Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

BACKGRUOUND: Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. METHODS: This study included two types of research. RESULTS: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. RESULTS: Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. CONCLUSION: This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

Proposition of Adaptive Read Bias: A Solution to Overcome Power and Scaling Limitations in Ferroelectric-Based Neuromorphic System.

Hardware neuromorphic systems are crucial for the energy-efficient processing of massive amounts of data. Among various candidates, hafnium oxide ferroelectric tunnel junctions (FTJs) are highly promising for artificial synaptic devices. However, FTJs exhibit non-ideal characteristics that introduce variations in synaptic weights, presenting a considerable challenge in achieving high-performance neuromorphic systems. The primary objective of this study is to analyze the origin and impact of these variations in neuromorphic systems. The analysis reveals that the major bottleneck in achieving a high-performance neuromorphic system is the dynamic variation, primarily caused by the intrinsic 1/f noise of the device. As the device area is reduced and the read bias (VRead ) is lowered, the intrinsic noise of the FTJs increases, presenting an inherent limitation for implementing area- and power-efficient neuromorphic systems. To overcome this limitation, an adaptive read-biasing (ARB) scheme is proposed that applies a different VRead to each layer of the neuromorphic system. By exploiting the different noise sensitivities of each layer, the ARB method demonstrates significant power savings of 61.3% and a scaling effect of 91.9% compared with conventional biasing methods. These findings contribute significantly to the development of more accurate, efficient, and scalable neuromorphic systems.

Effect of Attenuated Light Through Translucent Zirconia on the Interfacial Adaptation and Polymerization of Resin Cements.

PURPOSE: The first objective was to determine if dual-curing of resin cement with reduced light could affect interfacial adaptations of zirconia restoration. The second objective was to examine whether cement type and pretreatment method of universal adhesive affected interfacial adaptation. The final objective was to compare the polymerization degree of cement under different reduced-light conditions. MATERIALS AND METHODS: Inlay cavities were prepared on extracted third molars. Translucent zirconia restorations were milled using Katana UTML (Kuraray Noritake) in three groups with restoration thicknesses of 1, 2, and 3 mm, respectively. Each group had three subgroups using different cementation methods. For subgroup 1, restorations were cemented with self-adhesive cement. For subgroup 2, universal adhesive was applied and light cured. After the restoration was seated with conventional resin cement, light curing was performed. For subgroup 3, after adhesive was applied, the restoration was seated with conventional resin cement. Light curing was performed for the adhesive and cement simultaneously. After thermocycling, interfacial adaptation at the restoration-tooth interface was investigated using swept-source optical coherence tomography imaging. Finally, polymerization shrinkage of the cement was measured using a linometer and compared under the conditions of different zirconia thicknesses and light-curing durations. RESULTS: Interfacial adaptation varied signficantly depending on the zirconia thickness, pretreatment, polymerization mode and cements used (p < 0.05). The effects of the adhesive and polymerization shrinkage differed signficantly, depending on the reduced light under the zirconia (p < 0.05). CONCLUSION: Lower curing-light irradiance may lead to inferior adaptation and lower polymerization of the cement. Polymerization of resin cement can differ depending on the light irradiance and exposure duration.

Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.

Reconfigurable neuromorphic computing block through integration of flash synapse arrays and super-steep neurons.

Neuromorphic computing (NC) architecture inspired by biological nervous systems has been actively studied to overcome the limitations of conventional von Neumann architectures. In this work, we propose a reconfigurable NC block using a flash-type synapse array, emerging positive feedback (PF) neuron devices, and CMOS peripheral circuits, and integrate them on the same substrate to experimentally demonstrate the operations of the proposed NC block. Conductance modulation in the flash memory enables the NC block to be easily calibrated for output signals. In addition, the proposed NC block uses a reduced number of devices for analog-to-digital conversions due to the super-steep switching characteristics of the PF neuron device, substantially reducing the area overhead of NC block. Our NC block shows high energy efficiency (37.9 TOPS/W) with high accuracy for CIFAR-10 image classification (91.80%), outperforming prior works. This work shows the high engineering potential of integrating synapses and neurons in terms of system efficiency and high performance.

Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases. To explore the role of TonEBP, we examined kidney biopsy samples from patients with LN. Kidney TonEBP expression was found to be elevated in these patients compared to control patients - in both kidney cells and infiltrating immune cells. Kidney TonEBP mRNA was elevated in LN and correlated with mRNAs encoding inflammatory cytokines and the degree of proteinuria. In a pristane-induced SLE model in mice, myeloid TonEBP deficiency blocked the development of SLE and LN. In macrophages, engagement of various toll-like receptors (TLRs) that respond to damage-associated molecular patterns induced TonEBP expression via stimulation of its promoter. Intracellular signaling downstream of the TLRs was dependent on TonEBP. Therefore, TonEBP can act as a transcriptional cofactor for NF-κB, and activated mTOR-IRF3/7 via protein-protein interactions. Additionally, TonEBP-deficient macrophages displayed elevated efferocytosis and animals with myeloid deficiency of TonEBP showed reduced Th1 and Th17 differentiation, consistent with macrophages defective in TLR signaling. Thus, our data show that myeloid TonEBP may be an attractive therapeutic target for SLE and LN.

The effects of gingival blood flow on pulpal blood flow detection using ultrasound Doppler flowmetry: animal study.

Objectives: This study evaluated the effect of adjacent gingival blood flow on detection of pulpal blood flow (PBF) using ultrasound Doppler flowmetry (UDF) through animal study. Materials and Methods: The study included 36 right and left maxillary the third incisors and canines in 9 experimental dogs. The study included 2 main steps: In the first step, the pulse sound level (PSL) was recorded on the cervical part of each tooth without flap elevation (Group 1), with flap elevation (Group 2), and after it was repositioned in place (Group 3). In the second step, the PSL was recorded on the cervical part of each tooth (Group 4), after pulpotomy (Group 5), after partial pulp extirpation (Group 6), after complete extirpation (Group 7), and after canal filling (Group 8). In Groups 5-8, the study was performed with and without flap elevation in the left and right teeth, respectively. The PSL was graded as follows: 0, inaudible; 1, heard faintly; and 2, heard well. The difference between each group was analyzed using Friedman's test with Wilcoxon signed-rank tests (α = 0.05). Results: In step 1, the PSL results were Group 1 > 2 and 3. In step 2, there was no significant difference between the groups when the flap was not elevated, while PSL results were Group 4 > 5 ≥ 6 and 7 ≥ 8 when the flap was elevated. Conclusions: PBF is affected by gingival blood flow when measured with UDF. UDF measurements require isolation of gingiva from the tooth.

Lactate oxidase/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth.

The aggressive proliferation of tumor cells often requires increased glucose uptake and excessive anaerobic glycolysis, leading to the massive production and secretion of lactate to form a unique tumor microenvironment (TME). Therefore, regulating appropriate lactate levels in the TME would be a promising approach to control tumor cell proliferation and immune suppression. To effectively consume lactate in the TME, lactate oxidase (LOX) and catalase (CAT) were displayed onto Aquifex aeolicus lumazine synthase protein nanoparticles (AaLS) to form either AaLS/LOX or AaLS/LOX/CAT. These complexes successfully consumed lactate produced by CT26 murine colon carcinoma cells under both normoxic and hypoxic conditions. Specifically, AaLS/LOX generated a large amount of H2O2 with complete lactate consumption to induce drastic necrotic cell death regardless of culture condition. However, AaLS/LOX/CAT generated residual H2O2, leading to necrotic cell death only under hypoxic condition similar to the TME. While the local administration of AaLS/LOX to the tumor site resulted in mice death, that of AaLS/LOX/CAT significantly suppressed tumor growth without any severe side effects. AaLS/LOX/CAT effectively consumed lactate to produce adequate amounts of H2O2 which sufficiently suppress tumor growth and adequately modulate the TME, transforming environments that are favorable to tumor suppressive neutrophils but adverse to tumor-supportive tumor-associated macrophages. Collectively, these findings showed that the modular functionalization of protein nanoparticles with multiple metabolic enzymes may offer the opportunity to develop new enzyme complex-based therapeutic tools that can modulate the TME by controlling cancer metabolism.

In-Memory-Computed Low-Frequency Noise Spectroscopy for Selective Gas Detection Using a Reducible Metal Oxide.

Concerns about indoor and outdoor air quality, industrial gas leaks, and medical diagnostics are driving the demand for high-performance gas sensors. Owing to their structural variety and large surface area, reducible metal oxides hold great promise for constructing a gas-sensing system. While many earlier reports have successfully obtained a sufficient response to various types of target gases, the selective detection of target gases remains challenging. In this work, a novel method, low-frequency noise (LFN) spectroscopy is presented, to achieve selective detection using a single FET-type gas sensor. The LFN of the sensor is accurately modeled by considering the charge fluctuation in both the sensing material and the FET channel. Exposure to different target gases produces distinct corner frequencies of the power spectral density that can be used to achieve selective detection. In addition, a 3D vertical-NAND flash array is used with the fast Fourier transform method via in-memory-computing, significantly improving the area and power efficiency rate. The proposed system provides a novel and efficient method capable of selectively detecting a target gas using in-memory-computed LFN spectroscopy and thus paving the way for the further development in gas sensing systems.

Efficacy and Safety of MED-01 Probiotics on Vaginal Health: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Bacterial vaginosis (BV) is the most common disease in women of childbearing age and is caused by the growth of abnormal microbiota in the vagina. Probiotic consumption can be an effective alternative treatment to preserve or improve vaginal health. In the present study, MED-01, a complex of five strains of probiotic candidates isolated from the vagina of Korean women, was used. This study was designed as a 12-week, randomized, multicenter, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of MED-01 on vaginal health. A total of 101 reproductive-aged women with a Nugent score of 4-6 took MED-01 (5.0 × 109 CFU) or a placebo once a day, and 76 participants completed the procedure. MED-01 significantly reduced the Nugent score compared with the placebo. Quantitative PCR analysis confirmed that Lactobacillus plantarum was significantly increased in the vagina, whereas harmful bacteria such as Mobiluncus spp., Gardnerella vaginalis, and Atopobium vaginae were suppressed after 12 weeks of MED-01 ingestion. No adverse events to the test food supplements were observed in the participants. These results confirmed that MED-01 can be used as a probiotic for treating BV, as it improves the vaginal microbiota.

RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts.

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions.

Effect of thickness on the translucency of resin-based composites and glass-ceramics.

This study was aimed to evaluate the effect of thickness (1, 2, 3, and 4 mm) on the translucency of resin-based composites (RBCs) and glass-ceramics, and compare the influence of the thickness of those materials on the translucency parameter (TP) value. The materials were divided into two groups, eight RBCs in Group 1 and five glass-ceramics in Group 2 and TP, ΔL*, Δa*, and Δb* were compared. Statistically significant differences were present in the 2, 3, and 4 mm in the TP, in the 2 and 4 mm in ΔL*, and in all thicknesses in Δa* and Δb* betweent the two groups. The TP of RBCs and glass-ceramics decreased as thickness increased, especially from 1 mm to 2 mm. The TP values of the RBCs were more significantly decreased as the thickness of the material increased from 2 mm to 4 mm than those of the glass-ceramics.

Variations in the morphology of apical constriction affecting electronic readings: An in vitro investigation using 3D-printed tooth models.

We investigated the interference of apical constriction position and diameter on the accuracy of electronic apex locators using 3D-printed tooth models. Single-rooted tooth models with the same length, canal taper and major foramen, but variation in apical constriction position or size, were designed and 3D-printed. A mounting model was custom-made for precise measurement of both marks (0.5 and APEX/0.0) of two electronic apex locators. The electronic measurements of both devices were correlated significantly to the major foramen rather than apical constriction. The mean measurements of the group with 0.45 mm in apical constriction width were significantly shorter than those of the other groups for both marks of the two devices (p < 0.05). The variations in apical constriction position and width negatively affected the precision of the 0.5 mark of the tested devices. The 0.0 or APEX mark was consistently located the major foramen.

Comparison of Surgical Outcomes of Robotic versus Conventional Laparoscopic Hysterectomy of Large Uterus with Gynecologic Benign Disease.

Hysterectomy is commonly performed for benign gynecological diseases. Minimally invasive surgical approaches offer several advantages. Unfortunately, few studies have compared the outcomes of different types of minimally invasive surgeries. Therefore, this study aimed to compare the surgical outcomes of robotic hysterectomy (RH) and conventional laparoscopic hysterectomy (CLH) in benign gynecologic diseases. We performed a retrospective cohort study at a single center between January 2014 and July 2022. A total of 397 patients (RH: 197 and CLH: 200) who underwent minimally invasive hysterectomy for benign diseases with uterine size exceeding 250 g were enrolled, and factors related to the surgical outcomes were compared. The median age was 46 (range, 35-74) years, and the median uterine weight was 400 (range, 250-2720) g. There were no significant differences between the two groups regarding age, body mass index, uterine weight, hospital stay, estimated blood loss, or operating time. Intraoperative and postoperative complication rates were not significantly different between the two groups. RH was not inferior to CLH in terms of perioperative and immediate postoperative outcomes in our study.

Evaluation of the Quality and Influence of YouTube as a Source of Information on Robotic Myomectomy.

BACKGROUND: We aimed to evaluate the usefulness of YouTube videos for helping patients become informed about robotic myomectomy. METHODS: We searched YouTube using "robotic myomectomy" and "Da Vinci myomectomy." Videos were sorted by view count, with the 150 most highly viewed videos being selected. From each video, content type, source, view count, video length, time on YouTube, likes, and dislikes were extracted. A scoring system was used to evaluate video quality. RESULTS: The most prevalent content was recordings of actual surgical procedures of robotic myomectomy, and the most common provider was gynecologic surgeons. Videos directly related to robotic myomectomy were mainly provided by medical groups, had been present on YouTube for a significantly longer time (p = 0.003), and had a higher rate of no responses from viewers (p = 0.014) than videos indirectly related to robotic myomectomy. Videos uploaded by nonmedical groups had more likes, more dislikes, and a higher view ratio (p = 0.029, 0.042, and 0.042, respectively). Scores reflecting video quality did not differ between the two groups. Multiple logistic regression revealed that low-quality videos (less than score 5) were significantly correlated with content indirectly related to robotic myomectomy, poor general quality, fewer views, fewer likes, and no response by viewers. CONCLUSIONS: Patients who want to get informed about robotic myomectomy on YouTube should exclude low-quality videos according to such parameters as content, views, and response by viewers. In addition, medical groups should provide videos of good quality for instructing patients about this procedure.

2'-5' oligoadenylate synthetase­like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability.

Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2'-5' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-κB activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease.

Red blood cell indices as an effective marker for the existence and severity of endometriosis (STROBE).

To evaluate the association between red blood cell (RBC) indices (mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], MCH concentration [MCHC], red cell distribution width [RDW], hemoglobin [Hb], hematocrit [Hct], and neutrophil-to-lymphocyte ratio [NLR]) and the severity of endometriosis. Data were obtained from the medical records of 200 patients with endometriosis (stage I/II and stage III/IV groups), and 100 patients with benign ovarian tumors (control group), treated between September 2011 and April 2021. The mean Hb and Hct were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .015 and P = .004, respectively). The mean MCV, MCH, and Hb at postoperative day (POD)#1 were significantly lower in the stage III/IV group compared to those in the control and stage I/II group (P = .007, P = .032, and P < .0001, respectively). In addition, NLR at POD#1 was significantly higher in stage III/IV group compared to that in the control and stage I/II group. Multivariate analysis revealed that younger age (≤38 years old), lower preoperative MCV (≤88.5 fL), lower POD#1 Hb (<11.6g/dL), and higher POD#1 NLR (>2.5) were independent risk factors of stage III/IV endometriosis. Lower levels of RBC indices, including preoperative MCV and postoperative Hb, and higher postoperative NLR were significantly associated with the severity of endometriosis, which is potentially derived from a dysregulation in iron metabolism and inflammation.

YouTube as a source of information and education on endometriosis.

Many patients seek information online, including on social media, regarding various health topics. This study aimed to investigate whether YouTube videos on endometriosis could be a useful source for the general population, surgical trainees, and specialists. A YouTube search was conducted on December 26, 2021, using the search terms "endometriosis," "endometrioma," and "endometriotic cyst." Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. After excluding 48 videos for various reasons, 52 were included in the final analysis. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. We referred to a previous study to evaluate video quality. The 52 videos related to endometriosis had a total of 35,220,141 views (median 233,688, range 48,874-10,452,366). Based on authorship, the videos were categorized into videos uploaded by the medical group and the nonmedical group. The medical group mainly uploaded videos directly related to endometriosis, such as explanations or detailed surgical procedures for endometriosis (26/27, 96%), whereas the nonmedical group mainly uploaded videos about personal experiences and others (24/25, 96%; P <.001). Evaluating the score by each type of content, videos containing personal experiences (median score 6, range 3-10) scored significantly lower than videos containing other content such as explanations of the disease (median score 14, range 7-18; P < .001) and surgical procedures (median score 9, range 5-17; P < .001). Analysis according to the source, the number of views and video power index was significantly higher in the videos uploaded by the nonmedical group (P < .05). YouTube is currently not an appropriate source for patients to gain information on endometriosis. Credible videos with accurate information and clear, high-quality operative clips with proper scientific commentary should be uploaded by medical professionals and medical institutions to critically and rapidly appraise the quality of online video-disseminated information on endometriosis. In addition, advanced filtering using categories by YouTube's staff appears to be necessary.

Particulate matter 2.5 promotes inflammation and cellular dysfunction via reactive oxygen species/p38 MAPK pathway in primary rat corneal epithelial cells.

PURPOSE: Numerous studies have linked particulate matter2.5 (PM2.5) to ocular surface diseases, but few studies have been conducted on the biological effect of PM2.5 on the cornea. The objective of this study was to evaluate the harmful effect of PM2.5 on primary rat corneal epithelial cells (RCECs) in vitro and identify the toxic mechanism involved. MATERIALS AND METHODS: Primary cultured RCECs were characterized by pan-cytokeratin (CK) staining. In PM2.5-exposed RCECs, cell viability, microarray gene expression, inflammatory cytokine levels, mitochondrial damage, DNA double-strand break, and signalling pathway were investigated. RESULTS: Exposure to PM2.5 induced cytotoxicity and morphological changes in RCECs. In addition, PM2.5 markedly up-regulated pro-inflammatory mediators but down-regulated the wound healing-related transforming growth factor-ß. Furthermore, PM2.5 promoted mitochondrial reactive oxygen species (ROS) production and mediated cellular damage to mitochondria and DNA, whereas these cellular alterations induced by PM2.5 were markedly suppressed by a potential ROS scavenger. Noteworthy, removal of ROS selectively down-regulated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation of the nuclear factor-κB (NF-κB) p65 in PM2.5-stimulated cells. Additionally, SB203580, a p38 MAPK inhibitor, markedly suppressed these PM2.5-mediated cellular dysfunctions. CONCLUSIONS: Taken together, our findings show that PM2.5 can promote the ROS/p38 MAPK/NF-κB signalling pathway and lead to mitochondrial damage and DNA double-strand break, which is ultimately caused inflammation and cytotoxicity in RCECs. These findings indicate that the ROS/p38 MAPK/NF-κB signalling pathway is one mechanism involved in PM2.5-induced ocular surface disorders.

Inhibition of L-type voltage-gated calcium channel-mediated Ca2+ influx suppresses the collective migration and invasion of ameloblastoma.

OBJECTIVES: Ameloblastoma (AM) has been known as a benign but locally invasive tumour with high recurrence rates. Invasive behaviour of the AM results in destruction of the adjacent jawbone and the non-detectable remnants during surgery, interrupting the complete elimination of cancer cells. METHODS: To explore novel targets for the tumour cell invasion, a transcriptomic analysis between AM and odontogenic keratocyst were performed through next-generation sequencing in detail. RESULTS: Enrichment of CACNA1C gene (encoding Cav1.2) in AM, a subunit of the L-type voltage-gated calcium channel (VGCC) was observed for the first time. The expression and channel activity of Cav1.2 was confirmed by immunostaining and calcium imaging in the patient samples or primary cells. Verapamil, L-type VGCC blocker revealed suppression of the Ca2+ -induced cell aggregation and collective invasion of AM cells in vitro. Furthermore, the effect of verapamil in suppressing AM invasion into the adjacent bone was confirmed through orthotopic xenograft model specifically. CONCLUSION: Taken together, Cav1.2 maybe considered to be a therapeutic candidate to decrease the collective migration and invasion of AM.