Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy.

Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity. Annexin-V and 7-AAD double staining showed that DPDS could induce the apoptosis of breast cancer cells. Western blotting of the expression of Bax p21 and its cleaved form p18 suggested the activation of p18 Bax-induced apoptosis. Furthermore, the increased expression of the autophagy marker LC3B-II indicated autophagic lysosome accumulation induced by DPDS. Our findings suggest that DPDS has potential as a candidate for treating breast cancer, and further modifications and optimizations are warranted.

Realization of Forest Internet of Things Using Wireless Network Communication Technology of Low-Power Wide-Area Network.

This work implements an intelligent forest monitoring system using the Internet of things (IoT) with the wireless network communication technology of a low-power wide-area network (LPWAN), a long range (LoRa), and a narrow-band Internet of things (NB-IoT). A solar micro-weather station with LoRa-based sensors and communications was built to monitor the forest status and information such as the light intensity, air pressure, ultraviolet intensity, CO2, etc. Moreover, a multi-hop algorithm for the LoRa-based sensors and communications is proposed to solve the problem of long-distance communication without 3G/4G. For the forest without electricity, we installed solar panels to supply electricity for the sensors and other equipment. In order to avoid the problem of insufficient solar panels due to insufficient sunlight in the forest, we also connected each solar panel to a battery to store electricity. The experimental results show the implementation of the proposed method and its performance.

Castability of a Ti-7.5Mo alloy for fabricating frameworks for removable partial dentures.

STATEMENT OF PROBLEM: The properties of commercially pure titanium are better than those of cobalt chromium alloys in various ways. However, casting pure titanium is challenging because of its high melting point and chemical reactivity. Because of excellent mechanical strength, a titanium alloy, Ti-6Al-4V, has been commonly adopted, but the aluminum and vanadium ions released may be cytotoxic. PURPOSE: The purpose of the present study was to evaluate a new titanium alloy, Ti-7.5Mo, developed by the National Cheng Kung University for casting removable denture frameworks. The casting success rate, porosity, and guide plane or rest fit were compared among frameworks cast with Ti-7.5Mo alloy and pure titanium for 3 types of edentulism. MATERIAL AND METHODS: Ti-7.5Mo alloy and pure titanium were used to cast frameworks for Kennedy Class I and II and completely edentulous conditions, with 5 frameworks for each condition. Wax patterns of the frameworks were designed and fabricated by using computer-aided design and computer-aided manufacture (CAD-CAM) technology to ensure their geometrical consistency. They were then invested with aluminum oxide-based material and cast. The castings were examined with microcomputed tomography (µCT) for porosity, and fit was evaluated from the thickness of a vinyl polyether silicone material at the guide plane or the rest by using an optical microscope. The casting was determined to be successful if the frameworks were complete. The porosity and fit were statistically evaluated by using 2-way ANOVA (α=.05). RESULTS: Using pure titanium, the casting success rate was 80%, with only 64% of the major connectors in the deficient castings being complete. The µCT images showed that the percentage of casting defects in Ti-7.5Mo castings was one-third of the pure titanium castings. Furthermore, internal voids were detected in the clasps of the pure titanium castings, while the Ti-7.5Mo castings had few defects in the minor connectors and no radiographically detectable defects in the clasps. The fit analysis demonstrated smaller gaps over both guide planes and rests in the Ti-7.5Mo castings. CONCLUSIONS: Ti-7.5Mo alloy had better castability than pure titanium. Based on the results, Ti-7.5Mo alloy is suitable for dental casting and may provide better performance.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease.

BACKGROUND: Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). METHODS: This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. RESULTS: Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. CONCLUSION: Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

Simple Advanced Preparation Method for Improving the Thickness Stability of Powder Thickening Agents in Dysphagia Management.

Texture modification of foods by using thickening agents is a routine practice for assessing and treating dysphagic patients. However, a powder-thickened fluid's viscosity might change over time, and little has been proposed to overcome this inconsistency. This study aimed to evaluate variations in the thickness of a fluid thickened with a common xanthan gum-based powder and to explore the feasibility of a simple advanced preparation method for thickened liquids to improve thickness stability. Thickened fluids with concentrations of 1.0 g/100 mL, 0.7 g/100 mL, and 0.5 g/100 mL were prepared from both freshly opened and previously opened thickening powders. Fluid thickness was measured every 10 min in a series of International Dysphagia Diet Standardization Initiative flow tests. A significant time-dependent decline in thickness was observed for all three concentrations in both groups, namely those prepared with freshly opened and previously opened thickening powders, and the shortest periods to achieve a stable viscosity after liquid preparation for the two groups were 80 and 70 min, respectively. On diluting the thickened liquids from the base liquid, which was prepared at a concentration of 1.0 g/100 mL and stored at room temperature for 90 min, no significant time-dependent thickness changes were observed over the following 60 min. The simple protocol of preparing the thickest "base" liquid in advance and then diluting it to the desired thickness resulted in a consistent liquid thickness, with the prepared liquids ready to be clinically applied and consumed, with high stability within 60 min.

Identification and management of contraindicated drug-drug interactions through pharmaceutical care programs: Experience in direct-acting antivirals therapy.

BACKGROUND/PURPOSE: To investigate the impact of pharmaceutical care programs for the management of contraindicated drug-drug interactions (DDIs) in direct-acting antivirals (DAAs) therapy. METHODS: A prospective observational study was performed at Dalin Tzu Chi Hospital between January 2018 and December 2019. Pharmacists screened DDIs for all hepatitis C patients before DAA therapy. The study outcome included the frequency of contraindicated DDIs, acceptance rate, and cost avoidance of the pharmaceutical care program. RESULTS: A total of 1053 patients were enrolled in the study, with a mean age of 67.1 ± 11.9 years. Most patients received therapy with sofosbuvir/ledipasvir (37.1%; n = 391), elbasvir/grazoprevir (23.8%; n = 251), or glecaprevir/pibrentasvir (21.1%; n = 222). A total of 796 (75.6%) patients received at least one co-medication, with the average number of co-medications being 5.2 per patient (SD: 4.4/patient). In total, 1356 DDIs were identified, with the average DDIs per patient of 1.3 (SD: 1.7). For patients with contraindicated DDIs (2%, n = 102), statins and amiodarone were the most common co-medications. Physicians often accepted pharmacists' recommendations (acceptance rate of 72.5%) or withheld co-medication to avoid severe adverse drug events (ADEs). The estimated cost avoidance of preventable ADEs was USD 14,033 for contraindicated DDIs with pharmaceutical care programs. CONCLUSION: The implementation of pharmaceutical care programs in DAA therapy provides a favorable outcome and substantial cost avoidance.

Diguanylate Cyclase (DGC) Implicated in the Synthesis of Multiple Bacteriocins via the Flagellar-Type III Secretion System Produced by Pectobacterium carotovorum subsp. carotovorum.

The plant pathogen Pectobacterium carotovorum subsp. carotovorum (previously Erwinia carotovora subsp. carotovora) causes soft rot and stem rot diseases in a variety of crops, including Chinese cabbage, potato, and tomato. The flagellar-type III secretion systems were used by Pcc's virulence mechanism to export proteins or bacteriocins to the outside of the cell. DGC, a virulence factor that cyclizes c-di-GMP, a common secondary signal in physiological processes and toxin control systems of many bacteria, was discovered in Pcc's genomic DNA. The dgc gene in Pcc was blocked using the method of homologous recombination in our study. In the in vivo setting, the results demonstrated that the dgc knockout strain does not release low molecular weight bacteriocins. The bacteriocin gene (carocin S2, carocin S3, carocin S4) and the flagellar-type III secretion system genes were also unable to be transcribed by the dgc knockout strain in the transcription experiment. We also observed that the amount of bacteriocin expressed changed when the amount of L-glutamine in the environment exceeded a particular level. These data suggested that L-glutamine influenced physiological processes in Pcc strains in some way. We hypothesized a relationship between dgc and the genes involved in Pcc LMWB external export via the flagellar-type secretion system based on these findings. In this study, the current findings led us to propose a mechanism in which DGC's cyclic di-GMP might bind to receptor proteins and positively regulate bacteriocin transcription as well as the synthesis, mobility, and transport of toxins.

Association between nucleos(t)ide analogue therapy for hepatitis B and Sjögren's syndrome: 15-year analysis of the national database of Taiwan.

Hepatitis B virus (HBV) infection has been proposed to play a role in the development of Sjögren's syndrome. However, to date, there are no reports on the risk of SS in HBV-infected patients following nucleos(t)ide analogue therapy. Due to Taiwan has higher prevalence of HBV infection and therapy was well recorded in the Taiwan's single-payer national health insurance database, we hypothesized that a long-term retrospective analysis of the risk of Sjögren's syndrome in HBV-infected patients following nucleotide therapy will increase our understanding of Sjögren's syndrome development following HBV infection. We identified 26,147 adults diagnosed with HBV infection between 1997 and 2012 in claims data. Finally, a total of 3268 HBV-infected patients who ever received nucleotide therapy (treated cohort) were frequency-matched on age and sex at 1:4 ratios to select a control group of 13,072 counterparts without therapy (untreated cohort). To identify Sjögren's syndrome risk, competing risk analysis adjusted for all covariates was performed. The risk was significantly lower in the treated cohort (15-year cumulative incidence, 2.4%; 95% confidence interval [CI], 1.4%-3.7%) than in the untreated cohort (7.1%; 95% CI, 2.5%-15.2%) (p = .015), and the adjusted HR was 0.6 (95% CI, 0.41-0.88; p = .009). Multivariable stratified analysis further verified the consistent associations between nucleoside therapy and risk reduction of Sjögren's syndrome across all strata. Our finding suggests that HBV infection treated with nucleotides is associated with lower risk of Sjögren's syndrome, implying a potential role of HBV infection in the development of Sjögren's syndrome.

Correlation between the optical absorption and twisted angle of bilayer graphene observed by high-resolution reflectance confocal laser microscopy.

We report a systematic study of the optical absorption of twisted bilayer graphene (tBLG) across a large range of twist angles from 0° to 30° using a high-resolution reflectance confocal laser microscopy (RCLM) system. The high-quality single crystalline tBLG was synthesized via the efficient plasma enhanced chemical vapor deposition techniques without the need of active heating. The sensitivity of acquired images from the RCLM were better than conventional optical microscopes. Although the highest spatial resolution of RCLM is still lower than scanning electron microscopes, it possesses the advantages of beam-damage and vacuum free. Moreover, the high intensity-resolution (sensitivity) images firstly allowed us to distinguish the slight absorption differences and analyze the correlation between the optical absorption and twisted angle of tBLG after data processing procedures. A maximum absorption (minimum transmission) was observed at the stacking angle of tBLG from 10° to 20°, indicating the interplay between the laser and the electron/hole van-Hove singularities when tBLG oriented around the critical angle (θc∼13°). The twisted angle correlated optical absorption paves an alternative way not only to visibly identify the interlayer orientation of tBLG but also to reflect the characterization of the interlayer coupling via its band structure.

Baseline thrombopoietin level is associated with platelet count improvement in thrombocytopenic chronic hepatitis C patients after successful direct-acting antiviral agent therapy.

BACKGROUND: Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. METHODS: From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO. RESULTS: This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32-149) × 103/µL at BL to 116.5 (40-196) and 118.0 (35-275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P < 0.001; P12 vs. BL, P < 0.001). BL TPO was positively correlated with significant platelet count improvement (P < 0.001), platelet count improvement ratio at EOT (P = 0.004), and P12 (P < 0.001). The area under the receiver operating characteristic curve and optimal cutoffs (pg/ml) were 0.77 (95% confidence interval, 0.67-0.86) and 120, respectively, for significant platelet count improvement prediction. The sensitivity, specificity, and accuracy were 88.6%, 71.7%, and 78.8%, respectively. CONCLUSIONS: BL TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic patients after successful DAA therapy.

Office-based salivary gland ductal irrigation in patients with chronic sialoadenitis: A preliminary study.

BACKGROUND/PURPOSE: To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis. METHODS: Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department. RESULTS: The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic Tmin showed a significant positive correlation with the responsiveness of salivary irrigation (P = 0.046), whereas the treatment tended to be irresponsive in patients who previously took medicine for their related discomfort (P = 0.009). In the postradiotherapy and post-RAI groups, no significant factors were found to be associated with the responsiveness of irrigation. CONCLUSION: Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies.

Direct large-area growth of graphene on silicon for potential ultra-low-friction applications and silicon-based technologies.

Deposition of layers of graphene on silicon has the potential for a wide range of optoelectronic and mechanical applications. However, direct growth of graphene on silicon has been difficult due to the inert, oxidized silicon surfaces. Transferring graphene from metallic growth substrates to silicon is not a good solution either, because most transfer methods involve multiple steps that often lead to polymer residues or degradation of sample quality. Here we report a single-step method for large-area direct growth of continuous horizontal graphene sheets and vertical graphene nano-walls on silicon substrates by plasma-enhanced chemical vapor deposition (PECVD) without active heating. Comprehensive studies utilizing Raman spectroscopy, x-ray/ultraviolet photoelectron spectroscopy (XPS/UPS), atomic force microscopy (AFM), scanning electron microscopy (SEM) and optical transmission are carried out to characterize the quality and properties of these samples. Data gathered by the residual gas analyzer (RGA) during the growth process further provide information about the synthesis mechanism. Additionally, ultra-low friction (with a frictional coefficient ∼0.015) on multilayer graphene-covered silicon surface is achieved, which is approaching the superlubricity limit (for frictional coefficients <0.01). Our growth method therefore opens up a new pathway towards scalable and direct integration of graphene into silicon technology for potential applications ranging from structural superlubricity to nanoelectronics, optoelectronics, and even the next-generation lithium-ion batteries.

Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients.

BACKGROUNDS: Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. AIMS: This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment. METHODS: CHC patients (n = 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-ß with/without Treg inhibition were also detected. RESULTS: The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4+Foxp3+T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT, P = 0.0393; EOT vs. SVR 12, P = 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-ß was significantly increased at Week 4 and SVR 12 compared to baseline. CONCLUSIONS: The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-ß parallelled Treg function.

Altered monocyte differentiation and macrophage polarization patterns in patients with breast cancer.

BACKGROUND: Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. METHODS: Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited. The percentages and subsets of circulating macrophage-like cells were analysed by flow cytometry, and the polarization patterns of these cells in the peripheral blood of patients with breast cancer were compared with those of healthy controls. In addition, macrophage polarization patterns in different stages and HER2 status in breast cancer were investigated. RESULTS: The percentages of circulating macrophages, which are defined as PM-2 K+ cells in the peripheral blood, were significantly higher in patients with breast cancer than in healthy controls. The percentages of M1-like macrophages were significantly lower, but those of M2-like macrophages were significantly higher in patients with breast cancer than in healthy controls. The percentage of M2c-like macrophages was significantly higher in advanced (stages II and III) breast cancer. However, the patterns of macrophage polarization were not associated with HER2 status in breast cancer. CONCLUSIONS: Aberrant macrophage polarization was observed in breast cancer and was correlated with breast cancer stage. These quantitative data may provide new molecular biomarkers and potential therapeutic targets in breast cancer.

Suppressive effects of metformin on T-helper 1-related chemokines expression in the human monocytic leukemia cell line THP-1.

PURPOSE OF THE STUDY: Type 1 and type 2 diabetes mellitus (DM) are chronic T-cell-mediated inflammatory diseases. Metformin is a widely used drug for type 2 DM that reduces the need for insulin in type 1 DM. However, whether metformin has an anti-inflammatory effect for treating DM is unknown. We investigated the anti-inflammatory mechanism of metformin in the human monocytic leukemia cell line THP-1. MATERIALS AND METHODS: The human monocytic leukemia cell line THP-1 was pretreated with metformin and stimulated with lipopolysaccharide (LPS). The production of T-helper (Th)-1-related chemokines including interferon-γ-induced protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1), Th2-related chemokine macrophage-derived chemokine, and the proinflammatory chemokine tumor necrosis factor-α was measured using enzyme-linked immunosorbent assay. Intracellular signaling pathways were investigated using Western blot analysis and chromatin immunoprecipitation assay. RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB). Moreover, metformin suppressed LPS-induced acetylation of histones H3 and H4 at the IP-10 promoter. CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells. Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-κB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4. These results indicated the therapeutic anti-inflammatory potential of metformin.

Carbon Fiber Ionization Mass Spectrometry for the Analysis of Analytes in Vapor, Liquid, and Solid Phases.

Various ionization methods in mass spectrometry (MS) are available for the analysis of analytes with different properties. Nonetheless, the use of a single ionization method to analyze mixtures containing analytes with different polarities and volatilities in different phases at atmospheric pressure remains a challenge. Exploring an ionization method that can ionize small organics and large biomolecules with different properties for MS analysis is advantageous. Carbon fiber ionization mass spectrometry (CFI-MS), which uses a carbon fiber bundle as the ion source, is useful for the analysis of small organics with low polarities. Voltage needs to be applied on the carbon fiber bundle to initiate corona discharge for ionization of analytes. In this study, we explore the suitability of using CFI-MS in the analysis of analytes in vapor, liquid, and solid phases using a single carbon fiber (length : ∼1 cm; diameter: ∼10 µm) as the ion source. Furthermore direct electric contact on the carbon fiber is not required. We demonstrate that CFI-MS is useful for analyzing not only small and low-polarity organics but also polar biomolecules, such as peptides and proteins. The limits of detection for analytes with high polarities such as dodecyl trimethylammonium bromide and bradykinin are estimated to be ∼16 and ∼53 pM, respectively. Ionization mechanisms, including corona discharge and electrospray, are involved in the ionization of analytes with the polarity from low to high. Furthermore, sesame oil containing aromatic volatiles and compounds with different polarities is used as a model sample to demonstrate the capability of the developed ionization method to provide comprehensive chemical information from a complex sample. In addition, the feasibility of using the developed method for quantitative analysis of nonpolar as well as medium and high polarity analytes is also demonstrated. The sensitivity of the developed method toward analytes with high polarity is higher than those with low polarity. The method precision was estimated to be ∼7.8%.

Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells.

BACKGROUND: 2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinoline-11-one (BPIQ), is a synthetic quinoline analog. A previous study showed the anti-cancer potential of BPIQ through modulating mitochondrial-mediated apoptosis. However, the effect of BPIQ on cell migration, an index of cancer metastasis, has not yet been examined. Furthermore, among signal pathways involved in stresses, the members of the mitogen-activated protein kinase (MAPK) family are crucial for regulating the survival and migration of cells. In this study, the aim was to explore further the role of MAPK members, including JNK, p38 and extracellular signal-regulated kinase (ERK) in BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer (NSCLC) cells. METHODS: Western Blot assay was performed for detecting the activation of MAPK members in NSCLC H1299 cells following BPIQ administration. Cellular proliferation was determined using a trypan blue exclusion assay. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. Cellular migration was determined using wound-healing assay and Boyden's chamber assay. Zymography assay was performed for examining MMP-2 and -9 activities. The assessment of MAPK inhibition was performed for further validating the role of JNK, p38, and ERK in BPIQ-induced growth inhibition, apoptosis, and migration of NSCLC cells. RESULTS: Western Blot assay showed that BPIQ treatment upregulates the phosphorylated levels of both MAPK proteins JNK and ERK. However, only ERK inhibitor rescues BPIQ-induced growth inhibition of NSCLC H1299 cells. The results of Annexin V assay further confirmed the pro-apoptotic role of ERK in BPIQ-induced cell death of H1299 cells. The results of wound healing and Boyden chamber assays showed that sub-IC50 (sub-lethal) concentrations of BPIQ cause a significant inhibition of migration in H1299 cells accompanied with downregulating the activity of MMP-2 and -9, the motility index of cancer cells. Inhibition of ERK significantly enhances BPIQ-induced anti-migration of H1299 cells. CONCLUSIONS: Our results suggest ERK may play dual roles in BPIQ-induced apoptosis and anti-migration, and it would be worthwhile further developing strategies for treating chemoresistant lung cancers through modulating ERK activity.

Magnetic hyperthermia enhance the treatment efficacy of peri-implant osteomyelitis.

BACKGROUND: When bacteria colony persist within a biofilm, suitable drugs are not yet available for the eradication of biofilm-producing bacteria. The aim of this study is to study the effect of magnetic nano-particles-induced hyperthermia on destroying biofilm and promoting bactericidal effects of antibiotics in the treatment of osteomyelitis. METHODS: Sixty 12-weeks-old male Wistar rats were used. A metallic 18G needle was implanted into the bone marrow cavity of distal femur after the injection of Methicillin-sensitive Staphylococcus aureus (MSSA). All animals were divided into 5 different treatment modalities. The microbiological evaluation, scanning electron microscope examination, radiographic examination and then micro-CT evaluation of peri-implant bone resorption were analyzed. RESULTS: The pathomorphological characteristics of biofilm formation were completed after 40-days induction of osteomyelitis. The inserted implants can be heated upto 75 °C by magnetic heating without any significant thermal damage on the surrounding tissue. We also demonstrated that systemic administration of vancomycin [VC (i.m.)] could not eradicate the bacteria; but, local administration of vancomycin into the femoral canal and the presence of magnetic nanoparticles hyperthermia did enhance the eradication of bacteria in a biofilm-based colony. In these two groups, the percent bone volume (BV/TV: %) was significantly higher than that of the positive control. CONCLUSIONS: For the treatment of chronic osteomyelitis, we developed a new modality to improve antibiotic efficacy; the protection effect of biofilms on bacteria could be destroyed by magnetic nanoparticles-induced hyperthermia and therapeutic effect of systemic antibiotics could be enhanced.

A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression.

Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines. Interestingly, the colony formation results showed a discrepancy in the inhibitory effect of 4-HPPP on HCC and rat liver epithelial Clone 9 cells, suggesting the selective cytotoxicity of 4-HPPP toward HCC cells. Furthermore, the cell proliferation and apoptosis assay results illustrated the differences between the two HCC cell lines. The results of cellular proliferation assays, including trypan blue exclusion and colony formation, revealed that 4-HPPP inhibits the growth of Huh7 cells, but exerts less cytotoxicity in Ha22T cells. Furthermore, the annexin V assay performed for detecting the apoptosis showed similar results. Western blotting results showed 4-HPPP caused the increase of pro-apoptotic factors including cleaved caspase-3, Bid and Bax in HCC cells, especially in Huh-7. Furthermore, an increase of autophagy-associated protein microtubule-associated protein-1 light chain-3B (LC3B)-II and the decrease of Beclin-1 and p62/SQSTM1 were observed following 4-HPPP treatment. Additionally, the level of γH2A histone family, member X (γH2AX), an endogenous DNA damage biomarker, was dramatically increased in Huh7 cells after 4-HPPP treatment, suggesting the involvement of DNA damage pathway in 4-HPPP-induced apoptosis. On the contrary, the western blotting results showed that treatment up-regulates pro-survival proteins, including the phosphorylation of protein kinase B (Akt) and the level of survivin on Ha22T cells, which may confer a resistance toward 4-HPPP. Notably, the blockade of extracellular signal-regulated kinases (ERK), but not Akt, enhanced the cytotoxicity of 4-HPPP against Ha22T cells, indicating the pro-survival role of ERK in 4-HPPP-induced anti-HCC effect. Our present work suggests that selective anti-HCC activity of 4-HPPP acts through induction of DNA damage. Accordingly, the combination of ERK inhibitor may significantly enhance the anti-cancer effect of 4-HPPP for those HCC cells which overexpress ERK in the future.