The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers.     

Glass with hydration-induced compressive stress profiles

A novel potassium phospho-aluminosilicate composition is described that can be strengthened by water vapor to achieve deep compressive stress (CS) profiles. Water vapor treatment at (A) 85°C and 85% relative humidity for 40 days results in a CS of 389 ± 20 MPa and a compressive depth of layer (DOL) of 18 ± 2 μm. When treated at (B) 160°C and 0.1 MPa for 7 days, a CS of 245 ± 20 MPa and a DOL of 40 ± 2 μm is achieved. Glasses with hydration-induced stress profiles can provide high retained strength following flaw introduction compared with ion-exchanged soda-lime silicate glass. Sample treatment B also has an exemplary Vickers indentation cracking threshold value greater than 20 kgf. The hydration profile determined by secondary ion mass spectrometry (SIMS) is shown to closely match the stress profile for these samples. SIMS analysis also shows that the depth of water enrichment correlates well with the depletion depth of phosphorus. The high tendency towards water-induced strengthening for this new type of glass even enables self-strengthening by the generation of a near-surface CS profile following exposure to ambient conditions.     

Improved additive manufacturing of silicon carbide parts via pressureless electric field-assisted sintering

High solids loading silicon carbide (SiC)-based aqueous slurries containing only .5 wt. % organic additives were utilized to create specimens of various geometries via an extrusion-based additive manufacturing (AM) technique. Pressureless electric field-assisted sintering was performed to densify each specimen without deformation. The combination of these techniques produced parts with >98% relative density despite containing only 5 wt.% oxide sintering additives. After sintering, specimens contained only the α-SiC and yttrium aluminum perovskite phases. This suggests the evolution of a nonequilibrium yttrium aluminate phase, as well as transformation from β-SiC to α-SiC. The fabrication method presented in this work has advantages over other AM techniques commonly used with SiC, because it does not require significant organic additives nor additional postprocessing steps such as chemical vapor infiltration or polymer impregnation and pyrolysis.     

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum-Targeting Copper(II) Complex

Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4 , capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub-micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage-associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.     

Effect of Silicon Inclusion Carbonaceous Composite Particulate on the Thermal-Ageing Characteristics and Mechanical Performance of Low Carbon Steel

Silicon - This study focus on the effects of silicon inclusion carbonaceous particulate on the hardness and microstructural properties of carburized low carbon steel, at constant temperature of...     

The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury

Spinal cord injury (SCI) produces paralysis and a unique form of neurogenic disuse osteoporosis that dramatically increases fracture risk at the distal femur and proximal tibia. This bone loss is driven by heightened bone resorption and near-absent bone formation during the acute post-SCI recovery phase and by a more traditional high-turnover osteopenia that emerges more chronically, which is likely influenced by the continual neural impairment and musculoskeletal unloading. These observations have stimulated interest in specialized exercise or activity-based physical therapy (ABPT) modalities (e.g., neuromuscular or functional electrical stimulation cycling, rowing, or resistance training, as well as other standing, walking, or partial weight-bearing interventions) that reload the paralyzed limbs and promote muscle recovery and use-dependent neuroplasticity. However, only sparse and relatively inconsistent evidence supports the ability of these physical rehabilitation regimens to influence bone metabolism or to increase bone mineral density (BMD) at the most fracture-prone sites in persons with severe SCI. This review discusses the pathophysiology and cellular/molecular mechanisms that influence bone loss after SCI, describes studies evaluating bone turnover and BMD responses to ABPTs during acute versus chronic SCI, identifies factors that may impact the bone responses to ABPT, and provides recommendations to optimize ABPTs for bone recovery.     

SCR deactivation in a full-scale cofired utility boiler

The Energy and Environmental Research Center installed a portable slipstream selective catalytic reduction (SCR) reactor in the convective pass of a utility boiler cofiring wood waste and Powder River Basin (PRB) coal. Catalyst sections were removed after 43, 128, and 171 days of operation. SCR catalytic activity was determined for each section, and a sample of one section was examined under a scanning electron microscope to look for signs of catalyst blinding and/or poisoning. The catalyst deactivated at an apparently inverse rate with an initial deactivation rate of 18% every 1000 h. The major mode of deactivation appeared to be pore blocking by combined alkali and calcium sulfate deposition and growth.     

Integration of Emerging Biomedical Technologies in Meat Processing to Improve Meat Safety and Quality

Modern‐day processing of meat products involves a series of complex procedures designed to ensure the quality and safety of the meat for consumers. As the size of abattoirs increases, the logistical problems associated with large‐capacity animal processing can affect the sanitation of the facility and the meat products, potentially increasing transmission of infectious diseases. Additionally, spoilage of food from improper processing and storage increases the global economic and ecological burden of meat production. Advances in biomedical and materials science have allowed for the development of innovative new antibacterial technologies that have broad applications in the medical industry. Additionally, new approaches in tissue engineering and nondestructive cooling of biological specimens could significantly improve organ transplantation and tissue grafting. These same strategies may be even more effective in the preservation and protection of meat as animal carcasses are easier to manipulate and do not have the same stringent requirements of care as living patients. This review presents potential applications of emerging biomedical technologies in the food industry to improve meat safety and quality. Future research directions investigating these new technologies and their usefulness in the meat processing chain along with regulatory, logistical, and consumer perception issues will also be discussed.     

Microglial FABP4-UCP2 Axis Modulates Neuroinflammation and Cognitive Decline in Obese Mice

The microglial fatty-acid-binding protein 4-uncoupling protein 2 (FABP4-UCP2) axis is a key regulator of neuroinflammation in high-fat-diet (HFD)-fed animals, indicating a role for FABP4 in brain immune response. We hypothesized that the FABP4-UCP2 axis is involved in regulating diet-induced cognitive decline. We tested cognitive function in mice lacking microglial FABP4 (AKO mice). Fifteen-week-old male AKO and wild-type (WT) mice were maintained on 60% HFD or normal chow (NC) for 12 weeks. Body composition was measured using EchoMRI. Locomotor activity, working memory, and spatial memory were assessed using behavioral tests (open field, T-maze, and Barnes maze, respectively). Hippocampal microgliosis was assessed via immunohistochemical staining. An inflammatory cytokine panel was assayed using hippocampal tissue. Real-time RT-PCR was performed to measure microglial UCP2 mRNA expression. Our data support that loss of FABP4 prevents cognitive decline in vivo. HFD-fed WT mice exhibited impaired long- and short-term memory, in contrast with HFD-fed AKO mice. HFD-fed WT mice had an increase in hippocampal inflammatory cytokine expression (IFNγ, IL-1β, IL-5, IL-6, KC/GRO(CXCL1), IL-10, and TNFα) and microgliosis, and decreased microglial UCP2 expression. HFD-fed AKO mice had decreased hippocampal inflammatory cytokine expression and microgliosis and increased microglial UCP2 expression compared to HFD-fed WT mice. Collectively, our work supports the idea that the FABP4-UCP2 axis represents a potential therapeutic target in preventing diet-induced cognitive decline.