bluuebunny/crossref_metadata_2025 huggingface dataset:
PAX8 expression in high-grade serous ovarian cancer positively regulates attachment to ECM via Integrin β3
Authors: Soriano Amata Amy , de Cristofaro Tiziana , Di Palma Tina , Dotolo Serena , Gokulnath Priyanka , Izzo Antonella , Calì Gaetano , Facchiano Angelo , Zannini Mariastella
Published: November 2019

Background

Ovarian cancer is the third most common cause of death among gynecologic malignancies worldwide. Understanding the biology and molecular pathogenesis of ovarian epithelial tumors is key to developing improved prognostic indicators and effective therapies. We aimed to determine the effects of PAX8 expression on the migrative, adhesive and survival capabilities of high-grade serous carcinoma cells.

Methods

PAX8 depleted Fallopian tube secretory cells and ovarian cancer cells were generated using short interfering siRNA. Anoikis resistance, cell migration and adhesion properties of PAX8 silenced cells were analyzed by means of specific assays. Chromatin immunoprecipitation (ChIP) was carried out using a PAX8 polyclonal antibody to demonstrate that PAX8 is able to bind to the 5′-flanking region of the ITGB3 gene positively regulating its expression.

Results

Here, we report that RNAi silencing of PAX8 sensitizes non-adherent cancer cells to anoikis and affects their tumorigenic properties. We show that PAX8 plays a critical role in migration and adhesion of both Fallopian tube secretory epithelial cells and ovarian cancer cells. Inhibition of PAX8 gene expression reduces the ability of ovarian cancer cells to migrate and adhere to the ECM and specifically to fibronectin and/or collagen substrates. Moreover, loss of PAX8 strongly reduces ITGB3 expression and consequently the correct expression of the αvβ3 heterodimer on the plasma membrane.

Conclusions

Our results demonstrate that PAX8 modulates the interaction of tumor cells with the extracellular matrix (ECM). Notably, we also highlight a novel pathway downstream this transcription factor. Overall, PAX8 could be a potential therapeutic target for high-grade serous carcinoma.
Behavioral mapping of children’s physical activities and social behaviors in an indoor preschool facility: methodological challenges in revealing the influence of space in play
Authors: Onojeghuo Ajoke R. , Nykiforuk Candace I. J. , Belon Ana Paula , Hewes Jane
Published: November 2019

Background

GIS (Geographic Information Systems) based behavior maps are useful for visualizing and analyzing how children utilize their play spaces. However, a GIS needs accurate locational information to ensure that observations are correctly represented on the layout maps of play spaces. The most commonly used tools for observing and coding free play among children in indoor play spaces require that locational data be collected alongside other play variables. There is a need for a practical, cost-effective approach for extending most tools for analyzing free play by adding geospatial locational information to children’s behavior data collected in indoor play environments.

Results

We provide a non-intrusive approach to adding locational information to behavior data acquired from video recordings of preschool children in their indoor play spaces. The gridding technique showed to be a cost-effective method of gathering locational information about children from video recordings of their indoor physical activities and social behaviors. Visualizing the proportions of categories and observed intervals was done using bubble pie charts which allowed for the merging of multiple categorical information on one map. The addition of locational information to other play activity and social behavior data presented the opportunity to assess what types of equipment or play areas may encourage different physical activities and social behaviors among preschool children.

Conclusions

Gridding is an effective method for providing locational data when analyzing physical activities and social behaviors of preschool children in indoor spaces. It is also reproducible for most GIS behavior mapping focusing on indoor environments. This bypasses the need to have positioning devices attached to children during observations, which can raise ethical considerations regarding children’s privacy and methodological implications with children playing less naturally. It also supports visualizations on behavior maps making them easier to interpret.
Predicting drug−disease associations via sigmoid kernel-based convolutional neural networks
Authors: Jiang Han-Jing , You Zhu-Hong , Huang Yu-An
Published: November 2019

Background

In the process of drug development, computational drug repositioning is effective and resource-saving with regards to its important functions on identifying new drug–disease associations. Recent years have witnessed a great progression in the field of data mining with the advent of deep learning. An increasing number of deep learning-based techniques have been proposed to develop computational tools in bioinformatics.

Methods

Along this promising direction, we here propose a drug repositioning computational method combining the techniques of Sigmoid Kernel and Convolutional Neural Network (SKCNN) which is able to learn new features effectively representing drug–disease associations via its hidden layers. Specifically, we first construct similarity metric of drugs using drug sigmoid similarity and drug structural similarity, and that of disease using disease sigmoid similarity and disease semantic similarity. Based on the combined similarities of drugs and diseases, we then use SKCNN to learn hidden representations for each drug-disease pair whose labels are finally predicted by a classifier based on random forest.

Results

A series of experiments were implemented for performance evaluation and their results show that the proposed SKCNN improves the prediction accuracy compared with other state-of-the-art approaches. Case studies of two selected disease are also conducted through which we prove the superior performance of our method in terms of the actual discovery of potential drug indications.

Conclusion

The aim of this study was to establish an effective predictive model for finding new drug–disease associations. These experimental results show that SKCNN can effectively predict the association between drugs and diseases.
Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice
Authors: Zhao Weixing , Xu Zhipeng , Cao Jiangbei , Fu Qiang , Wu Yishuang , Zhang Xiaoying , Long Yue , Zhang Xuan , Yang Yitian , Li Yunfeng , Mi Weidong
Published: November 2019

Background

It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown.

Methods

We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus.

Results

Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity.

Conclusion

These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.
“A herder’s duty is to think”: landscape partitioning and folk habitats of Mongolian herders in a mountain forest steppe (Khuvsugul-Murun region)
Authors: Gantuya B. , Avar Á. , Babai D. , Molnár Á. , Molnár Zs
Published: November 2019

Background

Traditional habitat knowledge, like the classification of folk habitats and how people partition their landscape into habitats, is an emerging but still understudied part of traditional ecological knowledge. Our objectives were to reconstruct the folk habitats and the partitioning of the landscape into these folk habitats by Mongolian herders in Northern Mongolia and to compare it with other Northern Hemisphere boreal-temperate classifications.

Methods

The study area is located in Seruun Gilad (Khuvsugul province) and belongs to the mountain forest steppe of the Khangai region (dominated by meadow steppes and larch forests). Most herder families use the area for summer pasturing. Data collection was based on indoor and outdoor, structured and semi-structured interviews and interviews during landscape walks and participatory fieldwork. We interviewed 20 people using 76+ photos of plant species and 25+ photos of habitats and asked them to name and describe the habitats and describe the habitat preferences of the species.

Results

Mongolian herders distinguished at least 88 folk habitat categories and knew well the habitat preferences of the 76 plant species. They argued that a herder has to be observant of nature. The habitat classification was moderately lexicalized, with many descriptive expressions. Most habitats (77%) belonged to the meso-scale, while macro-scale habitats (liketaiga,Gobi) and micro-scale habitats (likemarmot burrow,top of the tussock) were few. Habitat names did not reflect directly the usefulness of the habitat. Classification was multidimensional; key dimensions were geomorphological and edaphic. There were some species (e.g.,botyuul,hyag,shireg) and species groups (hot plants,leafy plants) that were often used to describe habitat types.

Conclusions

Landscape partitionings in the Northern Hemisphere differed considerably in the importance of various dimensions used, with edaphic, geomorphological, hydrological, and dominant species-based dimensions having higher importance, while land use, successional, and zoological dimensions having lower importance. We argue that conducting research on folk habitats will contribute to a deeper understanding of how nature is perceived by locals and to a more efficient management of the Mongolian pastures.
Preoperative irrigation and vacuum sealing drainage with antibiotic-containing drainage fluid of foot and ankle wounds improves outcome of reconstructive skin flap surgery
Authors: Gao Xu , Yin Hailei , Sun Jixia
Published: November 2019

Objectives

By observing the infection and soft tissue defect on the wound surface of the foot and ankle, this paper attempts to explore the effect of preoperative irrigation and vacuum sealing drainage with antibiotic-containing drainage fluid (abPI-VSD) on the bacterial quantity and the local inflammatory response at the flap, and further to provide a basis for applying this technique before a reconstructive skin flap surgery of foot and ankle wounds.

Methods

Seventy-five patients were randomly divided into two groups, and all surgeries were done by one physician. The flap reconstructions were done to 31 cases with the abPI-VSD being used (group A); the flap reconstructions were done to the rest 44 cases after wound cleaning using antibiotic irrigation solution without the use of the abPI-VSD (group B). Quantitative bacteriology was made to group A before and after the use of abPI-VSD; quantitative bacteriology was made to group B before and after wound cleaning. Then, the reconstructive skin flap surgery was done. After the surgeries, the time of local inflammatory response at the flap in both groups were recorded. The measured bacterial quantity was evaluated in logarithm and by t test.

Results

The bacterial quantity was 3.2 ± 1.9 × 107 cfu/g in group A before the use of abPI-VSD and 2.3 ± 2.0 × 107 in group B (P > 0.05) before debridement. The bacterial quantity was 1.2 ± 2.0 × 104 cfu/g in group A after abPI-VSD and was 2.9 ± 4.0 × 106 in group B after wound cleaning (P < 0.05). The time of postoperative inflammatory response in the flap was 8 ± 2.5 days in group A and 13 ± 3.4 days in group B (P < 0.05).

Conclusions

abPI-VSD can distinctly reduce the bacterial quantity on the surface of the wound, provide a good condition of tissue bed for the flap reconstruction, and effectively control the local inflammatory response at the flap and hence improve the survival quality of the flap.
Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway
Authors: Lei Shan , He Zhiwei , Chen Tengxiang , Guo Xingjun , Zeng Zhirui , Shen Yiyi , Jiang Jianxin
Published: November 2019

Background

Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer.

Methods

In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway.

Results

linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth.

Conclusion

The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.
Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop
Authors: Liu Yan , Wang Jian-Xing , Nie Zi-Yuan , Wen Yue , Jia Xin-Ju , Zhang Li-Na , Duan Hui-Jun , Shi Yong-Hong
Published: November 2019

Background

ERp57 dysfunction has been shown to contribute to tumorigenesis in multiple malignances. However, the role of ERp57 in clear cell renal carcinoma (ccRCC) remains unclear.

Methods

Cell proliferation ability was measured by MTT and colony forming assays. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to measure protein and mRNA expression. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were performed to detect protein-protein interaction. Chromatin immunoprecipitation (ChIP), ribonucleoprotein immunoprecipitation (RIP), and oligo pull-down were used to confirm DNA–protein and RNA–protein interactions. Promoter luciferase analysis was used to detect transcription factor activity.

Results

Here we found ERp57 was overexpressed in ccRCC tissues, and the higher levels of ERp57 were correlated with poor survival in patients with ccRCC. In vivo and in vitro experiments showed that ccRCC cell proliferation was enhanced by ERp57 overexpression and inhibited by ERp57 deletion. Importantly, we found ERp57 positively regulated ILF3 expression in ccRCC cells. Mechanically, ERp57 was shown to bind to STAT3 protein and enhance the STAT3-mediated transcriptional activity of ILF3. Furthermore, ILF3 levels were increased in ccRCC tissues and associated with poor prognosis. Interestingly, we revealed that ILF3 could bind to ERp57 and positively regulate its expression by enhancing its mRNA stability. Furthermore, ccRCC cell proliferation was moderated via the ERp57/STAT3/ILF3 feedback loop.

Conclusions

In summary, our results indicate that the ERp57/STAT3/ILF3 feedback loop plays a key role in the oncogenesis of ccRCC and provides a potential therapeutic target for ccRCC treatment.
Factors affecting breast-feeding practice among a sample of Iranian women: a structural equation modeling approach
Authors: Rafizadeh Reyhaneh , Heidari Zahra , Karimy Mahmood , Zamani-Alavijeh Fereshteh , Araban Marzieh
Published: November 2019

Background

Breastfeeding is one of the most sensitive stages in the development of children, having many benefits for the mother and the child. The present study aimed to determine factors associated with breastfeeding intention and behavior in mothers living in Taft County, Iran.

Methods

In this cross-sectional design, the statistical population consisted of 420 mothers with infants under 1 year of age living in Taft County of Yazd province, Iran. The research data were collected from health records of infants under one in health centers of the county as well as a researcher-made questionnaire including demographic information, knowledge and attitude towards breastfeeding, social support and perceived self-efficacy, and breastfeeding intention and behavior. Structural Equation Modeling (SEM) based on AMOS 18 were employed to analyze the relationship between research variables.

Results

The mean age of mothers was 28.04 ± 6.49 year and the children were 10 ± 6 months. Half of the mothers (50.3%) had cesarean sections and more than half (55.8%) of the children were males. Mothers’ attitude (β = 0.442; 95% CI: 0.284, 0.599), self-efficacy (β = 0.186; 95% CI: 0.047, 0.324) and perceived social support (β = 0.178; 95% CI: 0.035, 0.322) were respectively the strongest predictors of breastfeeding intention. Besides, the breastfeeding intention affected breastfeeding behavior with a high coefficient (0.857; 95% CI: 0.735, 0.979).

Conclusions

The study provided informative pathways on the association of maternal attitude, social support and self-efficacy with breast feeding behavior. These findings could be useful for designing health education and promotion programs about breast feeding among women.
A simple strategy to effectively produce d-lactate in crude glycerol-utilizing Escherichia coli
Authors: Wang Yao-De , Liao Jin-Yi , Chiang Chung-Jen , Chao Yun-Peng
Published: November 2019

Background

Fed-batch fermentation has been conventionally implemented for the production of lactic acid with a high titer and high productivity. However, its operation needs a complicated control which increases the production cost.

Results

This issue was addressed by simplifying the production scheme.Escherichia coliwas manipulated for its glycerol dissimilation andd-lactate synthesis pathways and then subjected to adaptive evolution under high crude glycerol. Batch fermentation in the two-stage mode was performed by controlling the dissolved oxygen (DO), and the evolved strain deprived ofpoxBenabled production of 100 g/Ld-lactate with productivity of 1.85 g/L/h. To increase productivity, the producer strain was further evolved to improve its growth rate on crude glycerol. The fermentation was performed to undergo the aerobic growth with low substrate, followed by the anaerobic production with high substrate. Moreover, the intracellular redox of the strain was balanced by fulfillment of the anaerobic respiratory chain with nitrate reduction. Without controlling the DO, the microbial fermentation resulted in the homofermentative production ofd-lactate (ca. 0.97 g/g) with a titer of 115 g/L and productivity of 3.29 g/L/h.

Conclusions

The proposed fermentation strategy achieves the highest yield based on crude glycerol and a comparable titer and productivity as compared to the approach by fed-batch fermentation. It holds a promise to sustain the continued development of the crude glycerol-based biorefinery.
Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders
Authors: Hu Yubing , Wang Lin , Mbenda Huguette Gaelle Ngassa , Soe Myat Thu , Yu Chunyun , Feng Hui , Kyaw Myat Phone , Cui Liwang , Zhu Xiaotong , Cao Yaming
Published: November 2019

Background

Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology withPlasmodium vivaxbecoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity ofP. vivax Duffy-binding proteingene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from globalP. vivaxpopulations.

Methods

pvdbp-II sequences were obtained from 85 and 82 clinicalP. vivaxisolates from the eastern and western Myanmar borders, respectively. In addition, 504pvdbp-II sequences from nineP. vivaxpopulations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population.

Results

The nucleotide diversity of thepvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected inpvdbp-II gene inP. vivaxisolates from the eastern Myanmar area.P. vivaxparasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of thepvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) inP. vivaxpopulations from the eastern and western borders of Myanmar.

Conclusions

Thepvdbp-II gene is genetically diverse in the eastern and western Myanmar borderP. vivaxpopulations. Positive natural selection and recombination occurred inpvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of theP. vivaxpopulations in the GMS. These results can help understand the evolution of theP. vivaxpopulations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.
Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response
Authors: Mardis Elaine R.
Published: November 2019

The resurgence of immune therapies in cancer medicine has elicited a corresponding interest in understanding the basis of patient response or resistance to these treatments. One aspect of patient response clearly lies in the genomic alterations that are associated with cancer onset and progression, including those that contribute to genomic instability and the resulting creation of novel peptide sequences that may present as neoantigens. The immune reaction to these unique ‘non-self’ peptides is frequently suppressed by the tumor itself, but the use of checkpoint blockade therapies, personalized vaccines, or a combination of these treatments may elicit a tumor-specific immune response that results in cell death. Massively parallel sequencing, coupled with different computational analyses, provides unbiased identification of the germline and somatic alterations that drive cancer development, and of those alterations that lead to neoantigens. These range from simple point mutations that change single amino acids to complex alterations, such as frameshift insertion or deletion mutations, splice-site alterations that lead to exon skipping, structural alterations that lead to the formation of fusion proteins, and other forms of collateral damage caused by genome instability that result in new protein sequences unique to the cancer. The various genome instability phenotypes can be identified as alterations that impact DNA replication or mismatch repair pathways or by their genomic signatures. This review provides an overview of current knowledge regarding the fundamentals of genome replication and of both germline and somatic alterations that disrupt normal replication, leading to various forms of genomic instability in cancers, to the resulting generation of neoantigens and, ultimately, to immune-responsive and resistant phenotypes.
Hepatic and portal vein Dopplers in the clinical management of patients with right-sided heart failure: two case reports
Authors: Jefkins Matthew , Chan Barry
Published: November 2019

Background

Patients with right heart failure pose significant volume management challenges for hemodynamic optimization. We present two cases in which point of care ultrasound (POCUS) of the hepatic and portal veins contributed to the venous hypertension assessment and decongestive strategy for patients with right-sided heart failure.

Case presentation

Patient A was 91 years old with known pulmonary hypertension and right ventricular systolic dysfunction who presented in septic shock requiring vasopressor support. Hepatic and portal vein Dopplers were consistent with right heart failure and significant venous congestion, therefore, diuresis was initiated which resulted in portal flow normalization, renal recovery, and cessation of vasopressor support. Patient B was 82 years old with severe idiopathic pulmonary fibrosis on home oxygen who presented in decompensated right heart failure. Despite aggressive diuresis, a negative fluid balance was not achieved. The patient continued to deteriorate and prior to their death portal vein, Doppler showed significant flow reversal.

Conclusion

Hepatic and portal vein Doppler ultrasounds are venous hypertension assessment tools that can be readily used at the bedside by clinicians trained in POCUS that may contribute holistically to the hemodynamic profiling for patients with right heart failure and direct therapeutic interventions.
Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway
Authors: Liang Bo , Liang Jia-Ming , Ding Jia-Ning , Xu Jia , Xu Jian-Guang , Chai Yi-Min
Published: November 2019

Background

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.

Methods

To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization.

Results

DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo.

Conclusions

Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.
Extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers
Authors: Bodart-Santos Victor , de Carvalho Luiza R. P. , de Godoy Mariana A. , Batista André F. , Saraiva Leonardo M. , Lima Luize G. , Abreu Carla Andreia , De Felice Fernanda G. , Galina Antonio , Mendez-Otero Rosalia , Ferreira Sergio T.
Published: November 2019

Background

Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton’s jelly would act as mediators of the communication between hMSCs and neurons and could protect hippocampal neurons from damage induced by Alzheimer’s disease-linked amyloid beta oligomers (AβOs).

Methods

We isolated and characterized EVs released by human Wharton’s jelly mesenchymal stem cells (hMSC-EVs). The neuroprotective action of hMSC-EVs was investigated in primary hippocampal cultures exposed to AβOs.

Results

hMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of AβOs in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by AβOs. Neuroprotection by hMSC-EVs was mediated by catalase and was abolished in the presence of the catalase inhibitor, aminotriazole.

Conclusions

hMSC-EVs protected hippocampal neurons from damage induced by AβOs, and this was related to the transfer of enzymatically active catalase contained in EVs. Results suggest that hMSC-EVs should be further explored as a cell-free therapeutic approach to prevent neuronal damage in Alzheimer’s disease.
Autofluorescence of NADH is a new biomarker for sorting and characterizing cancer stem cells in human glioma
Authors: Yuan Ye , Yan Zexuan , Miao Jingya , Cai Ruili , Zhang Mengsi , Wang Yanxia , Wang Lihong , Dang Weiqi , Wang Di , Xiang Dongfang , Wang Yan , Zhang Peng , Cui Youhong , Bian Xiuwu , Ma Qinghua
Published: November 2019

Background

The existing cell surface markers used for sorting glioma stem cells (GSCs) have obvious limitations, such as vulnerability to the enzymatic digestion and time-consuming labeling procedure. Reduced nicotinamide adenine dinucleotide (NADH) as a cellular metabolite with property of autofluorescence has the potential to be used as a new biomarker for sorting GSCs.

Methods

A method for sorting GSCs was established according to the properties of the autofluorescence of NADH. Then, the NADHhighand NADHlowsubpopulations were sorted. The stem-like properties of the subpopulations were evaluated by qRT-PCR, western blot analyses, limiting dilution assay, cell viability assay, bioluminescence imaging, and immunofluorescence analysis in vitro and in vivo. The relationship between CD133+/CD15+cells and NADHhighsubpopulation was also assessed.

Results

NADHhighcells expressed higher stem-related genes, formed more tumor spheres, and harbored stronger pluripotency in vitro and higher tumorigenicity in vivo, compared to NADHlowsubpopulation. NADHhighglioma cells had the similar stemness with CD133+or CD15+GSCs, but the three subpopulations less overlaid each other. Also, NADHhighglioma cells were more invasive and more resistant to chemotherapeutic drug temozolomide (TMZ) than NADHlowcells. In addition, the autofluorescence of NADH might be an appropriate marker to sort cancer stem cells (CSCs) in other cancer types, such as breast and colon cancer.

Conclusion

Our findings demonstrate that intracellular autofluorescence of NADH is a non-labeling, sensitive maker for isolating GSCs, even for other CSCs.
Heart to spine measurements to detect left atrial enlargement in dogs with mitral insufficiency
Authors: Sánchez Salguero Xavier , Prandi David , Llabrés-Díaz Francisco , Manzanilla Edgar G. , Badiella Llorenç , Bussadori Claudio
Published: November 2019

Background

Radiography is useful to determine left atrial (LA) size when echocardiography is not available. Recently, the authors have described Radiographic Left Atrial Dimension (RLAD) as a new radiographic measurement to assess LA size. The objective of this study was to assess the clinical usefulness of 2 new radiographic measurements to detect and quantify left atrial enlargement (LAE) compared to RLAD and using left atrium to aortic root (LA/Ao) ratio as gold standard. These new measurements, bronchus-to-spine (Br-Spine) and RLAD-to-spine (RLAD-Spine) may be more precise in cases were LA boundaries are not well defined. Fifty dogs, 25 with and 25 without LAE were recruited. Reference LA/Ao ratio was assessed by 2D echocardiography and LAE was considered if LA/Ao > 1.6. Br-spine was measured as a straight vertical line from the main stem bronchus to the ventral border of the vertebra situated immediately dorsal to the heart base. RLAD-Spine was measured from RLAD endpoint perpendicularly to spine. The correlation of RLAD, Br-Spine and RLAD-Spine methods with LA/Ao and their sensitivity and specificity for detecting LAE were calculated. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal cut-off for each method.

Results

Correlations between Br-Spine, RLAD-Spine, RLAD and LA/Ao ratio were − 0.66, − 0.76 and 0.89 respectively (P < 0.001). Sensitivity at the optimal cut-off values for detecting LAE were 32.0, 64.0 and 96.0%, respectively. Specificity was 96.0% in all cases.

Conclusion

Br-Spine and RLAD-Spine were less sensitive radiographic measurements than RLAD in detecting LAE in dogs. Both Br-Spine and RLAD-Spine may not be good alternatives to RLAD.
The anti-virulence effect of cranberry active compound proanthocyanins (PACs) on expression of genes in the third-generation cephalosporin-resistant Escherichia coli CTX-M-15 associated with urinary tract infection
Authors: Samarasinghe Shivanthi , Reid Ruth , AL-Bayati Majid
Published: November 2019

Background

Urinary tract infections (UTIs) are one of the most common infections found in humans, with uropathogenic Escherichia coli (UPEC) being the most common cause. Prevention of UTI is a major global concern due to its recurrent nature, medical cost, and most importantly, the increased antimicrobial resistance among UPEC. The resistance in UPEC is mainly due to the Extended-Spectrum β-lactamases (ESBL), particularly the E. coli CTXM-15 type which is known for its rapid dissemination worldwide. Treatment options for E. coli CTXM-15 have become limited over recent years because of their multi-drug resistance, hence anti-virulent strategies based on herbal remedies, have considered as a viable option. The cranberry product, Cysticlean® capsules, contain 240 mg of proanthocyanins (PACs), which have been shown to significantly inhibit E. coli adherence, both in vitro and ex vivo, to uroepithelial cells.

Method

In this study, the cephalosporin-resistant E. coli isolate NCTC 1553 (E. coli CTXM-15) was analysed by qRT-PCR (quantitative Reverse Transcriptase -Polymerase Chain Reaction) for the expression of virulence factors after treatment with Cysticlean®. qRT-PCR was carried out to detect virulence determinants encoding for toxins SAT, and USP, the iron acquisition system ChuA, the protectins SoxS, KPSM, TraT and RecA, the antibiotic resistance gene CTX-M (encode β-lactamases), and the transporters IdfB and HcaT.

Results

Cysticlean® significantly reduced the expression of all ten selected genes encoding for virulence factors and β-lactamases.

Conclusion

Cranberry product Cysticlean® could represent a practicable alternative option for the prevention of recurrent UTI caused by multi-drug resistant E. coli CTXM-15, as the product acts on multiple bacterial targets.
Effect of straw incorporation on methane emission in rice paddy: conversion factor and smart straw management
Authors: Song Hyeon Ji , Lee Jin Ho , Jeong Hyun-Cheol , Choi Eun-Jung , Oh Taek-Keun , Hong Chang-Oh , Kim Pil Joo
Published: November 2019

Straw incorporation is strongly recommended in rice paddy to improve soil quality and mitigate atmospheric carbon dioxide (CO2), via increasing soil organic carbon (SOC) stock. However, straw application significantly increased methane (CH4) emission during rice cultivation, and then its incorporation area was not expanded effectively. To find the reasonable straw management practice which can reduce CH4 emission without productivity damage, the effect of straw incorporation season and method on CH4 emission was investigated at six different textured paddy fields in South Korea for 2 years. A straw was applied right after rice harvesting in autumn, and the other right before rice transplanting in spring. In the autumn application, straw was applied with two different methods: spreading over soil surface or mixing with soil. Straw application significantly increased seasonal CH4 flux by average 28–122% over 197–590 kg CH4 ha−1 of the no-straw, but its flux showed big difference among straw applications. Fresh straw application before transplanting increased seasonal CH4 flux by approximately 120% over the no-straw, but the autumn application reduced its CH4 flux by 24–43% over 509–1407 kg CH4 ha−1 of the spring application. In particular, the seasonal CH4 flux was approximately 24% lower in straw mixing with soil after autumn harvesting than 423–855 kg CH4 ha−1 in straw spreading over surface. However, CH4 fluxes were not significantly discriminated by soil and meteorological properties in the selected condition. Straw application slightly increased rice grain yield by approximately 4% over the no-straw, but rice productivity was not statistically different among straw applications. Spring straw application increased CH4 intensity which means seasonal CH4 flux per grain yield by the maximum 220% over the no-straw. Autumn straw application significantly decreased CH4 intensity by average 24–65% over the spring straw application. In particular, CH4 intensity in straw mixing with soil treatment was not statistically different with the no-straw. Therefore, autumn straw application with mixing inner soil could be a reasonable straw management practice to decrease CH4 emission impact with improving soil productivity.
Performance of an adapted household food insecurity access scale in measuring seasonality in household food insecurity in rural Ethiopia: a cohort analysis
Authors: Kabalo Bereket Yohannes , Gebreyesus Seifu Hagos , Loha Eskindir , Lindtjørn Bernt
Published: November 2019

Background

Seasonality poses a considerable food security challenge in Ethiopia. Yet, measuring seasonal variations in food insecurity, particularly the dimension of food access, lacks an adequately validated tool. We therefore evaluated the performance of an adapted Household Food Insecurity Access Scale (HFIAS) to estimate seasonal variations in food insecurity (FI) among subsistence villagers in Ethiopia.

Methods

We employed a cohort study design using a panel of four repeated measurements taken in June, September, and December in the year 2017, and in March 2018. The study recruited 473 villagers from the drought-affected Wolaita area in southwest Ethiopia. The performance of the HFIAS was evaluated via internal consistency (Chronbach’s alpha values) and criterion validation techniques. The set of criteria include: parallelism between affirmative responses to FI questions and wealth strata; dose-response relationship between FI and dietary intake; and also FI severity and household wealth status.

Results

This study revealed that the HFIAS had satisfactory performance in four repeated measurements. The likelihood of affirmative responses to questions about FI decreased with ascending wealth quintiles. We observed an inverse dose-response relationship between FI and wealth status, and between FI and household dietary diversity.

Conclusions

The HFIAS showed an acceptable potential for measuring seasonal variations in FI in the study area. Our findings complement efforts to evaluate the scale’s applicability in various settings, in order to promote cross-culture monitoring and comparisons. However, it required a careful adaption for contextual and cultural sensitivities.
STEM materials: a new frontier for an intelligent sustainable world
Authors: Moretti Pier F. , Grzybowski Bartosz A. , Basios Vasileios , Fortunato Elvira , Suarez Diez Maria , Speck Olga , Martins Rodrigo
Published: November 2019

Materials are addressed as possible enablers for solutions to many global societal challenges. A foresight exercise has been conducted to identify research paths to design, with a new approach, a generation of materials which can provide multi-functionalities. These material systems have been named “stem”, in analogy to living cells where a base of primitive units can be designed and assembled for self-reacting to external inputs. These materials will embed a concept of “internet in things”, where their processing capacity will enable the systems to interact with the environment and express diverse functionalities. Stem materials do not exist yet, but many clues from different theoretical and experimental results suggest they can be developed, and because living organisms exist. This article aims at launching this new approach and promoting the structuring of a multi-disciplinary community to fill the research gaps.
Prevalence and correlates of psychiatric morbidity in Egyptian sample of dementia patients’ caregivers: a comparative descriptive study
Authors: El Razek Yasser Abd , Sabry Walaa , Hendawy Heba , Hegazy Dalia , Soultan Marwa , El Banna Mohamed
Published: November 2019

Background

A strong relationship between dementia caregiving and negative consequences on psychological health of caregivers has been established in numerous studies. A meticulous evaluation of caregiver mental status function is of utmost importance to gain better insight into daily caregiver functioning and to alleviate their high levels of burden. This study evaluated the prevalence of psychiatric morbidities and their sociodemographic and clinical correlates among a sample of dementia caregivers in Egypt. Twenty-five caregivers of patients with dementia were collected and compared with regard to their psychiatric morbidity with 25 careers of patients with chronic physical diseases. Patients were subjected to Mini-Mental State Examination (MMSE) and Arabic versions of activities of daily living (ADL) and instrumental activities of daily living (IADL), and caregivers were interviewed using the Arabic version of the General Health Questionnaire (GHQ), Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and Zarit Burden Interview (ZBI).

Results

Caregiver’s burden was significantly higher among the dementia caregiver group than the non-dementia group. Moreover, dementia caregivers provided more aid with a higher total of ADLs and provided help for more IADLs than did the non-dementia caregivers. They also showed higher psychiatric morbidity. Such morbidity was found to be related to hours of caring, years of caring, GHQ, ZBI, ADL/IADL, BPSD, and MMSE. On the other hand, ADL, IADL, and GHQ scores had the highest predictive significance of caregiver’s burden in our study.

Conclusions

Caregivers of patients with dementia are subjected to more burden and vulnerability to psychiatric disorders than the other caregiver group. That should raise a flag to pay extra support and care for those people, which in turn will benefit both the patient and the health care authorities in terms of quality and cost of the care provided.
Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men
Authors: Nonaka Keisuke , Aida Junko , Takubo Kaiyo , Yamazaki Yuto , Gao Xin , Komatsu Akiko , Takakuma Shoichiro , Kakizaki Mototsune , Inoshita Naoko , Gomi Fujiya , Ishiwata Toshiyuki , Chong Ja-Mun , Arai Tomio , Sasano Hironobu
Published: November 2019

Context

Although numerous theories are reported on sex differences in longevity, the underlying biological mechanisms remain unknown. We previously reported that telomere length in the zona reticularis cells of the human adrenal cortex was significantly longer in older than that in younger subjects. However, we could not evaluate sex differences in the telomere lengths.

Objective

To compare the telomere lengths of adrenocortical and adrenal medullar cells between men and women from infancy through older adulthood.

Methods

Adrenal glands of 30 male (aged 0 to 100 years) and 25 female (aged 0 to 104 years) autopsied subjects were retrieved from autopsy files. Using quantitative fluorescence in situ hybridization, relative telomere lengths were determined in the parenchymal cells of the 3 adrenocortical zones and medulla. Age-related changes in the weight of adrenal glands were also investigated.

Main results

Older male subjects (aged 65 years or older) had significantly shorter telomere lengths in zona fasciculata (ZF) cells compared to the corresponding female subjects. In men, older subjects exhibited a significant age-related reduction in adrenal weight; however, no age-related changes in adrenal weight were detected in women.

Conclusion

Telomere attrition of ZF cells was correlated with adrenal weight reduction in older men but not in older women, suggesting a decreased number of ZF cells in older men. This may help us understand the possible biological mechanisms of sex difference in longevity of humans.
Does paternal immunocompetence affect offspring vulnerability to maternal androgens? A study in domestic chickens
Authors: Lelono Asmoro , Robledo-Ruiz Diana A. , Berghof Tom V. L. , Parmentier Henk K. , Riedstra Bernd , Groothuis Ton G.
Published: November 2019

Exposure of yolk androgens can positively stimulate chick growth and competitive ability, but may negatively affect immunity. It has been hypothesized that only chicks from immunologically superior fathers can bear the cost of prenatal exposure to high androgen levels. To test this hypothesis, we paired roosters from two selection lines, one up- and one down-selected for natural antibodies (NAbs), with hens from a control line. We measured yolk testosterone and androstenedione levels, and we injected the treatment group of eggs of each female with testosterone suspended in sesame oil and the control group with sesame oil only. We then measured hatching success and growth, and characterized the humoral and cellular immune responses using three different challenges: a phyto-hemagglutinin, a lipopolysaccharide and a sheep red blood cell challenge. We found that the hatching success, body mass, initial levels of natural antibodies and the chicks’ immunological responses to the three different challenges and development were affected neither by paternal immunocompetence nor by treatment. These results do not support the hypothesis that chicks from low-NAb line fathers are more sensitive to testosterone exposure during embryonic development than chicks from high-NAb line fathers.