Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI.

Autophagy is an important intracellular degradation system, which is related to various diseases. In preliminary experiments we found that D4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline (DMH1) inhibited autophagy responses. However DMH1 also inhibits the signalling pathway activated by bone morphogenetic protein-4 (BMP4). The aim of the present study was to elucidate the inhibitory effects of DMH1 on autophagy and the underlying mechanisms.

Lung metastasis and relapse in osteosarcoma (OS) patients indicate poor prognosis. Here, we identified significantly decreased expression of miR-382 in highly metastatic OS cell lines and relapsed OS samples compared to their parental cell lines and primary OS samples, respectively. In addition, our clinical data showed that the miR-382 expression level was inversely associated with relapse and positively associated with metastasis-free survival in OS patients. The overexpression of miR-382 suppressed epithelial-mesenchymal transition (EMT) and metastasis. This overexpression also decreased the cancer stem cell (CSC) population and function in OS cells. In contrast, inhibition of miR-382 stimulated EMT and metastasis and increased CSC population in OS cells. In addition, our in vivo experiments showed that the overexpression of miR-382 inhibited CSC-induced tumor formation, and the combination of miR-382 with doxorubicin prevented disease relapse in OS patients. Furthermore, we demonstrated that miR-382 exerted its tumor-suppressing potential by directly targeting Y box-binding protein 1 (YB-1) in OS. Taken together, our findings suggest that miR-382 functions as a tumor suppressor function and that the overexpression of miR-382 is a novel strategy to inhibit tumor metastasis and prevent CSC-induced relapse in OS.

Among patients with Charcot-Marie-Tooth disease (CMT), the X-linked variant (CMTX) caused by gap junction protein beta 1 (GJB1) gene mutation is the second most frequent type, accounting for approximately 90% of all CMTX. More than 400 mutations have been identified in the GJB1 gene that encodes connexin 32 (CX32). CX32 is thought to form gap junctions that promote the diffusion pathway between cells. GJB1 mutations interfere with the formation of the functional channel and impair the maintenance of peripheral myelin, and novel mutations are continually discovered.

Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy.

Abiotic stresses are serious threats to plant growth, productivity and result in crop loss worldwide, reducing average yields of most major crops. Although abiotic stresses might elicit different plant responses, most induce the accumulation of reactive oxygen species (ROS) in plant cells leads to oxidative damage. L-ascorbic acid (AsA, vitamin C) is known as an antioxidant and H2O2-scavenger that defends plants against abiotic stresses. In addition, vitamin C is also an important component of human nutrition that has to be obtained from different foods. Therefore, increasing the vitamin C content is important for improving abiotic stresses tolerance and nutrition quality in crops production.

The purpose of this study was to determine whether aldosterone has a rapid action in the nucleus tractus solitarius (NTS) that increases sodium intake, and to examine whether this effect of aldosterone, if present, is mediated by G protein-coupled estrogen receptor (GPER). Adult male Sprague-Dawley rats with a stainless-steel cannula in the NTS were used. Aldosterone was injected into the NTS at the doses of 1, 5, 10 and 20 ng 0.1 μl-1. A rapid dose-related increase of 0.3 M NaCl intake was induced within 30 min and this increase was not suppressed by the mineralocorticoid receptor (MR) antagonist spironolactone (10 ng 0.1 μl-1). Water intake was not affected by aldosterone. The GPER agonist G-1 produced a parallel and significant increase in sodium intake, while pre-treatment with GPER antagonist G15 (10 ng 0.1 μl-1) blocked the G-1 or aldosterone-induced rapid sodium intake. In addition, sodium intake induced by sodium depletion or low-sodium diet fell within 30 min after injection into the NTS of the MR antagonist spironolactone, while G15 had no effect. Our results confirm previous reports, and support the hypothesis that aldosterone evokes rapid sodium intake through a non-genomic mechanism involving GPER in NTS.

The aim of the present study was to investigate whether urinary kidney injury molecule‑1 (KIM‑1) presents a suitable early diagnostic biomarker of obstructive nephropathy‑induced acute kidney injury (AKI), and to develop a rapid detection method for urinary KIM‑1. Obstructive AKI was induced in an experimental rat model by a unilateral ureteral obstruction (UUO) operation. Macro‑ and micromorphological kidney alterations were determined by visual observation and hematoxylin and eosin (HE) staining, respectively. Kidney functions were evaluated by detecting urea nitrogen and creatinine levels in rat urine and blood. Urinary KIM‑1 levels were measured using an enzyme‑linked immunosorbent assay, and the protein expression levels of KIM‑1, α‑smooth muscle actin (α‑SMA) and vimentin in kidney tissues were detected using immunohistochemical assays. In order to measure KIM‑1 levels, colloidal gold immunochromatographic strips were developed based on the colloidal gold immunochromatographic assay. The results indicated that KIM‑1 levels were significantly higher in the UUO group when compared with the Sham group. KIM‑1 levels in the urine and kidney tissues exhibited a time‑dependent increase, together with increasing obstructive AKI in the UUO group. In addition, KIM‑1 levels were demonstrated to be a more sensitive biomarker of early obstructive AKI, when compared with α‑SMA and vimentin. A colloidal gold‑based immunochromatographic strip was developed, whereby the detection of urinary KIM‑1 could be completed within 5‑10 min. In conclusion, results of the present study demonstrated that urinary KIM‑1 may be a valuable biomarker for the early diagnosis of obstructive AKI, and the use of a colloidal gold immunochromatographic strip may be a promising method for the rapid detection of urinary KIM‑1.

Microbe plays an important role in driving biogeochemical cycles, thus it is of great interest to understand microbial responses and feedbacks to global changes. We have recently analyzed functional potentials of soil microbial community via a high-throughput, microarray-based metagenomic tool named GeoChip 3.0 to illustrate microbial responses to global changes simulated by soil transplant and/or maize cropping. Here we describe detailed experimental design, data collection and pre-processing to support our published studies by Liu et al. [5] and Zhao et al. [14].

Recently, we have successfully obtained functional IPCs efficiently from umbilical cord blood-derived mesenchymal stem cells by using hypoxia treatment. In this study, we further elaborated that the improved function and viability of IPCs are the result of the interaction β cell development pathway and c-Met/HGF axis induced by hypoxia. We found that hypoxia induced c-MET elevation is efficiently initiated the early stage differentiation IPCs from MSCs, and HGF improved the fully differentiation of IPCs by inducing the expression of NGN3. This finding may contribute to understanding β cell development and the development of stem cell therapy for diabetes.

Plants have an important impact on soil microbial communities and their functions. However, how plants determine the microbial composition and network interactions is still poorly understood. During a four-year field experiment, we investigated the functional gene composition of three types of soils (Phaeozem, Cambisols and Acrisol) under maize planting and bare fallow regimes located in cold temperate, warm temperate and subtropical regions, respectively. The core genes were identified using high-throughput functional gene microarray (GeoChip 3.0), and functional molecular ecological networks (fMENs) were subsequently developed with the random matrix theory (RMT)-based conceptual framework. Our results demonstrated that planting significantly (P < 0.05) increased the gene alpha-diversity in terms of richness and Shannon - Simpson's indexes for all three types of soils and 83.5% of microbial alpha-diversity can be explained by the plant factor. Moreover, planting had significant impacts on the microbial community structure and the network interactions of the microbial communities. The calculated network complexity was higher under maize planting than under bare fallow regimes. The increase of the functional genes led to an increase in both soil respiration and nitrification potential with maize planting, indicating that changes in the soil microbial communities and network interactions influenced ecological functioning.

The production of outer membrane vesicles by Gram-negative bacteria has been well documented; however, the mechanism behind the biogenesis of these vesicles remains unclear. Here a high-throughput experimental method and systems-scale analysis was conducted to determine vesiculation values for the whole genome knockout library of Escherichia coli mutant strains (Keio collection). The resultant dataset quantitatively recapitulates previously observed phenotypes and implicates nearly 150 new genes in the process of vesiculation. Gene functional and biochemical pathway analyses suggest that mutations that truncate outer membrane structures such as lipopolysaccharide and enterobacterial common antigen lead to hypervesiculation, whereas mutants in oxidative stress response pathways result in lower levels. This study expands and refines the current knowledge regarding the cellular pathways required for outer membrane vesiculation in E. coli.

Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been confirmed to play crucial regulatory roles in tumor progression. It exerts an impact on tumor suppression and functions as a competing endogenous RNA (ceRNA) by sponging miR-106a-5p in gastric cancer. However, its clinical significance in colon cancer is completely unknown. The aim of the present study was to annotate the role of FER1L4 and its clinical value in colon cancer. The results showed the aberrant expression of FER1L4 and miR-106a-5p in colon cancer tissues. In addition, significant negative correlation between FER1L4 and miR-106a-5p expression levels was observed. Among the colon cancer cell lines, FER1L4 levels were relatively lower, with concurrent high levels of miR-106a-5p. Restoration of FER1L4 decreased the expression of miR-106a-5p, and had a significant influence on colon cancer cell proliferation, migration and invasion. The FER1L4 expression was correlated with depth of tumor invasion, lymph node metastasis, vascular invasion and clinical stage. Moreover, striking differences in overall survival and disease-free survival were observed for the cases with both low FER1L4 expression and high miR-106a-5p expression compared with cases with high FER1L4 expression and low miR-106a-5p expression. Circulating FER1L4 and miR-106a-5p levels were decreased and increased, respectively, in colon cancer patients after surgery. Our findings indicated that FER1L4 could exert a tumor suppressive impact on colon cancer, which at least, in part, through suppressing miR-106a-5p expression, and depletion of FER1L4, alone or combined with overexpression of miR-106a-5p, is predictive of poor prognosis in colon cancer and may play a crucial role in cancer prevention and treatment.

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicating greater dissolution and cellular uptake of PNC than PPT. A single IP administration of PNC-gel extended the survival of tumor-bearing mice significantly better than Taxol, but PPT-gel did not. These results support the advantage of PNC over PPT and demonstrate the promise of a gel depot as an IP drug delivery system.

In this study, a new type of amphiphilic cetylated polyethyleneimine (PEI) was synthesized, and then polylactic-co-glycolic acid (PLGA)/cetylated PEI/hyaluronic acid nanoparticles (PCPH NPs) were developed by self-assembly as a novel type of gene-delivering vehicle. The PCPH NPs showed good DNA-condensation ability by forming polyplexes with small particle size and positive zeta potential. The transfection efficiency and cytotoxicity of PCPH NPs were evaluated as plasmid DNA vectors to transfect HepG2 in vitro. PCPH NPs exhibited much lower cytotoxicity and higher gene-transfection efficiency than PEI (25,000) and commercial transfection reagents. Furthermore, PCPH NPs were used as an anti-miR-221 vector for transfecting HepG2 cells, and anti-miR-221 was effectively transfected into cells and produced a greater inhibitory effect on cancer-cell growth by PCPH NPs. These results demonstrate that PCPH NPs can be a promising nonviral vector for gene-delivery systems.

The effects of glucose on aliphatic glucosinolate biosynthesis in Arabidopsis thaliana were investigated in this study by using mutants related to aliphatic glucosinolate biosynthesis and regulation, as well as glucose signalling. The results showed that glucose significantly increased the contents of individual and total aliphatic glucosinolates. Expression of MYB28 and MYB29, two key transcription factors in aliphatic glucosinolate biosynthesis, was also induced by glucose. Consistently, the increased accumulation of aliphatic glucosinolates and the up-regulated expression of CYP79F1 and CYP79F2 induced by glucose disappeared in the double mutant myb28myb29. MYB28 and MYB29 synergistically functioned in the glucose-induced biosynthesis of aliphatic glucosinolates, but MYB28 was predominant over MYB29. Interestingly, the content of total aliphatic glucosinolates and the expression level of MYB28 and MYB29 were substantially reduced in the glucose insensitive mutant gin2-1 and the ABA insensitive 5 (abi5-7) mutant compared with the wild type. In addition, total aliphatic glucosinolates accumulated much less in another sugar-insensitive RGS1 (regulator of G-protein signaling 1) mutant (rgs1-2) than in the wild type. These results suggest that glucose-promoted aliphatic glucosinolate biosynthesis is regulated by HXK1- and/or RGS1-mediated signalling via transcription factors, MYB28, MYB29, and ABI5.

Mesenchymal stem cells (MSCs) from human umbilical cord (UC) and cord blood (CB) share many common properties and exhibit promising clinical potential. Cellular senescence, which induces the loss of stem cells characters and disrupts their therapeutic functions, has been demonstrated to be under the regulation of microRNAs (miRNAs). In this study, we compared the miRNA profiles in early and late passage UCMSCs and CBMSCs based on deep sequencing. 224 and 170 miRNAs were significantly altered in UCMSCs and CBMSCs respectively. A functional annotation of the predicted miRNA targets revealed a series of common senescence pathways. However, Functional enrichment analysis revealed different bioprocesses involved in cellular senescence of UC- and CB-MSCs. The common miRNAs shared by the two kinds of MSCs also exert different function in terms of GO enrichment analysis. Our results supported MSCs derived from different origin may undergo senescence through different path.

Cerebral palsy (CP) has long been investigated to be associated with a range of motor and cognitive dysfunction. As the two most common CP subtypes, spastic cerebral palsy (SCP) and dyskinetic cerebral palsy (DCP) may share common and distinct elements in their pathophysiology. However, the common and distinct dysfunctional characteristics between SCP and DCP on the brain network level are less known. This study aims to detect the alteration of brain functional connectivity in children with SCP and DCP based on resting-state functional MRI (fMRI). Resting-state networks (RSNs) were established based on the independent component analysis (ICA), and the functional network connectivity (FNC) was performed on the fMRI data from 16 DCP, 18 bilateral SCP, and 18 healthy children. Compared with healthy controls, altered functional connectivity within the cerebellum network, sensorimotor network (SMN), left frontoparietal network (LFPN), and salience network (SN) were found in DCP and SCP groups. Furthermore, the disconnections of the FNC consistently focused on the visual pathway; covariance of the default mode network (DMN) with other networks was observed both in DCP and SCP groups, while the DCP group had a distinct connectivity abnormality in motor pathway and self-referential processing-related connections. Correlations between the functional disconnection and the motor-related clinical measurement in children with CP were also found. These findings indicate functional connectivity impairment and altered integration widely exist in children with CP, suggesting that the abnormal functional connectivity is a pathophysiological mechanism of motor and cognitive dysfunction of CP.

'Hongmian miyou' (Citrus grandis L. Osbeck) is mutated from 'Guanxi miyou', with a different spongy layer coloration. Trifoliate orange (Poncirus trifoliata) is widely used as rootstocks in 'Guanxi miyou' grafting, whereas 'Hongmian miyou' is incompatible with available trifoliate orange rootstocks. To explore the reasons for the etiolation of leaves of 'Hongmian miyou'/trifoliate orange, anatomical differences among different graft unions, gene expression profiles, and auxin levels of scion were investigated in this study. A histological assay indicated that there was no significant difference in anatomical structure between the compatible and incompatible combinations. A total of 1950 significant differentially-expressed genes (DEGs) were identified and analyzed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that genes involved in carbohydrate metabolism, energy metabolism, amino acid metabolism, and plant hormone signal transduction were significantly enriched. Moreover, the expression of nine genes in the auxin pathway were upregulated and three were downregulated in compatible combinations compared with those in the incompatible group. Further experiments verified that indole-3-acetic acid (IAA) content increases in the compatible graft combination, which suggests that IAA might promote graft compatibility.

Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could accelerate dermal wound healing and strong inflammation control in Sprague-Dawley rats (SD rat) and Bama minipigs. Due to its low solubility, PnAg led to low toxicity and blood enrichment in animals. Furthermore, PnAg could upregulate the promoter activity of Jak, Stat3, and Stat3 downstream proteins. Therefore, PnAg may serve as an effective therapeutic compound for wound healing through regulating the gp130/Jak/Stat3 signaling pathway.