MicroRNA-122 antagonism against hepatitis C virus genotypes 1-6 and reduced efficacy by host RNA insertion or mutations in the HCV 5' UTR.

MicroRNA-122 (miR-122) is believed to stimulate hepatitis C virus (HCV) replication through interaction with two adjacent sites downstream of stem loop I (SLI) within the HCV 5' untranslated region (5' UTR). Recently, it was demonstrated that locked nucleic acid SPC3649-induced miR-122 antagonism suppressed HCV genotype 1a and 1b infection in vivo. However, virus-producing culture systems with 5' UTR of different HCV genotypes have not been available for testing 5' UTR-based treatment approaches.

Beta3-integrin mediates satellite cell differentiation in regenerating mouse muscle.

Skeletal muscle satellite cells can sense various forms of environmental cues and initiate coordinated signaling that activates myogenesis. Although this process involves cellular membrane receptor integrins, the role of integrins in myogenesis is not well defined. Here, we report a regulatory role of β3-integrin, which was previously thought not expressed in muscle, in the initiation of satellite cell differentiation.

SNX25 regulates TGF-β signaling by enhancing the receptor degradation.

SNXs (sorting nexin), a family of proteins playing roles in cargo sorting and signaling from compartments within the endocytic network, regulate traffic of membrane proteins including TGF-β receptors. Here we report that the full length human and mouse SNX25, a SNX member with PX, PXA and RGS domains, co-localizes with TGF-β receptors, and forms internalized cytosolic punctae upon treatment with TGF-β. While overexpression of SNX25 inhibits TGF-β induced luciferase reporter activity, knocking down endogenous SNX25 by siRNA in NIH3T3 cells elevates the TGF-β receptor levels and facilitates TGF-β signaling.

Efficient culture adaptation of hepatitis C virus recombinants with genotype-specific core-NS2 by using previously identified mutations.

Hepatitis C virus (HCV) is an important cause of chronic liver disease, and interferon-based therapy cures only 40 to 80% of patients, depending on HCV genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell culture systems. We previously developed viable JFH1-based recombinants encoding the structural proteins (core, E1, E2), p7, and NS2 of prototype isolates of the seven major HCV genotypes; most recombinants required adaptive mutations.

Mutant (CCTG)n expansion causes abnormal expression of zinc finger protein 9 (ZNF9) in myotonic dystrophy type 2.

The mutation that underlies myotonic dystrophy type 2 (DM2) is a (CCTG)n expansion in intron 1 of zinc finger protein 9 (ZNF9). It has been suggested that ZNF9 is of no consequence for disease pathogenesis. We determined the expression levels of ZNF9 during muscle cell differentiation and in DM2 muscle by microarray profiling, real-time RT-PCR, splice variant analysis, immunofluorescence, and Western blotting.

Anterior visceral endoderm SMAD4 signaling specifies anterior embryonic patterning and head induction in mice.

SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.

Campylobacter jejuni induces an anti-inflammatory response in human intestinal epithelial cells through activation of phosphatidylinositol 3-kinase/Akt pathway.

Campylobacter jejuni (C. jejuni) is the most common cause of human acute bacterial gastroenteritis. Poultry is a major reservoir of C.

Toll-like receptor 4 mediates lipopolysaccharide-induced muscle catabolism via coordinate activation of ubiquitin-proteasome and autophagy-lysosome pathways.

Cachectic muscle wasting is a frequent complication of many inflammatory conditions, due primarily to excessive muscle catabolism. However, the pathogenesis and intervention strategies against it remain to be established. Here, we tested the hypothesis that Toll-like receptor 4 (TLR4) is a master regulator of inflammatory muscle catabolism.

Requirement of the epithelium-specific Ets transcription factor Spdef for mucous gland cell function in the gastric antrum.

Mucus-secreting cells of the stomach epithelium provide a protective barrier against damage that might result from bacterial colonization or other stimuli. Impaired barrier function contributes to chronic inflammation and cancer. Knock-out mice for the epithelium-specific transcription factor Spdef (also called Pdef) have defects in terminal differentiation of intestinal and bronchial secretory cells.

TIMP3: a physiological regulator of adult myogenesis.

Myogenic differentiation in adult muscle is normally suppressed and can be activated by myogenic cues in a subset of activated satellite cells. The switch mechanism that turns myogenesis on and off is not defined. In the present study, we demonstrate that tissue inhibitor of metalloproteinase 3 (TIMP3), the endogenous inhibitor of TNFalpha-converting enzyme (TACE), acts as an on-off switch for myogenic differentiation by regulating autocrine TNFalpha release.

G Protein and its signaling pathway in bone development and disease.

G protein signaling is comprised of G protein coupled receptors (GPCRs) that detect ligands or sense cations, heterotrimeric G proteins, and downstream effectors and regulators. G protein signaling plays important roles in bone development, remodeling, and disease. In human cases, mutations of certain GPCRs and G proteins impair bone development and metabolism, resulting in bone diseases.

Novel infectious cDNA clones of hepatitis C virus genotype 3a (strain S52) and 4a (strain ED43): genetic analyses and in vivo pathogenesis studies.

Previously, RNA transcripts of cDNA clones of hepatitis C virus (HCV) genotypes 1a (strains H77, HCV-1, and HC-TN), 1b (HC-J4, Con1, and HCV-N), and 2a (HC-J6 and JFH1) were found to be infectious in chimpanzees. However, only JFH1 was infectious in human hepatoma Huh7 cells. We performed genetic analysis of HCV genotype 3a (strain S52) and 4a (strain ED43) prototype strains and generated full-length consensus cDNA clones (pS52 and pED43).

The protective effects of alpha-ketoacids against oxidative stress on rat spermatozoa in vitro.

The aim of this study was to determine the effects of antioxidants, including alpha-ketoacids (alpha-ketoglutarate and pyruvate), lactate and glutamate/malate combination, against oxidative stress on rat spermatozoa. Our results showed that H(2)O(2) (250 micromol L(-1))-induced damages, such as impaired motility, adenosine triphosphate (ATP) depletion, inhibition of sperm protein phosphorylation, reduced acrosome reaction and decreased viability, could be significantly prevented by incubation of the spermatozoa with alpha-ketoglutarate (4 mmol L(-1)) or pyruvate (4 mmol L(-1)). Without exogenous H(2)O(2) in the medium, the addition of pyruvate (4 mmol L(-1)) significantly increased the superoxide anion (O(2)(-).

Energy taxis drives Campylobacter jejuni toward the most favorable conditions for growth.

Campylobacter jejuni is a serious food-borne bacterial pathogen in the developed world. Poultry is a major reservoir, and C. jejuni appears highly adapted to the gastrointestinal tract of birds.

Octreotide for advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

Purpose: To evaluate the effectiveness of octreotide in advanced hepatocellular carcinoma participants on the basis of randomized controlled trials.

Methods: We searched the Cochrane Center Register of Controlled Trials in The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature Database, China Journal Full-text Database, Chinese Scientific Journals Database up to June 2008 in any language. Randomized controlled trials of octreotide for advanced hepatocellular carcinoma were selected and evaluated by two investigators.

[Synthesis and characterization of urocanic acid-coupled chitosan as gene vector].

A new nonviral gene vector--urocanic acid-coupled chitosan (UAC) was prepared by the reaction of the activated urocanic acid (UA) with the amine group on the chitosan (CTS). The structure of UAC was confirmed with FT-IR, 1H NMR and element analysis. The influencing factors of substitution values were studied by orthogonal test, and the substitution values of UAC increased with the prolongation of activating time of UA and the increasing ratio of UA to CTS.

Signaling networks that control the lineage commitment and differentiation of bone cells.

Osteoblasts and osteoclasts are the two major bone cells involved in the bone remodeling process. Osteoblasts are responsible for bone formation while osteoclasts are the bone-resorbing cells. The major event that triggers osteogenesis and bone remodeling is the transition of mesenchymal stem cells into differentiating osteoblast cells and monocyte/macrophage precursors into differentiating osteoclasts.

[Experiment and model simulation of suspended solids in Taihu Lake under wind-wave disturbance].

The bottom mud in Taihu Lake was simulated indoors in a wave tank. The rules of starting principle of the bottom mud were analyzed under different kinds of disturbing intensity in this paper. The common wave intensity of Tai Lake could be systematically simulated in the wave tank.

Atp6v0d2 is an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption.

Bone resorption relies on the extracellular acidification function of vacuolar (V-) ATPase proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of osteoclast-specific V-ATPases remains largely unknown. In this study, we found that Atp6v0d2 (d2), an isoform of the d subunit in the V-ATPase, showed 5-fold higher expression than that of Atp6v0d1 (d1) in mature osteoclasts, indicating a potential function in osteoclastic bone resorption.

[Suspension-sedimentation of sediment and release amount of internal load in Lake Taihu affected by wind].

The water quality in Meiliang Bay of the Taihu Lake was totally tested five times in the four seasons. The suspension samples were obtained by using a sediment trap. The sediment settling flux and resuspended flux were calculated according to the observation data by using Gansith formula, and the relationships between these fluxes and wind speeds were established.

[Change patterns of protective enzyme activities in pre-diapause, diapause, and post-diapause larvae of Sitodiplosis mosellana Gehin].

The activities of protective enzymes peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) in pre-diapause, diapause, and post-diapause larvae of Sitodiplosis mosellana Gehin were determined by using protective enzyme testing kits. The results indicated that the activities of the three protective enzymes showed a decreasing trend from pre-diapause to early diapause larvae. In one-year cycle, the SOD and CAT activities of diapause larvae had the same responses to environmental temperature, i.

Urocanic acid-modified chitosan-mediated p53 gene delivery inducing apoptosis of human hepatocellular carcinoma cell line HepG2 is involved in its antitumor effect in vitro and in vivo.

The p53 tumor suppressor gene is the most frequently mutated gene identified in many tumors, including hepatocellular carcinoma (HCC). Gene therapy using the p53 gene has been proposed and performed with inactivation of p53 function. However, there have been few reports of nonviral vector-mediated p53 gene delivery in HCC.

Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.

The low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are coreceptors for Frizzled and transmit signals from the plasma membrane to the cytosol. However, the mechanism for LRP5/6 signal transmission remains undefined. Here, we identify cytoplasmic activation/proliferation-associated protein 2 (Caprin-2) as a LRP5/6-binding protein.

Utilization of an intron located polyadenlyation site resulted in four novel glutamate decarboxylase transcripts.

Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in central nervous system (CNS). Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 65 kDa (GAD65) and 67 kDa (GAD67). In the present study, four novel GAD67 transcripts produced by alternative splicing and polyadenlyation were cloned from rat testis.

Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer cells.

Bone is one of the most common sites of breast cancer metastasis while bone sialoprotein (BSP) is thought to play an important role in bone metastasis of malignant tumors. The objective of this study is to determine the role of BSP overexpression in osteolytic metastasis using two homozygous transgenic mouse lines in which BSP expression is elevated either in all the tissues (CMV-BSP mice) or only in the osteoclasts (CtpsK-BSP mice). The results showed that skeletal as well as systemic metastases of 4T1 murine breast cancer cells were dramatically increased in CMV-BSP mice.