Targeted cell delivery by a magnetically actuated microrobot with a porous structure is a promising technique to enhance the low targeting efficiency of mesenchymal stem cell (MSC) in tissue regeneration. However, the relevant research performed to date is only in its proof-of-concept stage. To use the microrobot in a clinical stage, biocompatibility and biodegradation materials should be considered in the microrobot, and its efficacy needs to be verified using an in vivo model. In this study, we propose a human adipose–derived MSC–based medical microrobot system for knee cartilage regeneration and present an in vivo trial to verify the efficacy of the microrobot using the cartilage defect model. The microrobot system consists of a microrobot body capable of supporting MSCs, an electromagnetic actuation system for three-dimensional targeting of the microrobot, and a magnet for fixation of the microrobot to the damaged cartilage. Each component was designed and fabricated considering the accessibility of the patient and medical staff, as well as clinical safety. The efficacy of the microrobot system was then assessed in the cartilage defect model of rabbit knee with the aim to obtain clinical trial approval.

Purpose The axillary reverse mapping (ARM) technique to identify and preserve arm nodes during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was developed to prevent lymphedema. The purpose of this study was to investigate the location and metastatic rate of the arm node, and to evaluate the short term incidence of lymphedema after arm node preserving surgery. Methods From January 2009 to October 2010, 97 breast cancer patients who underwent ARM were included. Blue-dye (2.5 mL) was injected into the ipsilateral upper-inner arm. At least 20 minutes after injection, SLNB or ALND was performed and blue-stained arm nodes and/or lymphatics were identified. Patients were divided into two groups, an arm node preserved group (70 patients had ALND, 10 patients had SLNB) and an unpreserved group (13 patients had ALND, 4 patients had SLNB). The difference in arm circumference between preoperative and postoperative time points was checked in both groups. Results The mean number of identified blue stained arm nodes was 1.4±0.6. In the majority of patients (92%), arm nodes were located between the lower level of the axillary vein and just below the second intercostobrachial nerve. In the arm node unpreserved group, 2 patients had metastasis in their arm node. Among ALND patients, in the arm node preserved group, the difference in arm circumference between preoperative and postoperative time points in ipsilateral and contralateral arms was 0.27 cm and 0.07 cm, respectively, whereas it was 0.47 cm and -0.03 cm in the unpreserved group; one case of lymphedema was found after 6 months. No difference was found between arm node preserved and unpreserved group among SLNB patients. Conclusion Arm node preserving was possible in all breast cancer patients with identifiable arm nodes, during ALND or SLNB, except for those with high surgical N stage, and lymphedema did not develop in patients with arm node preserving surgery.

Neuroblastoma (NB) originates from immature neuronal cells and currently has a poor clinical outcome. NB cells possess cancer stem cells (CSCs) characteristics that facilitate the initiation of a tumor, as well as its metastasis. Human bitter taste receptors, referred to as TAS2Rs, are one of five types of basic taste receptors and they belong to a family of G-protein coupled receptors. The recent finding that taste receptors are expressed in non-gustatory tissues suggest that they mediate additional functions distinct from taste perception. While it is generally admitted that the recognition of bitter tastes may be associated with a self-defense system to prevent the ingestion of poisonous food compounds, this recognition may also serve as a disease-related function in the human body. In particular, the anti-cancer stemness and invasion effects of TAS2Rs on NB cells remain poorly understood. In the present study, endogenous expression of TAS2R8 and TAS2R10 in SK-N-BE(2)C and SH-SY5Y cells was examined. In addition, higher levels of TAS2R8 and TAS2R10 expression were investigated in more differentiated SY5Y cells. Both TAS2Rs were up-regulated following the induction of neuronal cell differentiation by retinoic acid. In addition, ectopic transfection of the two TAS2Rs induced neurite elongation in the BE(2)C cells, and down-regulated CSCs markers (including DLK1, CD133, Notch1, and Sox2), and suppressed self-renewal characteristics. In particular, TAS2RS inhibited tumorigenicity. Furthermore, when TAS2Rs was over-expressed, cell migration, cell invasion, and matrix metalloproteinases activity were inhibited. Expression levels of hypoxia-inducible factor-1α, a well-known regulator of tumor metastasis, as well as its downstream targets, vascular endothelial growth factor and glucose transporter-1, were also suppressed by TAS2Rs. Taken together, these novel findings suggest that TAS2Rs targets CSCs by suppressing cancer stemness characteristics and NB cell invasion, thereby highlighting the chemotherapeutic potential of bitter taste receptors.

The present study investigated the effects of soybean leaf extracts (SLEs) on blood glucose, insulin resistance, body fat and dyslipidemia in prediabetes subjects, and compared them with the effects of banaba extracts (BE) which is known to ameliorate diabetes in several animals and clinical studies. Overweight subjects with mild hyperglycemia (fasting blood glucose level of 100-125 mg dL(-1)) were randomly assigned to three groups and administered four capsules containing starch (2 g per day, Placebo), BE (300 mg per day, 0.3% corosolic acid) or SLE (2 g per day) during regular meals for 12 weeks. The SLE as well as BE significantly decreased the baseline-adjusted final blood glucose, HbA1c, HOMA-IR and transaminase levels compared to the placebo group. The body weight, BMI and WHR were not different between the groups, but the baseline-adjusted final body fat content and waist circumference were lower in the BE and SLE groups than in the placebo group. Furthermore, the baseline-adjusted final plasma triglyceride concentration was lower in the BE and SLE groups compared to the placebo group. There were no significant differences in plasma total cholesterol and LDL-cholesterol concentrations between the groups. However, the SLE, but not the BE, significantly increased the plasma HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol after 12 weeks of supplementation compared to the placebo group, while the atherogenic index was decreased. Taken together, these data suggest that SLE may play an important role in improving blood glucose, insulin resistance, adiposity, and dyslipidemia in prediabetes subjects consuming their habitual diet, similar to or better than BE.

Abstract:This article explores the relations between network properties and the effect from moving rainstorms in terms of the peak response and time to centroid of hydrographs. A simple conceptual rectangular catchment is introduced with different configurations of drainage network simulated by the Gibbs stochastic model. The efficiency of the urban pipe networks varies widely compared with natural river networks; hence, the Gibbs model can be an appropriate approach to represent the network properties in urban drainage system. Simple cases of rainstorms moving with upstream and downstream directions and different speeds are considered to investigate the effect of rainstorm movement on urban drainage network runoff hydrographs. The results indicate that the effect of the direction and speed of the rainstorm movement varies significantly depending on the network properties. The relationship between storm speed and direction and the change in the peak runoff is dependent on the network configuration and network efficiency. In contrast to previous studies, this study indicates that the speed and direction of the rainfall movement that produces the maximum peak discharge changes depending on the network configuration.

PurposeThe purpose of this study is to evaluate imaging and histopathologic findings including the immunohistochemical characteristics of invasive micropapillary carcinoma (IMPC) of the breast.MethodsTwenty-nine patients diagnosed with IMPC were included in the present study. Mammographic, sonographic, and magnetic resonance imaging (MRI) findings were analyzed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings were also evaluated. Microscopic slides of surgical specimens were reviewed in consensus by two pathologists with a specialty in breast pathology.ResultsMost IMPCs presented as a high density irregular mass with a non-circumscribed margin associated with microcalcifications on mammography, as an irregular hypoechoic mass with a spiculated margin on ultrasound, and as irregular spiculated masses with washout patterns on MRI. PET-CT showed a high maximum standardized uptake value (SUVmax) (mean, 11.2). Axillary nodal metastases were identified in 65.5% of the patients. Immunohistochemical studies showed high positivities for estrogen receptor and c-erbB-2 (93.1% and 51.7µ, respectively).ConclusionEven though the imaging characteristics of IMPCs are not distinguishable from typical invasive ductal carcinomas, this tumor type frequently results in nodal metastases and high positivities for both estrogen receptor and c-erbB-2. The high SUVmax value that is apparent on PET-CT might be helpful in the diagnosis of IMPC.

[1] The aim of this paper is to investigate, in general terms, the effects of storm movement on the resulting flood peaks, and the underlying process controls. For this purpose, we utilize a broad theoretical framework that uses characteristic time and space scales associated with stationary rainstorms as well as moving rainstorms. For a stationary rainstorm the characteristic timescales that govern the peak response include two intrinsic timescales of a catchment and one extrinsic timescale of a rainstorm. On the other hand, for a moving rainstorm, two additional extrinsic scales are required, the storm travel time and storm size. The relationship between the peak response and the timescales appropriate for a stationary rainstorm can be extended in a straightforward manner to describe the peak response for a moving rainstorm. However, the interdependence between rainfall duration and storm travel time makes the behavior of the peak response for a moving rainstorm fundamentally different from that of a stationary rainstorm. We show that the relationship between peak response and characteristic timescales also depends on the relative size of the rainstorm with respect to catchment size. For moving rainstorms, we show that the augmentation of peak response arises from both the effect of overlaying the responses from subcatchments (resonance condition) and the effect of increased responses from subcatchments due to increased duration (interdependence), which results in maximum peak response when the moving rainstorm is slower than the channel flow velocity.

We compared metabolic biomarkers in the blood and peripheral blood mononuclear cell (PBMC) gene expression profiles among normal weight (BMI, 18·5-23 kg/m 2 ), mildly obese (BMI, 25-27·5 kg/m 2 ) and moderately obese Korean adult men (BMI, 27·5-30 kg/m 2 ). High leptin, lipids (except LDL-and HDL-cholesterol) and apoB levels and low adiponectin and HDL-cholesterol levels were present in the plasma of both mildly and moderately obese subjects. Circulating levels of inflammatory cytokines and markers of insulin resistance, oxidative stress and liver damage were altered in moderately obese subjects but not in mildly obese subjects. PBMC transcriptome data showed enrichment of pathways involved in energy metabolism, insulin resistance, bone metabolism, cancer, inflammation and fibrosis in both mildly and moderately obese subjects. Signalling pathways involved in oxidative phosphorylation, TAG synthesis, carbohydrate metabolism and insulin production; mammalian target of rapamycin, forkhead box O, ras-proximate-1, RAS and transforming growth factor-β signalling; as well as extracellular matrix-receptor interaction were enriched only in moderately obese subjects, indicating that changes in PBMC gene expression profiles, according to metabolic disturbances, were associated with the development and/or aggravation of obesity. In particular, fourteen and fifteen genes differentially expressed only in mildly obese subjects and in both mildly and moderately obese subjects, respectively, could be used as early or stable biomarkers for diagnosing and treating obesity-associated metabolic disturbance. We characterised BMI-associated metabolic and molecular biomarkers in the blood and provided clues about potential blood-based targets for preventing or treating obesityrelated complications.