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To improve the bio-performances of polyetheretherketone (PEEK) for orthopedic applications, submicro-particles of niobium pentoxide (Nb2O5) were synthesized using a sol-gel method, and PEEK/Nb2O5 composites (PNC) with a Nb2O5 content of 25v% (PNC25) and 50v% (PNC50) were fabricated by utilizing a process of pressing-sintering. The results showed that the Nb2O5 particles were not only dispersed in the composites but also exposed on the surface of the composites, which formed submicro-structural surfaces. In addition, the hydrophilicity, surface energy, surface roughness and absorption of proteins of the composites were improved with increasing Nb2O5 content. Moreover, the release of Nb ions with the highest concentration of 5.01 × 10-6 mol L-1 from the composite into the medium displayed no adverse effects on cell proliferation and morphology, indicating no cytotoxicity. Furthermore, compared with PEEK, the composites, especially PNC50, obviously stimulated adhesion and proliferation as well as osteogenic differentiation of bone mesenchymal stem cells of rats. The results suggested that the incorporation of Nb2O5 submicro-particles into PEEK produced novel bioactive composites with improved surface properties, which played important roles in regulating cell behaviors. In conclusion, the composites, especially PNC50 with good cytocompatibility and promotion of cellular responses, exhibited great potential as implantable materials for bone repair.

Poly(propylene carbonate) (PPC) has aroused extensive attention in the biomaterial field because of its excellent biocompatibility and appropriate degradability, but surface hydrophobicity and bioinertness limit its applications for bone repair and tissue engineering. In this study, a bioactive PPC/laponite (LAP) nanocomposite (PL) was prepared by a melt-blending method, and a microporous surface on PPC and PL (PT and PLT) was created by sodium hydroxide (NaOH) treatment. The results demonstrated that the surface roughness, hydrophilicity, surface energy, and degradability as well as protein adsorption of PLT were obviously improved compared with PPC. Moreover, the degradability of PLT was remarkably enhanced with a slight increase of pH values in Tris-HCl solution. Furthermore, adhesion and proliferation as well as osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) to PLT were significantly promoted compared with PPC. The results suggested that incorporating LAP into PPC obviously improved the surface performance of PL (with nanotopography), and surface treatment with NaOH further enhanced surface properties of PLT (with micronanotopography and hydrophilic groups), which significantly promoted responses of rBMSCs. In short, PLT displayed excellent cytocompatibility, which would have great potential for bone regeneration.

Dental implanted materials require excellent mechanical properties, biocompatibility as well as integration with bone tissue and gingival tissue to achieve early loading and long-term stability. In this study, cubic shape sodium tantalite (ST) submicro-particles with the size of around 180 nm were synthesized by a hydrothermal method, and ST/polyetheretherketone (PEEK) composites (TPC) with ST content of 20 w% (TPC20) and 40 w% (TPC40) were prepared by melting blend. The results showed that the compressive strength, thermal properties, surface roughness, hydrophilicity and surface energy as well as adsorption of proteins on TPC40 were also significantly enhanced compared with TPC20 and PEEK. Moreover, the responses (adhesion and proliferation as well as differentiation) of rat bone marrow mesenchymal stem cells (rBMSCs), and responses (adhesion, and proliferation) of human gingival epithelial (HGE-1) cells to TPC40 were significantly promoted compared with TPC20 and PEEK. The results demonstrated that ST content in TPC had remarkable effects on the surface properties, which played key roles in stimulating the responses of both rBMSCs and HGE-1 cells. TPC40 with increased surface properties and excellent cytocompatibility might have great potential as an implanted material for dental application.

BACKGROUND Over 30 million people in the United States (over 9%) have been diagnosed with diabetes. About 25% of people with diabetes will experience a diabetic foot ulcer (DFU) in their lifetime. Unresolved DFUs may lead to sepsis and are the leading cause of lower-limb amputations. DFU rates can be reduced by screening patients with diabetes to enable risk-based interventions. Skin temperature assessment has been shown to reduce the risk of foot ulceration. While several tools have been developed to measure plantar temperatures, they only measure temperature once a day or are designed for clinic use only. In this report, wireless sensor-embedded socks designed for daily wear are introduced, which perform continuous temperature monitoring of the feet of persons with diabetes in the home environment. Combined with a mobile app, this wearable device informs the wearer about temperature increases in one foot relative to the other, to facilitate early detection of ulcers and timely intervention. OBJECTIVE A pilot study was conducted to assess the accuracy of sensors used in daily wear socks, obtain user feedback on how comfortable sensor-embedded socks were for home use, and examine whether observed temperatures correlated with clinical observations. METHODS Temperature accuracy of sensors was assessed both prior to incorporation in the socks, as well as in the completed design. The measured temperatures were compared to the reference standard, a high-precision thermostatic water bath in the range 20°C-40°C. A total of 35 patients, 18 years of age and older, with diabetic peripheral neuropathy were enrolled in a single-site study conducted under an Institutional Review Board–approved protocol. This study evaluated the usability of the sensor-embedded socks and correlated the observed temperatures with clinical findings. RESULTS The temperatures measured by the stand-alone sensors were within 0.2°C of the reference standard. In the sensor-embedded socks, across multiple measurements for each of the six sensors, a high agreement (R2=1) between temperatures measured and the reference standard was observed. Patients reported that the socks were easy to use and comfortable, ranking them at a median score of 9 or 10 for comfort and ease of use on a 10-point scale. Case studies are presented showing that the temperature differences observed between the feet were consistent with clinical observations. CONCLUSIONS We report the first use of wireless continuous temperature monitoring for daily wear and home use in patients with diabetes and neuropathy. The wearers found the socks to be no different from standard socks. The temperature studies conducted show that the sensors used in the socks are reliable and accurate at detecting temperature and the findings matched clinical observations. Continuous temperature monitoring is a promising approach as an early warning system for foot ulcers, Charcot foot, and reulceration.

A series of silicon-containing aromatic bispropargyl ether resins—poly(dimethylsilylene-co-propynylene ether resorcinol) [–Si(CH3)2–C≡C–CH2–O–Ar–O–CH2–C≡C–]n (polymer a), poly(dimethylsilylene-co-propynylene ether bisphenol A) [–Si(CH3)2–C≡C–CH2–O–Ar–C(CH3)2–Ar–O–CH2–C≡C–]n (polymer b) and poly(dimethylsilylene-co-propynylene ether hexafluorobisphenol A) [–Si(CH3)2–C≡C–CH2–O–Ar–C(CF3)2–Ar–O–CH2–C≡C–]n (polymer c)—were synthesized from bispropargyl ethers bisphenol and dimethyldichlorosilane by a Grignard reaction. The polymers were characterized by Fourier transform infrared, hydrogen-1 nuclear magnetic resonance, gel-permeation chromatography, rheological analysis, differential scanning calorimetry and thermogravimetric analysis. The results showed that the obtained polymers could be cured at ∼240 °C and displayed good heat resistance and processing properties. Degradation temperatures of the three cured polymers at 5% weight loss (Td5) were above 400 °C, and thermal stabilities increased in the order polymer c

The mammalian protein SPAG16L, the ortholog of Chlamydomonas Pf20, is an axoneme central apparatus protein necessary for flagellar motility. The SPAG16L protein sequence contains multiple potential phosphorylation sites, and the protein was confirmed to be phosphorylated in vivo. A yeast two-hybrid screen identified the testis-specific kinase, TSSK2, to be a potential SPAG16L binding partner. SPAG16L and TSSK2 interactions were confirmed by coimmunoprecipitation of both proteins from testis extracts and cell lysates expressing these proteins, and their colocalization was also noted by confocal microscopy in Chinese hamster ovary cells, where they were coexpressed. TSSK2 associates with SPAG16L via its C-terminal domain bearing WD repeats. The N-terminal domain containing a coiled coil motif does not associate with TSSK2. SPAG16L can be phosphorylated by TSSK2 in vitro. Finally, TSSK2 is absent or markedly reduced from the testes in most of the SPAG16L-null mice. These data support the conclusion that SPAG16L is a TSSK2 substrate.

Octa(aminophenyl)silsesquioxane (OAPS) was prepared in two steps by the nitration of octaphenylsilsesquioxane (OPS) in fuming nitric acid to form octa(nitrophenyl)silsesquioxane (ONPS), followed by the mild reduction of ONPS with Pd/C as a catalyst. OPS, ONPS and OAPS were characterized by FTIR, 1H NMR, and 29Si NMR techniques. Modification of a bismaleimide (BMI) resin with OAPS and dipropargyl ether of bisphenol A (DPBPA) was investigated. The modified resins, OAPS/DPBPA/BMI, were characterized with DSC, FTIR and rheology analyses. The results showed that the modified resins have good processability. The DMA results indicated that the glass transition temperature (Tg) of the cured OAPS/DPBPA/BMI hybrid resins reached 350°C. The decomposition temperature (Td5) of the cured resins decreased but the char yield (Yc, 800°C) increased as the OAPS loading increased, especially in air. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers

A kind of modified bismaleimide resin, with good heat resistance and processing properties for advanced composites, was developed. The modifier, dipropargyl ether of bisphenol A (DPBPA), was prepared by a phase-transfer catalyzing procedure, characterized by FTIR, 1H NMR, and elementary analysis, and used to modify 4,4′-bismaleimidodiphenylmethane (BMDPM). The thermopolymerization of a DPBPA-modified BMDPM resin was followed up by FTIR. The curing of the resin was investigated by differential scanning calorimeter and gelation characterization. The relation of viscosity and temperature was used to characterize the processability of the resin. The results of DMA analysis showed that the cured DPBPA-modified BMDPM resins had a glass transition temperature higher than 320°C. The carbon fiber (T700) reinforced composites showed excellent flexural properties at ambient temperature and at 250°C. DPBPA could effectively improve mechanical properties without deteriorating heat resistance of the BMDPM resin a lot. POLYM. COMPOS., 2008. © 2008 Society of Plastics Engineers

The SPAG16 gene encodes two major transcripts, one for the 71-kDa SPAG16L, which is the orthologue of the Chlamydomonas rheinhardtii central apparatus protein PF20, and a smaller transcript, which codes for the 35-kDa SPAG16S nuclear protein that represents the C-terminus (exons 11–16) of SPAG16L. We have previously reported that a targeted mutation in exon 11 of the Spag16 gene impairs spermatogenesis and prevents transmission of the mutant allele in chimeric mice. In the present report, we describe a heterozygous mutation in exon 13 of the SPAG16 gene, which causes a frame shift and premature stop codon, affording the opportunity to compare mutations with similar impacts on SPAG16L and SPAG16S for male reproductive function in mice and men. We studied two male heterozygotes for the SPAG16 mutation, both of which were fertile. Freezing-boiling of isolated sperm from both affected males resulted in the loss of the SPAG16L protein, SPAG6, another central apparatus protein that interacts with SPAG1...

SPAG6 and SPAG16L are proteins localized to the "9+2" axoneme central apparatus. Both are essential for sperm motility and male fertility. These two proteins are also expressed in other tissues containing ciliated cells, such as brain and lung. To study the effects of combined deficiency of these two proteins, a double mutant mouse model was created. The double mutant mice displayed a more profound phenotype of growth retardation and hydrocephalus compared to mice nullizygous for SPAG6 and SPAG16L alone. The double mutant mice died younger, and mortality was significantly higher than in single mutant mice. In addition, the double mutant mice demonstrated pneumonia and its complications, including hemorrhage, edema, and atelectasis, phenotypes not observed in mice nullizygous for mutations in the individual genes. No other cilia-related phenotypic change was detected in double mutant mice including lateralization defects. The ultrastructure of cilia in both the brain and lung of the double mutant mice appeared normal. This model of combined SPAG6 and SPAG16L deficiency provides a new platform to study primary ciliary dyskinesia. The findings also demonstrate that SPAG6 and SPAG16L have related roles in controlling the function of cilia in the brain and lung.

A novel polytriazole resin prepared from p-xylylene diazide (XDA) and N,N,N′,N′-tetrapropargyl-p,p′-diaminodiphenylmethane (TPDDM) was synthesized and characterized. The resin is soluble in common solvents like acetone. The results show that the polytriazole resin can be cured at 70°C. The glass transition temperature and thermal decomposition temperature of the cured resin are 218 and 350°C, respectively. The tensile and flexural strengths of the cured resin achieve 99.0 and 200 MPa, respectively. It is potential as a low cost and easy processing thermal resistant polymer matrix for advanced composite applications. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1038–1042, 2007

A novel poly(1,2,3-triazole) (PTA) resin was prepared from a diazide and a multialkyne. The thermal stability and degradation kinetics of the cured PTA resin were investigated with the aid of the thermogravimetric analysis (TGA) technique. The degradation temperature of the cured PTA resin reaches 360 °C (Td5). Apparent kinetic parameters of the degradation of the cured resin is obtained by using Ozawa's method. The average apparent degradation activation energies of the PTA resin are about 190 kJ/mol under nitrogen and 160 kJ/mol under air. The cured PTA resin was pyrolyzed at 400 and 570 °C separately and the pyrolysis fragments were determined by using the Py/GC/MS combined technique. The results show that the degradation of the cured PTA resin initiates at CH2 N bonds. Nitrogen and related compounds which result from the cleavage of C N and N N bonds of 1,2,3-triazole ring were found in the pyrolysis products at 570 °C but no at 400 °C. Finally, a degradation mechanism of the cured polytriazole resin was proposed.

Benzocyclobutene-terminated imides were prepared and fully characterized with 1H NMR, MS, and FT-IR. The thermal degradation of polymers was investigated by using thermogravimetric analyzer (TGA) and high-resolution pyrolysis-gas chromatography–mass spectrometry (HR-Py-GC–MS). TGA showed that thermal degradation of the polymer was a single-stage process in N2, whereas a three-stage degradation in air atmosphere. The major involved products were found to be CO2, naphthalene and naphthalene derivatives. Degradation mechanism of the polymer was suggested and the relationship between structures of the polymer and degradation products was also discussed.

Several new bisbenzocyclobutene-terminated aromatic imides, 2,2′-bis(N-4-benzocyclobutenyl) phthalimide, 2,2′-bis[4-(N-4-benzocyclobutenylphthalimide)]-ether, 2,2′-bis[4-(N-4-benzocyclobutenylphthalimide)]-ketone, and 2,2′-bis[4-(N-4-benzo cyclobutenylphthalimid-4-oxy) phenyl]-propane, have been synthesized in high yields and characterized by FTIR, MS, EA, and 1H NMR spectroscopy. The polymers cured from benzocyclobutene-terminated imides have high glass transition temperature and good thermal stabilities. The cure reaction of an imide was studied by FTIR-ATR (attenuated total reflection) and DSC techniques. Apparent kinetic parameters of the cure reaction are obtained. The apparent cure reaction order, activation energy, and pre-exponential factor determined by isothermal DSC method are 1, 143.4 kJ/mol, and 3.88× 1013 min−1, and by nonisothermal DSC methods 1, 139.4 kJ/mol, and 2.27× 1013 min−1, respectively. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1705–1719, 2006

Elevation of serum interleukin-6 (IL-6) levels is always associated with alcoholic liver disease (ALD), but the significance of such elevation is not clear. Here we show that chronic ethanol consumption induces significant apoptosis in the liver of IL-6 (-/-) mice but not IL-6 (+/+) mice. IL-6 (-/-) hepatocytes are more susceptible to ethanol- and tumor necrosis factor alpha- (TNFalpha-) induced apoptotic killing, which can be corrected by IL-6. Expression of both anti-apoptotic (such as Bcl-2 and Bcl-x(L)) and proapoptotic (such as Bax) proteins is markedly elevated in the liver of human ALD and chronically ethanol-fed IL-6 (+/+) mice. On the contrary, induction of Bcl-2 and Bcl-x(L) is not observed in the liver of chronically ethanol-fed IL-6 (-/-) mice, whereas expression of Bax protein remains elevated. Injection of IL-6 markedly induces expression of Bcl-2 and Bcl-x(L) but not Bax in the liver. Finally, high concentrations of ethanol inhibit IL-6-activated anti-apoptotic signal, but increasing the concentrations of IL-6 is able to overcome such inhibitory effect. These findings suggest that elevated serum IL-6 levels in ALD may overcome the inhibitory effect of ethanol on IL-6-mediated anti-apoptotic signals and prevent alcohol-induced hepatic apoptosis by induction of Bcl-2 and Bcl-x(L).

Interleukin 1beta (IL-1beta) suppresses the IL-6-dependent induction of type II acute-phase response genes, but the underlying mechanism for this suppression remains uncertain. Here we report that treatment of human hepatocullular carcinoma HepG2 cells with IL-1beta inhibited the IL-6-dependent binding of signal transducer and activator of transcription factor (STAT)1, but not that of STAT3, to the high-affinity serum-inducible element ('SIE'). Furthermore, IL-1beta selectively down-regulated the IL-6-induced tyrosine phosphorylation of STAT1 without affecting the level of STAT1 or tyrosine phosphorylation of STAT3. Kinase assays in vitro indicated that the inhibition of STAT1 phosphorylation by IL-1beta was not due to an upstream blockade of Janus kinase (JAK1 or JAK2) activation. However, pretreatment with the proteasome inhibitor MG132 under conditions that prevented the IL-1beta-dependent activation of the nuclear factor NF-kappaB also blocked the inhibitory effect of IL-1beta on IL-6-activated STAT1. In related experiments, the protein tyrosine phosphatase inhibitor Na(3)VO(4) also antagonized the inhibitory effect of IL-1beta on the activation of STAT1 by IL-6. Taken together, these findings indicate that, by using a proteasome-dependent mechanism, IL-1beta concomitantly induces NF-kappaB activation and dephosphorylates IL-6-activated STAT1; the latter might partly account for the inhibition by IL-1beta of the IL-6-dependent induction of type II acute-phase genes.

Stimulation of transfected HepG2 cells (TFG2) with the alpha(1)-adrenergic agonist phenylephrine (PE) significantly activated p21(waf1/cip1) gene expression without affecting p53 gene expression. Northern blotting and reporter assay demonstrated that this induction was due to PE stimulation of p21(waf1/cip1) mRNA stability. To further define the underlying mechanism, we prepared a chloramphenicol acetyltransferase (CAT)-p21(waf1/cip1) 3'-untranslated region (3'-UTR) hybrid construct by inserting the 3'-UTR of p21(waf1/cip1) mRNA just downstream from the CAT coding sequence and transfected it into TFG2 cells. PE treatment enhanced the activity of this construct by 6-fold. Deletion analyses indicated that an AU-rich element (AURE) located between 553 to 625 within the p21(waf1/cip1) 3'-UTR was required for this induction. RNA gel shift assays demonstrated that this AURE bound an RNA-binding protein. This protein has been purified 5000-fold from PE-treated TFG2 cells by heparin-Sepharose and RNA affinity chromatography. SDS-polyacrylamide gel electrophoresis, UV cross-linking, and Northwestern analyses indicated the molecular mass of this protein as 24 and 52 kDa. Finally, PE treatment markedly enhanced this RNA-protein binding by a p42/44 mitogen-activated protein kinase-dependent mechanism. These data suggest that the AURE located between 553 and 625 within the p21(waf1/cip1) mRNA 3'-UTR, which binds an RNA-binding protein, is responsible for PE-induced p21(waf1/cip1) mRNA stability.

SOX5 is a transcription factor with homology to the high mobility group box region of the testis-determining factor, SRY. Both the mouse and human SOX5 genes encode a 48-kDa SOX5 protein (S-SOX5) that is only present in tissues containing cells with motile cilia/flagella. The mammalian sperm-associated antigen 6 gene (SPAG6) encodes an axoneme central apparatus protein. Because human and mouse SPAG6 gene promoters contain multiple potential binding sites for SOX5, SPAG6 gene regulation by S-SOX5 was investigated in BEAS-2B cells, a line derived from human bronchial cells. Like FOXJ1, a transcription factor known to be essential for motile ciliogenesis, S-SOX5 stimulated mouse and human SPAG6 promoter function in BEAS-2B cells, but the effect was abrogated when the SOX5 binding sites were mutated or deleted. S-SOX5 and FOXJ1 functioned cooperatively in stimulating SPAG6 promoter activity. The SPAG6 message was up-regulated when S-SOX5 was overexpressed in BEAS-2B cells, and silencing of S-SOX5 by RNA interference down-regulated SPAG6 transcripts. Chromatin immunoprecipitation and EMSA experiments demonstrated that S-SOX5 associates with the SPAG6 promoter directly. The present study demonstrates that SPAG6 is a S-SOX5 target gene, indicating a key role for S-SOX5 in the formation and function of motile cilia.

Spermatogenesis can be divided into three stages: spermatogonial mitosis, meiosis of spermatocytes, and spermiogenesis. During spermiogenesis, spermatids undergo dramatic morphological changes including formation of a flagellum and chromosomal packaging and condensation of the nucleus into the sperm head. The genes regulating the latter processes are largely unknown. We previously discovered that a bi-functional gene, Spag16 , is essential for spermatogenesis. SPAG16S, the 35 kDa, testis-specific isoform derived from the Spag16 gene, was found to bind to meiosis expressed gene 1 product (MEIG1), a protein originally thought to play a role in meiosis. We inactivated the Meig1 gene and, unexpectedly, found that Meig1 mutant male mice had no obvious defect in meiosis, but were sterile as a result of impaired spermatogenesis at the stage of elongation and condensation. Transmission electron microscopy revealed that the manchette, a microtubular organelle essential for sperm head and flagellar formation was disrupted in spermatids of MEIG1-deficient mice. We also found that MEIG1 associates with the Parkin co-regulated gene (PACRG) protein, and that testicular PACRG protein is reduced in MEIG1-deficient mice. PACRG is thought to play a key role in assembly of the axonemes/flagella and the reproductive phenotype of Pacrg -deficient mice mirrors that of the Meig1 mutant mice. Our findings reveal a critical role for the MEIG1/PARCG partnership in manchette structure and function and the control of spermiogenesis.

The SPAG16 gene encodes two major transcripts, one for the 71-kDa SPAG16L, which is the orthologue of the Chlamydomonas rheinhardtii central apparatus protein PF20, and a smaller transcript, which codes for the 35-kDa SPAG16S nuclear protein that represents the C-terminus (exons 11-16) of SPAG16L. We have previously reported that a targeted mutation in exon 11 of the Spag16 gene impairs spermatogenesis and prevents transmission of the mutant allele in chimeric mice. In the present report, we describe a heterozygous mutation in exon 13 of the SPAG16 gene, which causes a frame shift and premature stop codon, affording the opportunity to compare mutations with similar impacts on SPAG16L and SPAG16S for male reproductive function in mice and men. We studied two male heterozygotes for the SPAG16 mutation, both of which were fertile. Freezing-boiling of isolated sperm from both affected males resulted in the loss of the SPAG16L protein, SPAG6, another central apparatus protein that interacts with SPAG16L, and the 28-kDa fragment of SPAG17, which associates with SPAG6. These proteins were also lost after freezing-boiling cycles of sperm extracts from mice that were heterozygous for an inactivating mutation (exons 2 and 3) in Spag16. Our findings suggest that a heterozygous mutation that affects both SPAG16L and SPAG16S does not cause male infertility in man, but is associated with reduced stability of the interacting proteins of the central apparatus in response to a thermal challenge, a phenotype shared by the sperm of mice heterozygous for a mutation that affects SPAG16L.

Liver regeneration is controlled by multiple signaling pathways induced by a variety of growth factors, hormones, and cytokines. Here we report that protein kinase B (PKB)/Akt, part of a key cell survival signaling pathway, is markedly activated after partial hepatectomy (PHX). The antiapoptotic protein Bad, a downstream target of PKB/Akt, is also phosphorylated. This cascade can be activated by various factors in primary hepatocytes, with the strongest activation by insulin and the alpha1-adrenergic agonist phenylephrine (PE), followed by IL-6, epidermal growth factor (EGF), and hepatocyte growth factor (HGF). Pretreatment of cells with the specific PI3 kinase inhibitor LY294002 abolished insulin- or PE-activation of PKB/Akt, suggesting that activation of PKB/Akt is mediated by a PI3 kinase-dependent mechanism. In vivo administration of PE, insulin, IL-6, HGF, or EGF to mice markedly stimulated PKB/Akt in the liver, with the strongest stimulation induced by insulin and PE. Moreover, HGF and insulin were able to attenuate transforming growth factor beta-induced apoptosis in hepatic cells, and these effects were antagonized by LY294002. Taken together, these findings suggest that rapid activation of PKB/Akt is a key antiapoptotic signaling pathway involved in liver regeneration.

IFN-alphabeta is the only established treatment for viral hepatitis; however, more than 60% of patients are poorly responsive. Because viral hepatitis is associated with inflammation, we hypothesized that inflammation may attenuate the efficacy of IFN therapy. To test this hypothesis, the effect of IL-1beta, one of the major proinflammatory cytokines, on IFN signaling pathway in the liver was examined. Administration of IL-1beta in vivo attenuated IFN-alphabeta-induced STAT1 tyrosine phosphorylation in the liver but not in the spleen. The inhibitory action of IL-1beta in vivo was not affected by depleting hepatic Kupffer cells, suggesting that IL-1beta may directly target IFN-alphabeta signaling in hepatocytes. Indeed, pretreatment of human hepatocellular carcinoma HepG2 cells with IL-1beta suppressed IFN-alphabeta-induced antiviral activity and antiviral protein MxA mRNA expression. Furthermore, IL-1beta attenuated IFN-alphabeta-induced STAT1 binding and tyrosine phosphorylation without affecting the level of STAT1 protein. This inhibitory effect can be reversed by pretreatment with either proteasome inhibitors or transfection of dominant negative NF-kappaB inducing kinase mutants. Taken together, these findings suggest that IL-1beta attenuates IFN-alphabeta-induced STAT1 activation by a proteasome-dependent mechanism. In view of high levels of IL-1beta in the serum or within the liver of patients with chronic liver diseases, attenuation of IFN-alphabeta signaling in the liver by IL-1beta could be one of the mechanisms underlying the resistance to IFN therapy in chronic hepatitis C, and IL-1beta could be a potential therapeutic target for improving the efficacy of IFN therapy.

A new automated fingerprint identification system is proposed. In this system, based on some local properties of digital image, the shape and minutiae features of fingerprint can be extracted from the grey level image without binarizing and thinning. In query, a latent fingerprint can be matched with the filed fingerprints by shape and/or minutiae features. Matching by shape features is much faster than by minutiae.

Germ-line mutations of the breast cancer susceptibility gene 1 (BRCA1) confer a high risk for breast and ovarian cancer in women and prostate cancer in men. The BRCA1 protein contributes to cell proliferation, cell cycle regulation, DNA repair and apoptosis; however, the mechanisms underlying these functions of BRCA1 remain largely unknown. Here, we showed that, in Du-145 human prostate cancer cells, enhanced expression of BRCA1 resulted in constitutive activation of signal transducer and activator transcription factor 3 (STAT3) tyrosine and serine phosphorylation. Moreover, Janus kinase 1 (JAK1) and JAK2, the upstream activators of STAT3, were also activated by BRCA1. Immunoprecipitation assay showed that BRCA1 interacted with JAK1 and JAK2. Blocking STAT3 activation using antisense oligonucleotides significantly inhibited cell proliferation and triggered apoptosis in Du-145 cells with enhanced expression of BRCA1. These findings indicate that BRCA1 interacts with the components of the JAK–STAT signaling cascade and modulates its activation, which may provide a new critical survival signal for the growth of breast, ovarian and prostate cancers in the presence of normal BRCA1.

Interleukin-10 (IL-10) has been used in the treatment of viral hepatitis in interferon-alpha (IFN-alpha) non-responders while patients who have high levels of IL-10 are poorly responsive to IFN-alpha. The mechanism underlying such controversial functions of IL-10 remains unknown. Here we demonstrated that injection of IL-10 into mice attenuated IFN-alpha-induced signal transducer and activator transcription factor (STAT)1 tyrosine phosphorylation in the liver. Reverse transcriptase-polymerase chain reaction assay demonstrated that mouse liver expressed high levels of IL-10 receptor 2 (IL-10R2) but low levels of IL-10R1. Injection of IL-10 into mice activated STAT3 but not STAT1 tyrosine phosphorylation and induced suppressor of cytokine signal 2 (SOCS2), SOCS3, and cytokine-inducible SH2 protein (CIS) mRNA expression in the liver. Furthermore, overexpression of SOCS2 or SOCS3 inhibited IFN-alpha-induced reporter activity in hepatic cells. These findings suggest that IL-10 inhibits IFN-alpha-activated STAT1 in the liver, at least in part, by inducing SOCS2, SOCS3, and CIS expression, which may be responsible for the resistance of IFN-alpha therapy in patients who have high levels of IL-10 and recommends that IL-10 treatment for viral hepatitis should be cautious.