Apoptosis is critical for the development of cerebral ischemia/reperfusion injury. Thioredoxin-1(Trx-1) protein has been reported to have anti-apoptotic effects in a variety of cell types, and it has been implicated in brain injury after middle cerebral artery occlusion (MCAO). Thus, we studied the effects of Trx1 silencing after MCAO in rats and examined whether inhibition of endogenous Trx1 could increase tissue levels of apoptosis. Male Sprague-Dawley rats (N=170) were subjected to 1h of middle cerebral arterial occlusion followed by 24h of reperfusion. Trx1 siRNAs were injected into rat brains 24h prior to MCAO. Then, 24h after MCAO, brains were collected from euthanized rats for investigation. Treatment with Trx1 siRNA significantly increased mortality, behavioral deficits, and cerebral infarction volume and exacerbated neuronal cell apoptotic death after MCAO injury. Western blot revealed increased expression of apoptotic proteins such as P-ASK1, P-JNK, P-p38, cleaved caspase-3 and increased the level of cytochrome c in the cytosolic fraction in the Trx1 siRNA-treated group. Co-immunoprecipitation assay suggested an interaction between Trx1 and ASK1 in normal rat brains and Trx1 siRNA dissociated ASK1-Trx1 binding complex. Our data suggest that Trx1 siRNA increases apoptotic stress-induced ASK1 activation and this represents further evidence that Trx1 is an endogenous anti-apoptotic molecule that diminishes focal cerebral ischemia/reperfusion injury. Its mechanism of action is likely related to attenuation of the ASK1-JNK/p38 signaling pathway.

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective, antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In the present study, we employed a high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. Differential proteins were identified, among which 13 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (vimentin and Gap43) were randomly selected, and their expression levels were further confirmed by western blots analysis. The results matched well with those of proteomics. Furthermore, network analysis of protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated proteins were carried out to illustrate its underlying molecular mechanism. Proteins associated with signal transduction, immune system, signaling molecules and interaction, and energy metabolism play important roles in neuroprotective effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This study demonstrates that comparative proteomics based on shotgun approach is a valuable tool for molecular mechanism studies, since it allows the simultaneously evaluate the global proteins alterations.

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of transcription, mRNA degradation and protein degradation. Therefore, it is essential to investigate translation in a global scale. Like the other "omics"-methods, translatomics investigates the totality of the components in the translation process, including but not limited to translating mRNAs, ribosomes, tRNAs, regulatory RNAs and nascent polypeptide chains. Technical advances in recent years have brought breakthroughs in the investigation of these components at global scale, both for their composition and dynamics. These methods have been applied in a rapidly increasing number of studies to reveal multifaceted aspects of translation control. The process of translation is not restricted to the conversion of mRNA coding sequences into polypeptide chains, it also controls the composition of the proteome in a delicate and responsive way. Therefore, translatomics has extended its unique and innovative power to many fields including proteomics, cancer research, bacterial stress response, biological rhythmicity and plant biology. Rational design in translation can enhance recombinant protein production for thousands of times. This brief review summarizes the main state-of-the-art methods of translatomics, highlights recent discoveries made in this field and introduces applications of translatomics on basic biological and biomedical research.

Measuring conditional relatedness between a pair of genes is a fundamental technique and still a significant challenge in computational biology. Such relatedness can be assessed by gene expression similarities while suffering high false discovery rates. Meanwhile, other types of features, e.g., prior-knowledge based similarities, is only viable for measuring global relatedness. In this paper, we propose a novel machine learning model, named Multi-Features Relatedness (MFR), for accurately measuring conditional relatedness between a pair of genes by incorporating expression similarities with prior-knowledge based similarities in an assessment criterion. MFR is used to predict gene-gene interactions extracted from the COXPRESdb, KEGG, HPRD, and TRRUST databases by the 10-fold cross validation and test verification, and to identify gene-gene interactions collected from the GeneFriends and DIP databases for further verification. The results show that MFR achieves the highest area under curve (AUC) values for identifying gene-gene interactions in the development, test, and DIP datasets. Specifically, it obtains an improvement of 1.1% on average of precision for detecting gene pairs with both high expression similarities and high prior-knowledge based similarities in all datasets, comparing to other linear models and coexpression analysis methods. Regarding cancer gene networks construction and gene function prediction, MFR also obtains the results with more biological significances and higher average prediction accuracy, than other compared models and methods. A website of the MFR model and relevant datasets can be accessed from http://bmbl.sdstate.edu/MFR .

Homeobox D4 (HOXD4) belongs to the homeobox (HOX) family, which plays a crucial role in the early embryo development and cell differentiation. The role of HOXD4 in human gastric adenocarcinoma has not been elucidated. In the present study, we aimed to examine the expression levels of HOXD4 and dissect whether the HOXD4 expression is associated with aggressive clinicopathological outcomes of patients with gastric adenocarcinoma.

Gut microbiota have been implicated in the development of many human diseases, including both digestive diseases and non-digestive diseases. In this study, we investigated whether the gut bacteria differed in cervical cancer (CCa) patients compared with healthy controls by 16S rRNA sequencing analysis. Subjects including eight CCa and five healthy controls were included. Microbiota profiles in fecal DNA were characterized by PCR amplification of the 16S rRNA V4 variable region and deep sequencing using the Illumina HiSeq platform. The CCa-associated gut microbiota had an increasing trend in alpha diversity, although statistical significance was not reached. Inter-group variability in community structure by beta diversity analysis showed a clear separation between cancer patients and healthy controls. Gut microbiota profiles were different between patients and controls; namely, the proportions of Proteobacteria phylum was notably higher in patients with CCa (ρ = 0.012). Seven genera differentiated significantly in relative abundance between CCa and controls (all ρ < 0.05), including Escherichia-Shigella, Roseburia, Pseudomonas, Lachnoclostridium, Lachnospiraceae_UCG-004, Dorea and Succinivibrio. The characteristic microbiome in CCa patients was also identified by linear discriminant analysis effect size (LEfSe). The phylum Proteobacteria, and the genus Parabacteroides, Escherichia_Shigells and Roseburia may provide novel potential biomarkers for CCa. Taken together, this is the first study on gut microbiota in patients with CCa, and demonstrated the significantly altered diversity and composition.

Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in lung cancer patients. We retrospectively investigated the clinical characteristics, treatment responses, and prognoses in 16 PLE patients who were subsequently diagnosed with lung cancer. Fifteen patients initially presented with disturbance of consciousness, 13 with disorientation, and 12 with seizures. Thirteen patients had autoantibodies, including eight with gamma aminobutyric acid B receptor (GABABR) antibodies and eight with Hu antibodies. PET-CT revealed lung neoplasms in 13 patients, nine of whom exhibited abnormal metabolic activity in the temporal lobe and hippocampus. Fifteen cases were confirmed as limited-stage small cell lung cancer and one as stage IV large cell neuroendocrine carcinoma. Eleven patients received immunomodulatory therapy, and four showed neurological improvement, who all had antibodies against GABABR. Fifteen patients received chemotherapy, of which 14 maintained or improved their PLE status. The overall cancer response rate was 75%, and two-year overall survival was 74.7%. Our results suggest patients with GABAB encephalitis might respond better to immunotherapy than the classical PLE patients with anti-Hu antibodies. Anti-cancer treatment could further improve neurological symptoms. Lung cancer patients with PLE, especially those in limited stage, might have better outcome due to earlier diagnosis and prompt anti-cancer treatment.

Purpose. To observe the effect of intravitreal ranibizumab injection on wet age-related macular degeneration (wAMD) over 5 years in Chinese patients. Methods. Thirty-seven patients who were diagnosed with wAMD in our hospital from June 2007 to June 2014 were retrospectively reviewed. The PRN regimen and the treatment and extend regimen were applied. Best corrected visual acuity (BCVA), number of ranibizumab injections, and changes in the choroidal neovascularization (CNV) lesion over 5 years were analyzed. Results. The mean BCVA measured by the ETDRS chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters, which was significantly different (p = 0.013). Fourteen eyes (37.8%) had improved visual acuity after 5 years. The number of injections in 5 years was 11.53, and most of the injections were in the first two years. Seventeen (45.9%) cases developed fibrous lesions, and 2 (5.4%) cases had atrophic lesions after 5 years. The fibrosis/atrophy was significantly correlated with the injection numbers (Pearson, r = 0.663, and p = 0.000). Conclusion. Most of the patients can maintain visual acuity treated by ranibizumab in the first 3 years. After 5 years, some patients can still improve or maintain visual acuity. Fibrous scarring of the lesion is the main reason for a decrease in vision of wAMD patients.

Adipose tissue is hyper-vascularized. Vessels in adipose tissue not only supply nutrients and oxygen to nourish adipocytes, but also provide cytokines that regulate mass and function of adipose tissue. Understanding the fundamental mechanisms how vessels modulate adipocyte functions would provide new therapeutic options for treatment of metabolic disease and obesity. In recent years, researches about ghrelin are focused on glucose and lipid metabolism, but its effect on vascular function remains uncharacterized. In the present study, ghrelin receptor gene deletion mice (Ghsr-/- mice) were used to study ghrelin-regulated vascular metabolism in white adipose tissue. Ghsr-/- mice demonstrated lower food intake, lower body weight, and resistance to high-fat diet-induced obesity. The number of vessels in white adipose tissue was decreased in Ghsr-/- mice when compared with wild type mice fed with high-fat diet. To further define ghrelin effects in vitro, we used endothelial progenitor cells from wild type and Ghsr-/- mice as well as human umbilical vein endothelial cells in our experiments. We found that ghrelin stimulated endothelial cells angiogenesis and migration through the MEK-ERK signaling pathway. [d-Lys3]-GHRP-6 and PD98059 could reverse the effects of ghrelin on endothelial cells. Our study indicates that ghrelin activates its receptor on endothelial cells to promote angiogenesis and migration via a mechanism involving the extracellular regulated protein kinases (ERK) signaling pathway.

Since the first case of human avian influenza A (H7N9) virus infection in 2013, five H7N9 epidemics have occurred in China, all of which caused severe diseases, including pneumonia and acute respiratory distress syndrome, and the fatality rates of these epidemics were as high as 30-40%. To control the prevalence of H7N9 influenza, an effective vaccine is urgently needed. In the present study, we used chitosan and recombinant human interleukin-2 as an adjuvant (JY) to promote the systemic and mucosal immune responses induced by the H7N9 vaccine. Mice were immunized intranasally with the inactivated split influenza A (H7N9) virus (A/Shanghai/02/2013) vaccine with or without JY. The hemagglutination inhibition (HI) titers of mice immunized with the JY-adjuvanted vaccine were significantly higher than those of mice immunized with the vaccine without adjuvant (21.11 ± 9.58 vs. 5.04 ± 3, P < 0.05). The JY-adjuvanted H7N9 nasal spray vaccine induced higher HI titers (8 ± 0.82 vs. 6.7 ± 0.67, P = 0.0035) than those did the poly (I:C)-adjuvanted H7N9 vaccine or the LTB-adjuvanted H7N9 vaccine (8 ± 0.82 vs. 6.9 ± 0.88, P = 0.0186). The optimal immunization regimen for the nasal spray H7N9 vaccine was determined to be a 21-day interval between the primary immunization and booster, with a dose of 4.5 μg hemagglutinin per mouse. The immunogenicities of the nasal spray H7N9 vaccine and intramuscular vaccine (containing only the inactivated split virus) were compared in mice. Two doses of the nasal spray H7N9 vaccine induced higher titers of HI (6.7 ± 0.67 vs. 5.3 ± 1.16, P = 0.004) and anti-HA IgG in sera (19.26 ± 0.67 vs. 13.97 ± 0.82, P < 0.0001) and of anti-HA sIgA (7.13 ± 2.54 vs. 0, P = 0.0000) in bronchoalveolar lavage fluid (BALF) than one dose of intramuscular H7N9 vaccine 3 weeks after the last immunization. However, when we immunized the mice with two doses of both vaccines separately, the nasal spray H7N9 vaccine induced higher titers of anti-HA IgG (19.26 ± 0.67 vs. 17.56 ± 0.57, P < 0.0001) and anti-HA sIgA (7.13 ± 2.54 vs. 4.02 ± 0.33, P = 0.0026) than did the intramuscular H7N9 vaccine, and there was no difference in HI titer between the two groups (P = 0.3745). This finding indicates that the JY-adjuvanted nasal spray H7N9 vaccine induced not only the systemic immune response but also a local mucosal response, which may improve the efficacy of H7N9 influenza prevention through respiratory tract transmission.

Teduglutide, a glucagon-like peptide-2 analog, has demonstrated efficacy in reducing parenteral support (PS) among patients with short bowel syndrome with intestinal failure (SBS-IF). This study aims to identify a subpopulation of SBS-IF patients for whom teduglutide has an especially pronounced effect.

The increasing number of biological applications for black phosphorus (BP) nanomaterials has precipitated considerable concern about their interactions with physiological systems. Here we demonstrate the adsorption of plasma protein onto BP nanomaterials and the subsequent immune perturbation effect on macrophages. Using liquid chromatography tandem mass spectrometry, 75.8% of the proteins bound to BP quantum dots were immune relevant proteins, while that percentage for BP nanosheet-corona complexes is 69.9%. In particular, the protein corona dramatically reshapes BP nanomaterial-corona complexes, influenced cellular uptake, activated the NF-κB pathway and even increased cytokine secretion by 2-4-fold. BP nanomaterials induce immunotoxicity and immune perturbation in macrophages in the presence of a plasma corona. These findings offer important insights into the development of safe and effective BP nanomaterial-based therapies.

To investigate the effectiveness and mechanism of the Chinese herbal formula Sini Tang (SNT) which consists of Aconitum carmichaelii (Fuzi), Zingiber officinale (Gan Jiang), and Glycyrrhiza uralensis (Gancao) in heart failure after myocardial infarction in rats.

The fruiting body formation mechanisms of Cordyceps sinensis are still unclear. To explore the mechanisms, proteins potentially related to the fruiting body formation, proteins from fruiting bodies, and mycelia of Cordyceps species were assessed by using two-dimensional fluorescence difference gel electrophoresis, and the differential expression proteins were identified by matrix-assisted laser desorption/ionisation tandem time of flight mass spectrometry. The results showed that 198 differential expression proteins (252 protein spots) were identified during the fruiting body formation of Cordyceps species, and 24 of them involved in fruiting body development in both C. sinensis and other microorganisms. Especially, enolase and malate dehydrogenase were first found to play an important role in fruiting body development in macro-fungus. The results implied that cAMP signal pathway involved in fruiting body development of C. sinensis, meanwhile glycometabolism, protein metabolism, energy metabolism, and cell reconstruction were more active during fruiting body development. It has become evident that fruiting body formation of C. sinensis is a highly complex differentiation process and requires precise integration of a number of fundamental biological processes. Although the fruiting body formation mechanisms for all these activities remain to be further elucidated, the possible mechanism provides insights into the culture of C. sinensis.

Orthographic neighborhood size (N size) effect in Chinese character naming has been studied in adults. In the present study, we aimed to explore the developmental characteristics of Chinese N size effect. One hundred and seventeen students (40 from the 3(rd) grade with mean age of 9 years; 40 from the 5(th) grade with mean age of 11 years; 37 from the 7(th) grade with mean age of 13 years) were recruited in the study. A naming task of Chinese characters was adopted to elucidate N-size- effect development. Reaction times and error rates were recorded. Results showed that children in the 3(rd) grade named characters from large neighborhoods faster than named those from small neighborhoods, revealing a facilitatory N size effect; the 5(th) graders showed null N size effect; while the 7(th) graders showed an inhibitory N size effect, with longer reaction times for the characters from large neighborhoods than for those from small neighborhoods. The change from facilitation to inhibition of neighborhood size effect across grades suggested the transition from broadly tuned to finely tuned lexical representation in reading development, and the possible inhibition from higher frequency neighbors for higher graders.

Phosphorus (P) is essential for plant growth and development. Phosphate (Pi) transporter genes in the Pht1 family play important roles in Pi uptake and translocation in plants. Although Pht1 family genes have been well studied in model plants, little is known about their functions in soybean, an important legume crop worldwide.

Complex chronic diseases are usually not caused by changes in a single causal gene but by an unbalanced regulating network resulting from the dysfunctions of multiple genes or their products. Therefore, network based systems approach can be helpful for the identification of candidate genes related to complex diseases and their relationships. Axial spondyloarthropathy (SpA) is a group of chronic inflammatory joint diseases that mainly affect the spine and the sacroiliac joints. The pathogenesis of SpA remains largely unknown.

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA. A total of 39 putative targets were identified. Three of these targets, calcineurin (CN), angiotensin-converting enzyme (ACE), and c-Jun N-terminal kinase (JNK), were experimentally validated at a molecular level. Protective effects of AGS-IV were also compared with the CN inhibitor cyclosporin A (CsA) in cultured cardiomyocytes exposed to adriamycin. Network analysis of protein-protein interactions (PPI) was carried out with reference to the therapeutic profiles of approved CVD drugs. The results suggested that the therapeutic effects of AGS-IV are based upon a combination of blocking calcium influx, vasodilation, anti-thrombosis, anti-oxidation, anti-inflammation and immune regulation.

Mutations in the leucine-rich repeat kinase-2 (LRRK2) have been linked to Parkinson's disease. Recent studies show that inhibition of LRRK2 kinase activity decreased the level of phosphorylation at its own Ser910 and Ser935, indicating that these sites are prime targets for cellular readouts of LRRK2 inhibition.