LncRNA RP6-65G23.1 accelerates proliferation and inhibits apoptosis via p-ERK1/2/p-AKT signaling pathway on keratinocytes

Long non-coding RNAs (LncRNAs) play essential roles in the development of various diseases including hepatic carcinoma, melanoma, and psoriasis. Meanwhile, lncRNA-RP6-65G23.1 was upregulated in psoriasis. However, it is still unclear whether lncRNA-RP6-65G23.1 expression is upregulated and contributes to keratinocytes proliferation and apoptosis, and which mechanisms are responsible for these processes. The aims of this study are to address these issues. RP6-65G23.1 was significantly upregulated in M5-stimulated keratinocytes and stimulated the proliferation and inhibited the apoptosis of HaCaT cells. Knockdown of RP6-65G23.1 resulted in defects of growth and increased rates of apoptosis in HaCaT cells, while overexpression of RP6-65G23.1 manifested the opposite effects. Consistently, the expression of antiapoptotic proteins Bcl-xl and Bcl2 were decreased in RP6-65G23.1-knockdown cells but elevated in RP6-65G23.1 overexpression cells. In addition, RP6-65G23.1 depletion blunted the activity of extracellular regulated kinase 1/2 (ERK1/2) and AKT signaling pathways and induced G₁/S-growth arrest. By contrast, overexpression of RP6-65G23.1 activates the ERK1/2 and AKT signaling pathways and inhibits the expression of p21 and p27 in an AKT-dependent manner leading to promote the G1/S progression. Our results suggested that lncRNA-RP6-65G23.1 would contribute to the pathogenesis of psoriasis by regulating the proliferation and apoptosis of keratinocytes via the p-ERK1/2 and p-AKT pathways.     

Simulating forest ecosystem response to climate warming incorporating spatial effects in north-eastern China

Aim Predictions of ecosystem responses to climate warming are often made using gap models, which are among the most effective tools for assessing the effects of climate change on forest composition and structure. Gap models do not generally account for broad‐scale effects such as the spatial configuration of the simulated forest ecosystems, disturbance, and seed dispersal, which extend beyond the simulation plots and are important under changing climates. In this study we incorporate the broad‐scale spatial effects (spatial configurations of the simulated forest ecosystems, seed dispersal and fire disturbance) in simulating forest responses to climate warming. We chose the Changbai Natural Reserve in China as our study area. Our aim is to reveal the spatial effects in simulating forest responses to climate warming and make new predictions by incorporating these effects in the Changbai Natural Reserve. Location Changbai Natural Reserve, north‐eastern China. Method We used a coupled modelling approach that links a gap model with a spatially explicit landscape model. In our approach, the responses (establishment) of individual species to climate warming are simulated using a gap model (linkages ) that has been utilized previously for making predictions in this region; and the spatial effects are simulated using a landscape model (LANDIS) that incorporates spatial configurations of the simulated forest ecosystems, seed dispersal and fire disturbance. We used the recent predictions of the Canadian Global Coupled Model (CGCM2) for the Changbai Mountain area (4.6 °C average annual temperature increase and little precipitation change). For the area encompassed by the simulation, we examined four major ecosystems distributed continuously from low to high elevations along the northern slope: hardwood forest, mixed Korean pine hardwood forest, spruce‐fir forest, and sub‐alpine forest. Results The dominant effects of climate warming were evident on forest ecosystems in the low and high elevation areas, but not in the mid‐elevation areas. This suggests that the forest ecosystems near the southern and northern ranges of their distributions will have the strongest response to climate warming. In the mid‐elevation areas, environmental controls exerted the dominant influence on the dynamics of these forests (e.g. spruce‐fir) and their resilience to climate warming was suggested by the fact that the fluctuations of species trajectories for these forests under the warming scenario paralleled those under the current climate scenario. Main conclusions With the spatial effects incorporated, the disappearance of tree species in this region due to the climate warming would not be expected within the 300‐year period covered by the simulation. Neither Korean pine nor spruce‐fir was completely replaced by broadleaf species during the simulation period. Even for the sub‐alpine forest, mountain birch did not become extinct under the climate warming scenario, although its occurrence was greatly reduced. However, the decreasing trends characterizing Korean pine, spruce, and fir indicate that in simulations beyond 300 years these species could eventually be replaced by broadleaf tree species. A complete forest transition would take much longer than the time periods predicted by the gap models.     

Diagnosis of <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection using an UPLC–MS based metabolomics method

Introduction

The fecal metabolome of Clostridium difficile (CD) infection is far from being understood, particularly its non-volatile organic compounds. The drawbacks of current tests used to diagnose CD infection hinder their application.

Objective

The aims of this study were to find new characteristic fecal metabolites of CD infection and develop a metabolomics model for the diagnosis of CD infection.

Methods

Ultra-performance liquid chromatography-mass spectrometry (UPLC–MS) was used to characterize the fecal metabolome of CD positive and negative diarrhea and healthy control stool samples.

Results

Diarrhea and healthy control samples showed distinct clusters in the principal components analysis score plot, and CD positive group and CD negative group demonstrated clearer separation in a partial least squares discriminate analysis model. The relative abundance of sphingosine, chenodeoxycholic acid, phenylalanine, lysophosphatidylcholine (C16:0), and propylene glycol stearate was higher, and the relative abundance of fatty amide, glycochenodeoxycholic acid, tyrosine, linoleyl carnitine, and sphingomyelin was lower in CD positive diarrhea groups, than in the CD negative group. A linear discriminant analysis model based on capsiamide, dihydrosphingosine, and glycochenodeoxycholic acid was further constructed to identify CD infection in diarrhea. The leave-one-out cross-validation accuracy and area under receiver operating characteristic curve for the training set/external validation set were 90.00/78.57%, and 0.900/0.7917 respectively.

Conclusions

Compared with other hospital-onset diarrhea, CD diarrhea has distinct fecal metabolome characteristics. Our UPLC–MS metabolomics model might be useful tool for diagnosing CD diarrhea.

     

Activation of PhoBR under phosphate‐rich conditions reduces the virulence of Xanthomonas oryzae pv. oryzae

The two‐component signal transduction system PhoBR regulates the adaptation to phosphate limitation and the virulence of many animal bacterial pathogens. However, PhoBR in phytopathogens has rarely been investigated. In this study, we found that PhoBR in Xanthomonas oryzae pv. oryzae (Xoo), the pathogen of rice bacterial leaf blight, also regulates the adaptation to phosphate starvation. Unexpectedly, rice leaves infected by the phoBR‐deleted mutant and wild‐type PXO99^A showed similar lesions, indicating that PhoBR is unnecessary for the virulence of Xoo. phoBR was found to be silenced during host infection, whereas artificially constitutive PhoBR expression attenuated virulence on host rice and growth in phosphate‐rich media. RNA‐sequencing (RNA‐seq) was then performed to investigate the global effect caused by constitutive PhoBR activation. RNA‐seq and further experiments revealed that the PhoBR regulon in Xoo comprised a wide range of genes. Nutrient transport and metabolism readjustments that resulted from PhoBR regulon activation may be responsible for growth attenuation. Our findings suggest that growth reduction regulated by PhoBR is a fitness cost of adaptation to phosphate starvation. PhoBR in Xoo is activated under phosphate‐limited conditions, which could exist in epiphytic and saprophytic surviving phases, and is strictly repressed within phosphate‐rich host plants to minimize fitness costs.     

CD155 downregulation synergizes with adriamycin to induce breast cancer cell apoptosis

CD155 has been implicated in migration, invasion, proliferation and apoptosis of human cancer cells, and DNA damage response caused by chemotherapeutic agents or reactive oxygen species has been shown to attribute to CD155 induction. Adriamycin (Adr) is one of the most common chemotherapeutic drugs used to treat breast cancer. Here we reported that treatment with Adr upregulated CD155 expression on several in vitro cultured breast cancer cells and in breast cancer cell 4T1 xenografts. We also found that CD155 knockdown or Adr treatment induced apoptosis of in vitro cultured cancer cells and cancer cells in 4T1 xenografts, and a combination of CD155 knockdown with Adr treatment induced more cell death than either of them. Furthermore, we revealed that the combination of CD155 knockdown with Adr treatment suppressed the growth of 4T1 xenografts more significantly than them alone. In summary, our results demonstrate that CD155 downregulation synergizes with Adr to induce breast cancer cell apoptosis, thereby to suppress tumor growth. Our results also suggest that CD155 upregulation may be a mechanism underlying Adr resistance by breast cancer cells.     

Critical contribution of RIPK1 mediated mitochondrial dysfunction and oxidative stress to compression-induced rat nucleus pulposus cells necroptosis and apoptosis

The aim of this study was to investigate whether RIPK1 mediated mitochondrial dysfunction and oxidative stress contributed to compression-induced nucleus pulposus (NP) cells necroptosis and apoptosis, together with the interplay relationship between necroptosis and apoptosis in vitro. Rat NP cells underwent various periods of 1.0 MPa compression. To determine whether compression affected mitochondrial function, we evaluated the mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP), mitochondrial ultrastructure and ATP content. Oxidative stress-related indicators reactive oxygen species, superoxide dismutase and malondialdehyde were also assessed. To verify the relevance between oxidative stress and necroptosis together with apoptosis, RIPK1 inhibitor necrostatin-1(Nec-1), mPTP inhibitor cyclosporine A (CsA), antioxidants and small interfering RNA technology were utilized. The results established that compression elicited a time-dependent mitochondrial dysfunction and elevated oxidative stress. Nec-1 and CsA restored mitochondrial function and reduced oxidative stress, which corresponded to decreased necroptosis and apoptosis. CsA down-regulated mitochondrial cyclophilin D expression, but had little effects on RIPK1 expression and pRIPK1 activation. Additionally, we found that Nec-1 largely blocked apoptosis; whereas, the apoptosis inhibitor Z-VAD-FMK increased RIPK1 expression and pRIPK1 activation, and coordinated regulation of necroptosis and apoptosis enabled NP cells survival more efficiently. In contrast to Nec-1, SiRIPK1 exacerbated mitochondrial dysfunction and oxidative stress. In summary, RIPK1-mediated mitochondrial dysfunction and oxidative stress play a crucial role in NP cells necroptosis and apoptosis during compression injury. The synergistic regulation of necroptosis and apoptosis may exert more beneficial effects on NP cells survival, and ultimately delaying or even retarding intervertebral disc degeneration.     

Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?

Introduction: Many lines of evidence indicate that low levels of HDL cholesterol increase the risk of cardiovascular disease (CVD). However, recent clinical studies of statin-treated subjects with established atherosclerosis cast doubt on the hypothesis that elevating HDL cholesterol levels reduces CVD risk.

Areas covered: It is critical to identify new HDL metrics that capture HDL’s proposed cardioprotective effects. One promising approach is quantitative MS/MS-based HDL proteomics. This article focuses on recent studies of the feasibility and challenges of using this strategy in translational studies. It also discusses how lipid-lowering therapy and renal disease alter HDL’s functions and proteome, and how HDL might serve as a platform for binding proteins with specific functional properties.

Expert commentary: It is clear that HDL has a diverse protein cargo and that its functions extend well beyond its classic role in lipid transport and reverse cholesterol transport. MS/MS analysis has demonstrated that HDL might contain >80 different proteins. Key challenges are demonstrating that these proteins truly associate with HDL, are functionally important, and that MS-based HDL proteomics can reproducibly detect biomarkers in translational studies of disease risk.