bluuebunny/crossref_metadata_2025 huggingface dataset:
Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature
Authors: Guerini Andrea Emanuele , Triggiani Luca , Maddalo Marta , Bonù Marco Lorenzo , Frassine Francesco , Baiguini Anna , Alghisi Alessandro , Tomasini Davide , Borghetti Paolo , Pasinetti Nadia , Bresciani Roberto , Magrini Stefano Maria , Buglione Michela
Published: September 2019

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.
Near-Infrared Fluorescent Sorbitol Probe for Targeted Photothermal Cancer Therapy
Authors: Lee Sungsu , Jung Jin Seok , Jo Gayoung , Yang Dae Hyeok , Koh Yang Seok , Hyun Hoon
Published: September 2019

Photothermal therapy (PTT) using a near-infrared (NIR) heptamethine cyanine fluorophore has emerged as an alternative strategy for targeted cancer therapy. NIR fluorophores showing a high molar extinction coefficient and low fluorescence quantum yield have considerable potential applications in photothermal cancer therapy. In this study, a bifunctional sorbitol–ZW800 conjugate was used as an advanced concept of photothermal therapeutic agents for in vivo cancer imaging and therapy owing to the high tumor targetability of the sorbitol moiety and excellent photothermal property of NIR heptamethine cyanine fluorophore. The sorbitol–ZW800 showed an excellent photothermal effect increased by 58.7 °C after NIR laser irradiation (1.1 W/cm2) for 5 min. The HT-29 tumors targeted by sorbitol–ZW800 showed a significant decrease in tumor volumes for 7 days after photothermal treatment. Therefore, combining the bifunctional sorbitol–ZW800 conjugate and NIR laser irradiation is an alternative way for targeted cancer therapy, and this approach holds great promise as a safe and highly efficient NIR photothermal agent for future clinical applications.
Artificial Intelligence Modelling Approach for the Prediction of CO-Rich Hydrogen Production Rate from Methane Dry Reforming
Authors: Ayodele Bamidele , Mustapa Siti , Alsaffar May , Cheng Chin
Published: September 2019

This study investigates the applicability of the Leven–Marquardt algorithm, Bayesian regularization, and a scaled conjugate gradient algorithm as training algorithms for an artificial neural network (ANN) predictively modeling the rate of CO and H2 production by methane dry reforming over a Co/Pr2O3 catalyst. The dataset employed for the ANN modeling was obtained using a central composite experimental design. The input parameters consisted of CH4 partial pressure, CO2 partial pressure, and reaction temperature, while the target parameters included the rate of CO and H2 production. A neural network architecture of 3 13 2, 3 15 2, and 3 15 2 representing the input layer, hidden neuron layer, and target (output) layer were employed for the Leven–Marquardt, Bayesian regularization, and scaled conjugate gradient training algorithms, respectively. The ANN training with each of the algorithms resulted in an accurate prediction of the rate of CO and H2 production. The best prediction was, however, obtained using the Bayesian regularization algorithm with the lowest standard error of estimates (SEE). The high values of coefficient of determination (R2 > 0.9) obtained from the parity plots are an indication that the predicted rates of CO and H2 production were strongly correlated with the observed values.
Transport of Ca2+ and Ca2+-Dependent Permeability Transition in Rat Liver Mitochondria under the Streptozotocin-Induced Type I Diabetes
Authors: Belosludtsev Konstantin N. , Talanov Eugeny Yu. , Starinets Vlada S. , Agafonov Alexey V. , Dubinin Mikhail V. , Belosludtseva Natalia V.
Published: September 2019

Although diabetes mellitus is known to be a disease associated with mitochondrial dysfunction, not everything is clear about mitochondrial Ca2+ transport and Ca2+-induced permeability transition in diabetic cells. The objective of this work was to study the operation of MCU and Ca2+-dependent mitochondrial permeabilization in the liver cells of Sprague-Dawley rats under the streptozotocin-induced type I diabetes. It was shown that two weeks after the induction of diabetes, the rate of Ca2+ uptake by the mitochondria of diabetic animals increased ~1.4-fold. The expression of MCU and MICU1 subunits did not change, yet the quantity of dominant-negative MCUb channel subunits was almost twice as lower. The organelles also became more resistant to the induction of CsA-sensitive MPT pore and less resistant to the induction of CsA-insensitive palmitate/Ca2+-induced pore. The mitochondria of diabetic liver cells also showed changes in the lipid matrix of their membranes. The content of fatty acids in the membranes grew, and microviscosity of the lipid bilayer (assessed with laurdan) increased. At the same time, lipid peroxidation (assessed by the production of malonic dialdehyde) was stimulated. The paper discusses the consequences of the diabetes-related changes in mitochondria in the context of cell physiology.
Review on the Evolution of Darrieus Vertical Axis Wind Turbine: Large Wind Turbines
Authors: Mohan Kumar Palanisamy , Sivalingam Krishnamoorthi , Lim Teik-Cheng , Ramakrishna Seeram , Wei He
Published: September 2019

The objective of the current review is to present the development of a large vertical axis wind turbine (VAWT) since its naissance to its current applications. The turbines are critically reviewed in terms of performance, blade configuration, tower design, and mode of failure. The early VAWTs mostly failed due to metal fatigue since the composites were not developed. Revisiting those configurations could yield insight into the future development of VAWT. The challenges faced by horizontal axis wind turbine (HAWT), especially in the megawatt capacity, renewed interest in large scale VAWT. VAWT provides a solution for some of the immediate challenges faced by HAWT in the offshore environment in terms of reliability, maintenance, and cost. The current rate of research and development on VAWT could lead to potential and economical alternatives for HAWT. The current summary on VAWT is envisioned to be an information hub about the growth of the Darrieus turbine from the kW capacity to megawatt scale.
Corrosion and Magnetization Analyses of Iron Encapsulated Aluminum Particles by Numerical Simulations
Authors: Guo Jing , Sun Ruochen , Qi Hui , Lv Fangwei
Published: September 2019

In this study, the effects of corrosion and magnetization on iron (Fe) encapsulated aluminum (Al) particles were uncovered through the assistance of molecular dynamic (MD) simulations and finite element analysis (FEA). The corrosion of metal particles with two phases was designed to be surrounded by O2 or H2O molecules. Next, the magnetization was simulated to be under a constant magnetic field. According to the obtained results, a portion of O2 molecules did not react with Fe atoms. They were actually adsorbed on the particle surface and the adsorption eventually reached a saturated state. However, the saturated effect did not appear to be due to the oxidation behavior of other O2 molecules. Both oxidation and adsorption effects released pressure on Fe atoms and caused different extents of displacements. Next, a similar saturated effect was also observed for adsorbed H2O molecules. At the same time, other reacted H2O molecules produced a significant amount of OH− and caused charge transfer from Fe atoms. Additionally, the geometrical distribution of particles’ magnetic flux density and magnetization intensity were also studied.
Effectiveness of Ball Attachment Systems in Implant Retained- and Supported-Overdentures: A Three- to Five-Year Retrospective Examination
Authors: Ortensi Luca , Martinolli Matteo , Borromeo Carlo , Ceruso Francesco Mattia , Gargari Marco , Xhanari Erta , Tallarico Marco
Published: September 2019

Purpose: To evaluate implant and prosthetic survival rates, complications, patient satisfaction, and biological outcomes of patients rehabilitated with a ball attachment system for implant retained- and supported-overdentures (IOV), which was in function for 3 to 5 years. Methods: This retrospective study evaluated data collected from patients treated between April 2001 and May 2018 with IOV on splinted and non-splinted implants and a ball attachment system. Patients were followed for 36 to 206 months (mean follow-up was 128.1 ± 51.9 months). Data were collected at the 3- and 5-year follow-up examination. Outcome measures were implant and prosthetic survival rates, technical complications, marginal bone loss (MBL), oral health impact profile (OHIP), and periodontal parameters (bleeding on probing and plaque index). Results: A total of 46 patients (16 males and 30 females) with 124 implants were included in this study. Twenty-five implant-retained overdentures were delivered on 53 unsplinted implants, while the other 21 patients received an implant-supported overdentures and the implants were splinted. At the five-year follow-up examination, one implant and one prosthesis failed in the unsplinted group, resulting in a cumulative survival rate of 97.8% at the patient level. Two minor technical complications were experienced. Conclusions: Implant overdenture retained or supported by ball attachment systems showed high implant and prosthetic survival and success rates. A low number of complications, high patient satisfaction, and successful biological parameters were experienced in the mid-term follow-up. Data need to be confirmed by further randomized trials.
An Insight into Acute Pericoronitis and the Need for an Evidence-Based Standard of Care
Authors: Wehr Chelsea , Cruz Gianncarlo , Young Simon , Fakhouri Walid D.
Published: September 2019

Background: Pericoronitis is inflammation of the operculum associated with a partially erupted third molar. It is a highly prevalent infection of the oral cavity and presents as a painful sensation of the soft tissue encompassing the crown of the involved tooth. Though pericoronitis is common, there is no evidence-based standard-of-care for treatment of emergency patients with acute pericoronitis. Study Design: In this study, anonymous clinicians were asked to participate in an online survey with questions formulated to identify professional clinical background, emergency treatment preferred for acute pericoronitis, number of associated complications, frequency of third molar extraction, and patient satisfaction. Results and Conclusion: A statistical analysis of the collected data regarding the variance among different treatment plans and associated complications revealed little consensus in the treatment of pericoronitis. The lack of consistency of the responses focusing on the preferred treatment for emergency patients with acute pericoronitis reinforces the need for developing a standard-of-care to train future dental professionals based on well-designed randomized controlled clinical trials and meta-analyses. Practical Implications: The ultimate goal is developing a treatment option with the fewest complications to provide the best health care for patients with pericoronitis. This issue is seen not only as an acute infection but also has the potential to impact overall health.
A Watermarking Technique for Biomedical Images Using SMQT, Otsu, and Fuzzy C-Means
Authors: Shoron Shaekh Hasan , Islam Monamy , Uddin Jia , Shon Dongkoo , Im Kichang , Park Jeong-Ho , Lim Dong-Sun , Jang Byungtae , Kim Jong-Myon
Published: September 2019

Digital watermarking is a process of giving security from unauthorized use. To protect the data from any kind of misuse while transferring, digital watermarking is the most popular authentication technique. This paper proposes a novel digital watermarking scheme for biomedical images. In the model, initially, the biomedical image is preprocessed using improved successive mean quantization transform (SMQT) which uses the Otsu’s threshold value. In the next phase, the image is segmented using Otsu and Fuzzy c-means. Afterwards, the watermark is embedded in the image using discrete wavelet transform (DWT) and inverse DWT (IDWT). Finally, the watermark is extracted from the biomedical image by executing the inverse operation of the embedding process. Experimental results exhibit that the proposed digital watermarking scheme outperforms the typical models in terms of effectiveness and imperceptibility while maintaining robustness against different attacks by demonstrating a lower bit error rate (BER), a cross-correlation value closer to one, and higher values of structural similarity index measures (SSIM) and peak signal-to-noise ratio (PSNR).
Low-Profile Frequency Reconfigurable Antenna for Heterogeneous Wireless Systems
Authors: Iqbal Amjad , Smida Amor , Abdulrazak Lway Faisal , Saraereh Omar A. , Mallat Nazih Khaddaj , Elfergani Issa , Kim Sunghwan
Published: September 2019

A low-profile (0.21 λ g × 0.35 λ g × 0.02 λ g ) and a simply-structured frequency-switchable antenna with eight frequency choices is presented in this paper. The radiating structure (monopole) is printed on a 1.6-mm thicker, commercially-available substrate of FR-4 ( ϵ r = 4.4, tan δ = 0.020). Specifically, it uses three PIN diodes in the designated places to shift the resonant bands of the antenna. The antenna operates at four different modes depending on the ON and OFF states of the PIN diodes. While in each mode, the antenna covers two unique frequencies (Mode 1 = 1.8 and 3.29 GHz, Mode 2 = 2.23 and 3.9 GHz, Mode 3 = 2.4 and 4.55 GHz, and Mode 4 = 2.78 and 5.54 GHz). The performance results show that the proposed antenna scheme explores significant gain (>1.5 dBi in all modes) and reasonable efficiency (>82% in all modes) for each mode. Using a high-frequency structure simulator (HFSS), the switchable antenna is designed and optimized. The fabricated model along with the PIN diode and biasing network is tested experimentally to validate the simulation results. The proposed antenna may also be combined in compact and heterogeneous radio frequency (RF) front-ends because of its small geometry and efficient utilization of the frequency spectrum.
Preparation of Nanocellulose Aerogel from the Poplar (Populus tomentosa) Catkin Fiber
Authors: Wu Yan , Sun Meng , Wu Xinyu , Shi Tianlin , Chen Hong , Wang Hankun
Published: September 2019

The effects of chemical pretreatment on the purification of poplar (Populus tomentosa) catkin fiber and the effect of ultrasonic time for the microfibrillarization of poplar catkin fiber (PCF) were studied. The nanocellulose aerogels were prepared by freeze drying the cellulose solutions. The density, porosity, micro morphology, thermal stability and mechanical properties of the aerogels were analyzed. It was found that the dewaxing time of PCF is shorter than that of unsonicated nanocellulose. After the treatment of 0.5 wt% sodium chlorite for 2 h, the lignin of PCF was removed. After the chemical purification, the PCF was treated with 2 and 5 wt% NaOH solution and ultrasonicated for 5 and 10 min, respectively. When the ultrasonic time was 10 min, the diameter of the nanocellulose was 20–25 nm. When the ultrasonic time was 5 min, the aerogels with porous honeycomb structure can be prepared by using the nanocellulose sol of PCF as raw material. The density of the aerogels was only 0.3–0.4 mg/cm3 and the porosities of the aerogels were all larger than 99%. The difference between the pyrolysis temperature of aerogels was small, the elastic modulus of aerogels was 30–52 kPa, and the compressive strength was 22–27 kPa. With the increase of the concentration of NaOH solution (5 wt%) and ultrasonic time (10 min), the elastic modulus of aerogels increased gradually and reached the maximum value of 52 kPa, while the compressive strength reached the maximum value of 27 kPa when the PCF being treated in 5 wt% NaOH solution and was ultrasonicated for 5 min.
Detection of Salmonella in Food Matrices, from Conventional Methods to Recent Aptamer-Sensing Technologies
Authors: Paniel Nathalie , Noguer Thierry
Published: September 2019

Rapid detection of the foodborne pathogen Salmonella in food processing is of crucial importance to prevent food outbreaks and to ensure consumer safety. Detection and quantification of Salmonella species in food samples is routinely performed using conventional culture-based techniques, which are labor intensive, involve well-trained personnel, and are unsuitable for on-site and high-throughput analysis. To overcome these drawbacks, many research teams have developed alternative methods like biosensors, and more particularly aptasensors, were a nucleic acid is used as biorecognition element. The increasing interest in these devices is related to their high specificity, convenience, and relative rapid response. This review aims to present the advances made in these last years in the development of biosensors for the detection and the quantification of Salmonella, highlighting applications on meat from the chicken food chain.
Relation between the Recipe of Yeast Dough Dishes and Their Glycaemic Indices and Loads
Authors: Raczkowska Ewa , Łoźna Karolina , Bienkiewicz Maciej , Jurczok Karolina , Bronkowska Monika
Published: September 2019

The aim of the study was to evaluate the glycaemic indices (GI) and glycaemic loads (GL) of four food dishes made from yeast dough (steamed dumplings served with yoghurt, apple pancakes sprinkled with sugar powder, rolls with cheese and waffles with sugar powder), based on their traditional and modified recipes. Modification of the yeast dough recipe consisted of replacing wheat flour (type 500) with whole-wheat flour (type 2000). Energy value and the composition of basic nutrients were assessed for every tested dish. The study was conducted on 50 people with an average age of 21.7 ± 1.1 years, and an average body mass index of 21.2 ± 2.0 kg/m2. The GI of the analysed food products depended on the total carbohydrate content, dietary fibre content, water content, and energy value. Modification of yeast food products by replacing wheat flour (type 500) with whole-wheat flour (type 2000) contributed to the reduction of their GI and GL values, respectively.
Metschnikowia pulcherrima Selected Strain for Ethanol Reduction in Wine: Influence of Cell Immobilization and Aeration Condition
Authors: Canonico Laura , Comitini Francesca , Ciani Maurizio
Published: September 2019

One of the most important problems in the winemaking field is the increase of ethanol content in wine. Wines with high ethanol level negatively affect wine flavor and human health. In this study, we evaluated the use of a selected strain of Metschnikowia pulcherrima in immobilized form and under different aeration conditions, to reduce the ethanol content evaluating the volatile profile of the resulting wines. In a preliminary screening the best conditions regarding free/immobilized cells, static/aerated fermentation and inoculation level were identified. Bench-Top fermentation trials with different aeration conditions showed that the use of M. pulcherrima selected strain with aeration flow of 20 mL/L/min during the first 72 h of fermentation, led an ethanol reduction of 1.38% (v/v) in comparison with Saccharomyces cerevisiae control strain. The analytical profile of the resulting wines did not show any negative feature. Indeed, the concentration of ethyl acetate, that above its sensory threshold impacts negatively the wine sensory profile, was found at an acceptable level. On the other hand, an increase in the concentration of significant fruity and flower compounds was found.
Associations between Self-Reported Physical Activity, Heel Ultrasound Parameters and Bone Health Measures in Post-Menopausal Women
Authors: Ilesanmi-Oyelere Bolaji Lilian , Roy Nicole C. , Coad Jane , Kruger Marlena Cathorina
Published: September 2019

Physical activity plays an important role in the maintenance of bone health from childhood through adulthood. This study aimed to explore the associations between self-reported physical activity (PA), activity energy expenditure (AEE), heel ultrasound parameters and bone health measures among older adult women. The AEE was estimated from the responses of questionnaires for 125 older adult women aged 54–81 years. The bone parameters were measured by dual energy x-ray absorptiometry (DXA) and heel ultrasound parameters by the heel quantitative ultrasound (QUS). This study showed that AEE and the metabolic equivalent task (MET) were positively correlated with the bone and heel ultrasound parameters. However, fat mass (FM) and fat percentage were negatively correlated with AEE and MET. In addition, the regression analysis showed that higher AEE was a strong predictor of a higher spine T-score (β = 0.212, p = 0.015), QUS T-score (β = 0.239, p = 0.011) and stiffness index (β = 0.240, p = 0.010) after adjusting for age, fat mass, lean mass, height and calcium intake. These results contribute to our understanding of the importance of physical activity in postmenopausal women by reiterating the benefits of physical activity for older adult women. Physical activity is an important tool for the prevention and management of osteoporosis.
Assessment of Safe Listening Intentional Behavior Toward Personal Listening Devices in Young Adults
Authors: Gopal Kamakshi V. , Champlin Sara , Phillips Bryce
Published: September 2019

Recreational noise-induced hearing loss (RNIHL) is a highly preventable disorder that is commonly seen in teenagers and young adults. Despite the documented negative effects of RNIHL, it is still challenging to persuade people to adopt safe listening behaviors. More research is needed to understand the underlying factors guiding listeners’ intentions to engage in safe listening habits. We used the Theory of Planned Behavior (TPB) to identify attitudes, social norms, and behavioral control in 92 young adults toward two intentional behaviors related to safe listening habits while listening to their personal listening devices: (1) lowering the intensity of loud music, and (2) shortening the listening duration of loud music. Using a Qualtrics survey, the major factors of the TPB model as they relate to the participants’ intention to engage in risk-controlling behavior were assessed. Behavioral intentions to turn the music down and listen for shorter durations were thought to be predicted by the TPB factors (attitudes, social norms, and perceived behavioral control). Linear regression findings indicated that the overall TPB models were significant. Positive attitudes toward turning the music down and shortening the durations were significantly associated with intentions to engage in non-risky behavior, more so for the former behavior.
The Efficacy of Device Designs (Mono-block or Bi-block) in Oral Appliance Therapy for Obstructive Sleep Apnea Patients: A Systematic Review and Meta-Analysis
Authors: Ishiyama Hiroyuki , Hasebe Daichi , Sato Kazumichi , Sakamoto Yuki , Furuhashi Akifumi , Komori Eri , Yuasa Hidemichi
Published: September 2019

Oral appliance (OAm) therapy has demonstrated efficacy in treating obstructive sleep apnea (OSA). The aim of this systematic review was to clarify the efficacy of device designs (Mono-block or Bi-block) in OAm therapy for OSA patients. We performed a meta-analysis using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Two studies (Mono-block OAm versus Bi-block OAm) remained eligible after applying the exclusion criteria. When comparing Mono-block OAm and Bi-block OAm, Mono-block OAm significantly reduced the apnea–hypopnea index (2.92; 95% confidence interval (95%CI), 1.26 to 4.58; p = 0.0006), and patient preference for Mono-block OAm was significantly higher (2.06; 95%CI, 1.44 to 2.06; p < 0.0001). Lowest SpO2, arousal index, non-REM stage 3, sleep efficiency, Epworth Sleepiness Scale (ESS), Snoring Scale, and side effects were not significantly different between the two groups (lowest SpO2: −11.18; 95%CI, −26.90 to 4.54; p = 0.16, arousal index: 4.40; 95%CI, −6.00 to 14.80; p = 0.41, non-REM stage 3: −2.00; 95%CI, −6.00 to 14.80; p = 0.41, sleep efficiency: −1.42, 95%CI, −4.71 to 1.86; p = 0.40, ESS: 0.12; 95%CI, −1.55 to 1.79; p = 0.89, Snoring Scale: 0.55; 95%CI, −0.73 to 1.83, p = 0.55, side effects: 1.00, 95%CI, 0.62 to 1.61, p = 1.00). In this systematic review, the use of Mono-block OAm was more effective than Bi-block OAm for OSA patients.
Comparison of the Modulatory Effect on Intestinal Microbiota between Raw and Bran-Fried Atractylodis Rhizoma in the Rat Model of Spleen-Deficiency Syndrome
Authors: Ma Shanpeng , Jiang Yujun , Zhang Beixue , Pang Jian , Xu Xiaoying , Sun Jianzhi , Lv Xin , Cai Qian
Published: September 2019

Atractylodis Rhizoma (AR), a kind of well-known traditional Chinese medicine (TCM), has a long history of being used to treat spleen-deficiency syndrome (SDS). Stir frying with bran is a common method of processing AR, as recorded in the Chinese Pharmacopoeia, and is thought to enhance the therapeutic effect in TCM. Our previous studies have confirmed that bran-fried AR is superior to raw AR in terms of the improvement of gastrointestinal tract function. However, the biological mechanism of action is not yet clear. Here, we report the difference between raw and bran-fried AR in terms of the modulatory effect of intestinal microbiota. We found that the composition of intestinal microbiota of SDS rats changed significantly compared with healthy rats and tended to recover to normal levels after treatment with raw and bran-fried AR. Nine bacteria closely related to SDS were identified at the genus level. Among them, the modulatory effect between the raw and bran-fried AR was different. The improved modulation on Bacteroides, Escherichia-Shigella, Phascolarctobacterium, Incertae-Sedis (Defluviitaleaceae Family) and Incertae-Sedis (Erysipelotrichaceae Family) could be the mechanism by which bran-fried AR enhanced the therapeutic effect. Correlation analysis revealed that the modulation on intestinal microbiota was closely related to the secretion and expression of cytokines and gastrointestinal hormones. These findings can help us to understand the role and significance of bran-fried AR against SDS.
Subgingival Microbiota of Mexicans with Type 2 Diabetes with Different Periodontal and Metabolic Conditions
Authors: Rodríguez-Hernández Adriana-Patricia , Márquez-Corona María de Lourdes , Pontigo-Loyola América Patricia , Medina-Solís Carlo Eduardo , Ximenez-Fyvie Laurie-Ann
Published: September 2019

Background: Type-2-Diabetes (T2D) and Periodontitis are major inflammatory diseases. However, not much is known about the specific subgingival microbiota in Mexicans with diabetes and metabolic dysbiosis. The aim of this study was to describe the subgingival microbiota of Mexicans with T2D and the different periodontal and metabolic conditions, through “Checkerboard” DNA–DNA hybridization. Methods: Subjects were divided into two groups—periodontal-health (PH) (PH_non-T2D; n = 59, PH_T2D; n = 14) and generalized-periodontitis (GP) (GP_non-T2D; n = 67, GP_T2D; n = 38). Obesity (BMI ≥ 30 kg/m2) and serum levels of glycated-hemoglobin (HbA1c), total-lipids, triglycerides, total-cholesterol, high-density-lipids, and low-density-lipids were measured for the T2D individuals. Subgingival microbial identification was processed for 40 species through DNA-probes. Results: Subjects with T2D harbored significantly higher mean total levels (PH: p < 0.001, and GP_NS), a lower proportion of “red” complex (GP: p < 0.01), a higher proportion of “yellow” (GP; p < 0.001), and “orange” (GP; p < 0.01) complex than the non-T2D. GP_T2D individuals exhibited a greater proportion of putative-species—Campylobacter gracilis and S. constellatus (p < 0.001), and Parvimonas micra and Prevotella nigrescens (p < 0.01), than GP_non-T2D. T2D individuals with HbA1c > 8% had presented significantly higher mean pocket-depth and higher levels of G. morbillorum (p < 0.05) and those with obesity or dyslipidemia harbored higher levels, prevalence, or proportion of Streptococcus sp., Actinomyces sp., and Capnocytophaga sp. Conclusions: T2D individuals harbored a particular microbial profile different to non-T2D microbiota. Metabolic control was related to dysbiosis of microbiota—HbA1c>8% related to periodontitis and obesity or dyslipidemia with the predominance of saccharolytic bacteria, irrespective of their periodontal condition.
The Relationship between Functional Health Literacy, Self-Rated Health, and Social Support between Younger and Older Adults in Ghana
Authors: Amoah Padmore
Published: September 2019

It is well established that health literacy positively affects health outcomes, and social support influences this association. What remains unclear is which aspect of social support (instrumental, informational, and emotional support) is responsible for this effect and whether the influence differs from one population group to another. This study addresses these lacunae. It examines the impact each type of support makes on the relation between functional health literacy (FHL) and self-rated health status among younger and older adults in Ghana. Data were pooled from two cross-sectional surveys, together comprising 521 participants in the Ashanti Region. The results indicated that young adults were more likely to possess sufficient FHL and perceive their health more positively than older adults. While FHL was positively associated with health status, the relation was stronger when young adults received a high level of emotional support. Among older persons, informational support substantially moderated the association between FHL and health status. Thus, social support modifies the relations between FHL and health status among younger and older adults in different ways and to different degrees. Therefore, interventions to improve FHL and health amongst younger and older adults should pay due regard to relevant aspects of social support.
Interpolation of Instantaneous Air Temperature Using Geographical and MODIS Derived Variables with Machine Learning Techniques
Authors: Ruiz-Álvarez Marcos , Alonso-Sarria Francisco , Gomariz-Castillo Francisco
Published: September 2019

Several methods have been tried to estimate air temperature using satellite imagery. In this paper, the results of two machine learning algorithms, Support Vector Machines and Random Forest, are compared with Multiple Linear Regression and Ordinary kriging. Several geographic, remote sensing and time variables are used as predictors. The validation is carried out using two different approaches, a leave-one-out cross validation in the spatial domain and a spatio-temporal k-block cross-validation, and four different statistics on a daily basis, allowing the use of ANOVA to compare the results. The main conclusion is that Random Forest produces the best results (R2 = 0.888 ± 0.026, Root mean square error = 3.01 ± 0.325 using k-block cross-validation). Regression methods (Support Vector Machine, Random Forest and Multiple Linear Regression) are calibrated with MODIS data and several predictors easily calculated from a Digital Elevation Model. The most important variables in the Random Forest model were satellite temperature, potential irradiation and cdayt, a cosine transformation of the julian day.
Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor
Authors: Russo Alexandra , Paret Claudia , Alt Francesca , Burhenne Jürgen , Fresnais Margaux , Wagner Wolfgang , Glaser Martin , Bender Hannah , Huprich Sabrina , Harter Patrick N. , Filipski Katharina , Lehmann Nadine , Backes Nora , Roth Lea , Seidmann Larissa , Sommer Clemens , Brockmann Marc A. , Pietsch Torsten , Neu Marie A. , Wingerter Arthur , Faber Jörg
Published: September 2019

The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.
Neurodegeneration and Neuro-Regeneration—Alzheimer’s Disease and Stem Cell Therapy
Authors: Vasic Verica , Barth Kathrin , Schmidt Mirko H.H.
Published: September 2019

Aging causes many changes in the human body, and is a high risk for various diseases. Dementia, a common age-related disease, is a clinical disorder triggered by neurodegeneration. Brain damage caused by neuronal death leads to cognitive decline, memory loss, learning inabilities and mood changes. Numerous disease conditions may cause dementia; however, the most common one is Alzheimer’s disease (AD), a futile and yet untreatable illness. Adult neurogenesis carries the potential of brain self-repair by an endogenous formation of newly-born neurons in the adult brain; however it also declines with age. Strategies to improve the symptoms of aging and age-related diseases have included different means to stimulate neurogenesis, both pharmacologically and naturally. Finally, the regulatory mechanisms of stem cells neurogenesis or a functional integration of newborn neurons have been explored to provide the basis for grafted stem cell therapy. This review aims to provide an overview of AD pathology of different neural and glial cell types and summarizes current strategies of experimental stem cell treatments and their putative future use in clinical settings.
Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications
Authors: Jarrar Yazun Bashir , Lee Su-Jun
Published: September 2019

Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.
Mapping the Interactions of HBV cccDNA with Host Factors
Authors: Mohd-Ismail Nur K. , Lim Zijie , Gunaratne Jayantha , Tan Yee-Joo
Published: September 2019

Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has reduced new infections, a cure for chronic hepatitis B (CHB) is still unavailable. Current anti-HBV therapies slow down disease progression but are not curative as they cannot eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The cccDNA minichromosome persists in the nuclei of infected hepatocytes where it forms the template for all viral transcription. Interactions between host factors and cccDNA are crucial for its formation, stability, and transcriptional activity. Here, we summarize the reported interactions between HBV cccDNA and various host factors and their implications on HBV replication. While the virus hijacks certain cellular processes to complete its life cycle, there are also host factors that restrict HBV infection. Therefore, we review both positive and negative regulation of HBV cccDNA by host factors and the use of small molecule drugs or sequence-specific nucleases to target these interactions or cccDNA directly. We also discuss several reporter-based surrogate systems that mimic cccDNA biology which can be used for drug library screening of cccDNA-targeting compounds as well as identification of cccDNA-related targets.
Trefoil Factor 3 (TFF3) Is Involved in Cell Migration for Skeletal Repair
Authors: Krüger Katharina , Schmid Sebastian , Paulsen Friedrich , Ignatius Anita , Klinger Patricia , Hotfiel Thilo , Swoboda Bernd , Gelse Kolja
Published: September 2019

The aim of the study was to explore the possible role of Trefoil Factor Family peptide 3 (TFF3) for skeletal repair. The expression of TFF3 was analyzed in human joint tissues as well as in a murine bone fracture model. Serum levels of TFF3 following a defined skeletal trauma in humans were determined by ELISA. The mRNA expression of TFF3 was analyzed under normoxia and hypoxia. Expression analysis after stimulation of human mesenchymal progenitor cells (MPCs) with TFF3 was performed by RT2 Profiler PCR Array. The effect of recombinant human (rh)TFF3 on MPCs was analysed by different migration and chemotaxis assays. The effect on cell motility was also visualized by fluorescence staining of F-Actin. TFF3 was absent in human articular cartilage, but strongly expressed in the subchondral bone and periosteum of adult joints. Strong TFF3 immunoreactivity was also detected in murine fracture callus. Serum levels of TFF3 were significantly increased after skeletal trauma in humans. Expression analysis demonstrated that rhTFF3 significantly decreased mRNA of ROCK1. Wound healing assays showed increased cell migration of MPCs by rhTFF3. The F-Actin cytoskeleton was markedly influenced by rhTFF3. Cell proliferation was not increased by rhTFF3. The data demonstrate elevated expression of TFF3 after skeletal trauma. The stimulatory effects on cell motility and migration of MPCs suggest a role of TFF3 in skeletal repair.
Ginsenoside Compound K Induces Ros-Mediated Apoptosis and Autophagic Inhibition in Human Neuroblastoma Cells In Vitro and In Vivo
Authors: Oh Jung-Mi , Kim Eunhee , Chun Sungkun
Published: September 2019

Autophagy can result in cellular adaptation, as well as cell survival or cell death. Modulation of autophagy is increasingly regarded as a promising cancer therapeutic approach. Ginsenoside compound K (CK), an active metabolite of ginsenosides isolated from Panax ginseng C.A. Meyer, has been identified to inhibit growth of cancer cell lines. However, the molecular mechanisms of CK effects on autophagy and neuroblastoma cell death have not yet been investigated. In the present study, CK inhibited neuroblastoma cell proliferation in vitro and in vivo. Treatment by CK also induced the accumulation of sub-G1 population, and caspase-dependent apoptosis in neuroblastoma cells. In addition, CK promotes autophagosome accumulation by inducing early-stage autophagy but inhibits autophagic flux by blocking of autophagosome and lysosome fusion, the step of late-stage autophagy. This effect of CK appears to be mediated through the induction of intracellular reactive oxygen species (ROS) and mitochondria membrane potential loss. Moreover, chloroquine, an autophagy flux inhibitor, further promoted CK-induced apoptosis, mitochondrial ROS induction, and mitochondria damage. Interestingly, those promoted phenomena were rescued by co-treatment with a ROS scavenging agent and an autophagy inducer. Taken together, our findings suggest that ginsenoside CK induced ROS-mediated apoptosis and autophagic flux inhibition, and the combination of CK with chloroquine, a pharmacological inhibitor of autophagy, may be a novel therapeutic potential for the treatment of neuroblastoma.
Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine
Authors: Zhou Yunfeng , Tao Xue , Wang Zhi , Feng Li , Wang Lisha , Liu Xinmin , Pan Ruile , Liao Yonghong , Chang Qi
Published: September 2019

An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.
Dynamic mRNA Expression Analysis of the Secondary Palatal Morphogenesis in Miniature Pigs
Authors: Liu Jia , Chen Jing , Yuan Dong , Sun Lindong , Fan Zhipeng , Wang Songlin , Du Juan
Published: September 2019

Normal mammalian palatogenesis is a complex process that requires the occurrence of a tightly regulated series of specific and sequentially regulated cellular events. Cleft lip/palate (CLP), the most frequent craniofacial malformation birth defects, may occur if any of these events undergo abnormal interference. Such defects not only affect the patients, but also pose a financial risk for the families. In our recent study, the miniature pig was shown to be a valuable alternative large animal model for exploring human palate development by histology. However, few reports exist in the literature to document gene expression and function during swine palatogenesis. To better understand the genetic regulation of palate development, an mRNA expression profiling analysis was performed on miniature pigs, Sus scrofa. Five key developmental stages of miniature pigs from embryonic days (E) 30–50 were selected for transcriptome sequencing. Gene expression profiles in different palate development stages of miniature pigs were identified. Nine hundred twenty significant differentially expressed genes were identified, and the functional characteristics of these genes were determined by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Some of these genes were associated with HH (hedgehog), WNT (wingless-type mouse mammary tumor virus integration site family), and MAPK (mitogen-activated protein kinase) signaling, etc., which were shown in the literature to affect palate development, while some genes, such as HIP (hedgehog interacting protein), WNT16, MAPK10, and LAMC2 (laminin subunit gamma 2), were additions to the current understanding of palate development. The present study provided a comprehensive analysis for understanding the dynamic gene regulation during palate development and provided potential ideas and resources to further study normal palate development and the etiology of cleft palate.
Confined Dynamics of Water in Transmembrane Pore of TRPV1 Ion Channel
Authors: Trofimov Yury A. , Krylov Nikolay A. , Efremov Roman G.
Published: September 2019

Solvation effects play a key role in chemical and biological processes. The microscopic properties of water near molecular surfaces are radically different from those in the bulk. Furthermore, the behavior of water in confined volumes of a nanometer scale, including transmembrane pores of ion channels, is especially nontrivial. Knowledge at the molecular level of structural and dynamic parameters of water in such systems is necessary to understand the mechanisms of ion channels functioning. In this work, the results of molecular dynamics (MD) simulations of water in the pore and selectivity filter domains of TRPV1 (Transient Receptor Potential Vanilloid type 1) membrane channel are considered. These domains represent nanoscale volumes with strongly amphiphilic walls, where physical behavior of water radically differs from that of free hydration (e.g., at protein interfaces) or in the bulk. Inside the pore and filter domains, water reveals a very heterogeneous spatial distribution and unusual dynamics: It forms compact areas localized near polar groups of particular residues. Residence time of water molecules in such areas is at least 1.5 to 3 times larger than that observed for similar groups at the protein surface. Presumably, these water “blobs” play an important role in the functional activity of TRPV1. In particular, they take part in hydration of the hydrophobic TRPV1 pore by localizing up to six waters near the so-called “lower gate” of the channel and reducing by this way the free energy barrier for ion and water transport. Although the channel is formed by four identical protein subunits, which are symmetrically packed in the initial experimental 3D structure, in the course of MD simulations, hydration of the same amino acid residues of individual subunits may differ significantly. This greatly affects the microscopic picture of the distribution of water in the channel and, potentially, the mechanism of its functioning. Therefore, reconstruction of the full picture of TRPV1 channel solvation requires thorough atomistic simulations and analysis. It is important that the naturally occurring porous volumes, like ion-conducting protein domains, reveal much more sophisticated and fine-tuned regulation of solvation than, e.g., artificially designed carbon nanotubes.