Metformin inhibits lung cancer cells proliferation through repressing microRNA-222

Metformin, which is commonly used as an oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including lung cancer, remains unknown. MiR-222 induces cell growth and cell cycle progression via direct targeting of p27, p57 and PTEN in cancer cells. In the present study, we used A549 and NCI-H358 human lung cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment reduced expression of miR-222 in these cells (p < 0.05). As a result, protein abundance of p27, p57 and PTEN were increased in cells exposed to metformin. Therefore, these data provide novel evidence for a mechanism that may contribute to the anti-neoplastic effects of metformin suggested by recent population studies and justifying further work to explore potential roles for it in lung cancer treatment.     

The comparison of immune-enhancing activity of sulfated polysaccharidses from Tremella and Condonpsis pilosula

Based on our previous research, four sulfated polysaccharide (sPSs) from Tremella and Condonpsis pilosula, sTPS_tp, sTPS_70c, sCPPS_tp and sCPPS_50c, were prepared and their effects on splenic lymphocytes proliferation in vitro and the immune response of ND vaccine in chicken were compared taking the unmodified polysaccharide (uPS) TPS_tp as control. The results showed that four sPSs could significantly or numerically stimulate splenic lymphocyte proliferation singly or synergistically with LPS in vitro, sTPS_70c and sCPPS_tp demonstrated better effect; promote peripheral lymphocytes proliferation and enhance serum HI antibody titer in chickens vaccinated with ND vaccine, the actions of sPSs were stronger than that of uPS, and sTPS_70c at medium dosage presented the best efficacy. These indicated that sulfation modification could improve the immune-enhancing activity of TPS and CPPS, sTPS_70c possessed the strongest activity and would be expected as a component of new-type immunopotentiator.     

Isolation of Paenibacillus sp. and Assessment of its Potential for Enhancing Mineral Weathering

One mineral-solubilizing bacterial strain designated KT was isolated from a soil in Henan Province, China. The full-length 16S rRNA gene sequence showed 95.2 to 96.7% similarity to the bacteria of the genus Paenibacillus, indicating that the strain KT belonged to the genus Paenibacillus. The potential of this strain to release potassium from silicate minerals was investigated using a potassium-bearing rock as the sole source of potassium to support its growth. After inoculation for 7 days, the concentrations of water-soluble Al, Ca and Fe released from the potassium-bearing rock in active bacterial culture were higher than those from the control with autoclaved inoculum, but the concentration of water-soluble K in active bacterial culture was similar to that in the control. The concentrations of HNO₃-extractable Al, Ca, Fe and K from the bacterial culture were also higher than those in the control. These results showed strain KT was able to release potassium from potassium-bearing rock. These results have important implications for extraction of potassium from rocks to support plant growth.     

Microbial Diversity and Community Structure on Corroding Concretes

The objective of this study was to analyze bacterial diversity in two different concrete samples to understand the dominant types of bacteria that may contribute to concrete corrosion. Two concrete samples, HN-1 from the sunny side and HN-2 from dark and damp side, were collected from Zijin Mountain in Nanjing and genomic DNA was extracted. The partial bacterial 16S rRNA gene fragment was PCR amplified and two clone libraries were constructed. Amplified ribosomal DNA restriction analysis (ARDRA) was performed by digestion of the 16S rRNA gene and each unique restriction fragment polymorphism pattern was designated as an operational taxonomic unit (OTU). Phylogenetic trees of bacterial 16S rDNA nucleotide sequences were constructed. Sample HN-1 and HN-2 contained 21 OTUs and 26 OTUs, respectively. Proteobacteria and Planctomycetes were the predominant bacteria in both samples, and they are distributed among Herbaspirillum, Archangium, Phyllobacteriaceae and Planctomycetaceae. Cyanobacteria and Rubrobacter sp. are dominant in HN-1; while Acidobacteriaceae, Adhaeribacter sp. and Nitrospira sp. are predominant in HN-2. This distribution pattern was consistent with local environmental conditions of these two samples. The inferred physiological characteristics of these bacteria, based on relatedness of the DNA clone sequences to cultivated species, revealed different mechanisms of concrete corrosion depending on the local environmental conditions.     

Struvite Precipitation Induced by a Novel Sulfate-Reducing Bacterium Acinetobacter calcoaceticus SRB4 Isolated from River Sediment

This article presents a study of struvite formation in liquid medium induced by the sulfate-reducing bacterium Acinetobacter calcoaceticus SRB4, a strain isolated from river sediment. We identified the bacterial strain A. calcoaceticus SRB4 and analyzed its micromorphology. The minerals formed were studied with an electroprobe microanalyzer, Fourier transform infrared spectroscopy, high-resolution transmission electron microscopy, selected-area electron diffraction, X-ray diffraction, thermogravimetry, differential thermogravimetry, and differential scanning calorimetry. Acinetobacter calcoaceticus SRB4 was found to induce struvite precipitation, whereas sterile control cultures did not. Many transparent stick-shaped struvite precipitates were distributed at the bottom of the conical flasks in the experimental group. Most bacteria were spherical and a large quantity of spherical struvite particles (less than 200 nm in diameter) adhered to the bacterial surface. An electron probe microanalysis showed that the precipitates contained C, O, P, Mg, and other elements. Fourier transformation infrared spectra showed that the precipitates contained crystalline water, NH₄⁺, and PO₄^3? groups. X-ray diffraction spectra showed that the precipitates were struvite crystals, with preferential orientation and lattice distortion. Thermogravimetry showed that the weight loss was caused by the evaporation of crystalline water at temperatures lower than 136°C and the release of ammonia from struvite at temperatures of 136–228.5°C. In this article, we discuss the possible mechanism of struvite formation and the possible role played by A. calcoaceticus SRB4. Our study extends our understanding of the phosphate biomineralization mechanism and should prove useful in recycling phosphorus in wastewater.     

Arctigenin Exhibits Relaxation Effect on Bronchus by Affecting Transmembrane Flow of Calcium

Arctigenin, a lignan extract from Arctium lappa (L.), exhibits anti-inflammation, antioxidation, vasodilator effects, etc. However, the effects of arctigenin on bronchus relaxation are not well investigated. This study aimed to investigate how arctigenin regulates bronchus tone and calcium ion (Ca²⁺) flow. Trachea strips of guinea pigs were prepared for testing the relaxation effect of arctigenin to acetylcholine, histamine, KCl, and CaCl₂, respectively. Furthermore, l-type calcium channel currents were detected by patch–clamp, and intracellular Ca²⁺ concentration was detected by confocal microscopy. The results showed that arctigenin exhibited relaxation effect on tracheae to different constrictors, and this was related to decreasing cytoplasmic Ca²⁺ concentration by inhibiting Ca²⁺ influx partly through l-type calcium channel as well as promoting Ca²⁺ efflux. In summary, this study provides new insight into the mechanisms by which arctigenin exhibits relaxation effect on bronchus and suggests its potential use for airway disease therapy.     

Iodine Excess Induces Hepatic Steatosis Through Disturbance of Thyroid Hormone Metabolism Involving Oxidative Stress in BaLB/c Mice

Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L) in drinking water for 1 or 3 months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (r?=?0.680, P?<?0.01) in iodine-loaded groups. Evident hepatic steatosis was observed in 2.4 and 4.8 mg I/L iodine-loaded groups. The activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) were decreased, and the malondialdehyde level was increased by excessive iodine in both serum and liver in a dose-dependent manner, accompanying the decrease of hepatic D1 activity. That resulted in the increase of serum total thyroxine and the decrease of serum total triiodothyronine in iodine-loaded groups. The mRNA expression of SREBP-1c and FAS was increased in iodine-loaded groups in response to the change of serum triiodothyronine. Present findings demonstrated that iodine excess could dose dependently induce hepatic steatosis. Furthermore, our data suggested that the disturbance of thyroid hormone metabolism involving oxidative stress may play a critical role in iodine excess-induced hepatic steatosis.     

Role of Pigment Epithelium-Derived Factor (PEDF) in Arsenic-Induced Cell Apoptosis of Liver and Brain in a Rat Model

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.     

Facilitated Hyperpolarization Signaling in Vascular Smooth Muscle-overexpressing TRIC-A Channels

The TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation-specific channels and likely mediate counterion movements to support efficient Ca²⁺ release from the sarco/endoplasmic reticulum. Vascular smooth muscle cells (VSMCs) contain both TRIC subtypes and two Ca²⁺ release mechanisms; incidental opening of ryanodine receptors (RyRs) generates local Ca²⁺ sparks to induce hyperpolarization and relaxation, whereas agonist-induced activation of inositol trisphosphate receptors produces global Ca²⁺ transients causing contraction. Tric-a knock-out mice develop hypertension due to insufficient RyR-mediated Ca²⁺ sparks in VSMCs. Here we describe transgenic mice overexpressing TRIC-A channels under the control of a smooth muscle cell-specific promoter. The transgenic mice developed congenital hypotension. In Tric-a-overexpressing VSMCs from the transgenic mice, the resting membrane potential decreased because RyR-mediated Ca²⁺ sparks were facilitated and cell surface Ca²⁺-dependent K⁺ channels were hyperactivated. Under such hyperpolarized conditions, L-type Ca²⁺ channels were inactivated, and thus, the resting intracellular Ca²⁺ levels were reduced in Tric-a-overexpressing VSMCs. Moreover, Tric-a overexpression impaired inositol trisphosphate-sensitive stores to diminish agonist-induced Ca²⁺ signaling in VSMCs. These altered features likely reduced vascular tonus leading to the hypotensive phenotype. Our Tric-a-transgenic mice together with Tric-a knock-out mice indicate that TRIC-A channel density in VSMCs is responsible for controlling basal blood pressure at the whole-animal level.