33.0% higher, respectively. In summary, seed bract in C. arborescens through delaying seed germination and seed size through influencing the survival of the early state of seedling were the most important strategies to adapt extremely arid environment.

Analysis of the risk factors for contrast-induced nephropathy in over-aged patients receiving coronary intervention.

Contrast-induced nephropathy has been the common cause of hospital-acquired acute kidney injury in the elderly patients. This study aimed to analyze the risk factors for contrast-induced nephropathy in over-aged patients undergoing coronary angiography or percutaneous coronary intervention. A total of 470 over-aged patients (≥80 years old) were judged as the contrast-induced nephropathy group ( n = 46) and non-contrast-induced nephropathy group ( n = 424) according to the postoperative 48-h serum creatinine levels. The patients' clinical information such as hypertension grade, number and degree of coronary artery stenosis, and death rate was compared. The risk factors for contrast-induced nephropathy were also analyzed. The hypertension grade in the contrast-induced nephropathy group was significantly higher than that in the non-contrast-induced nephropathy group ( P = 0.004). The degree of coronary artery stenosis was significantly more in the contrast-induced nephropathy group compared with the non-contrast-induced nephropathy group ( P = 0.003). The death rate of the contrast-induced nephropathy group (15.8%) was significantly higher than that of the non-contrast-induced nephropathy group (0.6%; P = 0.000). The percentage of patients with abnormal urine microalbumin was significantly bigger in the contrast-induced nephropathy group (62.5%) when comparing to the non-contrast-induced nephropathy group (23.6%; P = 0.00). Besides, there was also significant difference in the emergency/selective operation between the contrast-induced nephropathy group and non-contrast-induced nephropathy group ( P = 0.001). Further, hypertension grade ( P = 0.019), emergency/selective operation ( P = 0.025), degree of coronary artery stenosis ( P = 0.038), eGFR ( P = 0.034), and urine microalbumin ( P = 0.005) were the risk factors for contrast-induced nephropathy. Hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for contrast-induced nephropathy in over-aged patients receiving coronary angiography and percutaneous coronary intervention, providing guidance for the clinical prevention of contrast-induced nephropathy. Impact statement In this work, we evaluated the risk factors for contrast-induced nephropathy (CIN) in over-aged patients receiving coronary angiography (CAG) and percutaneous coronary intervention (PCI). We found that hypertension grade, emergency/selective operation, degree of coronary artery stenosis, eGFR, and urine microalbumin were the risk factors for CIN in over-aged patients receiving CAG and PCI. This study provides guidance for the clinical prevention of CIN in over-aged patients undergoing coronary intervention, highlighting that a perioperative comprehensive management strategy is needed to improve the prognosis.

Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial Dysfunction and Activation of Nrf2.

BACKGROUND: Allicin, a major component of garlic, is regarded as a cardioprotective agent and is associated with increased endothelial function. METHODS: The effects of allicin on lipopolysaccharide (LPS)-induced vascular oxidative stress and inflammation in cultured human umbilical vein endothelial cells (HUVECs) and the mechanisms underlying these effects were studied. The protective effects were measured using cell viability, a lactate dehydrogenase (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was determined by measuring reactive oxygen species (ROS) generation, oxidative products and endogenous antioxidant enzyme activities. HUVEC mitochondrial function was assessed by determining mitochondrial membrane potential (MMP) collapse, cytochrome c production and mitochondrial ATP release. To investigate the potential underlying mechanisms, we also measured the expression of dynamic mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2 antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Our results demonstrated that allicin enhanced HUVEC proliferation, which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS-induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and decreased the endogenous antioxidant enzyme activities in HUVECs. These protective effects were associated with the inhibition of mitochondrial dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced inflammatory responses, including endothelial cell adhesion and TNF-α and IL-8 production. Furthermore, allicin increased the expression of LXRα in a dose-dependent manner. Allicin-induced attenuation of inflammation was inhibited by LXRα siRNA treatment. Finally, allicin activated NF-E2-related factor 2 (Nrf2), which controls the defense against oxidative stress and inflammation. CONCLUSIONS: Taken together, the present data suggest that allicin attenuated the LPS-induced vascular injury process, which may be closely related to the oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2 activation and protected the cells against LPS-induced vascular injury. Our findings suggest that allicin attenuated the LPS-induced inflammatory response in blood vessels.

Epigallocatechin-3-gallate attenuates microcystin-LR induced oxidative stress and inflammation in human umbilical vein endothelial cells.

Epigallocatechin-3-gallate (EGCG) has been shown to possess anti-inflammatory effects. Microcystin-LR (MC-LR) is a potent toxin and our past research suggested that it also mediated human umbilical vein endothelial cell (HUVEC) injury. The aim of this study was to investigate the effects of EGCG on MC-LR-induced oxidative stress and inflammatory responses in HUVECs. HUVECs were stimulated with MC-LR in the presence or absence of EGCG. MC-LR (40 µM) significantly increased cell death and decreased cell viability, migration, and tube formation, whereas EGCG (50 µM) inhibited these effects. Furthermore, the results indicated that EGCG inhibited the production of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in MC-LR-stimulated HUVECs. Compared with MC-LR, EGCG significantly increased superoxide dismutase (SOD) and glutathione (GSH) levels and decreased malondialdehyde (MDA) levels. Moreover, the analysis indicated that EGCG suppressed MC-LR-induced NF-κB activation. In conclusion, the effects of EGCG were associated with inhibition of the NF-κB signaling pathway, which resulted in decreased ROS and TNF-α, thereby attenuating MC-LR-mediated oxidative and inflammatory responses.