Guohua Yu

Inflammation may be associated with Alzheimer’s disease (AD). This meta-analysis aimed to compare the level of C-reactive protein (CRP) in patients having AD to healthy controls. A total of 10 cross-sectional studies (n = 2093) were identified from PubMed and EMBASE after systematic searching and evaluation. The combined standardized mean difference (SMD) of CRP level between the disease and control group was analyzed. In the meta-analysis, there was no significant difference in serum between the CRP level of patients with AD and that of healthy controls (SMD: −0.400, 95% confidence interval [CI]: −0.827 to 0.027, P = .066). However, when we stratified the studies by Mini-Mental State Examination (MMSE) scores, the level of CRP in the mild and moderate dementia subgroup (MMSE ≥ 10) was significantly lower than that in the control group (SMD: −0.582, 95% CI: −0.957 to −0.208, P = .002). Therefore, the diagnostic value of CRP for mild and moderate AD may be useful in clinical practice.

Prion protein (PrP) is well studied for its pathogenic role in prion disease, but its potential contribution to other pathological processes is less understood. PrP is expressed in a variety of cancers and at least in pancreatic and breast cancers, its expression appears to be associated with poor prognosis. To understand the role of PrP in breast cancer cells, we knocked down PrP expression in MDA-MB-435 breast cancer cells with small interfering RNA and subjected these cells to a series of analyses. We found that PrP knockdown in these cells does not affect cell proliferation or colony formation, but significantly influences the cellular response to cytotoxic stimuli. Compared to control cells, PrP knockdown cells exhibited an increased susceptibility to serum deprivation induced apoptosis, no change to staurosporine- or paclitaxel-induced cell deaths, and a reduced susceptibility to chemotherapy drug doxorubicin-induced cell death. To understand the mechanism of unexpected role of PrP in exacerbating doxorubicin-induced cytotoxicity, we analyzed cell death related Bcl-2 family proteins. We found that PrP knockdown alters the expression of several Bcl-2 family proteins, correlating with increased resistance to doxorubicin-induced cytotoxicity. Moreover, the enhanced doxorubicin resistance is independent of DNA damage related p53 pathway, but at least partially through the ERK1/2 pathway. Together, our study revealed that silencing PrP in MDA-MB-435 breast cancer cells results in very different responses to various cytotoxic stimuli and ERK1/2 signaling pathway is involved in PrP silencing caused resistance to doxorubicin.