SummaryTumour necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumour necrosis factor (TNF) family, has been implicated as a proinflammatory cytokine in many types of autoimmune and infectious diseases. However, information about TWEAK in dermatological diseases is limited. Herein, we investigated the role of TWEAK in patients with Henoch-Schonlein purpura (HSP) and the ability of TWEAK on chemokine production in the human dermal microvascular endothelial cell line (HMEC-1). Serum TWEAK levels in patients with HSP, together with patients with psoriasis vulgaris (PV) and atopic dermatitis (AD), were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with TWEAK at concentrations ranging from 1 ng/ml to 100 ng/ml. Serum levels of TWEAK were elevated in patients with HSP in the acute stage but not in patients with PV or AD. Moreover, TWEAK levels were correlated with the severity of HSP. TWEAK markedly induced CCL5 and CXCL8 production at both mRNA and protein levels in HMEC-1 cells. In addition, TWEAK-stimulated HMEC-1 supernatant enhanced HL-60 or human acute monocytic leukaemia cell line (THP-1) cell migration. Finally, Western blot data revealed that TWEAK can induce rapid phosphorylation of inhibitor of kB-a (IkBa) in HMEC-1 cells. In conclusion, we show that serum levels of TWEAK were elevated in patients with acute stage HSP. TWEAK may act as a regulator of nuclear factor-kB (NF-kB) activation and chemokine production in human dermal microvascular endothelial cells, thus promoting leucocyte migration in cutaneous vasculitis.

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Benzo[a]pyrene (B[a]P), a well-known carcinogen, is widespread in the environment. Although the neurotoxic effect of B[a]P has not drawn much attention, toxic effects of B[a]P on learning and memory have been reported. Since it is well known that neuronal apoptosis plays a major role in impairment of learning and memory triggered by many stimuli, an effort has been made to examine whether the B[a]P-induced neurotoxicity occurs through mitochondria-mediated apoptosis. Cultured newborn rat cerebral neurons were used to clarify the apoptosis induced by B[a]P in the study. After incubating with different doses of B[a]P in presence of S9 for 40 h, the apoptotic rates of B[a]P-treated neurons increased in a dose-dependent manner. Further analysis showed that B[a]P-induced apoptosis was accompanied by loss of mitochondrial membrane potential, release of cytochrome c from mitochondria to the cytosol, downregulation of antiapoptotic protein B-cell lymphoma-2 (Bcl-2) levels with concurrent upregulation in proapoptotic Bcl-2-associated X protein (Bax) levels, and increase in the levels and activities of caspases-9 and -3. However, there was no difference in the activity of caspase-8 between B[a]P-exposed neurons and controls. Collectively, these results showed that B[a]P upregulates Bax and downregulates Bcl-2 expression in cultured cerebral neurons, which leads to mitochondrial release of cytochrome c, caspase-3 activation and neuronal apoptotic death.

Abstract. The 14 April 2010 M s = 7.1 Yushu Earthquake (YE) had caused severe damage in the Jiegu township, the residential centre of Yushu Tibetan Autonomous Prefecture, Qinghai Province, China. In view of the fragile geological conditions after YE, risk assessment of secondary geohazards becomes an important concern for the reconstruction. A quantitative methodology was developed to assess the risk of debris flow by taking into account important intensity information. Debris flow scenarios were simulated with respect to rainfall events with 10, 50 and 100 yr returning period, respectively. The possible economic loss and fatalities caused by damage to buildings were assessed both in the settlement area and in the low hazard settlement area regarding the simulated debris flow events. Three modelled building types were adopted, i.e. hollow brick wood (HBW), hollow brick concrete (HBC) and reinforced concrete (RC) buildings. The results suggest that HBC structure achieves a good balance for the cost-benefit relationship compared with HBW and RC structures and thus could be an optimal choice for most of the new residential buildings in the Jiegu township. The low hazard boundary presents significant risk reduction efficiency in the 100 yr returning debris flow event. In addition, the societal risk for the settlement area is unacceptable when the 100 yr returning event occurs but reduces to ALARP (as low as reasonably practicable) level as the low hazard area is considered. Therefore, the low hazard area was highly recommended to be taken into account in the reconstruction. Yet, the societal risk might indeed approach an unacceptable level if one considers that YE has inevitably increased the occurrence frequency of debris flow. The quantitative results should be treated as a perspective for the reconstruction rather than precise numbers of future losses, owing to the complexity of the problem and the deficiency of data.