DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.

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The main purpose of this study was to investigate effect of salidroside (Sal) on myocardial ischemia reperfusion injury in rats and the underlying mechanism. Myocardial ischemia reperfusion injury (MI/RI) model was treated with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. The male Sprague-Dawley rats were randomly divided into 7 groups: (1) Sham; (2) Sham + diltiazem (Dit, 10 mg/kg); (3) Sham + Sal (40 mg/kg); (4) I/R; (5) I/R + diltiazem (Dit, 10 mg/kg); (6) I/R + Sal (20 mg/kg); (7) I/R + Sal (40 mg/kg). Sal could ameliorate myocardial ischemia reperfusion injury as evidenced by Histopathological examination and triphenyl tetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL) assay demonstrated that Sal suppressed myocardial apoptosis, which may be related to up-regulation of Bcl-2/Bax ratio and inhibition of caspase-3, caspase-9 activation. Pretreatment with Sal affected serum biochemical parameters and cardiac dysfunction compared with I/R group. Sal also attenuated the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in serum by inhibiting TLR4/NF-κB signaling pathway. Sal exerts strong favorable cardioprotective function on myocardial I/R injury which may relate to the down-regulation of the TLR4/NF-κB signaling pathway and the inhibition of cell apoptosis.

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Age-related inflammation is the predominant factor for neurodegenerative diseases like Alzheimer's disease (AD). In the present study, we examined memory performance and neuroinflammation in D-galactose (D-gal)-induced sub-acute aging model of rats. Our results demonstrated that chronic administration of D-gal (120 mg/kg) produced cognitive impairment as determined by Morris water maze (MWM) test and step-down passive avoidance test. D-gal also activated nuclear factor kappa B (NF-κB) p65/RelA by down-regulating the expression level of sirtuins 1 (SIRT1) in the hippocampus. Treatment with Salidroside (Sal, 20, 40 mg/kg) for 28 days ameliorated D-gal-induced memory deficits and inflammatory mediators including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, D-gal-induced activation of NF-κB signaling pathway in the brain was also inhibited by Sal via up-regulating SIRT1. These results suggest that D-gal-triggered memory impairment and inflammatory response may be associated with SIRT1/NF-κB signaling pathway, whereas treatment with Sal could positively affect these changes in hippocampus.

A highly water-soluble BODIPY dye bearing electron-rich o-diaminophenyl groups at 2,6-positions was prepared as a highly sensitive and selective fluorescent probe for detection of nitric oxide (NO) in living cells. The fluorescent probe displays an extremely weak fluorescence with fluorescence quantum yield of 0.001 in 10 mM phosphate buffer (pH 7.0) in the absence of NO as two electron-rich o-diaminophenyl groups at 2,6-positions significantly quench the fluorescence of the BODIPY dye via photoinduced electron transfer mechanism. The presence of NO in cells enhances the dye fluorescence dramatically. The fluorescent probe demonstrates excellent water solubility, membrane permeability, and compatibility with living cells for sensitive detection of NO.