Hypothesis Paper Effects of Intracellular Superoxide Removal at Acupoints with TAT-SOD on Obesity

TAT-SOD is a recombinant protein of superoxide dismutase fused with TAT peptide. By pure accident, we discovered that topical application of TAT-SOD to acupoints could result in acupuncture-like action. This study aimed to validate the accidental discovery by investigating the effect on simple obesity of the topical application of TAT-SOD to acupoints in comparison with acupuncture. 90 subjects were divided into 3 groups for 12-week treatments. Regular hospital acupuncture treatment was given to Acupuncture Group 3 times a week. TAT-SOD Group were instructed first to locate acupoints and apply 0.1 ml of 5000u SOD/ml TAT-SOD cream in an area of 1 cm 2 to each of the same set of acupoints, which they then conducted at home three times daily. Placebo Group applied the vehicle cream the same manner as TAT-SOD Group. Both TAT-SOD and acupuncture treatments decreased adiposity with overall clinical effective rates of 60.0% and 76.7%, respectively. The placebo group showed no improvement. The results validate that the enzymatic removal of the intracellular superoxide at acupoints could generate acupuncture-like effects, and indicate a possibility of the new method as a simple substitute to acupuncture and an insight of superoxide modulation along meridians for acupuncture mechanism. © 2011 Elsevier Inc. All rights reserved. Introduction Superoxide is one of the main reactive oxygen species (ROS) in the cell, which act as second messengers in the intracellular signaling pathways involved in activation of proinflammatory responses and mediate degradation of aggregan and collagen Although a variety of exogenous anti-oxidant enzymes are available to protect against oxidative stresses, the major problem in using these enzymes is that they can not be delivered into cells, thus resulting in their inability to detoxify intracellular RO

Scintillation efficiency measurement of Na recoils in NaI(Tl) below the DAMA/LIBRA energy threshold

The dark matter interpretation of the DAMA modulation signal depends on the NaI(Tl) scintillation efficiency of nuclear recoils. Previous measurements for Na recoils have large discrepancies, especially in the DAMA/LIBRA modulation energy region. We report a quenching effect measurement of Na recoils in NaI(Tl) from 3keV$_{\text{nr}}$ to 52keV$_{\text{nr}}$, covering the whole DAMA/LIBRA energy region for light WIMP interpretations. By using a low-energy, pulsed neutron beam, a double time-of-flight technique, and pulse-shape discrimination methods, we obtained the most accurate measurement of this kind for NaI(Tl) to date. The results differ significantly from the DAMA reported values at low energies, but fall between the other previous measurements. We present the implications of the new quenching results for the dark matter interpretation of the DAMA modulation signal

Cannabinoid Receptor Subtype 2 (Cb2R) Agonist Gw405833 Reduces Agonist-Induced Ca2+ Oscillations In Mouse Pancreatic Acinar Cells

Emerging evidence demonstrates that the blockade of intracellular Ca 2+ signals may protect pancreatic acinar cells against Ca 2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB 2 R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB 2 Rs modulate intracellular Ca 2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB 2 R agonist, GW405833 (GW) in agonist-induced Ca 2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB 1 R-knockout (KO), and CB 2 R-KO mice. Immunohistochemical labeling revealed that CB 2 R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB 2 Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca 2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB 2 R antagonist, AM630, or was absent in CB 2 R-KO but not CB 1 R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca 2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB 2 Rs eliminates ACh-induced Ca 2+ oscillations and L-arginine-induced enhancement of Ca 2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB 2 R-mediated protection in acute pancreatitis

Novel Zinc Matrix Nanocomposite as Biodegradable Material with Tunable Mechanical Properties

In the past decade, zinc-based biodegradable materials have gained tremendous attention from researchers due to their promising biodegradability and biocompatibility [1] [2]. However, there are several limitations to pure Zn and Zn alloys and their use as biodegradable implants. The most critical drawbacks of pure zinc as biodegradable structural support are its poor strength and low stability, making it unsuitable in most biomedical implant use. This work reports the homogeneous incorporation of WC nanoparticles into the Zn and Zn-Fe matrix as an effective method for mechanical strengthening, namely microhardness strengthening and Young’s modulus enhancement. This work also demonstrates the tunability of Zn-WC’s mechanical properties and discusses how this tunability makes Zn-WC an ideal candidate for the material selection of bioresorbable implants. Lastly, this study successfully designed and fabricated a novel high-performance implant spring made of Zn-WC biodegradable nanocomposite for the treatment of short bowel syndrome

Fundamental Study of Zinc Matrix Nanocomposites for Medical Implant Applications

The prevalence of biomedical implants has grown substantially in modern healthcare, benefiting a substantial portion of the population in developed nations. The historical use of metals as materials for medical implants is attributed to their advantageous qualities such as robust mechanical strength, ductility, stability, and machinability. These inherent attributes position metals as the preferred selection for various medical implant applications, enabling seamless integration and optimal performance within the human body. Among the array of potential biodegradable metals, Zn stands out as an innovative and promising choice. Its corrosion rate attributes and alloying potential render zinc a compelling solution in the pursuit of advanced and efficacious biodegradable implant materials. Although Zn shows potential as a biodegradable material, it is not without its constraints. In particular, it demonstrates inadequate mechanical properties and lacks thermal stability, leading to a reduction in ductility due to the natural aging of secondary phases and low resistance to creep. These drawbacks can present obstacles in specific medical implant scenarios. As a result, there is an urgent call for research efforts aimed at enhancing Zn's ability to surmount its mechanical vulnerabilities and thermal instability, all the while retaining its advantageous biodegradability and biocompatibility. This study presents the investigation and analysis of innovative Zn nanocomposites and their potential utility in biomedical implants. The primary emphasis was placed on the comprehensive examination of the influence of nanoparticles on diverse aspects of distinct Zn matrices, encompassing mechanical characteristics, thermal stability, biodegradability, and biocompatibility. During the initial phase of this study, three distinct Zn matrix nanocomposites with WC nanoparticles—namely, Zn-WC, Zn-Mg-WC, and Zn-Li-WC—were developed. This research endeavor encompassed the successful formulation and subsequent comprehensive characterization of these three specific Zn matrix nanocomposite systems. Each system underwent a detailed examination, focusing on its microstructural attributes, elemental compositions, and mechanical properties. This investigation not only demonstrates the viable integration of WC nanoparticles into the pure Zn system, but also showcases their potential application in promising Zn alloy variants, such as Zn-Mg and Zn-Li. Upon study, WC nanoparticles exhibited a substantial reinforcing effect on the system, leading to notable strength enhancement. Additionally, these nanoparticles were found to contribute to the reduction of grain size in the Zn system during solidification. Intriguingly, WC nanoparticles played a pivotal role in influencing and modifying the secondary phases of Zn-Mg and Zn-Li alloys, thereby contributing to enhanced ductility compared to the original pure alloys. The subsequent phase of this study delved into an examination of the impact of nanoparticles on the thermal stability of Zn matrices, with a specific focus on addressing the natural aging concerns associated with Zn-Mg alloy and the inherent low creep resistance of Zn systems. This investigation was prompted by Zn's susceptibility to microstructural evolution due to its comparatively low recrystallization temperature. The growth of a brittle secondary phase (Mg2Zn11) was observed under aging in both ambient and physiologically relevant temperatures. This occurrence has the potential to undermine the overall mechanical integrity of Zn-Mg alloys, thus possibly influencing their suitability as biodegradable materials for medical implant applications. Notably, the inclusion of nanoparticles was found to mitigate the growth of the brittle Mg2Zn11 phase during storage at room temperature, effectively preserving the ductility of Zn-0.1Mg alloy for long shelf life. Furthermore, Zn alloys exhibit compromised creep performance, particularly due to their propensity for creep deformation even at room temperature, exacerbated by their low melting point and hexagonal close-packed (HCP) crystal structure. This study revealed that the incorporation of WC nanoparticles yields a significant enhancement in creep resistance within the nanocomposite materials, accompanied by the introduction of a threshold stress for creep. In addition, the WC nanoparticles effectively impede dislocation movement along grain boundaries, leading to significantly diminished creep rates and improved mechanical characteristics. The first chapters of this study have demonstrated that WC plays a substantial role in enhancing the mechanical properties and thermal stability of Zn systems. Nevertheless, for Zn systems to attain success as biodegradable materials, they must satisfy two other pivotal criteria: biodegradability and biocompatibility. Despite progress, investigations into the in vitro and in vivo biocompatibility and degradation behavior of Zn-based nanocomposites remain absent. Consequently, a comprehensive understanding of how nanoparticles impact the biodegradability and biocompatibility of Zn matrix systems is urgently required. The next section focuses on the Zn nanocomposites and their corrosion behavior and biocompatibility, conducted by an analysis of their electrochemical behavior, immersion degradation characteristics, and cytotoxicity in vitro. Furthermore, the in vivo degradation behavior and biocompatibility of Zn matrix nanocomposites were evaluated and discussed using rodent animal models. These endeavors proved the potential of these materials as secure and efficient degradable metallic implant biomaterials. Finally, the last chapter presents the implementation of two distinct functional implants employing the Zn matrix nanocomposite: Zn-WC and Zn-Mg-WC. The spring engineered for Short Bowel Syndrome and the stent devised for Congenital Heart Defects not only showcased functionality but also yielded encouraging outcomes. These results underscore the potential of Zn-WC and Zn-Mg-WC in effectively addressing specific medical conditions, thereby laying the foundation for extended research and eventual clinical applications

Novel Zinc Matrix Nanocomposite as Biodegradable Material with Tunable Mechanical Properties

In the past decade, zinc-based biodegradable materials have gained tremendous attention from researchers due to their promising biodegradability and biocompatibility [1] [2]. However, there are several limitations to pure Zn and Zn alloys and their use as biodegradable implants. The most critical drawbacks of pure zinc as biodegradable structural support are its poor strength and low stability, making it unsuitable in most biomedical implant use. This work reports the homogeneous incorporation of WC nanoparticles into the Zn and Zn-Fe matrix as an effective method for mechanical strengthening, namely microhardness strengthening and Young’s modulus enhancement. This work also demonstrates the tunability of Zn-WC’s mechanical properties and discusses how this tunability makes Zn-WC an ideal candidate for the material selection of bioresorbable implants. Lastly, this study successfully designed and fabricated a novel high-performance implant spring made of Zn-WC biodegradable nanocomposite for the treatment of short bowel syndrome