Artemether Attenuates Aß25-35-Induced Cognitive Impairments by Downregulating Aß, BACE1, mTOR and Tau Proteins.

BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.

Effects and mechanism of microRNA­218 against lung cancer.

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)­218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR­218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR­218 in XWLC­05 cells were markedly lower compared with those in immortalized lung epithelial BEAS­2B cells. The present study also demonstrated that overexpression of miR­218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC­05 and NSCLC cell line NCI­H157. Additionally, the results revealed that overexpression of miR­218 could induce XWLC­05 and NCI­H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR­218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B­cell lymphoma 2 (BCL­2) and BMI1 proto­oncogene, polycomb ring finger (BMI­1) at the mRNA and protein level in XWLC­05 and NCI­H157 cell lines. However, we did not observe any remarkable difference in the roles of miR­218 and miR­218­mediated regulation of BCL­2, BMI­1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR­218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL­2 and BMI­1 in Xuanwei lung cancer. The results demonstrated that miR­218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR­218 may be a novel approach for the treatment of Xuanwei lung cancer.

Difference in hematocrit and plasma albumin levels as an additional biomarker in the diagnosis of infectious disease.

INTRODUCTION: In clinical practice, it has been observed that patients with severe infections show changes to their hematocrit (HCT) and serum albumin (ALB) levels. This study aimed to evaluate whether the difference of HCT and ALB (HCT-ALB) levels can be used as an additional biomarker for fast diagnosis of severe infections. MATERIAL AND METHODS: This was a retrospective case-control study which included adult patients with severe infections, patients with non-infective conditions and healthy individuals. A total of 7,117 individuals were recruited in Yunnan Province, China, from January 2012 to January 2018, and were divided into three groups: 1,033 patients with severe infections (group 1); 1,081 patients with non-infective conditions (group 2); and 5,003 healthy individuals from the general population (group 3). The potential diagnostic threshold of HCT-ALB for severe infectious patients was determined by the receiver operating characteristic (ROC) curve analysis. Group 3 was used as the reference to draw the ROC curves of the HCT-ALB value in group 1 or group 2. RESULTS: HCT-ALB values in each group were significantly different. We found that the area under the ROC curve (AUC) of group 1 reached 0.87 (95% CI: 0.86-0.89), whereas the AUC of group 2 was 0.60 (95% CI: 0.58-0.62). To reach a higher specificity of 99.0% (95% CI: 98.8-99.3%, and with sensitivity of 37.5%, 95% CI: 34.5-40.5%), a HCT-ALB value of 10.25 was recommended as the standard for diagnosis of severe infection. CONCLUSIONS: The HCT-ALB value was increased in patients with infectious disease. The measurement of the HCT-ALB value (> 10.25) might be useful in the fast diagnosis of infectious disease.

The expression and distribution of α-Gal gene in various species ocular surface tissue.

AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue. METHODS: α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence. RESULTS: A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue. CONCLUSION: This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.