The severe acute respiratory syndrome coronavirus (SARS-CoV) infects host cells with its surface glycosylated spike-protein (S-protein). Here we expressed the SARS-CoV S-protein to investigate its interactions with innate immune mechanisms in the lung. The purified S-protein was detected as a 210 kDa glycosylated protein. It was not secreted in the presence of tunicamycin and was detected as a 130 kDa protein in the cell lysate. The purified S-protein bound to Vero but not 293T cells and was itself recognized by lung surfactant protein D (SP-D), a collectin found in the lung alveoli. The binding required Ca(2+) and was inhibited by maltose. The serum collectin, mannan-binding lectin (MBL), exhibited no detectable binding to the purified S-protein. S-protein binds and activates macrophages but not dendritic cells (DCs). It suggests that SARS-CoV interacts with innate immune mechanisms in the lung through its S-protein and regulates pulmonary inflammation.

Background HIV self-testing (HIVST) offers an opportunity to increase HIV testing among people not reached by facility-based services. However, the promotion of HIVST is limited due to insufficient community engagement. We built a Social Entrepreneurship Model (SET) to promote HIVST linkage to care among Chinese MSM in Guangzhou. Method SET model includes a few key steps: Each participant first completed an online survey, and paid a $23 USD (refundable) deposit to get a HIVST kit and a syphilis self-testing (SST) kit. After the testing, the results were sent to the platform by the participants and interpreted by CDC staff. Meanwhile, the deposit was returned to each participant. Finally, the CBO contacted the participants to provide counseling services, confirmation testing and linkage to care. Result During April–June of 2015, a total of 198 MSM completed a preliminary survey and purchased self-testing kits. Among them, the majority were aged under 34 (84.4%) and met partners online (93.1%). In addition, 68.9% of participants ever tested for HIV, and 19.5% had ever performed HIVST. Overall, feedback was received from 192 (97.0%) participants. Among these, 14 people did not use kits, and the HIV and syphilis prevalence among these users were of 4.5% (8/178) and 3.7% (6/178), respectively. All of the screened HIV-positive cases sought further confirmation testing and were linked to care. Conclusion Using an online SET model to promote HIV and syphilis among Chinese MSM is acceptable and feasible, and this model adds a new testing platform to the current testing service system.

Endoplasmic reticulum stress-mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress-induced apoptosis in HCC have not been tested. Differences in ER stress-induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). Significant differences were observed in the rate of apoptosis between HepG2 cells (hepatoma cells) and HL-7702 cells (normal human hepatocyte cells). The expression of cyclooxygenase-2 (COX-2) was increased in HepG2 cells but not in HL-7702 cells. Furthermore, down-regulation of COX-2 expression using the COX-2 inhibitor, celecoxib, increased tunicamycin-induced apoptosis concomitant with the up-regulation of pro-apoptotic transcription factor CHOP (GADD153) and down-regulation of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, suggesting that inhibition of COX-2 sensitized human hepatoma cells to ER stress-induced apoptosis. Interestingly, co-treatment with tunicamycin and melatonin also decreased the expression of COX-2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl-2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress-induced apoptosis by down-regulating COX-2 expression, increasing the levels of CHOP and decreasing the Bcl-2/Bax ratio.

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Chemoresistance in hepatocellular carcinoma (HCC) is associated with multiple cellular responses to environmental stresses, such as nutrient deprivation and hypoxia. Nevertheless, whether ER stress resulting from nutrient deprivation and tumor hypoxia contributes to drug resistance remains unclear. Melatonin increased the efficacy of chemotherapeutic drugs in hepatocellular carcinoma in our previous studies. However, the effects of melatonin on endoplasmic reticulum (ER) stress-induced resistance to chemotherapeutic agents in HCC have not been tested. The effect of the endoplasmic reticulum (ER) stress response during resistance of human hepatocellular carcinoma cells against doxorubicin was investigated in this study. Pretreatment of HepG2 and SMMC-7721 cells (two human hepatocellular carcinoma cell lines) with tunicamycin, an ER stress inducer, drastically decreased the rate of apoptosis generated by doxorubicin. Interestingly, co-pretreatment with tunicamycin and melatonin significantly increased apoptosis induced by doxorubicin. Simultaneously, the expression of phosphorylated AKT (p-AKT) was elevated in HepG2 and SMMC-7721 cells given tunicamycin but reduced in the presence of melatonin. Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. These results demonstrate that melatonin attenuates ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by down-regulating the PI3K/AKT pathway, increasing the levels of CHOP and decreasing the levels of Survivin.

A respondent-driven sampling survey was conducted to investigate HIV related serological and behavioral characteristics of men who have sex with men (MSM) in Guangzhou, China, and to identify associated factors potentially driving the epidemic. Respondent-Driven Sampling Analysis Tool and SPSS were used to generate adjusted estimates and to explore associated factors. Three hundred seventy-nine eligible participants were recruited. The adjusted prevalence of HIV and current syphilis infection are 5.2% and 17.5% respectively. 60.3% have unprotected anal sex in the past 6 months. Unprotected anal sex, having receptive anal sex and current syphilis infection are significant factors associated with HIV infection. The potential for a rapid rise of HIV and syphilis infections among MSM in Guangzhou exists. Targeted interventions with voluntary counseling and testing (VCT) and sexually transmitted infection (STI) services are needed to address the epidemic, with a focus on such subgroups as those of with current syphilis, and non-official Guangzhou residence status.

ProblemIn China, human immunodeficiency virus (HIV) care provided by community-based organizations and the public sector are not well integrated.ApproachA community-based organization and experts from the Guangzhou Center for Disease Control and Prevention developed internet-based services for men who have sex with men, in Guangzhou, China. The internet services were linked to clinical services offering HIV testing and care.Local settingThe expanding HIV epidemic among men who have sex with men is a public health problem in China. HIV control and prevention measures are implemented primarily through the public system. Only a limited number of community organizations are involved in providing HIV services.Relevant changesThe programme integrated community and public sector HIV services including health education, online HIV risk assessment, on-site HIV counselling and testing, partner notification, psychosocial care and support, counting of CD4+ T-lymphocytes and treatment guidance.Lessons learntThe internet can facilitate HIV prevention among a subset of men who have sex with men by enhancing awareness, service uptake, retention in care and adherence to treatment. Collaboration between the public sector and the community group promoted acceptance by the target population. Task sharing by community groups can increase access of this high-risk group to available HIV-related services.

Exposure to nickel (Ni(2+)) can trigger allergic reactions in susceptible individuals, which is widely accepted as the major cause of allergic contact hypersensitivity (CHS) worldwide. Although Ni(2+)-induced proinflammatory responses clearly play a pivotal role in CHS, the underlying molecular mechanism has not been fully defined. Here we report that Ni(2+) activates the NLRP3-ASC-caspase-1 immune signaling pathway in antigen-presenting cells, leading to the proteolytic processing and secretion of a proinflammatory cytokine, interleukin-1β (IL-1β). The activation of this signaling axis is independent of phagolysosome-cathepsin B pathway. Instead, Ni(2+) induces mitochondrial reactive oxygen species accumulation and cation fluxes, both of which are required for activating the NLRP3-ASC-caspase-1 pathway. Together, these results identified a novel innate immune signaling pathway (NLRP3-ASC-caspase-1-IL-1β) activated by Ni(2+) and provided a mechanistic basis for optimizing the therapeutic intervention against Ni(2+)-induced allergy in patients.