Learning outcomes of a mobile application for dental infection control education.

PURPOSE/OBJECTIVES: This study aimed to apply and verify the effectiveness of a mobile-based dental infection control education application to enable students majoring in dental hygiene to learning dental infection control education without time and space constraints. METHODS: This study used a nonequivalent control group pretest-posttest design to examine differences in learning outcomes between an experimental group that learned through the mobile application and a control group that learned with handouts. The Infection Prevention and Control Mobile Application (IPC App) and handouts were developed by referring to the Center for Disease Control's (CDC) guidelines for Infection Prevention and Control in Dental Settings. Both the experimental and control groups were guided to perform self-regulated learning, where they independently led and managed their learning for two weeks. The study was conducted at the D university college with 42 students from the second grade in the Department of Dental Hygiene from August to October 2021. Differences in knowledge, self-efficacy, and summative evaluation were analyzed using an independent sample t-test and repeated measures analysis of variance (p < 0.05). RESULTS: The findings confirmed that the experimental group who learned through the IPC mobile application had improved their knowledge and indicated a higher summative evaluation than the control group that learned via learning documents (p < 0.05). CONCLUSIONS: Owing to the high accessibility and repeatability of the learning content, the mobile application recommended in this study may serve as an effective self-directed learning tool for students to gain knowledge on the standard precautions for dental infection control.

Sestrin2 Regulates Osteoclastogenesis via the p62-TRAF6 Interaction.

The receptor activator of nuclear factor-kappa B ligand (RANKL) mediates osteoclast differentiation and functions by inducing Ca2+ oscillations, activating mitogen-activated protein kinases (MAPKs), and activating nuclear factor of activated T-cells type c1 (NFATc1) via the RANK and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) interaction. Reactive oxygen species (ROS) also plays an important role during osteoclastogenesis and Sestrin2, an antioxidant, maintains cellular homeostasis upon stress injury via regulation of ROS, autophagy, and inflammation. However, the role of Sestrin2 in osteoclastogenesis remains unknown. In this study, we investigated the role of Sestrin2 in the RANKL-RANK-TRAF6 signaling pathway during osteoclast differentiation. Deletion of Sestrin2 (Sesn2) increased bone mass and reduced the number of multinucleated osteoclasts on bone surfaces. RANKL-induced osteoclast differentiation and function decreased in Sesn2 knockout (KO) bone marrow-derived monocytes/macrophages (BMMs) due to inhibition of NFATc1 expression, but osteoblastogenesis was not affected. mRNA expression of RANKL-induced specific osteoclastogenic genes and MAPK protein expression were lower in Sesn2 KO BMMs than wild-type (WT) BMMs after RANKL treatment. However, the Sesn2 deletion did not affect ROS generation or intracellular Ca2+ oscillations during osteoclastogenesis. In contrast, the interaction between TRAF6 and p62 was reduced during osteoclasts differentiation in Sesn2 KO BMMs. The reduction in the TRAF6/p62 interaction and TRAP activity in osteoclastogenesis in Sesn2 KO BMMs was recovered to the WT level upon expression of Flag-Sesn2 in Sesn2 KO BMMs. These results suggest that Sestrin2 has a novel role in bone homeostasis and osteoclasts differentiation through regulation of NFATc1 and the TRAF6/p62 interaction.

The Role of Ca2+-NFATc1 Signaling and Its Modulation on Osteoclastogenesis.

The increasing of intracellular calcium concentration is a fundamental process for mediating osteoclastogenesis, which is involved in osteoclastic bone resorption. Cytosolic calcium binds to calmodulin and subsequently activates calcineurin, leading to NFATc1 activation, a master transcription factor required for osteoclast differentiation. Targeting the various activation processes in osteoclastogenesis provides various therapeutic strategies for bone loss. Diverse compounds that modulate calcium signaling have been applied to regulate osteoclast differentiation and, subsequently, attenuate bone loss. Thus, in this review, we summarized the modulation of the NFATc1 pathway through various compounds that regulate calcium signaling and the calcium influx machinery. Furthermore, we addressed the involvement of transient receptor potential channels in osteoclastogenesis.

Hypothalamic inflammation and obesity: a mechanistic review.

Obesity is one of the worldwide prevalent disease caused by the imbalance between food intake and energy expenditure. Over a 100 years of research demonstrate that hypothalamus is the critical brain region regulating energy homeostasis, and evidences suggest the participation of non-neuronal populations such as astrocytes and microglia in the regulation of energy homeostasis. Recently, fat-rich diet induced hypothalamic inflammation has been found to deregulate the energy homeostasis, leading to the insulin resistance, glucose intolerance, and obesity. Several underlying mechanisms have been proposed, yet compelling evidences require further elucidations. This review discusses the up to date proposed mechanisms by which fat-rich diet induces hypothalamic inflammation and obesity.

FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase.

PURPOSE: While leptin has been associated with various psycho-physiological functions, the molecular network in leptin-mediated mood regulation remains elusive. METHODS: Anxiolytic behaviors and tyrosine hydroxylase (TH) levels were examined after leptin administration. Functional roles of STAT3 and FoxO1 in regulation of TH expression were investigated using in vivo and in vitro systems. A series of animal behavioral tests using dopaminergic neuron-specific FoxO1 KO (FoxO1 KODAT) were performed and investigated the roles of FoxO1 in regulation of mood behaviors. RESULTS: Here, we show that administration of leptin induces anxiolytic-like phenotype through the activation of signal transducer and activator of transcription 3 (STAT3) and the inhibition of forkhead box protein O1 (FoxO1) in dopaminergic (DA) neurons of the midbrain. Specifically, STAT3 and FoxO1 directly bind to and exert opposing effects on tyrosine hydroxylase (TH) expression, where STAT3 acts as an enhancer and FoxO1 acts as a prominent repressor. Accordingly, suppression of the prominent suppressor FoxO1 by leptin strongly increased TH expression. Furthermore, our previous results showed that specific deletion of FoxO1 in DA neurons (FoxO1 KODAT) led to a profound elevation of TH activity and dopamine contents. Finally, FoxO1 KODAT mice exhibited enhanced leptin sensitivity as well as displayed reduced anxiety- and depression-like behaviors. CONCLUSIONS: This work establishes a novel molecular mechanism of mood behavior regulation by leptin and suggests FoxO1 suppression by leptin might be a key for leptin-induced behavioral manifestation in DA neurons.

Carbonic anhydrase 12 mutation modulates membrane stability and volume regulation of aquaporin 5.

Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glands carrying the E143K. The intracellular pH of E143K cells was more acidic than that of the cells carrying wild type. To evaluate the role of carbonic anhydrase12 on the volume regulation of aquaporin 5, the submandibular gland cells were subjected to hypotonic stimuli. E143K enhanced the extent of swelling of cells on hypotonicity. Aquaporin 5 modulates water influx through ion transporters to prevent osmotic imbalance. These results suggest that the carbonic anhydrase12 E143K, including acidification or inflammation, mediates volume dysregulation by the loss of aquaporin 5. Thus, carbonic anhydrase12 may determine sensible effects on the cellular osmotic regulation by modulating aquaporin 5.

TRPM3/TRPV4 regulates Ca2+-mediated RANKL/NFATc1 expression in osteoblasts

Mechanical stress plays an important role in the regulation of bone turnover. However, the mechanism underlying hypo-osmotic stress-induced cellular response in osteoblasts remains poorly understood. In this study, we investigated the effect of hypotonic stress on the expression of bone remodeling factors, including the receptor activator of nuclear factor-kappa B ligand (RANKL) and the nuclear factor of activated T cells type c1 (NFATc1) in primary mouse osteoblasts and MC3T3-E1 cells. Hypo-osmotic stress induced significant increases in RANKL mRNA expression and intracellular Ca2+ concentration ([Ca2+]i) from the extracellular space. Hypo-osmotic stress-induced effects on [Ca2+]i and RANKL and NFATc1 protein expression were decreased by antagonists of transient receptor potential melastatin 3 (TRPM3) and vanilloid 4 (TRPV4). Agonists of TRPM3 and TRPV4 activated [Ca2+]i and RANKL and NFATc1 protein expression. Furthermore, genetic suppression of Trpm3 and Trpv4 reduced hypo-osmotic stress-induced effects in mouse osteoblasts. These results suggest that hypo-osmotic stress induces increases in [Ca2+]i through TRPM3 and TRPV4 to regulate RANKL and NFATc1 expression in mouse osteoblastic cells and that mechanical stress-activated TRP channels may play a critical role in bone remodeling.

Correction: Cytochrome P450 1B1 inhibition suppresses tumorigenicity of prostate cancer via caspase-1 activation.

[This corrects the article DOI: 10.18632/oncotarget.16598.].

A Novel Peptide, Nicotinyl⁻Isoleucine⁻Valine⁻Histidine (NA⁻IVH), Promotes Antioxidant Gene Expression and Wound Healing in HaCaT Cells.

Nicotinamide (NA), a water-soluble vitamin B3, has been shown to exert cellular-protective effects against reactive oxygen species (ROS). In order to improve the cellular-protective effects of NA, we synthesized a novel compound, nicotinyl⁻isoleucine⁻valine⁻histidine (NA⁻IVH), by combining NA with jellyfish peptides' IVH. In the present study, we examined the cellular-protective effects of the novel synthetic nicotinyl-peptide, NA⁻IVH. We found that NA⁻IVH enhances the radical scavenging activity with a robust increase of the nuclear factor (erythroid-derived 2)-like factor (Nrf2) expression in human HaCaT keratinocytes. In addition, NA⁻IVH protected the cells from hydrogen peroxide (H2O2)-induced cell death. Interestingly, NA⁻IVH exhibited an improved wound-healing effect in a high glucose condition, possibly through the regulation of reactive oxygen species (ROS). Collectively, our results imply that a novel nicotinyl-peptide, NA⁻IVH, has a wound-healing effect in a hyperglycemic condition, possibly by modulating excessive ROS.

Increased store-operated Ca2+ entry mediated by GNB5 and STIM1.

Recent human genetic studies have shown that Gß5 is related to various clinical symptoms, such as sinus bradycardia, cognitive disability, and attention deficit hyperactivity disorder. Although the calcium signaling cascade is closely associated with a heterotrimeric G-protein, the function of Gß5 in calcium signaling and its relevance to clinical symptoms remain unknown. In this study, we investigated the in vitro changes of store-operated calcium entry (SOCE) with exogenous expression of Gß5. The cells expressing Gß5 had enhanced SOCE after depletion of calcium ion inside the endoplasmic reticulum. Gß5 also augmented Stim1- and Orai1-dependent SOCE. An ORAI1 loss-of-function mutant did not show inhibition of Gß5-induced SOCE, and a STIM1-ERM truncation mutant showed no enhancement of SOCE. These results suggested a novel role of GNB5 and Stim1, and provided insight into the regulatory mechanism of SOCE.

Dust particles-induced intracellular Ca2+ signaling and reactive oxygen species in lung fibroblast cell line MRC5.

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established Ca2+ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular Ca2+ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular Ca2+ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than 10 µm, induced intracellular Ca2+ signaling, which was mediated by extracellular Ca2+. The PM10-mediated intracellular Ca2+ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

Cytochrome P450 1B1 inhibition suppresses tumorigenicity of prostate cancer via caspase-1 activation.

Cytochrome P450 1B1 (CYP1B1) is recognized as a universal tumor biomarker and a feasible therapeutic target due to its specific overexpression in cancer tissues. Despite its up-regulation in prostate cancer (PCa), biological significance and clinicopathological features of CYP1B1 are still elusive. Here, we show that overexpression or hyperactivation of CYP1B1 stimulated proliferative, migratory and invasive potential of non-tumorigenic PCa cells. Attenuation of CYP1B1 with its specific small hairpin (sh) RNAs greatly reduced proliferation through apoptotic cell death and impaired migration and invasion in PCa cells. Intratumoral injection of CYP1B1 shRNA attenuated growth of pre-existing tumors. The antitumor effect of CYP1B1 shRNA was also observed in prostate tumor xenograft mouse models. Among the genes altered by CYP1B1 knockdown, reduction of caspase-1 (CASP1) activity attenuated the antitumor effect of CYP1B1 inhibition. Indeed, CYP1B1 regulates CASP1 expression or activity. Finally, CYP1B1 expression was increased in higher grades of PCa and overall survival was significantly reduced in patients with high levels of CYP1B1 protein. CYP1B1 expression was reversely associated with CASP1 expression in clinical tissue samples. Together, our results demonstrate that CYP1B1 regulates PCa tumorigenesis by inhibiting CASP1 activation. Thus, the CYP1B1-CASP1 axis may be useful as a potential biomarker and a therapeutic target for PCa.