Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells

Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Amperometric microsensors monitoring glutamate-evoked in situ responses of nitric oxide and carbon monoxide from live human neuroblastoma cells

In the brain, nitric oxide (NO) and carbon monoxide (CO) are important signaling gases which have multifaceted roles, such as neurotransmitters, neuromodulators, and vasodilators. Even though it is difficult to measure NO and CO in a living system due to their high diffusibility and extremely low release levels, electrochemical sensors are promising tools to measure in vivo and in vitro NO and CO gases. In this paper, using amperometric dual and septuple NO/CO microsensors, real-time NO and CO changes evoked by glutamate were monitored simultaneously for human neuroblastoma (SH-SY5Y) cells. In cultures, the cells were differentiated and matured into functional neurons by retinoic acid and brain-derived neurotrophic factor. When glutamate was administrated to the cells, both NO and CO increases and subsequent decreases returning to the basal levels were observed with a dual NO/CO microsensor. In order to facilitate sensor’s measurement, a flower-type septuple NO/CO microsensor was newly developed and confirmed in terms of the sensitivity and selectivity. The septuple microsensor was employed for the measurements of NO and CO changes as a function of distances from the position of glutamate injection. Our sensor measurements revealed that only functionally differentiated cells responded to glutamate and released NO and CO. © 2017 by the authors. Licensee MDPI, Basel, Switzerland

Amperometric Microsensors Monitoring Glutamate-Evoked In Situ Responses of Nitric Oxide and Carbon Monoxide from Live Human Neuroblastoma Cells

In the brain, nitric oxide (NO) and carbon monoxide (CO) are important signaling gases which have multifaceted roles, such as neurotransmitters, neuromodulators, and vasodilators. Even though it is difficult to measure NO and CO in a living system due to their high diffusibility and extremely low release levels, electrochemical sensors are promising tools to measure in vivo and in vitro NO and CO gases. In this paper, using amperometric dual and septuple NO/CO microsensors, real-time NO and CO changes evoked by glutamate were monitored simultaneously for human neuroblastoma (SH-SY5Y) cells. In cultures, the cells were differentiated and matured into functional neurons by retinoic acid and brain-derived neurotrophic factor. When glutamate was administrated to the cells, both NO and CO increases and subsequent decreases returning to the basal levels were observed with a dual NO/CO microsensor. In order to facilitate sensor’s measurement, a flower-type septuple NO/CO microsensor was newly developed and confirmed in terms of the sensitivity and selectivity. The septuple microsensor was employed for the measurements of NO and CO changes as a function of distances from the position of glutamate injection. Our sensor measurements revealed that only functionally differentiated cells responded to glutamate and released NO and CO

Precision 3D surface measurement of step-structures using mode-locked femtosecond pulses

Fast, precise 3-D measurement of step-structures fabricated on microelectronic products is essential for quality assurance of semiconductor, flat panel display and photovoltaic products. Optical interferometers have long been used, but not that wide-spread for step-structures due to their phase ambiguity or low spatial coherence. Femtosecond pulse lasers can provide novel possibilities to optical profilometry both in the time and the frequency domain. In the time domain, step-surfaces can be measured over wide area by exploiting low temporal but high spatial coherence of femtosecond pulses; in the frequency domain, multi-wavelength interferometry permits the absolute measurement over the discontinued surface profiles while maintaining the sub-wavelength measurement precision.Published versio

Securing Resection Margin Using Indocyanine Green Diffusion Range on Gastric Wall during NIR Fluorescence-Guided Surgery in Early Gastric Cancer Patients

Near-infrared (NIR) fluorescence lymphography-guided minimally invasive gastrectomy using indocyanine green (ICG) is employed to visualize draining lymphatic vessels and lymph nodes. Endoscopically injected ICG spreads along the gastric wall and emits fluorescence from the serosal surface of the stomach. We aimed to assess the efficacy of ICG diffusion in securing the resection margin. We retrospectively analyzed 503 patients with early gastric cancer located in the body of the stomach who underwent fluorescence lymphography-guided gastrectomy from 2018 to 2021. One day before surgery, ICG was endoscopically injected into four points of the submucosal layer peritumorally. We measured the extent of resection and the resection line based on the ICG diffusion area from the specimen using NIR imaging. The mean area of the ICG diffusion was 82.7 × 75.3 and 86.7 × 80.2 mm2 on the mucosal and serosal sides, respectively. After subtotal gastrectomy, the length of the proximal resection margin was 38.1 ± 20.1, 33.4 ± 22.2, and 28.7 ± 17.2 mm in gastroduodenostomy, loop gastrojejunostomy, and Roux-en-Y gastrojejunostomy, respectively. The ICG diffusion area along the gastric wall secured a resection margin of >28 mm. The ICG diffusion range can be used as a simple and easy method for determining the resection margin during gastrectomy using NIR imaging

Changes in failure to rescue after gastrectomy at a large-volume center with a 16-year experience in Korea

Abstract Failure to rescue (FTR), the mortality rate among patients with complications, is gaining attention as a hospital quality indicator. However, comprehensive investigation into FTR has rarely been conducted after radical gastrectomy for gastric cancer patients. This study aimed to assess FTR after radical gastrectomy and investigate the associations between FTR and clinicopathologic factors, operative features, and complication types. From 2006 to 2021, 16,851 gastric cancer patients who underwent gastrectomy were retrospectively analyzed. The incidence and risk factors were analyzed for complications, mortality, and FTR. Seventy-six patients had postoperative mortality among 15,984 patients after exclusion. The overall morbidity rate was 10.49% (1676/15,984 = 10.49%), and the FTR rate was 4.53% (76/1676). Risk factor analysis revealed that older age (reference: < 60; vs. 60–79, adjusted odds ratio [OR] 2.07, 95% confidence interval [CI] 1.13–3.79, P = 0.019; vs. ≥ 80, OR 3.74, 95% CI 1.57–8.91, P = 0.003), high ASA score (vs. 1 or 2, OR 2.79, 95% CI 1.59–4.91, P < 0.001), and serosa exposure in pathologic T stage (vs. T1, OR 2.74, 95% CI 1.51–4.97, P < 0.001) were associated with FTR. Moreover, patients who underwent gastrectomy during 2016–2021 were less likely to die when complications occurred than patients who received the surgery in 2006–2010 (OR 0.35, 95% CI 0.18–0.68, P = 0.002). This investigation of FTR after gastrectomy demonstrated that the risk factors for FTR were old age, high ASA score, serosa exposure, and operation period. FTR varied according to the complication types and the period, even in the same institution

Patient Visits and Prescribing Patterns Associated with Rosacea in Korea: A Real-World Retrospective Study Based on Electronic Medical Records

Rosacea is a common and chronic inflammatory skin disorder. The visiting trends and prescribing patterns involving Korean patients with rosacea have not been thoroughly examined. To examine the visiting trends of patients with rosacea, and to analyze the prescription patterns of Korean dermatologists managing such patients, a retrospective cross-sectional study on dermatology outpatients who visited the seven affiliated hospitals of The Catholic University of Korea between 2007 and 2018 was performed. A total of 56,651 visits were made by rosacea patients. The mean annual number of hospital visits made by rosacea patients over a 6-year period increased from 2456 in 2007&ndash;2012 to 6985 in 2013&ndash;2018. Hospital visits were most prevalent in female patients aged 40 to 59 years. There was no statistically significant difference in patient visitation between the seasons. As for prescriptions, systemic antibiotics were most commonly prescribed, followed by antihistamines, non-steroidal anti-inflammatory drugs, and retinoids. Among the topical agents, metronidazole was the most prescribed agent during 2007&ndash;2012, whereas calcineurin inhibitors were favored most during 2013&ndash;2018. Dermatology outpatient visits by individuals with rosacea have increased in Korea over time. The real-world prescription trend presented here may help dermatologists facilitate better treatment strategies and provide appropriate guidance to patients with rosacea