ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments

The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.     

Lead discovery of alpha,beta-unsaturated sulfones from a combinatorial library as inhibitors of inducible VCAM-1 expression

alpha,beta-Unsaturated sulfones have been discovered from a combinatorial library as leads for a new series of inhibitors of inducible VCAM-1 expression. Although not essential, further conjugation of the sulfonyl group to another vinyl group or a phenyl group increases the potency dramatically.     

Developmental transcriptome analysis of floral transition in <Emphasis Type="Italic">Rosa odorata</Emphasis> var. <Emphasis Type="Italic">gigantea</Emphasis>

Key message

Expression analyses revealed that floral transition of Rosa odorata var. gigantea is mainly regulated by VRN1, COLs, DELLA and KSN, with contributions by the effects of phytohormone and starch metabolism.

Abstract

Seasonal plants utilize changing environmental and developmental cues to control the transition from vegetative growth to flowering at the correct time of year. This study investigated global gene expression profiles at different developmental stages of Rosa odorata var. gigantea by RNA-sequencing, combined with phenotypic characterization and physiological changes. Gene ontology enrichment analysis of the differentially expressed genes (DEGs) between four different developmental stages (vegetative meristem, pre-floral meristem, floral meristem and secondary axillary buds) indicated that DNA methylation and the light reaction played a large role in inducing the rose floral transition. The expression of SUF and FLC, which are known to play a role in delaying flowering until vernalization, was down-regulated from the vegetative to the pre-floral meristem stage. In contrast, the expression of VRN1, which promotes flowering by repressing FLC expression, increased. The expression of DELLA proteins, which function as central nodes in hormone signaling pathways, and probably involve interactions between GA, auxin, and ABA to promote the floral transition, was well correlated with the expression of floral integrators, such as AGL24, COL4. We also identified DEGs associated with starch metabolism correlated with SOC1, AGL15, SPL3, AGL24, respectively. Taken together, our results suggest that vernalization and photoperiod are prominent cues to induce the rose floral transition, and that DELLA proteins also act as key regulators. The results summarized in the study on the floral transition of the seasonal rose lay a foundation for further functional demonstration, and have profound economic and ornamental values.

     

Lyoniresinol 3α-O-β-D-Glucopyranoside-Mediated Hypoglycaemia and Its Influence on Apoptosis-Regulatory Protein Expression in the Injured Kidneys of Streptozotocin-Induced Mice

Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN). (±)-Lyoniresinol 3α-O-β-D-glucopyranoside (LGP1, LGP2) were two chiral lignan glucosides that were isolated from the ACLR. The purpose of this study was to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days. Hyperglycaemia and the expression of related proteins such as nuclear factor-κB (NF-κB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were markedly decreased by LGP1 treatment. However, LGP2 treatment had no hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular and tubular basement membrane thickening were improved after 14 days of LGP1 treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ-induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may regulate several pharmacological targets for treating or preventing diabetic nephropathy.     

Antimicrobial activity of essential oils and structurally related synthetic food additives towards Clostridium perfringens

Aims:  To assess the potential of essential oils and structurally related synthetic food additives in inhibiting the growth of Clostridium perfringens for the control of necrotic enteritis in chickens.
Methods and Results:  The antimicrobial activity of essential oils/compounds was measured by determining the inhibition of bacterial growth. Thirty-three of 66 oils/compounds exhibited ≥80% inhibition. Seven with the highest potency were further studied. The oils/compounds had MIC₉₅ values between 167 and 425  μ g ml⁻¹. Most of them were tolerant to low pH (2·0) and exhibited minor or no inhibition of Lactobacillus isolates from the chicken intestine. When mixed with chicken ileal digesta, the oils/compounds retained their efficacy against C . perfringens , but had little effect on the total number of lactobacilli and anaerobic bacteria in the digesta.
Conclusions:  Some essential oils/compounds demonstrated good potential in controlling C . perfringens .
Significance and Impact of the Study:  This study has identified candidates of essential oils/compounds for in vivo studies for the control of necrotic enteritis in chickens.     

Identification of a Potent Endothelium-Derived Angiogenic Factor

The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up₄U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up₄U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up₄U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up₄U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up₄U after stimulation with shear stress. Mean total plasma Up₄U concentrations of healthy subjects (N = 6) were sufficient to induce angiogenic and proliferative effects (1.34±0.26 nmol L^-1). In conclusion, Up₄U is a novel strong human endothelium-derived angiogenic factor.     

Voltammetric behavior of complexation of salbutamol with calf thymus DNA and its analytical application

The interaction of salbutamol (Sal), an animal growth promoter, with DNA was investigated by differential pulse voltammetry (DPV), cyclic voltammetry (CV), and fluorescence spectroscopy. An irreversible reduction was observed from the cyclic voltammograms, and the reaction mechanism involved a one-electron change irreversible oxidation. In the presence of DNA, the DPV peak current decreased and the Sal peak shifted to higher potentials, indicating that Sal interacted with DNA to form an intercalation Sal–DNA complex. In addition, reaction binding parameters were extracted from the DPV data with the use of the multivariate curve resolution–alternating least squares (MCR–ALS) method; the binding constant and ratio were found to be (2.0 ± 0.5) × 10⁵ M⁻¹ and 1:1, respectively. Quantitative voltammetric analysis of Sal was performed in the concentration range of 3.02 × 10⁻⁶ to 1.23 × 10⁻⁴ mol L⁻¹, and it was found that the detection limit was 5.11 × 10⁻⁷ mol L⁻¹ in the presence of 1.00 × 10⁻⁶ mol L⁻¹ DNA. The method was applied for the determination of Sal in spiked urine and human serum samples, and the calibration was successfully verified.     

Microbial diversity in deep-sea sediment from the cobalt-rich crust deposit region in the Pacific Ocean

Cobalt-rich crusts are important metallic mineral resources with great economic potential, usually distributed on seamounts located in the Pacific Ocean. Microorganisms are believed to play a role in the formation of crusts as well as in metal cycling. To explore the microbial diversity related to cobalt-rich crusts, 16S ribosomal RNA gene clone libraries were constructed from three consecutive sediment layers. In total, 417 bacterial clones were obtained from three bacterial clone libraries, representing 17 distinct phylogenetic groups. Proteobacteria dominated in the bacterial communities, followed by Acidobacteria and Planctomycetes. Compared with high bacterial diversity, archaea showed a remarkably low diversity, with all 137 clones belonging to marine archaeal group I except one novel euryarchaeotal clone. The microbial communities were potentially involved in sulfur, nitrogen and metal cycling in the area of cobalt-rich crusts. Sulfur oxidation and metal oxidation were potentially major sources of energy for this ecosystem. This is the first reported investigation of microbial diversity in sediments associated with cobalt-rich crusts, and it casts fresh light on the microbial ecology of these important ecosystems.