Attenuated memory impairment and neuroinflammation in Alzheimer's disease by aucubin via the inhibition of ERK-FOS axis.

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.

gp91phox, a Novel Biomarker Evaluating Oxidative Stress, Is Elevated in Subclinical Hypothyroidism.

BACKGROUND: gp91phox, the catalytic core of NADPH oxidase (NOX) and biomarker of NOX activation, has been recently recognized as a parameter of systemic oxidative stress in several studies. Subclinical hypothyroidism (SH) is characteristic of elevated level of serum thyroid stimulating hormone (TSH) and is frequently accompanied with cholesterolemia. In this study, the levels of serum soluble gp91phox were measured to assess the oxidative stress in patients with SH. And the relationship among gp91phox, low-density lipoprotein-C (LDL-C), and TSH was also investigated. METHODS: A total of 51 subjects were enrolled and categorized into four groups: the healthy controls subjects (n = 13), controls with high level of LDL-C alone (n = 12), SH with normal level of LDL-C (n = 11), and SH with high level of LDL-C (n = 15). The related clinical and laboratory data were collected for statistical analysis. All the patients were newly diagnosed and did not take any medication. The information of lipid profile and thyroid function was extracted, and the concentrations of gp91phox were obtained with ELISA. RESULTS: The levels of serum soluble gp91phox evidently increased in the patients with SH with a high level of LDL-C (81.52 ± 37.00 ug/mL) as compared to the healthy controls (54.98 ± 1.83ug/mL, p < 0.001), controls with high level of LDL-C (61.21 ± 4.48 ug/mL, p=0.038) and SH with a normal level of LDL-C (62.82 ± 11.67ug/mL, p=0.027). Additionally, the levels of gp91phox showed a significant positive correlation with both the levels of LDL-C (r = 0.595, p < 0.001) and TSH (r = 0.346, p=0.013) by the Spearman correlation analyses. The correlation remained significant even when the effect of another factor was controlled (TSH: when the effect of LDL-C was controlled, r = 0.453, p=0.001; LDL-C: when the effect of TSH was controlled, r = 0.291, p=0.040). The main effect analysis showed an independent main effect of either LDL-C (p = 0.041) or TSH (p=0.022) on gp91phox without interaction (p=0.299). CONCLUSIONS: Our work demonstrated that the levels of gp91phox, a novel biomarker for measuring the oxidative stress, were significantly elevated in the patients with SH. And LDL-C and TSH were both independent predictors of gp91phox. Abbreviations. BMI : Body mass index; TC : Total cholesterol; LDL-C : Low-density lipoprotein cholesterol; HDL-C : High-density lipoprotein cholesterol; TG : Triglyceride; FBG : Fasting blood glucose; FT3 : Free triiodothyronine; FT4 : Free thyroxine; TSH: Thyroid stimulating hormone; SBP : Systolic blood pressure; DBP : Diastolic blood pressure; SD : Standard deviation; LSD: Least significant difference.

Investigation of T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) polymorphisms in essential thrombocythaemia (ET).

OBJECTIVES: T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is preferentially expressed on terminally differentiated Th1 cells and inhibits their IFN-γ production. It has been reported that chronic inflammation may be an important driving force for myeloproliferative neoplasms (MPNs). Therefore, we hypothesized that as an important inflammation regulator, TIM-3 may be involved in essential thrombocythaemia (ET). The goal of this study was to investigate whether the -1516G > T, -574G > T and +4259T > G single-nucleotide polymorphisms (SNPs) within the TIM-3 gene contribute to the genetic susceptibility of individuals to ET. METHODS: Genotyping of the TIM-3 -1516G > T, -574G > T and + 4259T > G SNPs was performed in 175 patients with ET and in 151 controls via a polymerase chain reaction-restriction fragment length polymorphism assay. We also investigated the relationships between the genotypes of each SNP and the risk factors of ET such as routine blood indexes, age and JAK2 V617F mutation. RESULTS: The genotype and allele frequencies of the -1516G > T SNP (p = 0.016 and 0.019, respectively), the -574G > T SNP (p = 0.035 and 0.038, respectively) and the +4259T > G SNP (p = 0.036 and 0.038, respectively) of the ET patients and the controls were significantly different. A haplotype analysis found that the GGT and TGT haplotypes had significantly different distributions between ET and controls (p = 0.041 and 0.041, respectively). However, no significant differences were detected between the genotypes of all SNPs and routine blood indexes, age and JAK2V617F mutation. CONCLUSION: The -1516G > T, -574G > T and +4259T > G SNPs within TIM-3 gene might play an important role as a genetic risk factor in the pathogenesis of ET.

[A preliminary study on the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis].

OBJECTIVE: To analyze the relationship between HLA-Cw polymorphism and susceptibility to pulmonary tuberculosis (PTB), and therefore to explore the susceptible or resistant genes of PTB. METHODS: A hundred and twelve patients who were confirmed to have secondary PTB in Shandong Chest Hospital from May 2010 to May 2011 were selected as the PTB group, including 62 males and 50 females aged 19 - 69 years (mean 41.7). According to the acid-fast staining results, PTB patients were divided into a smear-negative group (SN group, 77 cases) and a smear-positive group (SP group, 35 cases). A hundred and ten subjects who underwent physical examination in Shandong Chest Hospital at the same period were selected as the control group, including 59 males and 51 females aged 21 - 67 years (mean 38.3). After genomic DNA was extracted, genotyping of HLA-Cw was conducted by sequence specific primer polymerase chain reaction (PCR-SSP) method. Then Hardy-Weinberg (H-W) equilibrium was tested, and gene frequencies(%) were estimated = 1-(1-phenotype frequencies)(1/2). Gene frequencies were compared between the PTB group and the control group, and between the SN group and SP group by χ(2) test. According to Bonferroni's principle, α was divided by the number of alleles (n = 8), and P < 0.006 25 was regarded as statistically significant. RESULTS: The frequency of HLA-Cw08 was significantly higher in PTB patients (43.6%, 75/112) compared with the controls (27.4%, 52/110), χ(2) = 8.790, P < 0.006 25. Among PTB patients, HLA-Cw04 had a significantly higher frequency in the SP group (20.7%, 13/35) than in the SN group (4.7%, 7/77), while HLA-Cw08 had a significantly lower frequency in the SP group (22.5%, 14/35) than in the SN group (54.4%, 61/77), χ(2) = 12.909, 16.732, both P < 0.006 25. CONCLUSIONS: HLA-Cw polymorphism is related to susceptibility to PTB. HLA-Cw08 may be one of the susceptible genes for PTB, and HLA-Cw04 and 08 may be related to MTB infectious status and clinical outcomes.