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.

Classification of facial vitiligo: A cluster analysis of 473 patients.

Vitiligo has a substantial negative impact on quality of life in affected patients, especially those with the involvement of the face. However, the current system can barely distinguish between specific patterns of facial involvement except for the segmental type when focusing only on facial lesions. We classified facial vitiligo into three distinct subtypes using cluster analysis based on facial topography (n = 473): centrofacial vitiligo (72.9%), panfacial vitiligo (18.0%), and hairline vitiligo (9.1%). Centrofacial vitiligo was the most common type and is thought to comprise the typical facial involvement of generalized vitiligo. Panfacial vitiligo was a distinct subtype with onset in old age and less involvement of other body parts. Hairline vitiligo was another distinct subtype with onset in old age and a poor response to conventional phototherapy. A relevant classification system could help us to explore the causes, anticipate the prognosis, and manage the condition in patients with vitiligo.

Increased risk of thyroid diseases in patients with systemic lupus erythematosus: A nationwide population-based Study in Korea.

We investigated the association between autoimmune thyroid disease and systemic lupus erythematosus (SLE) using nationwide insurance claims data for the entire Korean population. Claims data for the period 2009-2013 were retrieved from the National Health Insurance System database. SLE and thyroid disease were identified using the International Classification of Diseases codes and medication information. Logistic regression analyses were used to evaluate the association between SLE and thyroid disease. The study used records from 17,495 patients with SLE and 52,485 age- and sex-matched control subjects. A greater prevalence of Graves' disease (0.94% vs. 0.46%, P < 0.001), Hashimoto's thyroiditis (2.68% vs. 0.80%, P < 0.001), and thyroid cancer (1.81% vs. 1.30%, P < 0.001) was observed in SLE patients than in control subjects. Multivariate regression analyses demonstrated that SLE was significantly associated with an increased risk of both autoimmune thyroid disease and thyroid cancer (Graves' disease: odds ratio [OR] 2.07, 95% confidence interval [CI] 1.70-2.53; Hashimoto's thyroiditis: OR 3.42, 95% CI 3.00-3.91; thyroid cancer: OR 1.40, 95% CI 1.22-1.60). Age- and sex- stratified analyses revealed that the risk of autoimmune thyroid disease in SLE patients was increased for all age groups and the female group. An association between thyroid cancer and SLE was identified only in the 20- to 59-year-old age group and in the female group. Using a large population-based study, we demonstrated that patients with SLE are at a greater risk of developing thyroid disease than matched control individuals.

Assessment of the efficacy and safety of a new complex skin cream in Asian women: A controlled clinical trial.

BACKGROUND: Medical products such as hydroquinone and tretinoin have been widely used to treat various types of skin hyperpigmentation. However, these products are limited in daily use given their adverse effects. Other alternative agents with fewer adverse side effects have been developed. However, single agents often do not produce satisfactory results. AIMS: To evaluate the efficacy and safety of a new brightening complex cream containing niacinamide, tranexamic acid, oxyresveratrol, glutathione disulfide, and linoleic acid. PATIENTS AND METHODS: A total of 26 Korean women seeking to lighten their skin were enrolled. The product was applied on the face two times per day for 12 weeks. Standardized photographs were taken at baseline, 4 weeks, 8 weeks, and 12 weeks. Efficacy was assessed using melanin index (MI), erythema index (EI), and chromatic aberration values (L*, a*, and b*). Improvement perceived by investigators and patients was measured as well. RESULTS: The L*-value was increased at 8 weeks (0.7±2.5, P<.05) and at 12 weeks (0.8±2.5, P<.05). The MI was significantly decreased at 8 weeks (-4.2±4.5, P<.05) and at 12 weeks (-3.8±4.8, P<.001). The EI was significantly improved at 12 weeks (-3.2±2.2, P<.001). More than 80% of patients were considered improved at 12 weeks based on the view of the investigators and patients. CONCLUSIONS: The new brightening complex cream was proved to be effective and safe in Asian women.

A study on the in-vitro wear of the natural tooth structure by opposing zirconia or dental porcelain.

PURPOSE: This study was conducted to evaluate clinical validity of a zirconia full-coverage crown by comparing zirconia's wear capacity over antagonistic teeth with that of feldspathic dental porcelain. MATERIALS AND METHODS: THE SUBJECT GROUPS WERE DIVIDED INTO THREE GROUPS: the polished feldspathic dental porcelain group (Group 1), the polished zirconia group (Group 2), and the polished zirconia with glazing group (Group 3). Twenty specimens were prepared from each group. Each procedure such as plasticity, condensation, and glazing was conducted according to the manufacturer's manual. A wear test was conducted with 240,000 chewing cycles using a dual-axis chewing simulator. The degree of wear of the antagonistic teeth was calculated by measuring the volume loss using a three-dimensional profiling system and ANSUR 3D software. The statistical significance of the measured degree of wear was tested with a significant level of 5% using one-way ANOVA and the Tukey test. RESULTS: The degrees of wear of the antagonistic teeth were 0.119 ± 0.059 mm(3) in Group 1, 0.078 ± 0.063 mm(3) in Group 3, and 0.031 ± 0.033 mm(3) in Group 2. Statistical significance was found between Group 1 and Groups 2 and between Group 2 and 3, whereas no statistical significance was found between Group 1 and Group 3. CONCLUSION: Despite the limitations of this study on the evaluation of antagonistic teeth wear, the degree of antagonistic tooth wear was less in zirconia than feldspathic dental porcelain, representing that the zirconia may be more beneficial in terms of antagonistic tooth wear.