Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC patients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.

Taken together, our findings demonstrate that chronic NAC treatment alleviates acute LPS-induced working memory deficit through upregulating Cav-1 and SYP in mice.

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the world. We report that one oncogene amplified on chromosome 3q26, LMO1, a master transcriptional regulator of stemness, operates to drive strong growth phenotype in CRC. The gene expression changes of LMO1 in human CRC tissues compared with noncancerous tissues were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of LMO1 in CRC. Moreover, we discovered that LMO1 promoted cancer cell proliferation in vitro/in vivo and LMO1 expression correlated with elevated AKT phosphorylation in CRC while the AKT phosphorylation was required for oncogenic effects of LMO1. Next, our data point to the usefulness of LMO1 overexpression, as a new predictive marker for responsiveness to cetuximab. All in all, LMO1 is a commonly activated tumor promoter that activates AKT signaling in CRC and a new predictive marker for targeted therapy.

A high co-morbidity between Alzheimer's disease (AD) and depression suggests there might be similar mechanisms underlying the course of these diseases. Previous studies have shown that p38MAPK plays a critical role in the pathophysiology of AD and depression. However, little is known about whether SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated cognitive impairments and depression-like behavior, simultaneously. Herein, we have shown, for the first time, that SB203580 may reverse memory impairments and depression-like behavior induced by hippocampal infusion of β-amyloid 1-42 (Aβ), as measured by novel object recognition, Morris water maze, tail-suspension and forced-swimming tests. In addition, phorbol 12-myristate 13-acetate (PMA), a PKC activator which also activates p38MAPK, significantly abolished the effects of SB203580. Moreover, Aβ causes increased phosphorylation of p38MAPK and decreased phosphorylation of Ser9-glycogen synthase kinase 3β (GSK3β) and cAMP-response element binding protein (CREB) in the hippocampus of mice, which could be significantly reversed by SB203580. Our results suggest that SB203580 reversed Aβ-induced cognitive impairments and depression-like behavior via inhibiting p38MAPK signaling pathway, which not only supports p38MAPK as a therapeutic target for AD-associated cognitive dysfunction and depression-like behavior, but also provides experimental basis for the use of SB203580 in co-morbidity of AD and depression.

Bisphenol-A (BPA), a widely used synthetic compound in plastics, disrupts endocrine function and interferes with physiological actions of endogenous gonadal hormones. Chronic effects of BPA on reproductive function, learning and memory, brain structure, and social behavior have been intensively investigated. However, less is known about the influence of BPA on long-term potentiation (LTP), one of the major cellular mechanisms that underlie learning and memory. In the present study, for the first time we investigated the effect of different doses of BPA on hippocampal LTP in rat brain slices. We found a biphasic effect of BPA on LTP in the dentate gyrus: exposure to BPA at a low dose (100 nM) enhanced LTP and exposure to BPA at a high dose (1000 nM) inhibited LTP compared with vehicle controls. The rapid facilitatory effect of low-dose BPA on hippocampal LTP required membrane-associated estrogen receptor (ER) and involved activation of the extracellular signal-regulated kinase (ERK) signaling pathway. Coadministration of 17β-estradiol (E2, the primary estrogen hormone) and BPA (100 nM) abolished both the BPA-induced enhancement of LTP and the E2-induced enhancement of baseline fEPSP, suggesting a complex interaction between BPA- and E2-mediated signaling pathways. Our investigation implies that even nanomolar levels of endocrine disrupters (e.g., BPA) can induce significant effects on hippocampal LTP.