Blocking of tripartite motif 8 protects against lipopolysaccharide (LPS)-induced acute lung injury by regulating AMPKα activity

Acute lung injury (ALI) and its more serious form, respiratory distress syndrome (ARDS), are considered as an acute and severe inflammatory process existing in lungs, and still remain high mortality rates. Tripartite motif 8 (TRIM8) contains an N-terminal RING finger, which is followed by two B-boxes and a coiled-coil domain, belonging to the TRIM/RBCC family and playing significant role in meditating inflammation, oxidative stress and apoptosis. In the study, we investigated the role of TRIM8 in ALI induced by lipopolysaccharide (LPS) and the underlying molecular mechanisms. The in vitro results indicated that LPS time-dependently enhanced TRIM8 expression in lung epithelial cells. Suppressing TRIM8 markedly ameliorated LPS-elicited inflammatory response, as evidenced by the down-regulated mRNA levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in cells mainly through inactivating nuclear factor-kappa B (NF-κB) signaling pathway; however, over-expressing TRIM8 markedly promoted inflammation in LPS-challenged cells. In addition, LPS-induced oxidative stress was accelerated by TRIM8 over-expression, while being alleviated by TRIM8 knockdown by regulating Nrf2 signaling. Importantly, TRIM8 could negatively meditate AMP-activated protein kinase-α (AMPKα) activation to modulate LPS-triggered inflammatory response and ROS generation in vitro. Additionally, our in vivo findings suggested that TRIM8 knockdown effectively attenuated LPS-induced lung injury nu decrease of lung wet/dry (W/T) ratio, protein concentrations, neutrophil infiltration, myeloperoxidase (MPO) activity, reactive oxygen species (ROS) production and superoxide dismutase (SOD) depletion. Meanwhile, the loss of TRIM8 markedly lessened IL-1β, IL-6 and TNF-α expression in lung tissues of LPS-challenged mice, and reduced NF-κB phosphorylation. Furthermore, TRIM8 knockdown evidently improved nuclear factor-erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in lung of LPS-treated mice. The anti-inflammation and anti-oxidant role of TRIM8-silence might be associated with AMPKα phosphorylation. Together, our study firstly provided a support that TRIM8 knockdown effectively protected LPS-induced ALI against inflammation and oxidative stress largely dependent on the promotion of AMPKα pathway.     

Mechanics of the Formation,Interaction, and Evolution of Membrane Tubular Structures

Membrane nanotubes, also known as membrane tethers, play important functional roles in many cellular processes, such as trafficking and signaling. Although considerable progresses have been made in understanding the physics regulating the mechanical behaviors of individual membrane nanotubes, relatively little is known about the formation of multiple membrane nanotubes due to the rapid occurring process involving strong cooperative effects and complex configurational transitions. By exerting a pair of external extraction upon two separate membrane regions, here, we combine molecular dynamics simulations and theoretical analysis to investigate how the membrane nanotube formation and pulling behaviors are regulated by the separation between the pulling forces and how the membrane protrusions interact with each other. As the force separation increases, different membrane configurations are observed, including an individual tubular protrusion, a relatively less deformed protrusion with two nanotubes on its top forming a V shape, a Y-shaped configuration through nanotube coalescence via a zipper-like mechanism, and two weakly interacting tubular protrusions. The energy profile as a function of the separation is determined. Moreover, the directional flow of lipid molecules accompanying the membrane shape transition is analyzed. Our results provide new, to our knowledge, insights at a molecular level into the interaction between membrane protrusions and help in understanding the formation and evolution of intra- and intercellular membrane tubular networks involved in numerous cell activities.     

Benzo(a)pyrene inhibits endometrial cell apoptosis in early pregnant mice via the WNT5A pathway

Benzo(a)pyrene (BaP) is an endocrine-disrupting pollutant present in various aspects of daily life, and studies have demonstrated that BaP exerts reproductive toxicity. We previously showed that BaP damages endometrial morphology and decreases the number of implantation sites in early pregnant mice, but the mechanisms underlying these effects remain unclear. The endometrial function is crucial for implantation, which is associated with endometrial cell apoptosis. In this study, we focused on the effect of BaP on endometrial cell apoptosis and the role of WNT signaling during this process. Pregnant mice were gavaged with corn oil (control group) or 0.2 mg·kg⁻¹·day ⁻¹ BaP (treatment group) from Days 1 to 6 of pregnancy. BaP impaired endometrial function by decreasing the expression of HOXA10 and BMP2, two markers of receptivity and decidualization. WNT5A and β-catenin were activated in the BaP group. BaP affected the expression of apoptosis-related proteins and inhibited the apoptosis of endometrial stromal cells. In vitro, human endometrial stromal cells (HESCs) were treated with different concentrations of BaP (dimethyl sulfoxide (DMSO); 5, 10 µM). WNT5A and β-catenin were also upregulated in the BaP treatment group. HESC apoptosis was restrained by BaP. Inhibiting WNT5A by SFRP5 partially restored the effect of BaP on apoptosis. In summary, these results suggested that BaP exposure during early pregnancy activates WNT5A/β-catenin signaling pathway, which inhibits the endometrial cell apoptosis and potentially destroys endometrial function.     

Estrogen inhibits osteoclasts formation and bone resorption via microRNA-27a targeting PPARγ and APC

Inhibition of osteoclasts formation and bone resorption by estrogen is very important in the etiology of postmenopausal osteoporosis. The mechanisms of this process are still not fully understood. Recent studies implicated an important role of microRNAs in estrogen-mediated responses in various cellular processes, including cell differentiation and proliferation. Thus, we hypothesized that these regulatory molecules might be implicated in the process of estrogen-decreased osteoclasts formation and bone resorption. Western blot, quantitative real-time polymerase chain reaction, tartrate-resistant acid phosphatase staining, pit formation assay and luciferase assay were used to investigate the role of microRNAs in estrogen-inhibited osteoclast differentiation and bone resorption. We found that estrogen could directly suppress receptor activator of nuclear factor B ligand/macrophage colony-stimulating factor-induced differentiation of bone marrow-derived macrophages into osteoclasts in the absence of stromal cell. MicroRNA-27a was significantly increased during the process of estrogen-decreased osteoclast differentiation. Overexpressing of microRNA-27a remarkably enhanced the inhibitory effect of estrogen on osteoclast differentiation and bone resorption, whereas which were alleviated by microRNA-27a depletion. Mechanistic studies showed that microRNA-27a inhibited peroxisome proliferator-activated receptor gamma (PPARγ) and adenomatous polyposis coli (APC) expression in osteoclasts through a microRNA-27a binding site within the 3′-untranslational region of PPARγ and APC. PPARγ and APC respectively contributed to microRNA-27a-decreased osteoclast differentiation and bone resorption. Taken together, these results showed that microRNA-27a may play a significant role in the process of estrogen-inhibited osteoclast differentiation and function.     

Homologous shell microstructures in Cambrian hyoliths and molluscs

Hyoliths were among the earliest biomineralizing metazoans in Palaeozoic marine environments. They have been known for two centuries and widely assigned to lophotrochozoans. However, their origin and relationships with modern lophotrochozoan clades have been a longstanding palaeontological controversy. Here, we provide broad microstructural data from hyolith conchs and opercula from the lower Cambrian Xinji Formation of North China, including two hyolithid genera and four orthothecid genera as well as unidentified opercula. Results show that most hyolith conchs contain a distinct aragonitic lamellar layer that is composed of foliated aragonite, except in the orthothecid New taxon 1 that has a crossed foliated lamellar microstructure. Opercula are mostly composed of foliated aragonite and occasionally foliated calcite. These blade or lath‐like microstructural fabrics coincide well with biomineralization of Cambrian molluscs rather than lophophorates, as exemplified by the Cambrian members of the tommotiid‐brachiopod linage. Accordingly, we propose that hyoliths and molluscs might have inherited their biomineralized skeletons from a non‐mineralized or weakly mineralized common ancestor rather than as a result of convergence. Consequently, from the view of biomineralization, the homologous shell microstructures in Cambrian hyoliths and molluscs strongly strengthen the phylogenetic links between the two groups.     

Elevated temperature increased nitrification activity by stimulating AOB growth and activity in an acidic paddy soil

Plant and Soil - Cadmium (Cd) is the most widespread toxic heavy metal to plant growth. As the second leading oil crop, some genotypes of Brassica napus (B. napus) are potential Cd accumulators....     

Plant traits interacting with sediment properties regulate sediment microbial composition under different aquatic DIC levels caused by rising atmospheric CO2

Plant and Soil - Current knowledge of soil heterogeneity-diversity relationships (HDR) is largely based on studies manipulating single factor, but the advancements in HDR may require a...