Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction.

Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.

Spatio-temporal variability of particulate matter in the key part of Gansu Province, Western China.

To investigate the spatial and temporal behaviors of particulate matter in Lanzhou, Jinchang and Jiayuguan during 2014, the hourly concentrations of PM2.5 and PM10 were collected from the Ministry of Environmental Protection (MEP) in this study. The analysis indicated that the mean annual PM10 (PM2.5) concentrations during 2014 were 115 ± 52 µg/m3 (57 ± 28 µg/m3), 104 ± 75 µg/m3 (38 ± 22 µg/m3) and 114 ± 72 µg/m3 (32 ± 17 µg/m3) in Lanzhou, Jinchang and Jiayuguan, respectively, all of which exceeded the Chinese national ambient air quality II standards for PM. Higher values for both PM fractions were generally observed in spring and winter, and lower concentrations were found in summer and autumn. Besides, the trend of seasonal variation of particulate matter (PM) in each city monitoring site is consistent with the average of the corresponding cities. Anthropogenic activities along with the boundary layer height and wind scale contributed to diurnal variations in PM that varied bimodally (Lanzhou and Jinchang) or unimodally (Jiayuguan). With the arrival of dust events, the PM10 concentrations changed dramatically, and the PM10 concentrations during dust storm events were, respectively, 19, 43 and 17 times higher than the levels before dust events in Lanzhou, Jinchang and Jiayuguan. The ratios (PM2.5/PM10) were lowest, while the correlations were highest, indicating that dust events contributed more coarse than fine particles, and the sources of PM are similar during dust storms. The relationships between local meteorological parameters and PM concentrations suggest a clear association between the highest PM concentrations, with T ≤ 7 °C, and strong winds (3-4 scale). However, the effect of relative humidity is complicated, with more PM10 and PM2.5 exceedances being registered with a relative humidity of less than 40% and 40-60% in Lanzhou, while higher exceedances in Jinchang appeared at a relative humidity of 80-100%.

Distribution features and controls of heavy metals in surface sediments from the riverbed of the Ningxia-Inner Mongolian reaches, Yellow River, China.

Fifty-six riverbed surface sediment (RSS) samples were collected along the Ningxia-Inner Mongolian reaches of the Yellow River (NIMYR). These samples were analyzed to determine their heavy metal concentrations (Co, Cr, Ni, Cu, V and Zn), grain sizes, sediment sources and the causes of their heavy metal contamination. The cumulative distribution functions of the heavy metals in RSS of these reaches are plotted to identify the geochemical baseline level (GBL) of each element and determine the average background concentration of each heavy metal. Principal component analysis and hierarchical cluster analysis are conducted based on the grain sizes of RSS, and the samples are classified into two groups: coarse grained samples (CGS) and fine grained samples (FGS). The degree of heavy metal contamination for each sample is identified by its enrichment factor (EF). The results reveal that the coarse particle component (medium sand and coarse sand) in the bed materials is chiefly from the bordering deserts along the Yellow River. The clay and silt in the bed materials chiefly originate from the upper reaches of the Yellow River, and the fine sand is identified as a hybrid sediment derived from the upper reaches of the Yellow River and the bordering deserts. The CGS primarily appear in the reaches bordering deserts, and the sites are near the confluence of gullies and the Yellow River. The FGS are located adjacent to cities with especially strong industrial activity such as Wuhai, Bayan Nur, Baotou and Togtoh. The Cr, Ni, Cu, V and Zn concentrations (mg kg(-1)) are 84.34 ± 49.46, 30.21 ± 7.90, 25.01 ± 7.61, 73.17 ± 18.92 and 55.62 ± 18.93 in the FGS and 65.07 ± 19.51, 23.86 ± 6.84, 18.04 ± 3.8, 53.47 ± 10.57 and 34.89 ± 9.19 in the CGS respectively, and the concentrations of Co in the CGS (213.40 ± 69.71) are notably higher than in the FGS (112.02 ± 48.87) and greater than the Co GBL (210). The most contaminated samples in the NIMYR are adjacent to the cities of Wuhai (EF(Cr) = 5.19; EF(Ni) = 1.96), Bayan Nur (EF(Cr) = 5.88; EF(Ni )= 2.08) and Baotou (EF(Cu) = 1.55; EF(Zn) = 1.68) where the Cr, Ni, Cu, V and Zn concentrations are above the correlated GBLs (85, 34, 27, 75 and 62 mg kg(-1), respectively), which are mostly affected by industrial processes, and samples that are only moderately contaminated by heavy metals are found in the reaches bordering desert (Wuhai-Baotou) because contaminated sediments are diluted by uncontaminated desert sand. In contrast, all of the Cu, Cr, Ni, V and Zn concentrations in RSS of the Qingtongxia-Wuhai reach are lower than the correlated GBLs of elements.

Heavy metals in the riverbed surface sediment of the Yellow River, China.

One hundred and eleven riverbed surface sediment (RSS) samples were collected to determine the heavy metal concentration throughout the Inner Mongolia reach of the Yellow River (IMYR), which has been subjected to rapid economic and industrial development over the past several decades. Comprehensive analysis of heavy metal contamination, including the enrichment factor, geo-accumulation index, contamination factor, pollution load index, risk index, principal component analysis (PCA), hierarchical cluster analysis (HCA), and Pearson correlation analysis, was performed. The results demonstrated that a low ecological risk with a moderate level of heavy metal contamination was present in the IMYR due to the risk index (RI) being less than 150 and the pollution load index (PLI) being above 1, and the averaged concentrations of Co, Cr, Cu, Mn, Ni, Ti, V, and Zn in the RSS, with standard deviations, were 144 ± 69, 77.91 ± 39.28, 22.95 ± 7.67, 596 ± 151, 28.50 ± 8.01, 3793 ± 487, 69.11 ± 18.44, and 50.19 ± 19.26 mg kg-1, respectively. PCA, HCA, and Pearson correlation analysis revealed that most of the RSS was heavily contaminated with Zn, Ni, and Cu, due to the influence of anthropogenic activities; moderately contaminated with Ti, Mn, V and Cr because of the dual influence of anthropogenic activities and nature; and slightly to not contaminated with Co because it occurs mainly in the bordering desert areas. Graphic abstract ᅟ.