Background-Vagus nerve stimulation attenuates left ventricular (LV) remodeling after myocardial infarction (MI).Our previous study found a noninvasive approach to deliver vagus nerve stimulation by transcutaneous electric stimulation of auricular branch of vagus nerve. So we hypothesize that chronic intermittent low-level tragus stimulation (LL-TS) could attenuate LV remodeling in conscious dogs with healed MI. Methods and Results-Thirty beagle dogs were randomly divided into 3 groups, MI group (left anterior descending artery and major diagonal branches ligation to introduce MI, n=10), LL-TS group (MI plus chronic intermittent LL-TS, n=10), and control group (sham surgery without stimulation, n=10). Tragus stimulation was delivered to bilateral tragus with earclips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold for setting LL-TS at 80% below that. LL-TS group was given 4 hours stimulation at 7-9 AM and 4-6 pM on conscious dogs. At the end of 90-day follow-up, LL-TS group significantly reduced LA and LV dilatation, improved LV contractile and diastolic function, reduced infarct size by ≈50% compared with MI group. LL-TS treatment alleviated cardiac fibrosis and significantly decreased protein expression level of collagen I, collagen III, transforming growth factor β1, and matrix metallopeptidase 9 in LV tissues. The plasma level of high-specific C-reactive protein, norepinephrine, N-terminal pro-B-type-natriuretic peptide in LL-TS group was significantly lower than those in MI group from the 7th day to the end of follow-up. Conclusions-Chronic

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This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH) and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD), 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

BackgroundTumor-derived exosomes have been viewed as a source of tumor antigens that can be used to induce anti-tumor immune responses. In the current study, we aim to investigate the regulatory effect of the epigenetic drug MS-275 on hepatoma G2 (HepG2) cell-derived exosomes, especially for their immunostimulatory properties and alteration of some non-specific immune protein expression, such as heat shock protein (HSP) 70, major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) and MICB.MethodsMS-275 was used to modulate the secretion of exosomes in human HepG2 cells, and exosomes from untreated HepG2 cells served as negative controls. RT-PCR was used to test the expression of HSP70, MICA and MICB in HepG2 cells. Immunogold labeling of exosomes and western blotting analysis were carried out to compare the expression of HSP70, MICA and MICB proteins in exosomes with or without MS-275 treatment. A natural killer (NK) cell cytotoxicity assay and peripheral blood mononuclear cell (PBMC) proliferation assay were used to evaluate the effect of MS-275 on the immunostimulatory ability of exosomes.ResultsImmunogold labeling and western blot analysis showed that modification of MS-275 increased the expression of HSP70 and MICB in exosomes. RT-PCR showed the mRNA levels of HSP70 and MICB were upregulated in HepG2 cells and were consistent with their protein levels in exosomes. The exosomes modified by MS-275 could significantly increase the cytotoxicity of NK cells and proliferation of PBMC (P < 0.05).ConclusionsThe non-specific immune response of exosomes derived from HepG2 cells could be enhanced with treatment by the histone deacetylase inhibitor (HDACi) drug MS-275; this could provide a potential tumor vaccine strategy against liver cancer.

BACKGROUND: Blueberry is universally acknowledged as a kind of berry rich in antioxidants. Cold plasma, an emerging nonthermal treatment technology, has been proved to be able to maintain or improve the antioxidant level while inactivating the microorganisms on the surface of fruits and vegetables. Postharvest blueberries were treated with atmospheric cold plasma (ACP; 12 kV, 5 kHz) for 0 s (Control), 30 s (ACP-30), 60 s (ACP-60), and 90 s (ACP-90) in this study, and the effects of ACP on the antimicrobial properties, antioxidant activities, and reactive oxygen species (ROS) production were investigated during storage at 4 ± 1°C for 40 days. RESULTS: Total aerobic bacteria and mold populations on ACP-treated blueberries decreased significantly in a time-dependent manner (P < 0.05), and decreased by 0.34-1.24 and 0.57-0.87 log 10 CFU g −1 respectively on ACP-60-treated blueberries during storage. The decay rate of blueberries was decreased by 5.8-11.7% and the decrease of blueberry firmness was slowed down by ACP-60. But the total phenol, anthocyanin, and ascorbic acid contents increased, and superoxide dismutase, catalase, and peroxidase activities were enhanced in ACP-treated blueberries. The free radical scavenging activity and total antioxidant capacity (T-AOC) were enhanced. Hydrogen peroxide (H 2 O 2) and superoxide anion (O 2 −) production rates declined by 27.3% and 41.3% at day 40 of storage, respectively. CONCLUSION: It is suggested that ACP may be a promising non-thermal treatment technology for postharvest sterilization and preservation of blueberry under suitable conditions.