Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

Negative pressure wound therapy for soft tissue injuries around the foot and ankle

<p>Abstract</p> <p>Background</p> <p>This study was performed to evaluate the results of negative pressure wound therapy (NPWT) in patients with open wounds in the foot and ankle region.</p> <p>Materials and methods</p> <p>Using a NPWT device, 16 patients were prospectively treated for soft tissue injuries around the foot and ankle. Mean patient age was 32.8 years (range, 3–67 years). All patients had suffered an acute trauma, due to a traffic accident, a fall, or a crush injury, and all had wounds with underlying tendon or bone exposure. Necrotic tissues were debrided before applying NPWT. Dressings were changed every 3 or 4 days and treatment was continued for 18.4 days on average (range, 11–29 days).</p> <p>Results</p> <p>Exposed tendons and bone were successfully covered with healthy granulation tissue in all cases except one. The sizes of soft tissue defects reduced from 56.4 cm²to 42.9 cm²after NPWT (mean decrease of 24%). In 15 of the 16 cases, coverage with granulation tissue was achieved and followed by a skin graft. A free flap was needed to cover exposed bone and tendon in one case. No major complication occurred that was directly attributable to treatment. In terms of minor complications, two patients suffered scar contracture of grafted skin.</p> <p>Conclusion</p> <p>NPWT was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the foot and ankle region, and thus, to shorten healing time and minimize secondary soft tissue defect coverage procedures.</p

Pumpless, selective docking of yeast cells inside a microfluidic channel induced by receding meniscus

We present a simple cell docking method induced by receding meniscus to capture non-adherent yeast cells onto microwells inside a microfluidic channel. Microwells were fabricated either by capillary moulding of UV curable polyurethane acrylate (PUA) onto glass substrate or direct replica moulding of poly(dimethyl siloxane) (PDMS). A cell suspension of the budding yeast, Saccharomyces cerevisiae, was introduced into the microfluidic channel by surface tension driven capillary flow and a receding meniscus was subsequently generated by evaporation. As the meniscus progressed, one to multiple yeast cells were spontaneously captured onto microwells by lateral capillary force created at the bottom of the meniscus. Using this cell-based platform, we observed the response of yeast cells upon stimulation by a mating pheromone (alpha-factor) by monitoring the expression of green fluorescent protein (GFP) with time. It was observed that alpha-factor triggered the expression of GFP at 60 min after stimulation and the fluorescence intensity was sustained for an additional 60 min without changes.This work was supported by the Micro Thermal System Research Center of Seoul National University and the Ministry of Science and Technology through Bio Tool R&D Project for Cell Research. This work was also supported in part by the SRC program of MOST/KOSEF (R11-2005-009-02004-0) to S.-H. P

PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Locally Controlled Sensing Properties of Stretchable Pressure Sensors Enabled by Micro-Patterned Piezoresistive Device Architecture.

For wearable health monitoring systems and soft robotics, stretchable/flexible pressure sensors have continuously drawn attention owing to a wide range of potential applications such as the detection of human physiological and activity signals, and electronic skin (e-skin). Here, we demonstrated a highly stretchable pressure sensor using silver nanowires (AgNWs) and photo-patternable polyurethane acrylate (PUA). In particular, the characteristics of the pressure sensors could be moderately controlled through a micro-patterned hole structure in the PUA spacer and size-designs of the patterned hole area. With the structural-tuning strategies, adequate control of the site-specific sensitivity in the range of 47~83 kPa-1 and in the sensing range from 0.1 to 20 kPa was achieved. Moreover, stacked AgNW/PUA/AgNW (APA) structural designed pressure sensors with mixed hole sizes of 10/200 µm and spacer thickness of 800 µm exhibited high sensitivity (~171.5 kPa-1) in the pressure sensing range of 0~20 kPa, fast response (100~110 ms), and high stretchability (40%). From the results, we envision that the effective structural-tuning strategy capable of controlling the sensing properties of the APA pressure sensor would be employed in a large-area stretchable pressure sensor system, which needs site-specific sensing properties, providing monolithic implementation by simply arranging appropriate micro-patterned hole architectures

Prophylactic Nailing of Incomplete Atypical Femoral Fractures

Introduction. Recent reports have described the occurrence of low-energy subtrochanteric and femoral shaft fractures associated with long-term bisphosphonate use. Although information regarding the surgical treatment of these atypical femoral fractures is increasing, it is unclear if the preventive operation is useful in incomplete fractures. This study examined the results of preventive intramedullary nailing for incomplete atypical femoral fractures. Material and Methods. A retrospective search was conducted for patients older than 50 years receiving bisphosphonate therapy, with incomplete, nondisplaced fractures in either the subtrochanteric or diaphyseal area of the femur. Seventeen patients with a total of 20 incomplete, non-displaced lesions were included. The mean duration of bisphosphonate use was 50.5 months. Eleven of the 17 (64.7%) patients had complete or incomplete fractures on the contralateral femur. All were treated with prophylactic fixation of an intramedullary (IM) nail. The minimum followup was 12 months. Results. All cases healed with a mean period of 14.3 weeks. Nineteen of the 20 cases healed with the dissolution of incomplete fractures of the lateral aspect. A complete fracture developed at the time of nailing in one patient, but it healed with callus bridging. Conclusion. IM nailing appears to be a reliable way of preventing the progress of incomplete atypical femoral fractures

Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as "duro-repulsive" cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei.open11102sciescopu

Highly-Sensitive Textile Pressure Sensors Enabled by Suspended-Type All Carbon Nanotube Fiber Transistor Architecture.

Among various wearable health-monitoring electronics, electronic textiles (e-textiles) have been considered as an appropriate alternative for a convenient self-diagnosis approach. However, for the realization of the wearable e-textiles capable of detecting subtle human physiological signals, the low-sensing performances still remain as a challenge. In this study, a fiber transistor-type ultra-sensitive pressure sensor (FTPS) with a new architecture that is thread-like suspended dry-spun carbon nanotube (CNT) fiber source (S)/drain (D) electrodes is proposed as the first proof of concept for the detection of very low-pressure stimuli. As a result, the pressure sensor shows an ultra-high sensitivity of ~3050 Pa-1 and a response/recovery time of 258/114 ms in the very low-pressure range of <300 Pa as the fiber transistor was operated in the linear region (VDS = -0.1 V). Also, it was observed that the pressure-sensing characteristics are highly dependent on the contact pressure between the top CNT fiber S/D electrodes and the single-walled carbon nanotubes (SWCNTs) channel layer due to the air-gap made by the suspended S/D electrode fibers on the channel layers of fiber transistors. Furthermore, due to their remarkable sensitivity in the low-pressure range, an acoustic wave that has a very tiny pressure could be detected using the FTPS