Investigating the influence of XAV-939, a tankyrase inhibitor, on the density and gating of erg-mediated K+ currents in mouse MA-10 Leydig tumor cells.

XAV-939(XAV) is a chemical compound that inhibits the activity of tankyrase. However, the precise way in which XAV alters membrane ionic currents is not well understood. In this study,our goal was to examine the impact of XAV on the ionic currents in mouse MA-10 Leydig cells, specifically focusing on the magnitude, gating properties,and voltage-dependent hysteresis of erg-mediated K+currents(IK(erg)). In our whole-cell current recordings we observed that the addition of XAV inhibited the density of IK(erg) in a concentration-dependent manner with an IC50 of 3.1 µM. Furthermore we found that continued exposure to XAV, further addition of neither liraglutide nor insulin-like growth factor-1 counteracted XAV-mediated inhibition of IK(erg). Additionally the presence of XAV suppressed the mean current versus voltage relationship of IK(erg) across the entire voltage-clamp step analyzed. This compound shifted the steady-state activation curve of IK(erg) to a less negative potential by approximately 12 mV. The presence of XAV increased the time constant of deactivating IK(erg) in MA-10 cells. The voltage-dependent clockwise hysteresis of IK(erg) responding to prolonged upright isosceles-triangular ramp voltage became diminished by adding XAV; moreover subsequent addition of NS3623 effectively reversed XAV-induced decrease of hysteretic area of IK(erg). XAV also inhibited the proliferation of this cell line and the IC50 value of XAV-induced inhibition of cell proliferation was 2.8M. Overall the suppression of IK(erg) by XAV may serve as a significant ionic mechanism that contribute to the functional properties of MA-10 cells. However, it is important to note that this effect cannot be attributed solely to the inhibition of tankyrase.

Exploring the Impact of BKCa Channel Function in Cellular Membranes on Cardiac Electrical Activity.

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels' conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo.

Cannabidiol Modulates M-Type K+ and Hyperpolarization-Activated Cation Currents.

Cannabidiol (CBD) is a naturally occurring compound found in the Cannabis plant that is known for its potential therapeutic effects. However, its impact on membrane ionic currents remains a topic of debate. This study aimed to investigate how CBD modifies various types of ionic currents in pituitary GH3 cells. Results showed that exposure to CBD led to a concentration-dependent decrease in M-type K+ currents (IK(M)), with an IC50 of 3.6 µM, and caused the quasi-steady-state activation curve of the current to shift to a more depolarized potential with no changes in the curve's steepness. The CBD-mediated block of IK(M) was not reversed by naloxone, suggesting that it was not mediated by opioid receptors. The IK(M) elicited by pulse-train stimulation was also decreased upon exposure to CBD. The magnitude of erg-mediated K+ currents was slightly reduced by adding CBD (10 µM), while the density of voltage-gated Na+ currents elicited by a short depolarizing pulse was not affected by it. Additionally, CBD decreased the magnitude of hyperpolarization-activated cation currents (Ih) with an IC50 of 3.3 µM, and the decrease was reversed by oxaliplatin. The quasi-steady-state activation curve of Ih was shifted in the leftward direction with no changes in the slope factor of the curve. CBD also diminished the strength of voltage-dependent hysteresis on Ih elicited by upright isosceles-triangular ramp voltage. Collectively, these findings suggest that CBD's modification of ionic currents presented herein is independent of cannabinoid or opioid receptors and may exert a significant impact on the functional activities of excitable cells occurring in vitro or in vivo.

Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.

The hyperpolarization-activated cation current (Ih) exhibits a slowly activating time course of the current (Ih) when the cell membrane is hyperpolarized for an extended duration. It is involved in generating electrical activity in various excitable cells. Numerous structurally distinct compounds or herbal drugs have the potential to impact both the magnitude and gating kinetics of this current. Brivaracetam, a chemical analog of levetiracetam known to be a ligand for synaptic vesicle protein 2A, could directly suppress the Ih magnitude. Carisbamate, an anticonvulsant agent, not only inhibited the Ih amplitude but also reduced the strength of voltage-dependent hysteresis (Hys(V)) associated with Ih. Cilobradine, similar to ivabradine, inhibited the amplitude of Ih; however, it also suppressed the amplitude of delayed-rectifier K+ currents. Dexmedetomidine, an agonist of α2-adrenergic receptor, exerted a depressant action on Ih in a concentration-dependent fashion. Suppression of Ih amplitude was observed when GAL-021, a breathing control modulator, was present at a concentration exceeding 30 µM. Lutein, one of the few xanthophyll carotenoids, was able to suppress the Ih amplitude as well as to depress Hys(V)'s strength of Ih. Pirfenidone, a pyridine derivative known to be an anti-fibrotic agent, depressed the Ih magnitude in a concentration- and voltage-dependent fashion. Tramadol, a synthetic centrally active analgesic, was shown to reduce the Ih magnitude, independent of its interaction with opioid receptors. Various herbal drugs, including ent-kaurane-type diterpenoids from Croton tonkinensis, Ganoderma triterpenoids, honokiol, and pterostilbene, demonstrated efficacy in reducing the magnitude of Ih. Conversely, oxaliplatin, a platinum-based chemotherapeutic compound, was observed to effectively increase the Ih amplitude. Collectively, the regulatory effects of these compounds or herbal drugs on cellular function can be partly attributed to their perturbations on Ih.

Arsenic compounds activate MAPK and inhibit Akt pathways to induce apoptosis in MA-10 mouse Leydig tumor cells.

Arsenic compounds have been applied treating acute promyelocytic 1eukemia and solid tumors with brief mechanism investigations. In fact, we have demonstrated that sodium arsenite plus dimethylarsenic acid could activate apoptosis in MA-10 mouse Leydig tumor cells by inducing caspase pathways. However, detail underlying mechanisms how caspase cascade is regulated remains elusive. Therefore, the apoptotic mechanism of sodium arsenite plus dimethylarsenic acid were examined in MA-10 cells in this study. Our results reveal that Fas/FasL protein expressions were stimulated by sodium arsenite plus dimethylarsenic acid in MA-10 cells. In addition, reactive oxygen species (ROS) generation, cytochrome C release, Bid truncation, and Bax translocation were induced in MA-10 cells by arsenic compounds. Moreover, activation of p38, JNK and ERK1/2, MAPK pathways was stimulated while Akt phosphorylated levels and Akt expression were decreased by sodium arsenite plus dimethylarsenic in MA-10 cells. In conclusion, sodium arsenite and dimethylarsenic acid did activate MAPK pathway plus ROS generation, but suppress Akt pathway, to modulate caspase pathway and then induce MA-10 cell apoptosis.

Double-Lumen Endotracheal Tube-Predicting Insertion Depth and Tube Size Based on Patient's Chest X-ray Image Data and 4 Other Body Parameters.

In thoracic surgery, the double lumen endotracheal tube (DLT) is used for differential ventilation of the lung. DLT allows lung collapse on the surgical side that requires access to the thoracic and mediastinal areas. DLT placement for a given patient depends on two settings: a tube of the correct size (or 'size') and to the correct insertion depth (or 'depth'). Incorrect DLT placements cause oxygen desaturation or carbon dioxide retention in the patient, with possible surgical failure. No guideline on these settings is currently available for anesthesiologists, except for the aid by bronchoscopy. In this study, we aimed to predict DLT 'depths' and 'sizes' applied earlier on a group of patients (n = 231) using a computer modeling approach. First, for these patients we retrospectively determined the correlation coefficient (r) of each of the 17 body parameters against 'depth' and 'size'. Those parameters having r > 0.5 and that could be easily obtained or measured were selected. They were, for both DLT settings: (a) sex, (b) height, (c) tracheal diameter (measured from X-ray), and (d) weight. For 'size', a fifth parameter, (e) chest circumference was added. Based on these four or five parameters, we modeled the clinical DLT settings using a Support Vector Machine (SVM). After excluding statistical outliers (±2 SD), 83.5% of the subjects were left for 'depth' in the modeling, and similarly 85.3% for 'size'. SVM predicted 'depths' matched with their clinical values at a r of 0.91, and for 'sizes', at an r of 0.82. The less satisfactory result on 'size' prediction was likely due to the small target choices (n = 4) and the uneven data distribution. Furthermore, SVM outperformed other common models, such as linear regression. In conclusion, this first model for predicting the two DLT key settings gave satisfactory results. Findings would help anesthesiologists in applying DLT procedures more confidently in an evidence-based way.

Multi-Task Learning-Based Deep Neural Network for Steady-State Visual Evoked Potential-Based Brain-Computer Interfaces.

Amyotrophic lateral sclerosis (ALS) causes people to have difficulty communicating with others or devices. In this paper, multi-task learning with denoising and classification tasks is used to develop a robust steady-state visual evoked potential-based brain-computer interface (SSVEP-based BCI), which can help people communicate with others. To ease the operation of the input interface, a single channel-based SSVEP-based BCI is selected. To increase the practicality of SSVEP-based BCI, multi-task learning is adopted to develop the neural network-based intelligent system, which can suppress the noise components and obtain a high level of accuracy of classification. Thus, denoising and classification tasks are selected in multi-task learning. The experimental results show that the proposed multi-task learning can effectively integrate the advantages of denoising and discriminative characteristics and outperform other approaches. Therefore, multi-task learning with denoising and classification tasks is very suitable for developing an SSVEP-based BCI for practical applications. In the future, an augmentative and alternative communication interface can be implemented and examined for helping people with ALS communicate with others in their daily lives.

Lung Field Segmentation in Chest X-ray Images Using Superpixel Resizing and Encoder-Decoder Segmentation Networks.

Lung segmentation of chest X-ray (CXR) images is a fundamental step in many diagnostic applications. Most lung field segmentation methods reduce the image size to speed up the subsequent processing time. Then, the low-resolution result is upsampled to the original high-resolution image. Nevertheless, the image boundaries become blurred after the downsampling and upsampling steps. It is necessary to alleviate blurred boundaries during downsampling and upsampling. In this paper, we incorporate the lung field segmentation with the superpixel resizing framework to achieve the goal. The superpixel resizing framework upsamples the segmentation results based on the superpixel boundary information obtained from the downsampling process. Using this method, not only can the computation time of high-resolution medical image segmentation be reduced, but also the quality of the segmentation results can be preserved. We evaluate the proposed method on JSRT, LIDC-IDRI, and ANH datasets. The experimental results show that the proposed superpixel resizing framework outperforms other traditional image resizing methods. Furthermore, combining the segmentation network and the superpixel resizing framework, the proposed method achieves better results with an average time score of 4.6 s on CPU and 0.02 s on GPU.

Anticancer Effects of Midazolam on Lung and Breast Cancers by Inhibiting Cell Proliferation and Epithelial-Mesenchymal Transition.

Despite improvements in cancer treatments resulting in higher survival rates, the proliferation and metastasis of tumors still raise new questions in cancer therapy. Therefore, new drugs and strategies are still needed. Midazolam (MDZ) is a common sedative drug acting through the γ-aminobutyric acid receptor in the central nervous system and also binds to the peripheral benzodiazepine receptor (PBR) in peripheral tissues. Previous studies have shown that MDZ inhibits cancer cell proliferation but increases cancer cell apoptosis through different mechanisms. In this study, we investigated the possible anticancer mechanisms of MDZ on different cancer cell types. MDZ inhibited transforming growth factor ß (TGF-ß)-induced cancer cell proliferation of both A549 and MCF-7 cells. MDZ also inhibited TGF-ß-induced cell migration, invasion, epithelial-mesenchymal-transition, and Smad phosphorylation in both cancer cell lines. Inhibition of PBR by PK11195 rescued the MDZ-inhibited cell proliferation, suggesting that MDZ worked through PBR to inhibit TGF-ß pathway. Furthermore, MDZ inhibited proliferation, migration, invasion and levels of mesenchymal proteins in MDA-MD-231 triple-negative breast cancer cells. Together, MDZ inhibits cancer cell proliferation both in epithelial and mesenchymal types and EMT, indicating an important role for MDZ as a candidate to treat lung and breast cancers.

Midazolam's Effects on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-lymphocytes.

Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell's K+ currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 µM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 µM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of IK(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.

Differential mechanisms of synaptic plasticity for susceptibility and resilience to chronic social defeat stress in male mice.

Mood dysregulation refers to the inability of a person to control their negative emotions, and it is linked to various stressful experiences. Dysregulated neural synaptic plasticity and actin-filament dynamics are important regulators of stress response in animal models. However, until now, there is no evidence to differential the mechanisms of synaptic plasticity and actin-filament dynamics in stress susceptibility and stress-resistant. Here we found that depression-like behaviour was observed in the susceptible group following chronic social defeat stress (CSDS) exposure, but not in stress-resistant mice. High-frequency stimulation-induced long-term potentiation (LTP) was impaired in the CSDS-induced depression-susceptible group. Further, the levels of pro-brain derived neurotrophic factor (BDNF), mature BDNF, PSD-95, phosphorylated CaMKII, and phosphorylated Cofilin, an actin-filament dynamics regulator, were reduced in CSDS-induced depression-susceptible mice unlike in stress-resistant mice. These results demonstrate that synaptic plasticity-related molecules, such as BDNF and phosphorylated Cofilin, are important for maintaining synaptic functions and structure in mice that experience more stress.

A 36-Hour Unplugged Full-Scale Exercise: Closing the Gaps in Interagency Collaboration between the Disaster Medical Assistance Team and Urban Search and Rescue Team in Disaster Preparedness in Taiwan.

INTRODUCTION: Disaster medical assistance team (DMAT) and urban search and rescue team (USAR) need to cooperate seamlessly to save lives in disasters, but related research is limited. OBJECTIVES: To estimate the disaster preparedness of the DMAT and the barriers affecting interagency cooperation between the DMAT and the USAR team. METHODS: This was an observational study of a full-scale exercise conducted in Taiwan from November 16 to 18, 2018. The exercise scenario simulated a magnitude 7 earthquake in Tainan City. DMATs from other counties were deployed and cooperated with local USAR teams to carry out disaster relief. Our study invited 7 experts to evaluate DMATs on disaster preparedness capabilities and the interagency collaboration between DMATs and USAR. RESULTS: A total of eight DMATs, consisting of 30 physicians, 65 nurses, 74 logisticians, 5 health bureau personnel, and 85 USAR teams, participated in this exercise. During the mission, 176 patients were treated. The capabilities of each team were generally consistent with the basic technical standards for type I emergency medical teams, but the compliance rates for basic local anesthesia, cold chain equipment for medication, rapid blood test tools, and sterilization devices were only 50%, 12.5%, 12.5%, and 9%, respectively. In addition, 53% of participants reported abnormal vital signs, indicating that it was a high-stress situation. Moreover, the main barriers to interagency collaboration were differing perspectives and poor mutual understanding. CONCLUSION: A full-scale exercise carried out jointly with DMATs and USAR teams was valuable for disaster preparedness, particularly in terms of understanding the weaknesses of those teams and the barriers to interagency collaboration.

A novel optical technology based on 690 nm and 850 nm wavelengths to assist needle thoracostomy.

The sensitivity of pneumothorax diagnosis via handheld ultrasound is low, and there is no equipment suitable for use with life-threatening tension pneumothorax in a prehospital setting. This study proposes a novel technology involving optical fibers and near-infrared spectroscopy to assist in needle thoracostomy decompression. The proposed system via the optical fibers emitted dual wavelengths of 690 and 850 nm, allowing distinction among different layers of tissue in vivo. The fundamental principle is the modified Beer-Lambert law (MBLL) which is the basis of near-infrared tissue spectroscopy. Changes in optical density corresponding to different wavelengths (690 and 850 nm) and hemoglobin parameters (levels of Hb and HbO2) were examined. The Kruskal-Wallis H test was used to compare the differences in parameter estimates among tissue layers; all p-values were < 0.001 relevant to 690 nm and 850 nm. In comparisons of Hb and HbO2 levels relative to those observed in the vein and artery, all p-values were also < 0.001. This study proposes a new optical probe to assist needle thoracostomy in a swine model. Different types of tissue can be identified by changes in optical density and hemoglobin parameters. The aid of the proposed system may yield fewer complications and a higher success rate in needle thoracostomy procedures.

Successive treatment with naltrexone induces epithelial-mesenchymal transition and facilitates the malignant biological behaviors of bladder cancer cells.

Naltrexone is widely used for alleviating opioid-related side effects in cancer patients. However, the effects of naltrexone on cancer progression are controversial in the literature. The present study was carried out to investigate the effects of successive treatment with clinically relevant doses of naltrexone on the malignant biological behaviors of bladder cancer cells. The human bladder cancer T24 cells and mouse bladder cancer MB49 cells were treated with naltrexone. Cell proliferation, migration, and invasion abilities were analyzed. Morphological changes of the cells were confirmed by F-actin immunofluorescence staining. Epithelial-mesenchymal transition (EMT)-related markers and transcriptional factors, as well as activation of the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway, were analyzed. Results showed that, compared with the control group, successive treatment with naltrexone significantly promoted the proliferation and decreased the apoptosis of bladder cancer cells, together with increase in cell migration and invasion ability. Continuous treatment with naltrexone also significantly reduced the expression of epithelial markers (E-cadherin and cytokeratin 19), increased the expression of mesenchymal markers (N-cadherin and vimentin) and EMT-inducing transcription factors (Snail and Slug), and further shifted the morphological phenotype of bladder cancer cells to a mesenchymal phenotype. The PI3K/AKT signaling pathway was activated by successive treatment with naltrexone. Notably, incubation with the specific PI3K inhibitor LY294002 together with naltrexone reversed the naltrexone-induced EMT progression. In conclusion, successive treatment with naltrexone may be favorable for the progression of bladder tumors by activating the PI3K/AKT signaling pathway and inducing EMT. Long-term exposure to naltrexone should be used cautiously in patients with bladder cancer.

Dual-wavelength fiber-optic technique to assist needle cricothyroidotomy.

The traditional needle cricothyroidotomy procedure is performed blindly without any medical equipment. Complications including posterior tracheal wall perforation, accidental vessel puncture, and missed tracheal puncture are reported. Therefore, we proposed a dual-wavelength fiber-optic technique based on the technique of near-infrared spectroscopy to assist operators performing needle cricothyroidotomy in a swine model. We embedded optical fibers in a 16-gauge intravenous needle catheter. Real-time data were displayed on an oscilloscope, and we used the program to analyze the data immediately. The change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations) was analyzed immediately using the program in the laptop. Unique and significant optical differences were presented in this experiment. We could easily identify every different tissue by the change of optical density corresponding to 690-nm and 850-nm wavelengths and hemoglobin parameters (HbO2 and Hb concentrations). Statistical method (Kruskal-Wallis H test) was used to compare differences in tissues at each time-point, respectively. The p values in every tissue in optical density change corresponding to 690 nm and 850 nm were all < 0.001. Furthermore, the p values in every tissue in Hb and HbO2 were also all < 0.001. The results were statistically significant. This is the first and novel study to introduce a dual-wavelength embedded fibers into a standard cricothyroidotomy needle. This proposed system might be helpful to provide us real-time information of the advanced needle tip to decrease possible complications.

Two-Photon Photoexcited Photodynamic Therapy with Water-Soluble Fullerenol Serving as the Highly Effective Two-Photon Photosensitizer Against Multidrug-Resistant Bacteria.

BACKGROUND: Multidrug-resistant (MDR) bacterial strain is a serious medical problem. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many antibiotics and is often associated with several diseases such as arthritis, osteomyelitis, and endocarditis. The development of an alternative treatment for eliminating MDR bacteria such as MRSA has attracted a considerable amount of research attention. Moreover, the development of a material for highly efficient generation of reactive oxygen species (ROS) involving two-photon photodynamic therapy (PDT) is currently desirable. MATERIALS AND METHODS: We present an example demonstrating that the use of water-soluble C60(OH)30 fullerenol with a 0.89 singlet oxygen quantum yield serving as a photosensitizer in PDT has the superior ability in effectively generating ROS. RESULTS: It has ultra-low energy (228.80 nJ pixel-1) and can perform 900 scans under two-photon excitation (TPE) in the near-infrared region (760 nm) to completely eliminate the MDR species. Furthermore, the favorable two-photon properties are absorption of approximately 760 nm in wavelength, absolute cross-section of approximately 1187.50 Göeppert-Mayer units, lifetime of 6.640 ns, ratio of radiative to nonradiative decay rates of approximately 0.053, and two-photon stability under TPE. CONCLUSION: This enabled water-soluble C60(OH)30 fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.

Amino-Functionalized Nitrogen-Doped Graphene Quantum Dots for Efficient Enhancement of Two-Photon-Excitation Photodynamic Therapy: Functionalized Nitrogen as a Bactericidal and Contrast Agent.

BACKGROUND: Although graphene quantum dots (GQDs) have received considerable research attention for their applications in various fields, the use of GQDs, such as nitrogen-doped GQDs (N-GQDs) and amino-functionalized N-GQDs (amino-N-GQDs), as photosensitizers to facilitate photodynamic therapy (PDT) has received limited research intention. To address this research gap, this study prepared novel amino-N-GQDs and investigated their properties. METHODS: The amino-N-GQDs subjected to two-photon excitation (TPE) exhibited remarkable bactericidal capability in PDT. The bonding compositions of nitrogen and the amino-functionalized group played a critical role in their antimicrobial effects. RESULTS: Compared with amino-group-free N-GQDs and amino-N-free GQDs, the amino-N-GQDs generated a higher amount of reactive oxygen species, demonstrating their superior efficacy for two-photon PDT. Additionally, the intrinsic luminescence properties and high photostability of the amino-N-GQDs demonstrate their suitability as an effective two-photon contrast agent for tracking bacteria during two-photon biomedical imaging. CONCLUSION: The amino-N-GQD and their remarkable properties may provide an efficient alternative approach for observing and easily eliminating malignant microbes in the future.

Arsenic compounds activate the MAPK and caspase pathways to induce apoptosis in OEC­M1 gingival epidermal carcinoma.

Arsenic is a well­documented environmental toxicant that can induce neurotoxicity and peripheral vascular diseases. In fact, arsenic trioxide has been used to treat various cancer types. Oral cancer has been in the top ten common cancers for decades in Taiwan, and the incidence rate is continuously increasing. The majority of oral cancers are associated with excessive tobacco, alcohol consumption and betel chewing. To the best of our knowledge, no study has revealed the effect of arsenic compounds on oral cancers. Thus, the present study used OEC­M1 oral squamous carcinoma cells treated with sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA) to determine whether both arsenic compounds could exert anticancer effects on oral cancer. The results demonstrated that NaAsO2 and DMA induced rounding up and membrane blebbing in OEC­M1 cells, which are morphological characteristics of apoptosis. Annexin V/PI double staining analysis further confirmed that both arsenic compounds induced apoptosis of OEC­M1 cells. In addition, NaAsO2 and DMA significantly decreased the survival rate and increased the percentage of OEC­M1 cells in the subG1 and G2/M phases (P<0.05). Furthermore, both arsenic compounds significantly activated the cleavage of caspase­8, ­9, ­3 and PARP, and the phosphorylation of JNK, ERK1/2 and p38 in OEC­M1 cells (P<0.05). Collectively, the findings of the present study indicated that NaAsO2 and DMA stimulate extrinsic and intrinsic apoptotic pathways through the activation of the MAPK pathways to induce apoptosis of OEC­M1 cells, suggesting that NaAsO2 and DMA may be used as novel anticancer drugs for oral cancers.

Cordycepin Inhibits Human Gestational Choriocarcinoma Cell Growth by Disrupting Centrosome Homeostasis.

INTRODUCTION: Human gestational choriocarcinoma, a type of gestational trophoblastic disease, occurs after miscarriage, abortion, ectopic pregnancy, or molar pregnancy. Despite recent advances in the mechanism of anticancer drugs that induce human gestational choriocarcinoma apoptosis or block its growth, new therapeutic approaches are needed to be established. Cordycepin is an active anti-cancer component extracted from Cordyceps sinensis. It prevents cell proliferation both in vitro and in vivo. MATERIALS AND METHODS: Here, we examined cell growth by counting cell numbers, and performing a flow cytometry assay and EdU incorporation assay. Centrosome and cytoskeleton-related structures were observed by immunofluorescence assay. The DNA damage-related signaling was examined by Western blot assay. RESULTS: Here, we showed that cordycepin inhibited human gestational choriocarcinoma cell proliferation and induced cell death. In addition, treatment with cordycepin activated DNA-PK and ERK, thus inducing centrosome amplification and aberrant mitosis. These amplified centrosomes also disrupted microtubule arrays and actin networks, thus leading to defective cell adhesion. Furthermore, cordycepin induced autophagy for triggering cell death. CONCLUSION: Thus, our study demonstrates that cordycepin inhibits cell proliferation and disrupts the cytoskeleton by triggering centrosome amplification.