Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs

BACKGROUND: With the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and also in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). METHODS: Transperineal injection into the prostate using transrectal ultrasound (TRUS) was performed throughout the study. Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate. One or 3 months later, the prostate was harvested for morphologic and apoptotic study. In addition, eight BPH patients refractory to α-blockers were treated with ultrasound guided intraprostatic injection of 200 U of BTX-A. RESULTS: In the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom score, and quality of life index were significantly reduced by 18.8%, 73.1%, and 61.5% respectively. Maximal flow rate significantly increased by 72.0%. CONCLUSION: Intraprostatic BTX-A injection induces prostate apotosis in dogs and relieves BOO in humans. It is therefore a promising alternative treatment for refractory BOO due to BPH

Screening therapeutic EMT blocking agents in a three-dimensional microenvironment

Epithelial–mesenchymal transition (EMT) plays a critical role in the early stages of dissemination of carcinoma leading to metastatic tumors, which are responsible for over 90% of all cancer-related deaths. Current therapeutic regimens, however, have been ineffective in the cure of metastatic cancer, thus an urgent need exists to revisit existing protocols and to improve the efficacy of newly developed therapeutics. Strategies based on preventing EMT could potentially contribute to improving the outcome of advanced stage cancers. To achieve this goal new assays are needed to identify targeted drugs capable of interfering with EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial-like state. Current assays are limited to examining the dispersion of carcinoma cells in isolation in conventional 2-dimensional (2D) microwell systems, an approach that fails to account for the 3-dimensional (3D) environment of the tumor or the essential interactions that occur with other nearby cell types in the tumor microenvironment. Here we present a microfluidic system that integrates tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an endothelial monolayer. Drug candidates inhibiting receptor activation or signal transduction pathways implicated in EMT have been tested using dispersion of A549 lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate significant differences in response to drugs between 2D and 3D, and between monoculture and co-culture.Singapore. National Research Foundation (Singapore MIT Alliance for Research and Technology's BioSystems and Micromechanics Inter-Disciplinary Research programme)National University of Singapore (Cancer Science Institute)Singapore. Agency for Science, Technology and ResearchSingapore. Institute of Molecular and Cell Biology (IMCB core funding A*STAR

Screening therapeutic EMT blocking agents in a three-dimensional microenvironment

Epithelial–mesenchymal transition (EMT) plays a critical role in the early stages of dissemination of carcinoma leading to metastatic tumors, which are responsible for over 90% of all cancer-related deaths. Current therapeutic regimens, however, have been ineffective in the cure of metastatic cancer, thus an urgent need exists to revisit existing protocols and to improve the efficacy of newly developed therapeutics. Strategies based on preventing EMT could potentially contribute to improving the outcome of advanced stage cancers. To achieve this goal new assays are needed to identify targeted drugs capable of interfering with EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial-like state. Current assays are limited to examining the dispersion of carcinoma cells in isolation in conventional 2-dimensional (2D) microwell systems, an approach that fails to account for the 3-dimensional (3D) environment of the tumor or the essential interactions that occur with other nearby cell types in the tumor microenvironment. Here we present a microfluidic system that integrates tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an endothelial monolayer. Drug candidates inhibiting receptor activation or signal transduction pathways implicated in EMT have been tested using dispersion of A549 lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate significant differences in response to drugs between 2D and 3D, and between monoculture and co-culture.Singapore. National Research Foundation (Singapore MIT Alliance for Research and Technology's BioSystems and Micromechanics Inter-Disciplinary Research programme)National University of Singapore (Cancer Science Institute)Singapore. Agency for Science, Technology and ResearchSingapore. Institute of Molecular and Cell Biology (IMCB core funding A*STAR

Higher power of sensorimotor rhythm is associated with better performance in skilled air-pistol shooters

Cheng M-Y, Wang K-P, Hung C-L, et al. Higher power of sensorimotor rhythm is associated with better performance in skilled air-pistol shooters. Psychology of Sport and Exercise. 2017;32:47-53.Objectives Psychomotor efficiency has been linked with processing efficiency during sport performance. Reduced cortical activity in the sensorimotor area has been related to less variability in the movement preparation that is conducive to skilled motor performance. This study proposes sensorimotor rhythm (SMR), 12–15 Hz of the electroencephalography (EEG) in the sensorimotor area, may be used to investigate psychomotor efficiency in sports performance. Method Twenty-four skilled air pistol shooters were recruited to fire 40 shots while EEG and shooting accuracy were recorded. Results The data show that improved performance of skilled shooters is associated with higher SMR power during the last second and lower coherence on high alpha power at Fz-T3 before action initiation. A negative relationship is also exhibited between the SMR power and the shooting performance during the aiming. Conclusions This finding suggests that reduced interference from sensorimotor processing, as reflected by elevated SMR power, may be related to improved processing efficiency during the aiming period. We conclude that SMR may be used to understand psychomotor efficiency underlying air-pistol shooting performance

Unveiling the additive-assisted oriented growth of perovskite crystallite for high performance light-emitting diodes.

Solution-processed metal halide perovskites have been recognized as one of the most promising semiconductors, with applications in light-emitting diodes (LEDs), solar cells and lasers. Various additives have been widely used in perovskite precursor solutions, aiming to improve the formed perovskite film quality through passivating defects and controlling the crystallinity. The additive's role of defect passivation has been intensively investigated, while a deep understanding of how additives influence the crystallization process of perovskites is lacking. Here, we reveal a general additive-assisted crystal formation pathway for FAPbI3 perovskite with vertical orientation, by tracking the chemical interaction in the precursor solution and crystallographic evolution during the film formation process. The resulting understanding motivates us to use a new additive with multi-functional groups, 2-(2-(2-Aminoethoxy)ethoxy)acetic acid, which can facilitate the orientated growth of perovskite and passivate defects, leading to perovskite layer with high crystallinity and low defect density and thereby record-high performance NIR perovskite LEDs (~800 nm emission peak, a peak external quantum efficiency of 22.2% with enhanced stability)

A Novel Selective JAK2 Inhibitor Identified Using Pharmacological Interactions

The JAK2/STAT signaling pathway mediates cytokine receptor signals that are involved in cell growth, survival and homeostasis. JAK2 is a member of the Janus kinase (JAK) family and aberrant JAK2/STAT is involved with various diseases, making the pathway a therapeutic target. The similarity between the ATP binding site of protein kinases has made development of specific inhibitors difficult. Current JAK2 inhibitors are not selective and produce unwanted side effects. It is thought that increasing selectivity of kinase inhibitors may reduce the side effects seen with current treatment options. Thus, there is a great need for a selective JAK inhibitor. In this study, we identified a JAK2 specific inhibitor. We first identified key pharmacological interactions in the JAK2 binding site by analyzing known JAK2 inhibitors. Then, we performed structure-based virtual screening and filtered compounds based on their pharmacological interactions and identified compound NSC13626 as a potential JAK2 inhibitor. Results of enzymatic assays revealed that against a panel of kinases, compound NSC13626 is a JAK2 inhibitor and has high selectivity toward the JAK2 and JAK3 isozymes. Our cellular assays revealed that compound NSC13626 inhibits colorectal cancer cell (CRC) growth by downregulating phosphorylation of STAT3 and arresting the cell cycle in the S phase. Thus, we believe that compound NSC13626 has potential to be further optimized as a selective JAK2 drug

Thermal Conductivity of Carbon Nanotubes and their Polymer Nanocomposites: A Review

Thermally conductive polymer composites offer new possibilities for replacing metal parts in several applications, including power electronics, electric motors and generators, heat exchangers, etc., thanks to the polymer advantages such as light weight, corrosion resistance and ease of processing. Current interest to improve the thermal conductivity of polymers is focused on the selective addition of nanofillers with high thermal conductivity. Unusually high thermal conductivity makes carbon nanotube (CNT) the best promising candidate material for thermally conductive composites. However, the thermal conductivities of polymer/CNT nanocomposites are relatively low compared with expectations from the intrinsic thermal conductivity of CNTs. The challenge primarily comes from the large interfacial thermal resistance between the CNT and the surrounding polymer matrix, which hinders the transfer of phonon dominating heat conduction in polymer and CNT. This article reviews the status of worldwide research in the thermal conductivity of CNTs and their polymer nanocomposites. The dependence of thermal conductivity of nanotubes on the atomic structure, the tube size, the morphology, the defect and the purification is reviewed. The roles of particle/polymer and particle/particle interfaces on the thermal conductivity of polymer/CNT nanocomposites are discussed in detail, as well as the relationship between the thermal conductivity and the micro- and nano-structure of the composite

Interventions for preventing oral mucositis for patients with cancer receiving treatment

Interventions for preventing oral mucositis for patients with cancer receiving treatmentTreatment for cancer (including bone marrow transplant) can cause oral mucositis (severe ulcers in the mouth). This painful condition can cause difficulties in eating, drinking and swallowing, and may also be associated with infections which may require the patient to stay longer in hospital. Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte‐colony stimulating factor (G‐CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated