Objective: This study aimed to examine the changes and significance of matrix metalloproteinase 9 (MMP9), MMP2, tissue inhibitor of metalloproteinase 1 (TIMP1), and TIMP2 in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: Wistar rats were randomly divided into a control group (injected with saline) and an ALI group (injected with LPS), then subdivided into four time points (2, 6, 12, and 24 hours). Serum tumor necrosis factor alpha and interleukin-6 levels were detected by ELISA to investigate the inflammatory reaction after LPS injection. The degree of ALI was determined by hematoxylin–eosin staining of lung tissue, the lung wet/dry weight ratio, and pulmonary permeability index. Changes in lung MMP and TIMP protein and mRNA levels were detected by western blotting and quantitative real-time polymerase chain reaction. Results: Changes in the ratios of MMP9/TIMP1 and MMP2/TIMP2 were consistent with and strongly positively associated with the lung wet/dry weight ratio, the pulmonary permeability index, and serum tumor necrosis factor alpha and interleukin-6 levels in the ALI group. Conclusion: ALI induced by LPS may be related to upregulation of MMP9/TIMP1 and MMP2/TIMP2 ratios.

Inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2–4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. at Week 16, the changes from baseline in ADAS-cog were 1.4, −2.1, −2.2 and −4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.

As the most abundant excitatory neurotransmitter in the central nervous system, glutamate has been accepted to play a major role in the pathophysiology of migraine. The previous studies have reported the glutamate receptor ionotropic GRIA1 and GRIA3 genes variants associated with migraine. The project aims to investigate the polymorphisms in both genes for their association with migraine in the Chinese Han population. A Han-Chinese case-control population, including 331 unrelated female migraine patients and 330 matched controls, was studied. Variants in genes (GRIA1 and GRIA3) were genotyped by Multiplex SNaPshot assay. In the group of patients, the frequency of allele C was 84.1 % (557 C alleles) and allele T was 15.9 % (105 T alleles) for the GRIA1 (rs2195450) in migraineurs, this was significantly as compared with the controls (P = .001, OR = 1.786, 95 % CI: 1.28–2.49). And an association was also seen in the migraine with aura (MA) subtype (P = .012, OR = 2.092, 95 % CI: 1.17–3.76) and migraine without aura (MO) subtype (P = .002, OR = 1.737, 95 % CI: 1.23–2.45). However, no evidence was found that GRIA1 (rs548294) or GRIA3 (rs3761555) is associated with migraine. Our data of this study confirmed the association of GRIA1 (rs2195450) to female migraine (MA, MO) susceptibility in the Chinese Han population. The result provides evidence that the glutamatergic system is implicated in the pathophysiology of migraine.

Cadherin is an epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a key component of the noncanonical Wnt/planar cell polarity (PCP) pathway that critically regulates...