[TTV and HPV co-infection in cervical smears of patients with cervical lesions in littoral of Zhejiang province].

OBJECTIVE: To investigate the prevalence of transfusion-transmitted virus (TTV) and human papillomavirus (HPV) co-infection in cervical smears of patients with cervical lesions in littoral of Zhejiang province and analysis of transmitted route. METHODS: Nested polymerase chain reaction (nPCR) was established. TTV DNA were tested by nPCR in cervical smears of 95 patients with cervical lesions and 55 healthy women, paired serum samples were available from 55 and 42 women, and their viral titer. The genotypes of 95 specimens of cervical cytology were detected with HybriMax. The phylogenetic group of TTV was determined by means of nPCR with N22 primers. RESULTS: The prevalence of TTV DNA in cervical smears of patients with cervical lesions and healthy women was 52.7% (29/55) and was comparable with that in paired serum sample (50%). Symptomatic women had significantly higher prevalence of TTV DNA in cervical smears (74.7%) than healthy controls (P = 0.005). The TTV DNA prevalence in patient serum samples was 51%. The phylogenetic groups of TTV serum isolates were concordant with those of TTV from cervical smears of the same subjects, and genotype was G1b. The TTV viral titer in cervical smears were 10 to 1000 times as high as in serum. The total infection rate of HPV was 98.9% in patients, and was 27.3% in healthy women. The frequently detected genotype was HPV16, 18, 33 of HSIL, and HPV6 of LSIL. The HPV positive study subjects had significantly higher TTV DNA prevalence than HPV negatives (P = 0.02). CONCLUSION: High prevalence of TTV in cervical smears suggests that sexual transmission is another mode of expansion of TTV infection among the population. The higher viral titer in cervical smears than in the respective serum samples might indicate active TTV replication in the female genital tract. Nevertheless, cooperation between TTV and HPV needs to be further investigated.

Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation.

RATIONALE: Transforming growth factor (TGF)-beta has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin alpha(v)beta6, a key activator of TGF-beta in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF-beta at sites of alpha(v)beta6 up-regulation without affecting other homeostatic roles of TGF-beta. OBJECTIVES: To analyze the expression of alpha(v)beta6 in human pulmonary fibrosis, and to functionally test the efficacy of therapeutic inhibition of alpha(v)beta6-mediated TGF-beta activation in murine bleomycin-induced pulmonary fibrosis. METHODS: Lung biopsies from patients with a diagnosis of systemic sclerosis or idiopathic pulmonary fibrosis were stained for alpha(v)beta6 expression. A range of concentrations of a monoclonal antibody that blocks alpha(v)beta6-mediated TGF-beta activation was evaluated in murine bleomycin-induced lung fibrosis. MEASUREMENTS AND MAIN RESULTS: Alpha(v)beta6 is overexpressed in human lung fibrosis within pneumocytes lining the alveolar ducts and alveoli. In the bleomycin model, alpha(v)beta6 antibody was effective in blocking pulmonary fibrosis. At high doses, there was increased expression of markers of inflammation and macrophage activation, consistent with the effects of TGF-beta inhibition in the lung. Low doses of antibody attenuated collagen expression without increasing alveolar inflammatory cell populations or macrophage activation markers. CONCLUSIONS: Partial inhibition of TGF-beta using alpha(v)beta6 integrin antibodies is effective in blocking murine pulmonary fibrosis without exacerbating inflammation. In addition, the elevated expression of alpha(v)beta6, an activator of the fibrogenic cytokine, TGF-beta, in human pulmonary fibrosis suggests that alpha(v)beta6 monoclonal antibodies could represent a promising new therapeutic strategy for treating pulmonary fibrosis.

Fly SIX-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye development.

Two members from the Six class of homeobox transcription factors, Sine oculis (SO) and Optix, function during development of the fly visual system. Differences in gain-of-function phenotypes and gene expression suggest that these related factors play distinct roles in the formation of the fly eye. However, the molecular nature of their functional differences remains unclear. In this study, we report the identification of two novel factors that participate in specific partnerships with Sine oculis and Optix during photoreceptor neurons formation and in eye progenitor cells. This work shows that different cofactors likely mediate unique functions of Sine oculis and Optix during the development of the fly eye and that the repeated requirement for SO function at multiple stages of eye development reflects the activity of different SO-cofactor complexes.