bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study of Gut Microbiota in Wild and Captive Giant Pandas (Ailuropoda melanoleuca)
Authors: Guo Wei , Mishra Sudhanshu , Wang Chengdong , Zhang Hemin , Ning Ruihong , Kong Fanli , Zeng Bo , Zhao Jiangchao , Li Ying
Published: October 2019

Captive breeding has been used as an effective approach to protecting endangered animals but its effect on the gut microbiome and the conservation status of these species is largely unknown. The giant panda is a flagship species for the conservation of wildlife. With integrated efforts including captive breeding, this species has been recently upgraded from “endangered” to “vulnerable” (IUCN 2016). Since a large proportion (21.8%) of their global population is still captive, it is critical to understand how captivity changes the gut microbiome of these pandas and how such alterations to the microbiome might affect their future fitness and potential impact on the ecosystem after release into the wild. Here, we use 16S rRNA (ribosomal RNA) marker gene sequencing and shotgun metagenomics sequencing to demonstrate that the fecal microbiomes differ substantially between wild and captive giant pandas. Fecal microbiome diversity was significantly lower in captive pandas, as was the diversity of functional genes. Additionally, captive pandas have reduced functional potential for cellulose degradation but enriched metabolic pathways for starch metabolism, indicating that they may not adapt to a wild diet after being released into the wild since a major component of their diet in the wild will be bamboo. Most significantly, we observed a significantly higher level of amylase activity but a lower level of cellulase activity in captive giant panda feces than those of wild giant pandas, shown by an in vitro experimental assay. Furthermore, antibiotic resistance genes and virulence factors, as well as heavy metal tolerance genes were enriched in the microbiomes of captive pandas, which raises a great concern of spreading these genes to other wild animals and ecosystems when they are released into a wild environment. Our results clearly show that captivity has altered the giant panda microbiome, which could have unintended negative consequences on their adaptability and the ecosystem during the reintroduction of giant pandas into the wild.
Molecular Characterization of Leishmania RNA virus 2 in Leishmania major from Uzbekistan
Authors: Kleschenko Yuliya , Grybchuk Danyil , Matveeva Nadezhda S. , Macedo Diego H. , Ponirovsky Evgeny N. , Lukashev Alexander N. , Yurchenko Vyacheslav
Published: October 2019

Here we report sequence and phylogenetic analysis of two new isolates of Leishmania RNA virus 2 (LRV2) found in Leishmania major isolated from human patients with cutaneous leishmaniasis in south Uzbekistan. These new virus-infected flagellates were isolated in the same region of Uzbekistan and the viral sequences differed by only nineteen SNPs, all except one being silent mutations. Therefore, we concluded that they belong to a single LRV2 species. New viruses are closely related to the LRV2-Lmj-ASKH documented in Turkmenistan in 1995, which is congruent with their shared host (L. major) and common geographical origin.
Line Immunoblot Assay for Tick-Borne Relapsing Fever and Findings in Patient Sera from Australia, Ukraine and the USA
Authors: Shah Jyotsna S. , Liu Song , Du Cruz Iris , Poruri Akhila , Maynard Rajan , Shkilna Mariia , Korda Mykhaylo , Klishch Ivan , Zaporozhan Stepan , Shtokailo Kateryna , Andreychyn Mykhaylo , Stricker Raphael B. , Ramasamy Ranjan
Published: October 2019

Tick-borne relapsing fever (TBRF) is caused by spirochete bacteria of the genus Borrelia termed relapsing fever Borreliae (RFB). TBRF shares symptoms with Lyme disease (LD) caused by related Lyme disease Borreliae (LDB). TBRF and LD are transmitted by ticks and occur in overlapping localities worldwide. Serological detection of antibodies used for laboratory confirmation of LD is not established for TBRF. A line immunoblot assay using recombinant proteins from different RFB species, termed TBRF IB, was developed and its diagnostic utility investigated. The TBRF IBs were able to differentiate between antibodies to RFB and LDB and had estimated sensitivity, specificity, and positive and negative predictive values of 70.5%, 99.5%, 97.3%, and 93.4%, respectively, based on results with reference sera from patients known to be positive and negative for TBRF. The use of TBRF IBs and analogous immunoblots for LD to test sera of patients from Australia, Ukraine, and the USA with LD symptoms revealed infection with TBRF alone, LD alone, and both TBRF and LD. Diagnosis by clinical criteria alone can, therefore, underestimate the incidence of TBRF. TBRF IBs will be useful for laboratory confirmation of TBRF and understanding its epidemiology worldwide.
Flood Frequency Analysis Using Participatory GIS and Rainfall Data for Two Stations in Narok Town, Kenya
Authors: Houessou-Dossou Eva Audrey Yessito , Mwangi Gathenya John , Njuguna Mugwima , Abiero Gariy Zachary
Published: October 2019

Flood management requires in-depth computational modelling through assessment of flood return period and river flow data in order to effectively analyze catchment response. The participatory geographic information system (PGIS) is a tool which is increasingly used for collecting data and decision making on environmental issues. This study sought to determine the return periods of major floods that happened in Narok Town, Kenya, using rainfall frequency analysis and PGIS. For this purpose, a number of statistical distribution functions were applied to daily rainfall data from two stations: Narok water supply (WS) station and Narok meteorological station (MS). The first station has a dataset of thirty years and the second one has a dataset of fifty-nine (59) years. The parameters obtained from the Kolmogorov–Smirnov (K–S) test and chi-square test helped to select the appropriate distribution. The best-fitted distribution for WS station were Gumbel L-moment, Pareto L-moment, and Weibull distribution for maximum one day, two days, and three days rainfall, respectively. However, the best-fitted distribution was found to be generalized extreme value L-moment, Gumbel and gamma distribution for maximum one day, two days, and three days, respectively for the meteorological station data. Each of the selected best-fitted distribution was used to compute the corresponding rainfall intensity for 5, 10, 25, 50, and 100 years return period, as well as the return period of the significant flood that happened in the town. The January 1993 flood was found to have a return period of six years, while the April 2013, March 2013, and April 2015 floods had a return period of one year each. This study helped to establish the return period of major flood events that occurred in Narok, and highlights the importance of population in disaster management. The study’s results would be useful in developing flood hazard maps of Narok Town for different return periods.
The Development and Validation of the Healthcare Professional Humanization Scale (HUMAS) for Nursing
Authors: Pérez-Fuentes María del Carmen , Herera-Peco Iván , Molero Jurado María del Mar , Oropesa Ruiz Nieves Fátima , Ayuso-Murillo Diego , Gázquez Linares José Jesús
Published: October 2019

Introduction: The approach and use of the term “humanization” is very much present in healthcare. However, instruments for measuring the concept of the humanization of care are yet to be designed and developed. Objective: The main objective of this study was to evaluate and validate the Healthcare Professional Humanization Scale (HUMAS) for nursing professionals. Method: The sample was made up of 338 adults, who were nurses working at health centers and hospitals, and aged between 22 and 56. Results: The results of the analyses confirm that the Healthcare Professional Humanization Scale (HUMAS) has an adequate construct validity and reliability, and defines the humanization of care as a multidimensional construct, made up of five factors: Affection, Self-efficacy, Emotional understanding, Optimistic disposition and Sociability. Conclusions: The new HUMAS scale may be an easily administered and coded instrument for approaching the humanization of care, not only in research, but also in practice.
Men’s Intentions to Recommend Professional Help-Seeking to Their Partners in the Postpartum Period: the Direct and Indirect Effects of Gender-Role Conflict
Authors: Luís Catarina , Canavarro Maria Cristina , Fonseca Ana
Published: October 2019

Women’s partners may act as facilitators of professional help-seeking for mental health problems in the postpartum period. This study aimed to examine the sociodemographic and clinical correlates of men’s intentions to recommend professional help-seeking to their partners if they display postpartum mood and anxiety disorders and to explore the relationship between gender-role conflict and the intention to recommend help-seeking. A cross-sectional study included 214 adult men in a heterosexual relationship with a partner within the reproductive age. Men presented a high intention to recommend professional help to their partners. All dimensions of gender-role conflict were directly associated with the intention to recommend professional help-seeking (p < 0.05). High levels of gender-role conflict (dimensions success, power and competition, and restricted emotionality) were found to lead to increased levels of stigma and lower levels of intention to seek professional help, which, in turn, translated into lower intention to recommend help-seeking. These results emphasize the importance of developing universal awareness-raising and education campaigns directed at men aiming to reduce levels of gender-role conflict and stigma, and normalize the use of mental health services, to increase men’s intentions to recommend professional help-seeking to their partners.
Diet Education as a Success Factor of Glycemia Regulation in Diabetes Patients: A Prospective Study
Authors: Gvozdanović Zvjezdana , Farčić Nikolina , Placento Harolt , Lovrić Robert , Dujmić Željka , Jurić Ana , Miškić Blaženka , Prlić Nada
Published: October 2019

Background: The aim of this study was to examine the effect of dietary education on glycemic control in patients with any type of diabetes at four-week and two-year follow-ups. Methods: A two-year prospective study was conducted in three phases: before, four weeks after, and two years after an educational program. The participants were patients diagnosed with diabetes who were receiving insulin or oral hypoglycemics and who attended the Diabetes Clinic of the General County Hospital Našice, Croatia to receive their treatment. The questionnaire and educational program were created for the purpose of this study. Measurements were made (fasting blood glucose, glycated hemoglobin, body mass index, blood pressure, knowledge test) at baseline, four weeks and two years after education. Results: A total of 109 participants took part in the study, of which 56 (51.4%) were on insulin therapy and 53 (48.6%) were on oral therapy, after two years, 78 (72%) subjects were followed up with. There was no control group. At the two-year follow-up, participants with insulin therapy had significantly higher glycated hemoglobin (Mann–Whitney U test, p = 0.035). Significant differences were observed in fasted blood glucose (Friedman’s test, p = 0.001), diastolic pressure (Friedman’s test, P = 0.018), and glycated hemoglobin (Wilcoxon test, p < 0.001) between Phase 1 and Phase 3. Conclusions: Education has a positive effect on adherence to recommended diet and glycemia regulation in diabetes patients after four-week follow-ups. However, after two years, participants showed a decrease in adherence to recommended diet and increased glycemia.
Improved Estimates of Population Exposure in Low-Elevation Coastal Zones of China
Authors: Yang Xuchao , Yao Chenming , Chen Qian , Ye Tingting , Jin Cheng
Published: October 2019

With sea level predicted to rise and the frequency and intensity of coastal flooding expected to increase due to climate change, high-resolution gridded population datasets have been extensively used to estimate the size of vulnerable populations in low-elevation coastal zones (LECZ). China is the most populous country, and populations in its LECZ grew rapidly due to urbanization and remarkable economic growth in coastal areas. In assessing the potential impacts of coastal hazards, the spatial distribution of population exposure in China’s LECZ should be examined. In this study, we propose a combination of multisource remote sensing images, point-of-interest data, and machine learning methods to improve the performance of population disaggregation in coastal China. The resulting population grid map of coastal China for the reference year 2010, with a spatial resolution of 100 × 100 m, is presented and validated. Then, we analyze the distribution of population in LECZ by overlaying the new gridded population data and LECZ footprints. Results showed that the total population exposed in China’s LECZ in 2010 was 158.2 million (random forest prediction) and 160.6 million (Cubist prediction), which account for 12.17% and 12.36% of the national population, respectively. This study also showed the considerable potential in combining geospatial big data for high-resolution population estimation.
Frailty and Sarcopenia as a Geriatric Syndrome in Community-Dwelling Older Adults
Authors: Makizako Hyuma
Published: October 2019

Geriatric syndrome refers to a series of symptoms and observations caused by a variety of factors associated with aging, where the older adults show the treatment consciously or otherwise, and long-term care becomes important at the same time [...]
Target, Suspect and Non-Target Screening of Silylated Derivatives of Polar Compounds Based on Single Ion Monitoring GC-MS
Authors: Gumbi Bhekumuzi Prince , Moodley Brenda , Birungi Grace , Ndungu Patrick Gathura
Published: October 2019

There is growing interest in determining the unidentified peaks within a sample spectra besides the analytes of interest. Availability of reference standards and hyphenated instruments has been a key and limiting factor in the rapid determination of emerging pollutants in the environment. In this work, polar compounds were silylated and analyzed with gas chromatography mass spectrometry (GC-MS) to determine the abundant fragments within the single ion monitoring (SIM) mode and methodology. Detection limits and recoveries of the compounds were established in river water, wastewater, biosolid and sediment matrices. Then, specific types of polar compounds that are classified as emerging contaminants, pharmaceuticals and personal care products, in the environment were targeted in the Mgeni and Msunduzi Rivers. We also performed suspect and non-target analysis screening to identify several other polar compounds in these rivers. A total of 12 compounds were quantified out of approximately 50 detected emerging contaminants in the Mgeni and Msunduzi Rivers. This study is significant for Africa, where the studies of emerging contaminants are limited and not usually prioritized.
A Bibliometric Analysis of the Health Field Regarding Social Networks and Young People
Authors: Aparicio-Martinez Pilar , Perea-Moreno Alberto-Jesus , Martinez-Jimenez María Pilar , Redel-Macías María Dolores , Vaquero-Abellan Manuel , Pagliari Claudia
Published: October 2019

Social networks have historically been used to share information and support regarding health-related topics, and this usage has increased with the rise of online social media. Young people are high users of social media, both as passive listeners and as active contributors. This study aimed to map the trends in publications focused on social networks, health, and young people over the last 40 years. Scopus and the program VOSviewer were used to map the frequency of the publications, keywords, and clusters of researchers active in the field internationally. A structured keyword search using the Scopus database yielded 11,966 publications. The results reveal a long history of research on social networks, health, and young people. Research articles were the most common type of publication (68%), most of which described quantitative studies (82%). The main discipline represented in this literature was medicine, with 6062 documents. North American researchers dominate the field, both as authors and partners in international research collaborations. The present article adds to the literature by elucidating the growing importance of social networks in health research as a topic of study. This may help to inform future investments in public health research and surveillance using these novel data sources.
The Association Between Health Conditions, Consciousness, Involvement, and Knowledge and Dietary Supplement Intake among University Students in South Korea
Authors: Choi Jinkyung
Published: October 2019

Dietary supplements (DSs) are typically used by the elderly in a population, but younger age groups are increasingly purchasing these products. In consideration of this issue, the present study investigated the DS-related behaviors and general lifestyles of university students in South Korea. The health conditions, consciousness, involvement, and knowledge, as well as the future behavioral intentions, of DS users and non-users were determined and compared. A survey was administered to the respondents, and measurements were adapted and rephrased to suit the Korean context. Results showed that although the behaviors of DS users and non-users were characterized by similar patterns, significant differences in health involvement and future purchase were found between these groups. Health involvement influenced DSs buying intentions in the future, but no significant differences in the other variables were found. The findings suggested that university students take DSs regardless of their expectations about their efficacy and that their knowledge does not affect their intention to purchase such products.
Physicochemical and Biological Effects on Activated Sludge Performance and Activity Recovery of Damaged Sludge by Exposure to CeO2 Nanoparticles in Sequencing Batch Reactors
Authors: Feng Qian , Sun Yaqing , Wu Yang , Xue Zhaoxia , Luo Jingyang , Fang Fang , Li Chao , Cao Jiashun
Published: October 2019

Recently, the growing release of CeO2 nanoparticles (CeO2 NPs) into sewage systems has attracted great concern. Several studies have extensively explored CeO2 NPs’ potential adverse impacts on wastewater treatment plants; however, the impaired activated sludge recovery potentials have seldom been addressed to date. To explore the physicochemical and biological effects on the activated sludge performance and activity recovery of damaged sludge by exposure to CeO2 NPs in sequencing batch reactors (SBRs), four reactors and multiple indicators including water quality, key enzymes, microbial metabolites, the microbial community structure and toxicity were used. Results showed that 10-week exposure to higher CeO2 NP concentration (1, 10 mg/L) resulted in a sharp decrease in nitrogen and phosphorus removal efficiencies, which were consistent with the tendencies of key enzymes. Meanwhile, CeO2 NPs at concentrations of 0.1, 1, and 10 mg/L decreased the secretion of tightly bound extracellular polymeric substances to 0.13%, 3.14%, and 28.60%, respectively, compared to the control. In addition, two-week recovery period assays revealed that the functional bacteria Proteobacteria, Nitrospirae and Planctomycetes recovered slightly at the phyla level, as analyzed through high-throughput sequencing, which was consistent with the small amount of improvement of the effluent performance of the system. This reflected the small possibility of the activity recovery of damaged sludge.
Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression
Authors: Lunardi Baccetto Sarah , Lehmann Christian
Published: October 2019

Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression.
Protective Effects of Novel Antioxidant Peptide Purified from Alcalase Hydrolysate of Velvet Antler Against Oxidative Stress in Chang Liver Cells In Vitro and in a Zebrafish Model In Vivo
Authors: Ding Yuling , Ko Seok-Chun , Moon Sang-Ho , Lee Seung-Hong
Published: October 2019

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals.
Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish
Authors: Zwi Stephanie F. , Choron Clarisse , Zheng Dawei , Nguyen David , Zhang Yuxi , Roshal Camilla , Kikuchi Kazu , Hesselson Daniel
Published: October 2019

Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina requires foxp3a+ zebrafish regulatory T cells (zTregs). However, it remains unclear whether the muted regenerative responses in mammals are due to impaired recruitment and/or function of homologous mammalian regulatory T cell (Treg) populations. Here, we explore the possibility of enhancing zTreg recruitment with pharmacological interventions using the well-characterized zebrafish tail amputation model to establish a high-throughput screening platform. Injury-infiltrating zTregs were transgenically labelled to enable rapid quantification in live animals. We screened the NIH Clinical Collection (727 small molecules) for modulators of zTreg recruitment to the regenerating tissue at three days post-injury. We discovered that the dopamine agonist pramipexole, a drug currently approved for treating Parkinson’s Disease, specifically enhanced zTreg recruitment after injury. The dopamine antagonist SCH-23390 blocked pramipexole activity, suggesting that peripheral dopaminergic signaling may regulate zTreg recruitment. Similar pharmacological approaches for enhancing mammalian Treg recruitment may be an important step in developing novel strategies for tissue regeneration in humans.
Loss of Tumor Suppressor CYLD Expression Triggers Cisplatin Resistance in Oral Squamous Cell Carcinoma
Authors: Suenaga Naoki , Kuramitsu Mimi , Komure Kanae , Kanemaru Ayumi , Takano Kanako , Ozeki Kazuya , Nishimura Yuka , Yoshida Ryoji , Nakayama Hideki , Shinriki Satoru , Saito Hideyuki , Jono Hirofumi
Published: October 2019

Cisplatin is one of the most effective chemotherapeutic agents commonly used for several malignancies including oral squamous cell carcinoma (OSCC). Although cisplatin resistance is a major obstacle to effective treatment and is associated with poor prognosis of OSCC patients, the molecular mechanisms by which it develops are largely unknown. Cylindromatosis (CYLD), a deubiquitinating enzyme, acts as a tumor suppressor in several malignancies. Our previous studies have shown that loss of CYLD expression in OSCC tissues is significantly associated with poor prognosis of OSCC patients. Here, we focused on CYLD expression in OSCC cells and determined whether loss of CYLD expression is involved in cisplatin resistance in OSCC and elucidated its molecular mechanism. In this study, to assess the effect of CYLD down-regulation on cisplatin resistance in human OSCC cell lines (SAS), we knocked-down the CYLD expression by using CYLD-specific siRNA. In cisplatin treatment, cell survival rates in CYLD knockdown SAS cells were significantly increased, indicating that CYLD down-regulation caused cisplatin resistance to SAS cells. Our results suggested that cisplatin resistance caused by CYLD down-regulation was associated with the mechanism through which both the reduction of intracellular cisplatin accumulation and the suppression of cisplatin-induced apoptosis via the NF-κB hyperactivation. Moreover, the combination of cisplatin and bortezomib treatment exhibited significant anti-tumor effects on cisplatin resistance caused by CYLD down-regulation in SAS cells. These findings suggest the possibility that loss of CYLD expression may cause cisplatin resistance in OSCC patients through NF-κB hyperactivation and may be associated with poor prognosis in OSCC patients.
Atherosclerosis and Coenzyme Q10
Authors: Suárez-Rivero Juan M. , Pastor-Maldonado Carmen J. , de la Mata Mario , Villanueva-Paz Marina , Povea-Cabello Suleva , Álvarez-Córdoba Mónica , Villalón-García Irene , Suárez-Carrillo Alejandra , Talaverón-Rey Marta , Munuera Manuel , Sánchez-Alcázar José A.
Published: October 2019

Atherosclerosis is the most common cause of cardiac deaths worldwide. Classically, atherosclerosis has been explained as a simple arterial lipid deposition with concomitant loss of vascular elasticity. Eventually, this condition can lead to consequent blood flow reduction through the affected vessel. However, numerous studies have demonstrated that more factors than lipid accumulation are involved in arterial damage at the cellular level, such as inflammation, autophagy impairment, mitochondrial dysfunction, and/or free-radical overproduction. In order to consider the correction of all of these pathological changes, new approaches in atherosclerosis treatment are necessary. Ubiquinone or coenzyme Q10 is a multifunctional molecule that could theoretically revert most of the cellular alterations found in atherosclerosis, such as cholesterol biosynthesis dysregulation, impaired autophagy flux and mitochondrial dysfunction thanks to its redox and signaling properties. In this review, we will show the latest advances in the knowledge of the relationships between coenzyme Q10 and atherosclerosis. In addition, as atherosclerosis phenotype is closely related to aging, it is reasonable to believe that coenzyme Q10 supplementation could be beneficial for both conditions.
Inhibitory Effects of N-[2-(4-acetyl-1-piperazinyl) phenyl]-2-(2-chlorophenoxy) acetamide on Osteoclast Differentiation In Vitro via the Downregulation of TRAF6
Authors: Chen Zhihao , Cho Eunjin , Lee Jinkyung , Lee Sunwoo , Lee Tae-Hoon
Published: October 2019

Osteoclasts are poly-nuclear cells that resorb mineral components from old or damaged bone tissue. Primary mononuclear cells are activated by receptor activator of nuclear factor kappa-Β ligand (RANKL) and differentiate into large multinucleated cells. Dysregulation of osteoclast differentiation can lead to pathological bone loss and destruction. Many studies have focused on the development of new molecules to regulate RANKL-mediated signaling. In this study, N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(2-chlorophenoxy) acetamide (PPOA-N-Ac-2-Cl) led to a significant decrease in the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cells in a dose-dependent manner, without inducing significant cytotoxicity. PPOA-N-Ac-2-Cl affected the expression of osteoclast-specific marker genes, such as TRAF6, c-fos, DC-STAMP, NFATc1, MMP9, CtsK, and TRAP (Acp5), during RANKL-mediated osteoclastogenesis. Moreover, PPOA-N-Ac-2-Cl significantly attenuated the protein levels of CtsK, a critical protease involved in bone resorption. Accordingly, bone resorption activity and F-actin ring formation decreased in the presence of PPOA-N-Ac-2-Cl. In conclusion, this study shows that PPOA-N-Ac-2-Cl acts as an inhibitor of osteoclast differentiation and may serve as a potential candidate agent for the treatment of osteoclast-related bone diseases by virtue of attenuating bone resorption.
Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model
Authors: Dupuis Holly , Pest Michael Andrew , Hadzic Ermina , Vo Thin Xuan , Hardy Daniel B. , Beier Frank
Published: October 2019

Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. RXR agonist-treated rats had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence with p57 immunostaining. Additionally, SOX9-positive cells were found surrounding the calcified tissue. The epiphysis of SR11237-treated bones showed increased TRAP staining and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of the treated animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models
Cytoprotective Preconditioning of Osteoblast-Like Cells with N-Acetyl-L-Cysteine for Bone Regeneration in Cell Therapy
Authors: Yamada Masahiro , Watanabe Jun , Ueno Takeshi , Ogawa Takahiro , Egusa Hiroshi
Published: October 2019

Oxidative stress hinders tissue regeneration in cell therapy by inducing apoptosis and dysfunction in transplanted cells. N-acetyl-L-cysteine (NAC) reinforces cellular antioxidant capabilities by increasing a major cellular endogenous antioxidant molecule, glutathione, and promotes osteogenic differentiation. This study investigates the effects of pretreatment of osteoblast-like cells with NAC on oxidative stress-induced apoptosis and dysfunction and bone regeneration in local transplants. Rat femur bone marrow-derived osteoblast-like cells preincubated for 3 h with and without 5 mM NAC were cultured in a NAC-free osteogenic differentiation medium with continuous exposure to 50 μM hydrogen peroxide to induce oxidative stress. NAC preincubation prevented disruption of intracellular redox balance and alleviated apoptosis and negative impact on osteogenic differentiation, even under oxidative stress. Autologous osteoblast-like cells with and without NAC pretreatment in a collagen sponge vehicle were implanted in critical-size defects in rat femurs. In the third week, NAC-pretreated cells yielded complete defect closure with significantly matured lamellar bone tissue in contrast with poor bone healing by cells without pretreatment. Cell-tracking analysis demonstrated direct bone deposition by transplanted cells pretreated with NAC. Pretreatment of osteoblast-like cells with NAC enhances bone regeneration in local transplantation by preventing oxidative stress-induced apoptosis and dysfunction at the transplanted site.
Adverse Effects of Proton Pump Inhibitors—Evidence and Plausibility
Authors: Fossmark Reidar , Martinsen Tom C. , Waldum Helge L.
Published: October 2019

Proton pump inhibitors (PPIs) have been increasingly used over the last decades and there are concerns about overuse and the numerous reported side-effects. It is uncertain whether associations between PPI use and potential side effects are causal. However, important evidence from experimental and mechanistic studies that could support a causal relationship may have been underestimated by epidemiologists and meta-analysists. In the current manuscript we review the combined epidemiological and mechanistic evidence of the adverse effects of PPI use.
Anti-Diabetic Nephropathy Activities of Polysaccharides Obtained from Termitornyces albuminosus via Regulation of NF-κB Signaling in db/db Mice
Authors: Yang Chang , Feng Qi , Liao Huan , Yu Xinlei , Liu Yang , Wang Di
Published: October 2019

Termitornyces albuminosus is a kind of traditional Chinese edible fungus rich in nutrients and medicinal ingredients, and it has anti-oxidative, analgesic and anti-inflammatory effects. However, the hypoglycemic and nephroprotective effects of polysaccharides separated from T. albuminosus (PTA) have not been reported. The properties of PTA were analyzed in a BKS.Cg-Dock7m +/+ Leprdb/JNju (db/db) mouse model of diabetes. After the administration of PTA for eight weeks, the hypoglycemic and hypolipidemic activities of PTA in the db/db mice were assessed. The results of a cytokine array combined with an enzyme-linked immunosorbent assay confirmed the anti-oxidative and anti-inflammatory activities of PTA. An eight-week administration of PTA caused hypoglycemic and hypolipidemic functioning, as indicated by suppressed plasma glucose levels, as well as the modulation of several cytokines related to glycometabolism, in the sera and kidneys of the mice. PTA treatment also had a protective effect on renal function, restoring renal structures and regulating potential indicators of nephropathy. In the kidneys of the db/db mice, PTA treatment reduced the activation of protein kinase B, the inhibitor of κB kinase alpha and beta, and the inhibitor of κB alpha and nuclear factor-κB (NF-κB). We establish the hypoglycemic, hypolipidemic, and anti-diabetic nephropathy effects of PTA, and we find that the renal protection effects of PTA may be related to anti-inflammatory activity via the regulation of NF-κB signaling.
Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson’s Disease Models
Authors: Cho Bongki , Kim Taeyun , Huh Yu-Jin , Lee Jaemin , Lee Yun-Il
Published: October 2019

Parkinson’s disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD.
New Phosphorus Analogs of Bevirimat: Synthesis, Evaluation of Anti-HIV-1 Activity and Molecular Docking Study
Authors: Chrobak Elwira , Marciniec Krzysztof , Dąbrowska Aleksandra , Pęcak Paweł , Bębenek Ewa , Kadela-Tomanek Monika , Bak Andrzej , Jastrzębska Maria , Boryczka Stanisław
Published: October 2019

Since the beginning of the human immunodeficiency virus (HIV) epidemic, many groups of drugs characterized by diverse mechanisms of action have been developed, which can suppress HIV viremia. 3-O-(3′,3′-Dimethylsuccinyl) betulinic acid, known as bevirimat (BVM), was the first compound in the class of HIV maturation inhibitors. In the present work, phosphate and phosphonate derivatives of 3-carboxyacylbetulinic acid were synthesized and evaluated for anti-HIV-1 activity. In vitro studies showed that 30-diethylphosphonate analog of BVM (compound 14a) has comparable effects to BVM (half maximal inhibitory concentrations (IC50) equal to 0.02 μM and 0.03 μM, respectively) and is also more selective (selectivity indices: 3450 and 967, respectively). To investigate the possible mechanism of antiviral effect of 14a, molecular docking was carried out on the C-terminal domain (CTD) of HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1, which was described as a molecular target for maturation inhibitors. Compared with interactions between BVM and the protein, an increased number of strong interactions between ligand 14a and protein, generated by the phosphonate group, was observed.
Targeting NRF2 for the Treatment of Friedreich’s Ataxia: A Comparison among Drugs
Authors: Petrillo Sara , D’Amico Jessica , La Rosa Piergiorgio , Bertini Enrico Silvio , Piemonte Fiorella
Published: October 2019

NRF2 (Nuclear factor Erythroid 2-related Factor 2) signaling is impaired in Friedreich’s Ataxia (FRDA), an autosomal recessive disease characterized by progressive nervous system damage and degeneration of nerve fibers in the spinal cord and peripheral nerves. The loss of frataxin in patients results in iron sulfur cluster deficiency and iron accumulation in the mitochondria, making FRDA a fatal and debilitating condition. There are no currently approved therapies for the treatment of FRDA and molecules able to activate NRF2 have the potential to induce clinical benefits in patients. In this study, we compared the efficacy of six redox-active drugs, some already adopted in clinical trials, targeting NRF2 activation and frataxin expression in fibroblasts obtained from skin biopsies of FRDA patients. All of these drugs consistently increased NRF2 expression, but differential profiles of NRF2 downstream genes were activated. The Sulforaphane and N-acetylcysteine were particularly effective on genes involved in preventing inflammation and maintaining glutathione homeostasis, the dimethyl fumarate, omaxevolone, and EPI-743 in counteracting toxic products accumulation, the idebenone in mitochondrial protection. This study may contribute to develop synergic therapies, based on a combination of treatment molecules.
Trans-Kingdom Conjugation within Solid Media from Escherichia coli to Saccharomyces cerevisiae
Authors: Soltysiak Maximillian P. M. , Meaney Rebecca S. , Hamadache Samir , Janakirama Preetam , Edgell David R. , Karas Bogumil J.
Published: October 2019

Conjugation is a bacterial mechanism for DNA transfer from a donor cell to a wide range of recipients, including both prokaryotic and eukaryotic cells. In contrast to conventional DNA delivery techniques, such as electroporation and chemical transformation, conjugation eliminates the need for DNA extraction, thereby preventing DNA damage during isolation. While most established conjugation protocols allow for DNA transfer in liquid media or on a solid surface, we developed a procedure for conjugation within solid media. Such a protocol may expand conjugation as a tool for DNA transfer to species that require semi-solid or solid media for growth. Conjugation within solid media could also provide a more stable microenvironment in which the conjugative pilus can establish and maintain contact with recipient cells for the successful delivery of plasmid DNA. Furthermore, transfer in solid media may enhance the ability to transfer plasmids and chromosomes greater than 100 kbp. Using our optimized method, plasmids of varying sizes were tested for transfer from Escherichia coli to Saccharomyces cerevisiae. We demonstrated that there was no significant change in conjugation frequency when plasmid size increased from 56.5 to 138.6 kbp in length. Finally, we established an efficient PCR-based synthesis protocol to generate custom conjugative plasmids.
Novel Peptidomic Approach for Identification of Low and High Molecular Weight Tauopathy Peptides Following Calpain Digestion, and Primary Culture Neurotoxic Challenges
Authors: Yadikar Hamad , Johnson Connor , Pafundi Niko , Mouhawasse Edwin , Nguyen Lynn , Torres Isabel , Kurup Milin , Yang Zhihui , Kobeissy Firas , Yost Richard , Wang Kevin K.
Published: October 2019

Tauopathy is a class of a neurodegenerative disorder linked with tau hyperphosphorylation, proteolysis, and aggregation. Tau can be subjected to proteolysis upon calpain activation in Alzheimer disease (AD), and traumatic brain injury (TBI). We and others have extensively researched calpain-mediated tau breakdown products (Tau-BDP; 45K, 35K, and 17K). Tau proteolysis might also generate low molecular weight (LMW ≤10K) proteolytic peptides after neurodegenerative damage. In this study, we have subjected purified tau protein (phospho and non-phospho) and mouse brain lysate to calpain-1 digestion to characterize the LMW generated by nano-liquid chromatography coupled to electrospray ionization to tandem mass spectrometry (nano-LC-ESI-MS/MS). We have also challenged differentiated primary cerebrocortical neuronal cultures (CTX) with neurotoxic agents (calcium ionophore calcimycin (A23187), staurosporine (STS), N-methyl-D-aspartate (NMDA), and Maitotoxin (MTX)) that mimic neurodegeneration to investigate the peptidome released into the conditioned cell media. We used a simple workflow in which we fractionate LMW calpain-mediated tau peptides by ultrafiltration (molecular weight cut-off value (MWCO) of 10K) and subject filtrate fractions to nano-LC-MS/MS analysis. The high molecular weight (HMW) peptides and intact proteins retained on the filter were analyzed separately by western blotting using total and phospho-specific tau antibodies. We have identified several novel proteolytic tau peptides (phosphorylated and non-phosphorylated) that are only present in samples treated with calpain or cell-based calpain activation model (particularly N- and C-terminal peptides). Our findings can help in developing future research strategies emphasizing on the suppression of tau proteolysis as a target.
Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis
Authors: El-Aarag Bishoy , Khairy Asmaa , Khalifa Shaden A. M. , El-Seedi Hesham R.
Published: October 2019

The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human.
The Main (Glyco) Phospholipid (MPL) of Thermoplasma acidophilum
Authors: Freisleben Hans-Joachim
Published: October 2019

The main phospholipid (MPL) of Thermoplasma acidophilum DSM 1728 was isolated, purified and physico-chemically characterized by differential scanning calorimetry (DSC)/differential thermal analysis (DTA) for its thermotropic behavior, alone and in mixtures with other lipids, cholesterol, hydrophobic peptides and pore-forming ionophores. Model membranes from MPL were investigated; black lipid membrane, Langmuir-Blodgett monolayer, and liposomes. Laboratory results were compared to computer simulation. MPL forms stable and resistant liposomes with highly proton-impermeable membrane and mixes at certain degree with common bilayer-forming lipids. Monomeric bacteriorhodopsin and ATP synthase from Micrococcus luteus were co-reconstituted and light-driven ATP synthesis measured. This review reports about almost four decades of research on Thermoplasma membrane and its MPL as well as transfer of this research to Thermoplasma species recently isolated from Indonesian volcanoes.
Information Security Risk Propagation Model Based on the SEIR Infectious Disease Model for Smart Grid
Authors: Zhu Boyu , Deng Song , Xu Yunan , Yuan Xinya , Zhang Zi
Published: October 2019

With the high integration of smart grid information and physical systems, the security of information systems must affect the safe and stable operation of physical systems. Risk assessment is an effectual means to objectively evaluate the information security threats of the smart grid. However, the existing risk assessment methods are aim at solving the threat of security risks in communication networks and information systems in the smart grid, but there is no in-depth study on how the spread of information security risks between information systems and physical systems in the smart grid. Therefore, based on the traditional infectious disease transmission theory, the information security risk propagation model based on the Susceptible–Exposed–Infected–Recovered (SEIR) infectious disease model for smart grid (ISRP-SEIRIDM) is proposed in this paper. In ISRP-SEIRIDM, we analyze the information interaction between information collection devices and define the connection of nature and the security risks between the information collection devices in the smart grid. At the same time, we also study the impact of the number of information acquisition devices and information interaction capabilities of these devices on the speed of security risk transmission between information systems and physics systems in the smart grid and the maximum risk range. Experimental results show that the risk propagation range can be significantly reduced by optimizing the data interaction capability and information transmission path between information collection devices in the smart grid; when a probability from a susceptible state to an exposed state reduces by 0.15, the maximum spread and average spread of security risk will be reduced by 7% and 1.96%, respectively.