Human dopamine receptor nanovesicles for gate-potential modulators in high-performance field-effect transistor biosensors

The development of molecular detection that allows rapid responses with high sensitivity and selectivity remains challenging. Herein, we demonstrate the strategy of novel bio-nanotechnology to successfully fabricate high-performance dopamine (DA) biosensor using DA Receptor-containing uniform-particle-shaped Nanovesicles-immobilized Carboxylated poly(3,4-ethylenedioxythiophene) (CPEDOT) NTs (DRNCNs). DA molecules are commonly associated with serious diseases, such as Parkinson's and Alzheimer's diseases. For the first time, nanovesicles containing a human DA receptor D1 (hDRD1) were successfully constructed from HEK-293 cells, stably expressing hDRD1. The nanovesicles containing hDRD1 as gate-potential modulator on the conducting polymer (CP) nanomaterial transistors provided high-performance responses to DA molecule owing to their uniform, monodispersive morphologies and outstanding discrimination ability. Specifically, the DRNCNs were integrated into a liquid-ion gated field-effect transistor (FET) system via immobilization and attachment processes, leading to high sensitivity and excellent selectivity toward DA in liquid state. Unprecedentedly, the minimum detectable level (MDL) from the field-induced DA responses was as low as 10 pM in real- time, which is 10 times more sensitive than that of previously reported CP based-DA biosensors. Moreover, the FET-type DRNCN biosensor had a rapid response time (<1 s) and showed excellent selectivity in human serum

Higher metabolic variability increases the risk of depressive disorder in type 2 diabetes mellitus: a longitudinal nationwide cohort study

Background and objectivesWhile variabilities in metabolic parameters (METv) have been linked to adverse health outcomes in type 2 DM, their association with depression is yet to be studied. This research aimed to investigate the association between METv and depressive disorder in patients with type 2 DM.MethodsThe study involved a nationwide cohort of 1,119,631 type 2 DM patients who had undergone three or more serial health examinations between 2005 and 2012. At each visit, body mass index (BMI), fasting glucose (FG), systolic blood pressure (BP), and total cholesterol (TC) were measured and stratified into quartiles, with Q4 being the highest and Q1 the lowest. The risk of depressive disorder was evaluated using Cox proportional hazard regression models, which accounted for METs in the indexes, after adjusting for sex, income status, lifestyle habits, medical comorbidities, DM severity, and baseline levels of BMI, FG, BP, and TC.ResultsDuring a mean follow-up period of 6.00 ± 2.42 years, 239,477 (21.4%) cases of type 2 DM patients developed depressive disorder. The risk of developing depressive disorder was gradually increased as the number of METv increased (HR 1.18; 95% CI 1.13, 1.23 for the group with the highest METv in all parameters compared to those with the lowest METv in all parameters). In the subgroup analysis, the risk of developing depressive disorder was 43% higher in men (HR 1.43; 95% CI 1.34, 1.51), and 31% higher in those younger than 65 years of age (HR 1.31; 95% CI 1.23, 1.39) in the group with the highest number of METv compared to the group with the lowest number of METv.ConclusionIn type 2 DM, higher METv was an independent risk factor for depressive disorder. This risk is notably elevated in men and individuals under the age of 65 years

A case of primary hepatic actinomycosis: an enigmatic inflammatory lesion of the liver

Primary hepatic actinomycosis is one of the chronic abscess-forming infections of the liver. Accurate diagnosis is frequently delayed due to its indolent course and nonspecific clinical and radiological manifestations. We report a case of a 57-year-old man presenting with asymptomatic multiple hepatic masses on follow-up abdominal computed tomography performed 1 year after stomach cancer surgery. Although a percutaneous liver biopsy procedure was conducted twice in order to obtain confirmative pathology, only a nonspecific organizing abscess with plasma cell infiltration was revealed, without identification of any organism in the tissue cultures. Ultimately, actinomycosis was diagnosed following the detection of sulfur granules on open surgical biopsied tissue. This case suggests that primary hepatic actinomycosis should be considered as one of the possible causes for enigmatic inflammatory lesions of the liver

Comparison of Posterior Lumbar Interbody Fusion and Posterolateral Lumbar Fusion in Monosegmental Vacuum Phenomenon within an Intervertebral Disc

Study DesignRetrospective.PurposeTo compare the clinical and radiological outcomes of posterolateral lumbar interbody fusion (PLIF) and posterolateral lumbar fusion (PLF) in monosegmental vacuum phenomenon within an intervertebral disc.Overview of LiteratureThe vacuum phenomenon within an intervertebral disc is a serious form of degenerative disease that destabilizes the intervertebral body. Outcomes of PLIF and PLF in monosegmental vacuum phenomenon are unclear.MethodsMonosegmental instrumented PLIF and PLF was performed on 84 degenerative lumbar disease patients with monosegmental vacuum phenomenon (PLIF, n=38; PLF, n=46). Minimum follow-up was 24 months. Clinical outcomes of leg and back pain were assessed using visual analogue scales for leg pain (LVAS) and back pain (BVAS), and the Oswestry disability index (ODI). The radiographic outcome was the estimated bony union rate.ResultsLVAS, BVAS, and ODI improved in both groups. There was no significant difference in the degree of these improvements between PLIF and PLF patients (p>0.05). Radiological union rate was 91.1% in PLIF group and 89.4% in PLF group at postoperative 24 months (p>0.05).ConclusionsNo significant differences in clinical results and union rates were found between PLIF and PLF patients. Selection of the operation technique will reflect the surgeon's preferences and patient condition

Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells

Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutaome analysis for relevant mutation information. The results showed that magnolin efficacy on cell proliferation inhibition were lower in TOV‐112D ovarian cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase accumulation. Notably, magnolin suppressed colony growth of TOV‐112D cells in soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by magnolin treatment. Interestingly, phospho‐protein profiles in the MAPK and PI3 K signaling pathways indicated that SKOV3 cells showed marked increase of Akt phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels by EGF stimulation. The phospho‐protein profiles in TOV‐112D cells were the opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed phosphorylation of RSKs in TOV‐112D, but not in SKOV3 cells. Moreover, magnolin increased SA‐β‐galactosidase‐positive cells in a dose‐dependent manner in TOV‐112D cells, but not in SKOV3 cells. Notably, oral administration of Shin‐Yi fraction 1, which contained magnolin approximately 53%, suppressed TOV‐112D cell growth in athymic nude mice by induction of p16Ink4a and p27Kip1. Taken together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian cancer cells that do not harbor the constitutive active P13 K mutation and the loss‐of‐function mutations of the p16 and/or p53 tumor suppressor proteins

Comparison of volatile organic compounds between cigarette smoke condensate (CSC) and extract (CSE) samples

Cigarette smoke is a major risk factor for several diseases, including chronic obstructive pulmonary and cardiovascular diseases. The toxicity of the cigarette smoke can be determined in vitro. The cytotoxicity test of the cigarette smoke is commonly conducted using the cigarette smoke condensate (CSC) and cigarette smoke extract (CSE). The CSC and CSE methods are well known for sampling of the particles and water-soluble compounds in the cigarette smoke, respectively. In this study, the CSC and CSE were analyzed by using a gas chromatography-mass spectrometry (GC-MS) system equipped with a wax column for separation of the volatile organic compounds. The cytotoxic effect of the CSC and CSE were evaluated thoroughly by comparing the analytical results of the CSC and CSE samples. The total concentration of the volatile organic compounds detected in the CSC sample was similar to that in the CSE sample based on the peak area. Except for the dimethyl sulfoxide solvent, nicotine had the highest concentration in the CSC sample, while acetonitrile had the highest concentration in the CSE sample. The compositions were as follows: (1) CSC sample: 55.8% nicotine, 18.0% nicotyrine, 3.20% 1,2,3-propanetriol, triacetate, 1.28% ethyl chloride, 1.22% phenol, etc. and (2) CSE sample: 18.7% acetonitrile, 18.0% acetone, 12.5% 2-hydroxy-2-methyl-propanenitrile, 8.98% nicotine, 5.86% nicotyrine, etc. In this manner, to accurately examine the cytotoxicity of the cigarette smoke using CSC or CSE, the components and their concentrations in the CSC and CSE samples should be considered