A 4-gene prognostic signature predicting survival in hepatocellular carcinoma.

OBJECTIVE: To develop an independent prognostic signature for patients with hepatocellular carcinoma (HCC). METHODS: HCC gene expression profile the cancer genome atlas-liver hepatocellular carcinoma and GSE14520 were used as discovery and test set, respectively. Differentially expressed genes (DEGs) were identified between HCC tissues and adjacent normal liver tissues. Univariate Cox proportional hazards regression analysis was performed to identify DEGs correlated with survival of HCC patients. A 4-gene-based signature was constructed based on a least absolute shrinkage and selection operator Cox penalized regression model. The predictive value of the signature was analyzed and validated. RESULTS: Two hundred sixty-three DEGs were identified between HCC and adjacent liver tissues. After univariate survival analysis, 90 DEGs were found to be significantly correlated with the overall survival (OS) of HCC patients, of which 4 genes (KPNA2, CDC20, SPP1, and TOP2A) with non-zero coefficient were used to construct a prognostic signature. The 4-gene signature was significantly associated with the age (P = 0.046), grade ( P = 0.022), and T stage ( P = 0.023) of HCC patients in the discovery set and it also significantly associated with TNM stage ( P = 0.033), and serum alpha-fetoprotein lever ( P = 0.034). Patients in the 4-gene low-risk group were associated with better OS and recurrence-free survival (RFS) than those in the high-risk group in the discovery and test set. Meanwhile, the 4-gene signature is an independent prognostic factor regarding OS and RFS in the discovery and test set. CONCLUSION: We developed a 4-gene-based signature, which could be a candidate prognostic factor for patients with HCC.

Molecular basis underlying LuxR family transcription factors and function diversity and implications for novel antibiotic drug targets.

LuxR is a widespread and functional diverse transcription factors and belongs to TetR protein superfamily. It could both activate and inhibit the expression of many genes contingent on the contexts, thereby involving in many crucial physiological events, such as virulence factors production, biofilm formation, quorum sensing (QS), acetate metabolism, motility, bioluminescence, and ecological competition. We summarized the function diversity of LuxR and underlying mechanisms. The interchangeability of some transcriptional factors for secondary metabolites biosynthesis opens new avenue to obtain new chemical entities or higher yield of antibiotics via the manipulation of regulators instead of structural genes. Inhibitors of pathogen QS are under intensive screening for better new antibiotics against the drug resistance. A compendium of compounds capable of inhibiting LuxR family transcriptional factors is also presented.

[Impact of abdominal moxibustion in a period of day from 7 am to 9 am on improvement in post-stroke lower limb spasticity and muscle architecture parameter].

OBJECTIVE: To compare the therapeutic effect on post-stroke lower limb spasticity between the combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training and the simple rehabilitation training. METHODS: A total of 100 patients with post-stroke lower limb spasticity were randomized into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 4 cases dropped off ). In the control group, the basic treatment of internal medicine and rehabilitation training of the limbs were adopted. In the observation group, on the basis of the treatment in the control group, at the time zone from 7 am to 9 am, moxibustion on the abdomen with "eight-trigram" moxa box [the central moxa box accurately facing Shenque (CV 8)] was given, lasting for 2 h, once every two days. Both groups were treated for 6 weeks. Separately, before and after treatment, the score of Fugl-Meyer assessment of the lower extremity (FMA-LE) and the grade of modified Ashworth scale (MAS) of ankle joint were evaluated on the affected side in patients of the two groups. Muscle skeleton ultrasound (MSUS) was adopted to determine the first layer muscle thickness (MT) anterior to the tibia, the number of pennation angle (PA) and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side. Besides, after treatment, the therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of FMA-LE and the grade of MAS of ankle joint on the affected side were both improved as compared with those before treatment in patients of the two groups (P<0.01, P<0.05). The improvements in the observation group were better than those in the control group (P<0.01, P<0.05). After treatment, MT anterior to the tibia, the number of PA and the length of muscle fibers in the medial head of gastrocnemius muscle on the affected side were all increased as compared with before treatment in patients of the two groups (P<0.01). The increase degree in the observation group was larger than that in the control group (P<0.01). The total effective rate was 93.6% (44/47) in the observation group, better than 80.4% (37/46) in the control group (P<0.05). CONCLUSION: The combined treatment of abdominal moxibustion from 7 am to 9 am and rehabilitation training effectively relieves post-stroke lower limb spasticity and improves the limb functions and muscle structure. The total effective rate of this combined treatment is better than that of simple rehabilitation training.

Trichuris suis ova therapy in inflammatory bowel disease: A meta-analysis.

BACKGROUND: In recent years, Trichuris suis ova (TSO) therapy in inflammatory bowel disease (IBD) has attracted much attention. However, efficacy and safety of TSO therapy are still not well described. The aim of the study was to perform a meta-analysis to assess the effectiveness of TSO therapy in IBD. METHODS: PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library were searched from inception to August 2017. Only randomized, double-blind, placebo-controlled trials (RCTs) were included. The pooled estimate rates were performed by meta-analysis and reported according to the standard Cochrane guidelines and the PRISMA statement. RESULTS: In ulcerative colitis study (3 RCTs, n = 74), the induced rates of clinical remission and clinical response were 10.8% (4/37) and 53.8% (21/39) in TSO group, while 6.7% (2/30) and 29.0% (9/31) in placebo group (all P > .26). Twenty-two (9/41) percent of patients in TSO group experienced at least 1 adverse event compared with 27.3% (9/33) of placebo [relative ratio (RR) 0.75, 95% confidence interval (95% CI) 0.17-3.27]. In Crohn disease study (3 RCTs, n = 538), 40.7% (74/182) of patients in TSO group achieved clinical remission compared with 42.9% (90/210) of placebo (RR 0.95, 95% CI 0.75-1.20); 45.9% (141/307) of patients in TSO group entered clinical response compared with 45.1% (151/335) of placebo (RR 1.02, 95% CI 0.86-1.21). There were sparse data of adverse events reporting both TSO and placebo group (RR 1.00, 95% CI 0.88-1.13). CONCLUSION: TSO therapy showed no statistical benefit for IBD patients, so it suggested clinicians consider its value carefully before putting into clinical practice. Perhaps continued investigations of larger sample size are necessary due to the previous results with lack of power.

Ubiquitination-mediated protein degradation and modification: an emerging theme in plant-microbe interactions.

Post-translational modification is central to protein stability and to the modulation of protein activity. Various types of protein modification, such as phosphorylation, methylation, acetylation, myristoylation, glycosylation, and ubiquitination, have been reported. Among them, ubiquitination distinguishes itself from others in that most of the ubiquitinated proteins are targeted to the 26S proteasome for degradation. The ubiquitin/26S proteasome system constitutes the major protein degradation pathway in the cell. In recent years, the importance of the ubiquitination machinery in the control of numerous eukaryotic cellular functions has been increasingly appreciated. Increasing number of E3 ubiquitin ligases and their substrates, including a variety of essential cellular regulators have been identified. Studies in the past several years have revealed that the ubiquitination system is important for a broad range of plant developmental processes and responses to abiotic and biotic stresses. This review discusses recent advances in the functional analysis of ubiquitination-associated proteins from plants and pathogens that play important roles in plant-microbe interactions.

Classification, expression pattern, and E3 ligase activity assay of rice U-box-containing proteins.

Ubiquitin ligases play a central role in determining the specificity of the ubiquitination system by selecting a myriad of appropriate candidate proteins for modification. The U-box is a recently identified, ubiquitin ligase activity-related protein domain that shows greater presence in plants than in other organisms. In this study, we identified 77 putative U-box proteins from the rice genome using a battery of whole genome analysis algorithms. Most of the U-box protein genes are expressed, as supported by the identification of their corresponding expressed sequence tags (ESTs), full-length cDNAs, or massively parallel signature sequencing (MPSS) tags. Using the same algorithms, we identified 61 U-box proteins from the Arabidopsis genome. The rice and Arabidopsis U-box proteins were classified into nine major classes based on their domain compositions. Comparison between rice and Arabidopsis U-box proteins indicates that the majority of rice and Arabidopsis U-box proteins have the same domain organizations. The inferred phylogeny established the homology between rice and Arabidopsis U-box/ARM proteins. Cell death assay using the rice protoplast system suggests that one rice U-box gene, OsPUB51, might act as a negative regulator of cell death signaling. In addition, the selected U-box proteins were found to be functional E3 ubiquitin ligases. The identification and analysis of rice U-box proteins hereby at the genomic level will help functionally characterize this class of E3 ubiquitin ligase in the future.

Spotted leaf11, a negative regulator of plant cell death and defense, encodes a U-box/armadillo repeat protein endowed with E3 ubiquitin ligase activity.

The rice (Oryza sativa) spotted leaf11 (spl11) mutant was identified from an ethyl methanesulfonate-mutagenized indica cultivar IR68 population and was previously shown to display a spontaneous cell death phenotype and enhanced resistance to rice fungal and bacterial pathogens. Here, we have isolated Spl11 via a map-based cloning strategy. The isolation of the Spl11 gene was facilitated by the identification of three additional spl11 alleles from an IR64 mutant collection. The predicted SPL11 protein contains both a U-box domain and an armadillo (ARM) repeat domain, which were demonstrated in yeast and mammalian systems to be involved in ubiquitination and protein-protein interactions, respectively. Amino acid sequence comparison indicated that the similarity between SPL11 and other plant U-box-ARM proteins is mostly restricted to the U-box and ARM repeat regions. A single base substitution was detected in spl11, which results in a premature stop codon in the SPL11 protein. Expression analysis indicated that Spl11 is induced in both incompatible and compatible rice-blast interactions. In vitro ubiquitination assay indicated that the SPL11 protein possesses E3 ubiquitin ligase activity that is dependent on an intact U-box domain, suggesting a role of the ubiquitination system in the control of plant cell death and defense.