Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling.

Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway. Notably, its active site contains a cysteine residue that is susceptible to oxidation by hydrogen peroxide (H2O2). This oxidation inhibits the phosphatase function of PTEN, critically contributing to the activation of the PI3K/AKT pathway. Upon the stimulation of cell surface receptors, the activity of NADPH oxidase (NOX) generates a transient amount of H2O2, serving as a mediator in this pathway by oxidizing PTEN. The mechanism underlying this oxidation, occurring despite the presence of highly efficient and abundant cellular oxidant-protecting and reducing systems, continues to pose a perplexing conundrum. Here, we demonstrate that the presence of bicarbonate (HCO3-) promoted the rate of H2O2-mediated PTEN oxidation, probably through the formation of peroxymonocarbonate (HCO4-), and consequently potentiated the phosphorylation of AKT. Acetazolamide (ATZ), a carbonic anhydrase (CA) inhibitor, was shown to diminish the oxidation of PTEN. Thus, CA can also be considered as a modulator in this context. In essence, our findings consolidate the crucial role of HCO3- in the redox regulation of PTEN by H2O2, leading to the presumption that HCO4- is a signaling molecule during cellular physiological processes.

Redox Regulation of PTEN by Reactive Oxygen Species: Its Role in Physiological Processes.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth, and proliferation by downregulating the PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury, and immune responsiveness. Therefore, recently, PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Herein, we provide an overview of studies that highlight the role of the oxidative inhibition of PTEN in physiological processes.

Insulin signaling and its application.

The discovery of insulin in 1921 introduced a new branch of research into insulin activity and insulin resistance. Many discoveries in this field have been applied to diagnosing and treating diseases related to insulin resistance. In this mini-review, the authors attempt to synthesize the updated discoveries to unravel the related mechanisms and inform the development of novel applications. Firstly, we depict the insulin signaling pathway to explain the physiology of insulin action starting at the receptor sites of insulin and downstream the signaling of the insulin signaling pathway. Based on this, the next part will analyze the mechanisms of insulin resistance with two major provenances: the defects caused by receptors and the defects due to extra-receptor causes, but in this study, we focus on post-receptor causes. Finally, we discuss the recent applications including the diseases related to insulin resistance (obesity, cardiovascular disease, Alzheimer's disease, and cancer) and the potential treatment of those based on insulin resistance mechanisms.

The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease.

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

Development of Electromagnetic Acoustic Transducer System for Coin Classification.

In this work, a method for identifying counterfeit coins based on an electromagnetic acoustic transducer (EMAT) to detect the difference in the coin's natural acoustic frequency response is presented. In the experimental system, the acoustic oscillation induced by a pulsed magnetic field is received by a microphone and recorded by an oscilloscope. The natural acoustic frequency of the coin is resolved by the fast Fourier transform (FFT) method on the computer. It is found that the natural frequencies of the possible counterfeit coins deviate significantly from the standard ranges of 16.9 to 17.4 kHz for the authentic 50 New Taiwan Dollar (NTD) coins. The observed natural frequencies of the coin are consistent with the values predicted by analytical estimation. We also built a prototype EMAT coin classification system to detect the natural acoustic frequency by direct frequency counting using a microcontroller. The prototype system demonstrates that a counterfeit coin can be identified by its natural frequency in less than 30 ms using the EMAT method. The proposed technique can be applied to the vending machine to improve the accuracy in discriminating between authentic and counterfeit coins.

Two-Dimensional Position Tracking Using Gradient Magnetic Fields.

In this work, a two-dimensional (2D) position-detection device using a single axis magnetic sensor combined with orthogonal gradient coils was designed and fabricated. The sensors used were an induction coil and a GMR spin-valve sensor GF807 from Sensitec Inc. The field profiles generated by the two orthogonal gradient coils were analyzed numerically to achieve the maximum linear range, which corresponded to the detection area of the tracking system. The two coils were driven by 1-kHz sine wave currents with a 90° phase difference to generate the fields with uniform gradients along the x- and y-axis in the plane of the tracking stage. The gradient fields were detected by a single-axis sensor incorporated with a digital dual-phase lock-in detector to retrieve the position information. A linearity correction algorithm was used to improve the location accuracy and to extend the linear range for position sensing. The mean positioning error was found to be 0.417 mm, corresponding to the relative error of 0.21% in the working range of 200 mm × 200 mm, indicating that the proposed tracking system is promising for applications requiring accurate control of the two-dimensional position.

Detection of Surface and Subsurface Flaws with Miniature GMR-Based Gradiometer.

The eddy-current (EC) testing method is frequently utilized in the nondestructive inspection of conductive materials. To detect the minor and complex-shaped defects on the surface and in the underlying layers of a metallic sample, a miniature eddy-current probe with high sensitivity is preferred for enhancing the signal quality and spatial resolution of the obtained eddy-current images. In this work, we propose a novel design of a miniature eddy-current probe using a giant magnetoresistance (GMR) sensor fabricated on a silicon chip. The in-house-made GMR sensor comprises two cascaded spin-valve elements in parallel with an external variable resistor to form a Wheatstone bridge. The two elements on the chip are excited by the alternating magnetic field generated by a tiny coil aligned to the position that balances the background output of the bridge sensor. In this way, the two GMR elements behave effectively as an axial gradiometer with the bottom element sensitive to the surface and near-surface defects on a conductive specimen. The performance of the EC probe is verified by the numerical simulation and the corresponding experiments with machined defects on metallic samples. With this design, the geometric characteristics of the defects are clearly visualized with a spatial resolution of about 1 mm. The results demonstrate the feasibility and superiority of the proposed miniature GMR EC probe for characterizing the small and complex-shaped defects in multilayer conductive samples.

Redox Regulation of PTEN by Peroxiredoxins.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known as a tumor suppressor gene that is frequently mutated in numerous human cancers and inherited syndromes. PTEN functions as a negative regulator of PI3K/Akt signaling pathway by dephosphorylating phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3) to phosphatidylinositol (4, 5)-bisphosphate (PIP2), which leads to the inhibition of cell growth, proliferation, cell survival, and protein synthesis. PTEN contains a cysteine residue in the active site that can be oxidized by peroxides, forming an intramolecular disulfide bond between Cys124 and Cys71. Redox regulation of PTEN by reactive oxygen species (ROS) plays a crucial role in cellular signaling. Peroxiredoxins (Prxs) are a superfamily of peroxidase that catalyzes reduction of peroxides and maintains redox homeostasis. Mammalian Prxs have 6 isoforms (I-VI) and can scavenge cellular peroxides. It has been demonstrated that Prx I can preserve and promote the tumor-suppressive function of PTEN by preventing oxidation of PTEN under benign oxidative stress via direct interaction. Also, Prx II-deficient cells increased PTEN oxidation and insulin sensitivity. Furthermore, Prx III has been shown to protect PTEN from oxidation induced by 15s-HpETE and 12s-HpETE, these are potent inflammatory and pro-oxidant mediators. Understanding the tight connection between PTEN and Prxs is important for providing novel therapies. Herein, we summarized recent studies focusing on the relationship of Prxs and the redox regulation of PTEN.

Surgical treatment outcomes of angle splint use for trochanteric hip fractures

The study was conducted on 55 patients (39 males and 16 females) with 56 trochanteric hip fractures related to surgical treatment trauma. These patients were treated by internal bone fixation using angle splint in Orthopedic Department of Viet- Duc Hospital from 1/2000 - 12/2001. Good and very good outcomes were reached in 82% of patients, 14% of patients had moderate and 4% had poor outcomes. Mass angle splints were used for intertrochanteric fractures: Unstable intertrochanteric fractures, trochanteric fracture with femoral neck fracture line, intertrochanteric fractures with multiple fractures in 1/3 above and 1/3 below of ipsilateral femoral bone. Intertrochanteric fractures occurred in any patient with quick movement prior event. Inter- and inferior trochanteric fractures occurred with two points. DHS is applied with most efficiency. Internal bone fixation using angle splint for intertrochanteric fractures was the most effective method. There were no complication in terms of vascular obstruction related to fat and heart failure. Setting a broken bone wass carried out in surgical position and fixed by angle splints. Separated pieces in backside and inside can be rearranged under the surgery and fixed by soft screws. Rehabilitation and follow-up exammination was needed after surgery.