Aim: To investigate the effects of glucagon-like peptide-1 (GLP-1) on endothelial NO synthase (eNOS) in human umbilical vein endothelial cells (HUVECs), and elucidate whether GLP-1 receptor (GLP-1R) and GLP-1(9-36) are involved in these effects. Methods: HUVECs were used. The activity of eNOS was measured with NOS assay kit. Phosphorylated and total eNOS proteins were detected using Western blot analysis. The level of eNOS mRNA was quantified with real-time RT-PCR. Results: Incubation of HUVECs with GLP-1 (50-5000 pmol/L) for 30 min significantly increased the activity of eNOS. Incubation of HUVECs with GLP-1 (500-5000 pmol/L) for 5 or 10 min increased eNOS phosphorylated at ser-1177. Incubation with GLP-1 (5000 pmol/L) for 48 h elevated the level of eNOS protein, did not affect the level of eNOS mRNA. GLP-1R agonists exenatide and GLP-1(9-36) at the concentration of 5000 pmol/L increased the activity, phosphorylation and protein level of eNOS. GLP-1R antagonist exendin(9-39) or DPP-4 inhibitor sitagliptin, which abolished GLP-1(9-36) formation, at the concentration of 5000 pmol/L partially blocked the effects of GLP-1 on eNOS. Conclusion: GLP-1 upregulated the activity and protein expression of eNOS in HUVECs through the GLP-1R-dependent and GLP-1(9-36)-related pathways. GLP-1 may prevent or delay the formation of atherosclerosis in diabetes mellitus by improving the function of eNOS.

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Advances in bioelectronics have great potential to address unsolvable biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ε-caprolactone) (PLC) that encapsulates the liquid metal to make flexible and bio-degradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelization process through electrical stimulation and can enable controlled gene delivery into specific part of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency three months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of vascular tissue-machine interface.

BackgroundCandidemia is the worldwide life-threaten disease, especially in cancer patients. This study was aimed to identify and evaluate the risk factors of candidemia in cancer patients, which will prompt the improvement on current therapeutic strategies and prognosis.MethodsA retrospective, case-control study was conducted from inpatients of Tianjin Medical University Cancer Institute and Hospital, during 2006 to 2013. Analyses were performed between cancer patients with candidemia as study case, and patients with bacterial bloodstream infections as control. Each case was matched up with two controls, for gender and inpatient duration. Candida species, clinical characteristics, risk factors and outcomes were reviewed in details.ResultsTotal number of 80 cases and 160 controls were enrolled and analyzed in this study. Candida albicans was identified as the most prevalent species and account for 55.0% candidemia, followed by Candida parapsilosis complex (21.3%), Candida tropicalis (8.8%), Candida glabrata complex (7.5%), Candida lusitaniae (3.8%), and Candida famata (3.8%). The crude mortality at 30-days of candidemia was up to 30.0%, which is significantly higher than bacterial bloodstream infections (p = 0.006). Logistical analysis demonstrated that total parenteral nutrition >5 days (p = 0.036), urinary catheter >2 days (p = 0.001), distant organ metastasis of cancer (p = 0.002) and gastrointestinal cancer (p = 0.042) were the independent risk factors for candidemia.ConclusionsCandidemia showed significant higher mortality than bacterial bloodstream infections, C. albicans was cited as the primary pathogen. Total parenteral nutrition, urinary catheter, distant organ metastasis of cancer and gastrointestinal cancer are independent predictors for candidemia, this findings provides potential therapeutic targets for improving the outcome.

Comfort and mechanical stability are vital for epidermal electronics in daily use. In situ deposition of circuitry without the protection of substrates or encapsulation can produce imperceptible, conformal, and permeable epidermal electronics. However, they are easily destroyed by daily wear because the binding force between deposited materials and skin is usually weak. Here, we in situ deposited skin-adhesive liquid metal particles (ALMP) to fabricate epidermal electronics with robust wear resistance. It represents the most wear-resistant in situ deposited epidermal electronic materials. It can withstand ∼1600 cm, 175 g loaded paper tape wearing by a standard abrasion wear tester. Stretchability, conformality, permeability, and thinness of the ALMP coating provide an imperceptible and comfortable wearing experience. Without degradation of electrical property caused by solvent evaporation, the dry ALMP coating possesses natural advantages over gel electrodes. In situ deposited ALMP is an ideal material for fabricating comfortable epidermal electronics.

Mechanism by which α-synuclein affects the progression of Parkinson's disease through Pyrin Domain Containing Protein 3 (NLRP3) was explored. Peripheral blood plasma of 40 Parkinson's disease patients and 40 normal healthy people attending the department of neurology of the Third Affiliated Hospital of Qiqihar Medical University were collected from March 2018 to January 2019. The expression levels of oligomers, phosphorylated α-synuclein, interleukin-1β (IL-1β), interleukin-6 (IL-6) and transforming growth factor-α (TGF-α) in plasma were detected by ELISA. Astrocytes in mouse brain tissues were extracted by primary culture method, the cells were divided into drug group and the drug + inhibitor group. After adding 0, 5, 10 and 20 µg oligomerized α-synuclein or 5 mM autophagy inhibitor 3-Methyladenine (3-MA), the expression level of NLRP3, caspase-1, IL-1β and Atg5 proteins in the cells was detected. The expression level of IL-1β in peripheral blood of PD patients was significantly increased (0.604±0.136 µmol/l vs. 1.876±0.327 µmol/l, P=0.002), while there was no significant difference between IL-6 and TGF-α. Both oligomers (0.171±0.045 µmol/l vs. 0.676±0.084 µmol/l, P<0.0001) and phosphorylated α-synuclein (0.128±0.041 µmol/l vs. 0.849±0.108 µmol/l, P<0.0001) in peripheral blood of PD patients were significantly elevated. The expression levels of NLRP3, caspase-1 and IL-1β in mouse astrocytes all increased with the increase of the concentration of oligomerized α-synuclein, and Atg5 protein expression also increased gradually with the concentration, and reached the highest level when the concentration was 10 µg/ml. The expression levels of NLRP3, caspase-1 and IL-1β were inhibited after the addition of autophagy inhibitor 3-MA. α-synuclein mediates the activation of NLRP3 inflammasome in PD patients by up regulating Atg5 protein expression.

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Background-Geriatric cancer patients (age 65 or older) comprise a majority of cancer cases in the United States, yet they are underrepresented in therapeutic clinical trials. It is therefore important to increase our understanding of their participation, survival outcomes, and recruitment barriers. This study aims to describe the demographics, treatment, toxicity, and overall survival (OS) of all patients ≥ 65 years of age who presented to the Phase I Clinical Trials service at Karmanos Cancer Institute (KCI).Methods-A retrospective chart review was performed of all referred and seen patients ≥ 65 years of age at Phase I clinical service at KCI between 1995-2005. Data on demographics, comorbidities, tumor type, reason not enrolled, toxicities and OS were obtained.Results-A total of 216 patients met the study criteria. The median age was 71 years. 114 (59%) patients were performance status 1. 102 (47%) patients were enrolled and of those 95 (44%) patients were treated. More than half of the patients failed to enroll with predominant reasons being protocol ineligibility (30%), loss to follow up (12%), patient refusal (8%), or unavailability of trial (2%). The median OS duration of treated patients was 8.4 months (95% CI: 6.2-10.5). This was significantly longer than the patients who failed to enroll or did not receive treatment (p < 0.0001).Conclusion-This study suggests that elderly patients who were treated on a Phase I clinical trial(s) at our institution survived significantly longer than our elderly patients who did not receive treatment.