Demographics and medical disorders associated with smoking: a population-based study.

BACKGROUND: Few studies have investigated factors associated with smoking behaviors. In this population-based study, we investigated demographics and medical comorbid diseases to establish a prediction model for smoking behaviors by using the National Health Interview Survey (NHIS) and National Health Insurance Research Database (NHIRD). METHODS: We enrolled individuals aged ≥40 years who had participated in the NHIS in 2001, 2005, and 2009. We identified the smoking behaviors of the study participants in the NHIS. Smoking behaviors were divided into ever smokers (current smokers and ex-smokers) and nonsmokers (never smokers).We defined medical comorbid disorders of the study participants by using medical claim data from the NHIRD. We used multivariable logistic regression models to calculate the adjusted odds ratio and 95% confidence interval for variables associated with smoking. The significant variables in the multivariable model were included in the receiver operating characteristic curves (ROC) to predict the sensitivity and specificity of the model. RESULTS: In total, 26,375 participants (12,779 men and 13,596 women) were included in the analysis. The prevalence of smoking was 39.29%. The mean ages of the 16,012 nonsmokers were higher than those of the 10,363 smokers (57.86 ± 12.92 years vs. 53.59 ± 10.82 years). Men outnumbered women among smokers (68.18% vs. 31.82%). Male sex, young age and middle age, being insured categories, residence in suburban areas, and chronic obstructive pulmonary disease (COPD) were independent factors associated with smoking. The area under the ROC curve of these significant factors to predict smoking behaviors was 71.63%. CONCLUSION: Sex, age, insured categories, residence in suburban areas, and COPD were associated with smoking in people.

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection.

The interferons (IFNs) are a primary defense against pathogens because of the strong antiviral activities they induce. IFNs can be classified into three groups: type I, type II and type III, according to their genetic, structural, and functional characteristics and their receptors on the cell surface. The type I IFNs are the largest group and include IFN-α, IFN-ß, IFN-ε, IFN-ω, IFN-κ, IFN-δ, IFN-τ and IFN-ζ. The use of IFNs for the treatment of viral infectious diseases on their antiviral activity may become an important therapeutic option, for example, IFN-α is well known for the successful treatment of hepatitis B and C virus infections, and interest is increasing in the antiviral efficacy of other novel IFN classes and their potential applications. Therefore, in this review, we summarize the recent progress in the study of the biological activities of all the type I IFN classes and their potential applications in the treatment of infections with immunodeficiency virus, hepatitis viruses, and influenza viruses.

Interferon-omega: Current status in clinical applications.

Since 1985, interferon (IFN)-ω, a type I IFN, has been identified in many animals, but not canines and mice. It has been demonstrated to have antiviral, anti-proliferation, and antitumor activities that are similar to those of IFN-α. To date, IFN-ω has been explored as a treatment option for some diseases or viral infections in humans and other animals. Studies have revealed that human IFN-ω displays antitumor activities in some models of human cancer cells and that it can be used to diagnose some diseases. While recombinant feline IFN-ω has been licensed in several countries for treating canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections, it also exhibits a certain efficacy when used to treat other viral infections or diseases. This review examines the known biological activity of IFN-ω and its clinical applications. We expect that the information provided in this review will stimulate further studies of IFN-ω as a therapeutic agent.

Derlin-1 regulates mutant VCP-linked pathogenesis and endoplasmic reticulum stress-induced apoptosis.

Mutations in VCP (Valosin-containing protein), an AAA ATPase critical for ER-associated degradation, are linked to IBMPFD (Inclusion body myopathy with Paget disease and frontotemporal dementia). Using a Drosophila IBMPFD model, we have identified the ER protein Derlin-1 as a modifier of pathogenic TER94 (the fly VCP homolog) mutants. Derlin-1 binds to TER94 directly, and this interaction is essential for Derlin-1 overexpression to suppress the pathogenic TER94-induced neurodegeneration. Derlin-1 overexpression reduces the elevated ATPase activity of pathogenic TER94, implying that IBMPFD is caused by ATPase hyper-activation. Under physiological condition, Derlin-1 expression is increased upon ER stress to recruit TER94 to the ER. However, in response to severe ER stress, Derlin-1 is required for activating apoptosis to eliminate damaged cells. This pro-apoptotic response is mimicked by Derlin-1 overexpression, which elicits acute ER stress and triggers apoptosis via a novel C-terminal motif (α). As this Derlin-1-dependent cell death is negated by TER94 overexpression, we propose that while Derlin-1 and VCP work cooperatively in ER stress response, their imbalance has a role in removing cells suffering prolonged ER stress.

Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival.

Leucine-rich repeat kinase 2 (LRRK2) is a complex kinase and mutations in LRRK2 are perhaps the most common genetic cause of Parkinson's disease (PD). However, the identification of the normal physiological function of LRRK2 remains elusive. Here, we show that LRRK2 protects neurons against apoptosis induced by the Drosophila genes grim, hid and reaper. Genetic dissection reveals that Akt is the critical downstream kinase of LRRK2 that phosphorylates and inhibits FOXO1, and thereby promotes survival. Like human LRRK2, Drosophila lrrk also promotes neuron survival; lrrk loss-of-function mutant displays reduced cell numbers, which can be rescued by LRRK2 expression. Importantly, LRRK2 G2019S and LRRK2 R1441C mutants impair the ability of LRRK2 to activate Akt, and fail to prevent apoptotic death. Ectopic expression of a constitutive active form of Akt hence is sufficient to rescue this functional deficit. These data establish that LRRK2 can protect neurons from apoptotic insult through a survival pathway in which LRRK2 signals to activate Akt, and then inhibits FOXO1. These results might indicate that a LRRK-Akt therapeutic pathway to promote neuron survival and to prevent neurodegeneration in Parkinson's disease.

Caspase work model during pathogen infection.

Caspases are an evolutionarily conserved family of aspartate-specific cystein-dependent proteases with essential functions in apoptosis and normally exist in cells as inactive proenzymes. In addition to the inflammatory caspases, the initiator and effector caspases have been shown to have an important role in regulating the immune response, but are involved in different ways. We give a brief introduction on the benefit of apoptosis on the clearance of invasive pathogens, and the caspase functions involved in the immune response. Then we construct a working model of caspases during pathogen invasion. A detailed description of the three modes is given in the discussion. These three modes are regulated by different inhibitors, and there may be a novel way to treat intracellular pathogen and autoimmune diseases based on the specific inhibitors.

Develope monoclonal antibody against foot-and-mouth disease virus A type.

In order to develop an anti-FMDV A Type monoclonal antibody (mAb), BABL/c mice were immunized with FMDV A type. Monoclonal antibodies (mAbs) 7B11 and 8H4 against Foot-and-mouth disease virus (FMDV) serotype A were produced by fusing SP2/0 myeloma cells with splenocyte from the mouse immunized with A/AV88. The microneutralization titer of the mAbs 7B11 and 8H4 were 1024 and 512, respectively. Both mAbs contain kappa light chains, the mAbs were IgG1. In order to define the mAbs binding epitopes, the reactivity of these mAbs against A Type FMDV, were examined using indirect ELISA, the result showed that both mAbs reacted with A Type FMDV. These mAbs may be used for further vaccine studies, diagnostic methods, prophylaxis, etiological and immunological research on FMDV. Characterization of these ncindicated that prepared anti-FMDV A mAbs had no cross-reactivity with Swine Vesicular Disease (SVD) or FMDV O, Asia1 and C Type antigens. Their titers in abdomen liquor were 1:5×10(6) and 1:2×10(6), respectively. 7B11 was found to be of subtype IgG(1), 8H4 was classified as IgG(2b) subtype. The mAbs prepared in this study, are specific for detection of FMDV serotype A, and is potentially useful for pen-side diagnosis.

[Gene cloning of ligand binding domain of porcine beta3 as FMDV receptor and preparation of its polyclonal antibody].

AIM: To clone and express the ligand binding domain (LBD) cDNA of porcine integrin beta3 as foot-and-mouth disease virus (FMDV) receptor and prepare its polyclonal antibody. METHODS: The LBD cDNA of porcine beta3 was obtained from the lung tissue of pig infected with FMDV by RT-PCR, and the recombinant plasmid pGEM/beta3LBD was constructed. After digested with BamH I/Xho I, the beta3LBD fragment was subcloned into prokaryotic expression vector pGEX 4T-1. The recombinant expression plasmid pGEX/beta3LBD was constructed and transformed into E.coli BL21(DE3). The recombinant porcine beta3LBD protein was expressed after IPTG induction and purified from total protein of BL21(DE3). The rabbits from New Zealand were immunized with the purified fusion protein to prepare polyclonal antibody, which was identified by Western blot and ELISA. RESULTS: The 507 bp cDNA of porcine beta3LBD encoded a polypeptide of 169 amino acids. The similarity of nucleotide sequence beta3LBD between pigs and cattle, human being, chimpanzees, rhesus monkeys, horses, dogs, Norway rats, mice, chickens was 90.3%, 92.3%, 92.1%, 91.3%, 90.5%, 90.3%, 87.8%, 85.2%, 79.5%, respectively. The beta3LBD gene of mammals exhibited high sequence homology. The recombinant beta3LBD protein was expressed efficiently as inclusion body after IPTG induction and was approximately 44000. The titer of the polyclonal antibody against the purified beta3LBD protein was about 1:12 800 by ELISA. CONCLUSION: The gene cloning and expression of beta3LBD and the preparation of its polyclonal antibody lay a foundation for further research into the interaction of FMDV with beta3 subunit of porcine integrin.

[Molecular cloning and characteristics of cDNA encoding pig beta6 subunit for FMDV receptor].

In order to study the roles of integrin beta6 in Foot-and-Mouth Disease Virus infection, pig integrin beta6 was firstly molecularly cloned from RNA of the tongue and lung of recovered pig infected experimentally with foot-and-mouth-disease virus (FMDV), and was compared with the beta6 gene of other animals available in GenBank at nucleotide and amino acid leves. GeneBank association number of the beta6 gene is EF432729. Pig integrin beta6 gene (2367bp) encodes a polypeptide of 788 amino acids consisting of 9 potential N-linked glycosylation sites, 3 Glycosaminoglycan attachment sites, a cGMP-dependent protein kinase phosphorylation site, 10 Protein kinase C phosphorylation sites, 2 EGF-like domains and 2 cysteine-rich regions. Pig integrin beta6 subunit has a 26-residue putative signal peptide, a 681-residue ectodomain, a 29-residue transmembrane domain, and a 52-residue cytoplasmic domain. 11 mutant nucleotides were found in beta6 gene coding region and 9 amino acids were changed. The nucleotide sequence similarity of integrin beta6 gene between rheses monkey, mouse, Norway rat, dog, guinea pig, human, bovine, sheep is 79.5%, 84.9%, 85.4%, 85.2%, 88.7%, 90.1%, 91.9% and 91.9%, and the amino acid sequence similarity is 93.5%, 88.2%, 88.5%, 88.3%, 91.0%, 92.8%, 93.3% and 93.4% respectively. This study will lay a foundation for understanding the interactions of FMDV with receptors.

[Development and characterization of monoclonal antibodies against VP1 protein of AsiaI type foot-and-mouth virus].

AIM: To prepare the monoclonal antibodies against VP1 protein of type AsiaI foot-and mouth disease virus (FMDV) and identify the characterization. METHODS: Three cell of hybridization that strains secreted monoclonal antibody(mAb) against type AsiaI FMDV were produced by fusing mouse myeloma cells (Sp2/0) with spleen cells from BALB/c immunized with the purified recombinant VP1 protein. RESULTS: The three hybridized cell lines reacted with cattle type AsiaI FMDV, the titres of ascetic fluids of the three mAbs ranged from 1:10(5) to 1:10(6) indirect ELISA showed. Among the three mAbs,1B8 belonged to IgG1, 5E1 and 5E2 pertained to IgG2a. Besides, the three strain antibodies stably excreted antibodies and reacted with type AsiaI FMDV. CONCLUSION: VP1 protein of FMDV could replace FMDV can be use to replace FMDV to prepare mAbs.

[Cloning and sequence analysis of cDNA encoding porcine alphav subunit for FMDV receptor].

Receptors play a crucial role in determining the pathogenesis and tissue tropism of virus. Foot-and-mouth disease virus (FMDV) has been showed to use four integrins, alphavbeta1, alphavbeta3, alphavbeta6 and alphavbeta8 as receptors to initiate infection. In this study, the porcine integrin alphav gene was cloned by RT-PCR from the lung tissue of healed pig infected experimently with FMDV, and compared its nucleotide and deduced amino acid sequence with the av gene of other animals. The 3141bp cDNA of bovine integrin alphav encodes a polypeptide of 1046 amino acids consisting of a 30-residue putative signal peptide, a 955-residue ectodomain, a 29-residue transmembrane domain, and a 32-residue cytoplasmic domain. The ectodomain contains 11 potential N-linked glycosylation sites (NXT/NXS), 2 calcium binding domains (DX[D/N] XDGXXD) and 18 cysteine residues. The nucleotide sequence similarities of integrin alphav between pig and cattle, human, rheses monkey, house mouse, chicken, dog are 93.3%, 91.5%, 91.4%, 85.6%, 73.2% and 89.9% respectively; and the amino acid sequence similarities are 96.3%, 94.6%, 94.1%, 90.8%, 81.6% and 93.8%, respectively. The alphav gene of cattle and pig exhibited the highest sequence homology. It is possible that host tropism of FMDV may related to divergence in receptors among different species.