bluuebunny/crossref_metadata_2025 huggingface dataset:
The mitohormetic response as part of the cytoprotection mechanism of berberine
Authors: Zhu Xiaofei , Wei Yihui , Yang Beibei , Yin Xiaoxiao , Guo Xiaofang
Published: January 2020

It was well-known that Berberine, a major bioactive compound extracted from natural plants Coptis chinensis, has anti-diabetic effects for decades in china. Other types of pharmacological activities, such as anti-inflammatory, antimicrobial, hypolipidemic, and anti-cancer effects, have also been examined. At cellular level, these pharmacological activities were mostly an inhibitory effect. However, the cytoprotective effect of berberine was also observed in various types of cells, such as neurons, endothelial cells, fibroblasts, and β-cells. The paradoxical result may be closely associated with characteristics and distribution of berberine within cells, and they can be explained mechanically by mitohormesis, one particular form of hormesis. Here, we reviewed the mitohormetic response and assessed the berberine-induced effects and the possible signaling pathway involved. These findings may contribute to better clinical applications of berberine and indicate that some mitochondria-targeted conventional drugs should be considered carefully in clinical application.
The combination of transversus abdominis plane block and rectus sheath block reduced postoperative pain after splenectomy: a randomized trial
Authors: Zhu Jing-li , Wang Xue-ting , Gong Jing , Sun Hai-bin , Zhao Xiao-qing , Gao Wei
Published: January 2020

Background

Splenectomy performed with a curved incision results in severe postoperative pain. The aim of this study was to evaluate the effect of transversus abdominis plane block and rectus sheath block on postoperative pain relief and recovery.

Methods

A total of 150 patients were randomized into the control (C), levobupivacaine (L) and levobupivacaine/morphine (LM) groups. The patients in the C group received only patient-controlled analgesia. The patients in the L and LM groups received transversus abdominis plane block and rectus sheath block with levobupivacaine or levobupivacaine plus morphine. The intraoperative opioid consumption; postoperative pain score; time to first analgesic use; postoperative recovery data, including the times of first exhaust, defecation, oral intake and off-bed activity; the incidence of postoperative nausea and vomiting and antiemetics use; and the satisfaction score were recorded.

Results

Transversus abdominis plane block and rectus sheath block reduced intraoperative opioid consumption. The patients in the LM group showed lower postoperative pain scores, opioid consumption, postoperative nausea and vomiting incidence and antiemetic use and presented shorter recovery times and higher satisfaction scores.

Conclusions

The combination of transversus abdominis plane block and rectus sheath block with levobupivacaine and morphine can improve postoperative pain relief, reduce the consumption of analgesics, and partly accelerate postoperative recovery.

Trial registration

Chinese Clinical Trial Registry, ChiCTR 1,800,015,141, 10 March 2018.
Correction to: Forkhead Box F1 promotes breast cancer cell migration by upregulating lysyl oxidase and suppressing Smad2/3 signaling
Authors: Nilsson Gisela , Kannius-Janson Marie
Published: January 2020

Following publication of the original article [1], the authors reported an error in Fig. 6c and in the figure legends for Fig. 5c and Fig. 6c.
The prevalence of undiagnosed Prediabetes/type 2 diabetes, prehypertension/hypertension and obesity among ethnic groups of adolescents in Western Canada
Authors: Spurr Shelley , Bally Jill , Bullin Carol , Allan Diane , McNair Erick
Published: January 2020

Background

An increased incidence of type 2 diabetes in youth is occurring worldwide. While diverse ethnic groups are disproportionately affected by type 2 diabetes, studies that explore ethnic differences and undiagnosed prediabetes/type 2 diabetes in adolescents are scarce. This paper compares the prevalence of undiagnosed prediabetes and type 2 diabetes and the associated risk factors among various ethnic groups of adolescents living in Western Canada.

Methods

The data for this study were derived from two previous studies in which 396 adolescents, aged 14 to 19 years and living in a western Canadian province, were screened for undiagnosed prediabetes, diabetes, and any associated risk factors. Risk was determined by demographics, family history, anthropometric measurements (body mass index, BMI), blood pressure (BP), and HbA1c. Descriptive and inferential statistics (SPSS) were used to establish both risk and prevalence for prediabetes and type 2 diabetes. Chi-square analyses were done to determine if the risk factors occurred at higher frequencies in certain ethnicities.

Results

Based on BP, BMI, and HbA1c measurements, several statistically significant differences were identified in relation to ethnicity. Many of the adolescents had increased HbA1c levels, with 27.3% considered high risk and 2.3% in the prediabetes range; these high risk and prediabetes groups were heavily represented by Filipino (46%), Indigenous (22%), and European (10%) adolescents. Notable prevalence of prehypertension (17.7%) and hypertension (21.7%) were reported in European (59%) followed by Filipino (50%) and Indigenous (26%) adolescents. Higher numbers of adolescents in the European and Filipino ancestry groups had two or more risk factors (BP, BMI, & HbA1c) for developing type 2 diabetes in relation to the adolescents from the Indigenous group.

Conclusions

Ethnic adolescent groups demonstrate a notable prevalence of undiagnosed prediabetes and type 2 diabetes. Specifically, a significant number of Filipino adolescents had both increased HbA1c and blood pressure that has gone undetected. Earlier onset of type 2 diabetes is congruent with an increased risk of developing diabetes-associated complications and, ultimately, diabetes-related morbidity and mortality at a younger age. Future studies should explore how genetic and/or environmental factors among ethnic groups may contribute to early onset hypertension and prediabetes/type 2 diabetes.
Preoperative pelvic floor muscle exercise for early continence after holmium laser enucleation of the prostate: a randomized controlled study
Authors: Anan Go , Kaiho Yasuhiro , Iwamura Hiromichi , Ito Jun , Kohada Yuki , Mikami Jotaro , Sato Makoto
Published: January 2020

Background

Transient postoperative urinary incontinence is a bothersome complication of holmium laser enucleation of the prostate (HoLEP). The effects of preoperative pelvic floor muscle exercise (PFME) for early recovery of continence after HoLEP have never been elucidated. The aim of this study was to determine the benefit of preoperatively started PFME for early recovery of continence after HoLEP.

Methods

We randomly assigned patients to start PFME preoperatively and continue postoperatively (group A) or start PFME no earlier than the postoperative period (group B). The primary outcome was time to complete urinary control, defined as no pad usage. The secondary outcome was measured using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Univariate and multivariate analyses were performed to identify parameters associated with recovery of continence after HoLEP.

Results

Seventy patients were randomized across groups A (n = 35) and B (n = 35). Patients’ characteristics were not different between groups A and B. The postoperative urinary incontinence rate significantly decreased in group A compared with that in group B at 3 months postoperatively [3% vs. 26% (P = 0.01)]. However, there were no significant differences between groups A and B at 3 days [40% vs. 54% (P = 0.34)], 1 month [37% vs. 51% (P = 0.34)], and 6 months [0% vs. 3% (P = 1.00)] postoperatively, respectively. The postoperative ICIQ-SF score was not significantly different between groups A and B at any time point postoperatively. In univariate analysis, patients who performed preoperative PFME had a 0.56-fold lower risk of urinary incontinence 1 month after HoLEP and a 0.08-fold lower risk of urinary incontinence 3 months after HoLEP.

Conclusions

Preoperatively started PFME appears to facilitate improvement of early urinary continence after HoLEP.

Trial registration

The study was registered with the University Hospital Medical Information Network Clinical Trials Registry in Japan (UMIN000034713); registration date: 31 October 2018. Retrospectively registered.
A rapid quality control test to foster the development of the sterile insect technique against Anopheles arabiensis
Authors: Culbert Nicole J. , Somda Nanwintoum Séverin Bimbilé , Hamidou Maiga , Soma Dieudonné Diloma , Caravantes Silvana , Wallner Thomas , Wadaka Mamai , Yamada Hanano , Bouyer Jérémy
Published: January 2020

Background

With the fight against malaria reportedly stalling there is an urgent demand for alternative and sustainable control measures. As the sterile insect technique (SIT) edges closer to becoming a viable complementary tool in mosquito control, it will be necessary to find standardized techniques of assessing male quality throughout the production system and post-irradiation handling. Flight ability is known to be a direct marker of insect quality. A new version of the reference International Atomic Energy Agency/Food and Agricultural Organization (IAEA/FAO) flight test device (FTD), modified to measure the flight ability and in turn quality of maleAnopheles arabiensiswithin a 2-h period via a series of verification experiments is presented.

Methods

Anopheles arabiensisjuveniles were mass reared in a rack and tray system. 7500 male pupae were sexed under a stereomicroscope (2500 per treatment). Stress treatments included irradiation (with 50, 90, 120 or 160 Gy, using a Gammacell 220), chilling (at 0, 4, 8 and 10 °C) and compaction weight (5, 15, 25, and 50 g). Controls did not undergo any stress treatment. Three days post-emergence, adult males were subjected to either chilling or compaction (or were previously irradiated at pupal stage), after which two repeats (100 males) from each treatment and control group were placed in a FTD to measure flight ability. Additionally, one male was caged with 10 virgin females for 4 days to assess mating capacity (five repeats). Survival was monitored daily for a period of 15 days on remaining adults (two repeats).

Results

Flight ability results accurately predicted male quality following irradiation, with the first significant difference occurring at an irradiation dose of 90 Gy, a result which was reflected in both survival and insemination rates. A weight of 5 g or more significantly reduced flight ability and insemination rate, with survival appearing less sensitive and not significantly impacted until a weight of 15 g was imposed. Flight ability was significantly reduced after treatments at 4 °C with the insemination rate more sensitive to chilling with survival again less sensitive (8 and 0 °C, respectively).

Conclusions

The reported results conclude that the output of a short flight ability test, adapted from the previously testedAedesFTD, is an accurate indicator of male mosquito quality and could be a useful tool for the development of the SIT againstAn. arabiensis.
IgG antibody response against Anopheles salivary gland proteins in asymptomatic Plasmodium infections in Narino, Colombia
Authors: Montiel Jehidys , Carbal Luisa F. , Tobón-Castaño Alberto , Vásquez Gissella M. , Fisher Michael L. , Londono-Rentería Berlin
Published: January 2020

Background

The humoral immune response againstAnophelessalivary glands proteins in the vertebrate host can reflect the intensity of exposure toAnophelesbites and the risk ofPlasmodiuminfection. In Colombia, the identification of exposure biomarkers is necessary due to the severalAnophelesspecies circulating. The purpose of this study was to evaluate risk of malaria infection by measuring antibody responses against salivary glands extracts fromAnopheles(Nyssorhynchus)albimanusandAnopheles(Nys.)darlingiand also against the gSG6-P1 peptide ofAnopheles gambiaein people residing in a malaria endemic area in the Colombian Pacific coast.

Methods

Dried blood spots samples were eluted to measure the IgG antibodies against salivary gland extracts ofAn. albimanusstrains STECLA (STE) and Cartagena (CTG) andAn. darlingiand the gSG6-P1 peptide by ELISA in uninfected people and microscopic and submicroscopicPlasmodiumcarriers from the Colombia Pacific Coast. A multiple linear mixed regression model, Spearman correlation, and Mann–Whitney U-test were used to analyse IgG data.

Results

Significant differences in specific IgG levels were detected between infected and uninfected groups for salivary glands extracts fromAn. albimanusand for gSG6-P1, also IgG response to CTG and gSG6-P1 peptide were positively associated with the IgG response toPlasmodium falciparumin the mixed model.

Conclusion

The CTG and STEAn. albimanussalivary glands extracts are a potential source of newAnophelessalivary biomarkers to identify exposure to the main malaria vector and to calculate risk of disease in the Colombian Pacific coast. Also, the gSG6-P1 peptide has the potential to quantify human exposure to the subgenusAnophelesvectors in the same area.
Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation
Authors: Misawa Kiyoshi , Mima Masato , Satoshi Yamada , Imai Atsushi , Mochizuki Daiki , Ishikawa Ryuji , Kita Junya , Yamaguchi Yuki , Endo Shiori , Misawa Yuki , Mineta Hiroyuki
Published: January 2020

Background

Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC.

Methods

Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival.

Results

The mean number of methylated genes per sample was 2.05 ± 2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5–9 methylated genes had a significantly lower survival rate than that of patients with 0–4 methylated genes (log-rank test, P= 0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P = 0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P = 0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P = 0.028 and P = 0.006, respectively). Moreover, Patients with 5–9 methylated genes were extremely lower of 5hmC levels (P = 0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P < 0.05 and P < 0.05, respectively).

Conclusion

We characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.
Role of IL-24 in the mucosal remodeling of children with coeliac disease
Authors: Rokonay Réka , Veres-Székely Apor , Szebeni Beáta , Pap Domonkos , Lippai Rita , Béres Nóra J. , Veres Gábor , Szabó Attila J. , Vannay Ádám
Published: January 2020

Background

Recently, involvement of IL-19, IL-20 and IL-24 has been reported in inflammatory diseases associated with tissue remodeling. However, their impact on the pathomechanism of coeliac disease (CD) is still completely unknown.

Methods

Expression of IL19, IL20 and IL24 was measured by real-time RT-PCR, protein amount of IL-24, α smooth muscle actin (α-SMA) and fibronectin (FN) was determined by Western-blot analysis in the duodenal biopsies of therapy naive children with CD and controls. Localization of IL-24 and IL-20RB was investigated by immunofluorescent staining in the duodenal mucosa. Effect of recombinant IL-1β, TNF-α, TGF-β and IL-17 treatment on the expression of IL19, IL20, IL24 and their receptors was investigated by real-time RT-PCR in small intestinal epithelial cells (FHs74Int), in primary duodenal myofibroblasts (pdMFs) and in peripheral blood mononuclear cells (PBMCs). Effect of IL-24 on H2O2 treated FHs74Int cells and on pdMFs was measured by MTT, LDH, Annexin V assays, real-time RT-PCR and by fluorescent microscopy.

Results

We found increased level of IL-24 (3.3×, p < 0.05), α-SMA (2.4×, p < 0.05) and FN (2.3×, p < 0.05) in the duodenal mucosa and increased expression of IL19 (3.6×, p < 0.05) and IL24 (5.2×, p < 0.05) in the PBMCs of children with CD compared to that of controls. IL-1β was a strong inducer of IL24 expression of FHs74Int cells (9.9×, p < 0.05), pdMFs (552.9×, p < 0.05) or PBMCs (17.2×, p < 0.05), as well. IL-24 treatment reduced the number of apoptotic cells (0.5×, p < 0.05) and decreased the expression of inflammatory factors, including IL1A, IL6 and TNF of H2O2-treated FHs74Int cells. IL-24 decreased the proliferation (0.6×, p < 0.05) of PDGF-B treated pdMFs. Moreover, IL-24 treatment altered the morphology of pdMFs by influencing the size of the angles between stress fibers and the longitudinal axis of the cells (2.0×, p < 0.05) and the expression of cytoskeletal components, including ACTA2, ACTB, VIM, SNAI1 and SNAI2.

Conclusion

Our results suggest that IL-24 plays a significant role in the maintenance of duodenal mucosal integrity in CD.
Excessive BCAA regulates fat metabolism partially through the modification of m6A RNA methylation in weanling piglets
Authors: Heng Jinghui , Wu Zhihui , Tian Min , Chen Jiaming , Song Hanqing , Chen Fang , Guan Wutai , Zhang Shihai
Published: January 2020

Background

Fat percentage and distribution in pigs are associated with their productive efficiency and meat quality. Dietary branched-chain amino acids (BCAA) regulate fat metabolism in weanling piglets with unknown mechanism. It is reported that N6-methyl-adenosine (m6A) is involved in fat metabolism in mice. The current study was designed to investigate the relationship between dietary branched-chain amino acids and fat metabolism through N6-methyl-adenosine (m6A) in weanling piglets.

Methods

A total of 18 healthy crossbred weaned piglets (Duroc × Landrace × Large White, 10.45 ± 0.41 kg) were divided into 3 treatments and were fed the low BCAA dose diet (L-BCAA), the normal dose BCAA diet (N-BCAA), or the high dose BCAA (H-BCAA) diet for 3 weeks.

Results

Our results show that compared with the N-BCAA group, the L-BCAA group had higher concentration of serum leptin (P < 0.05), while the H-BCAA group had lower concentration of serum adiponectin (P < 0.05). Fatty acid synthesis in pigs from the H-BCAA group was lower than those from the N-BCAA group with the down-regulation of lipogenic genes (ACACA, FASN, PPAR-r, SREBP-1c in ventral and dorsal fat, SREBP-1c in liver) and up-regulation of lipolysis genes (HSL, ATGL, CPT-1A, FABP4 in ventral fat, HSL in liver) (P < 0.05). Similarly, fatty acid synthesis in pigs from the L-BCAA group was also lower than those from the N-BCAA group with the decrease of lipogenic genes (ACACA in ventral, ACACA and FASN in dorsal fat, ACACA, FASN, SREBP-1c in liver) and the increase of lipolysis genes (ATGL, CPT-1A CD36, FABP4 in ventral fat and HSL, ATGL, CPT-1A in dorsal fat, CPT-1A) (P < 0.05). Feeding H-BCAA diet significantly reduced total m6A levels in ventral and dorsal fat and liver tissues (P < 0.05). The decrease of total m6A is associated with down-regulation of METTL3, METTL14 and FTO in dorsal fat and METTL3 and FTO in liver (P < 0.05). Decreased m6A modification of ACACA and FASN in ventral and dorsal adipose tissues was observed in pig fed with excessive BCAA.

Conclusion

These results suggest that insufficient or excessive BCAA decreased the fat deposition by increasing lipolysis and deceasing lipogenesis in adipose and liver tissues. Dietary excessive BCAA might regulate the process of lipid metabolism partly through the m6A RNA methylation.
Development of a gp60-subtyping method for Cryptosporidium felis
Authors: Rojas-Lopez Laura , Elwin Kristin , Chalmers Rachel M. , Enemark Heidi L. , Beser Jessica , Troell Karin
Published: January 2020

Background

Feline cryptosporidiosis is an increasing problem, especially in catteries. In humans, close contact with cats could be a potential source of infection although the risk of contracting cryptosporidiosis caused by Cryptosporidium felis is considered to be relatively low. Sequencing of the 60-kDa glycoprotein gene is a commonly used tool for investigation of the genetic diversity and transmission dynamics of Cryptosporidium species. However, until now the sequence of gp60 from C. felis has not been available and genotyping has been limited to less discriminatory markers, such as 18S rRNA, COWP and HSP70.

Methods

We have identified the gp60 orthologue within the genome sequence of C. felis, and used the sequence to design a nested PCR for subtyping purposes. A total of 128 clinical isolates of both feline and human origin, were used to evaluate the marker.

Results

Sequence analysis revealed large variations between the different samples. The C. felis gp60 lack the characteristic serine-tract found in many other cryptosporidian orthologues, instead it has an insertion of variable length (361–742 nt). Also, two cases of suspected zoonotic transmission of C. felis between cats and humans were successfully confirmed.

Conclusions

We have identified the gp60 gene in C. felis and show how this highly variable marker can be used in epidemiological investigations.
Inclusion of MCQs written by radiology residents in their annual evaluation: innovative method to enhance resident’s empowerment?
Authors: Amini Nadia , Michoux Nicolas , Warnier Leticia , Malcourant Emilie , Coche Emmanuel , Vande Berg Bruno
Published: January 2020

Aim

We hypothesized that multiple-choice questions written by radiology residents (MCQresident) for their weekly case presentations during radiology staff meetings could be used along with multiple-choice questions written by radiology teachers (MCQteacher) for their annual evaluation. The current prospective study aimed at determining the educational characteristics of MCQresident and at comparing them with those of MCQteacher.

Methods

Fifty-one radiology residents of the first to the fifth year of training took the 2017 exam that contained 58 MCQresident and 63 of MCQteacher. The difficulty index, the discrimination power, and the distractor’s quality were calculated in the two series of MCQs and were compared by using Student t test. Two radiologists classified each MCQ according to Bloom’s taxonomy and frequencies of required skills of both MCQ series were compared.

Results

The mean ± SD difficulty index of MCQresident was statistically significantly higher than that of MCQteacher (0.81 ± 0.1 vs 0.64 ± 0.2; p < 0.0001). The mean ± SD discrimination index of MCQresident was statistically significantly higher than that of MCQteacher (0.34 ± 0.2 vs 0.23 ± 0.2; p = 0.0007). The mean number of non-functional distractors per MCQresident was statistically significantly higher than that per MCQteacher (1.36 ± 0.9 vs 0.86 ± 0.9; p = 0.0031). MCQresident required recalling skills more frequently than MCQteacher which required more advanced skills to obtain a correct answer.

Conclusions

Educational characteristics of MCQresident differ from those of MCQteacher. This study highlights the characteristics to optimize the writing of MCQs by radiology residents.
Scaffold vascularization method using an adipose-derived stem cell (ASC)-seeded scaffold prefabricated with a flow-through pedicle
Authors: Dębski Tomasz , Kurzyk Agata , Ostrowska Barbara , Wysocki Juliusz , Jaroszewicz Jakub , Święszkowski Wojciech , Pojda Zygmunt
Published: January 2020

Background

Vascularization is important for the clinical application of tissue engineered products. Both adipose-derived stem cells (ASCs) and surgical prefabrication can be used to induce angiogenesis in scaffolds. Our aim was to compare the angiogenic potential of ASC-seeded scaffolds combined with scaffold prefabrication with that of non-seeded, non-prefabricated scaffolds.

Methods

For prefabrication, functional blood vessels were introduced into the scaffold using a flow-through pedicle system. ASCs were isolated from rat fat deposits. Three-dimensional-printed cylindrical poly-ε-caprolactone scaffolds were fabricated by fused deposition modelling. Three groups, each containing six rats, were investigated by using non-seeded, ASC-seeded, and osteogenic induced ASC-seeded scaffolds. In each group, one rat was implanted with two scaffolds in the inguinal region. On the right side, a scaffold was implanted subcutaneously around the inferior epigastric vessels (classic prefabrication group). On the left side, the inferior epigastric vessels were placed inside the prefabricated scaffold in the flow-through pedicle system (flow-through prefabrication group). The vessel density and vascular architecture were examined histopathologically and by μCT imaging, respectively, at 2 months after implantation.

Results

The mean vessel densities were 10- and 5-fold higher in the ASC-seeded and osteogenic induced ASC-seeded scaffolds with flow-through prefabrication, respectively, than in the non-seeded classic prefabricated group (p < 0.001). μCT imaging revealed functional vessels within the scaffold.

Conclusion

ASC-seeded scaffolds with prefabrication showed significantly improved scaffold vasculogenesis and could be useful for application to tissue engineering products in the clinical settings.
Correction to: BM-MSC-derived exosomes alleviate radiation-induced bone loss by restoring the function of recipient BM-MSCs and activating Wnt/β-catenin signaling
Authors: Zuo Rui , Liu Minghan , Wang Yanqiu , Li Jie , Wang Wenkai , Wu Junlong , Sun Chao , Li Bin , Wang Ziwen , Lan Weiren , Zhang Chao , Shi Chunmeng , Zhou Yue
Published: January 2020

The original article [1] contains an error in Fig. 5 whereby sub-Fig. 5c, d & 5e are mistakenly mixed-up.
Mesenchymal stem cell-derived exosomes ameliorate cardiomyocyte apoptosis in hypoxic conditions through microRNA144 by targeting the PTEN/AKT pathway
Authors: Wen Zhuzhi , Mai Zun , Zhu Xiaolin , Wu Tao , Chen Yangxin , Geng Dengfeng , Wang Jingfeng
Published: January 2020

Background

A growing body of evidence suggests that stem cell-derived exosomal microRNAs (miRNAs) could be a promising cardioprotective therapy in the context of hypoxic conditions. The present study aims to explore how miRNA-144 (miR-144), a miRNA contained in bone marrow mesenchymal stem cell (MSC)-derived exosomes, exerts a cardioprotective effect on cardiomyocyte apoptosis in the context of hypoxic conditions and identify the underlying mechanisms.

Methods

MSCs were cultured using the whole bone marrow adherent method. MSC-derived exosomes were isolated using the total exosome isolation reagent and confirmed by nanoparticle trafficking analysis as well as western blotting using TSG101 and CD63 as markers. The hypoxic growth conditions for the H9C2 cells were established using the AnaeroPack method. Treatment conditions tested included H9C2 cells pre-incubated with exosomes, transfected with miR-144 mimics or inhibitor, or treated with the PTEN inhibitor SF1670, all under hypoxic growth conditions. Cell apoptosis was determined by flow cytometry using 7-ADD and Annexin V together. The expression levels of the miRNAs were detected by real-time PCR, and the expression levels of AKT/p-AKT, Bcl-2, caspase-3, HIF-1α, PTEN, and Rac-1 were measured by both real-time PCR and western blotting.

Results

Exosomes were readily internalized by H9C2 cells after co-incubation for 12 h. Exosome-mediated protection of H9C2 cells from apoptosis was accompanied by increasing levels of p-AKT. MiR-144 was found to be highly enriched in MSC-derived exosomes. Transfection of cells with a miR-144 inhibitor weakened exosome-mediated protection from apoptosis. Furthermore, treatment of cells grown in hypoxic conditions with miR-144 mimics resulted in decreased PTEN expression, increased p-AKT expression, and prevented H9C2 cell apoptosis, whereas treatment with a miR-144 inhibitor resulted in increased PTEN expression, decreased p-AKT expression, and enhanced H9C2 cell apoptosis in hypoxic conditions. We also validated that PTEN was a target of miR-144 by using luciferase reporter assay. Additionally, cells treated with SF1670, a PTEN-specific inhibitor, resulted in increased p-AKT expression and decreased H9C2 cell apoptosis.

Conclusions

These findings demonstrate that MSC-derived exosomes inhibit cell apoptotic injury in hypoxic conditions by delivering miR-144 to cells, where it targets the PTEN/AKT pathway. MSC-derived exosomes could be a promising therapeutic vehicle to facilitate delivery of miRNA therapies to ameliorate ischemic conditions.
Identification of ireA, 0007, 0008, and 2235 as TonB-dependent receptors in the avian pathogenic Escherichia coli strain DE205B
Authors: Zhang Zhonghua , Jiang Shan , Liu Yun , Sun Yu , Yu Peixin , Gong Qianwen , Zeng Hang , Li Yihao , Xue Feng , Zhuge Xiangkai , Ren Jianluan , Dai Jianjun , Tang Fang
Published: January 2020

Avian pathogenic Escherichia coli (APEC), a pathotype of extraintestinal pathogenic E. coli, causes one of the most serious infectious diseases of poultry and shares some common virulence genes with neonatal meningitis-associated E. coli. TonB-dependent receptors (TBDRs) are ubiquitous outer membrane β-barrel proteins; they play an important role in the recognition of siderophores during iron uptake. Here, in the APEC strain DE205B, we investigated the role of four putative TBDRs—ireA, 0007, 0008, and 2235—in iron uptake. Glutathione-S-transferase pulldown assays indicated that the proteins encoded by these genes directly interact with TonB. Moreover, the expression levels of all four genes were significantly upregulated under iron-depleted conditions compared with iron-rich conditions. The expression levels of several iron uptake-related genes were significantly increased in the ireA, 0007, 0008, and 2235 deletion strains, with the upregulation being the most prominent in the ireA deletion mutant. Furthermore, iron uptake by the ireA deletion strain was significantly increased compared to that by the wild-type strain. Moreover, a tonB mutant strain was constructed to study the effect of tonB deletion on the TBDRs. We found that regardless of the presence of tonB, the expression levels of the genes encoding the four TBDRs were regulated by fur. In conclusion, our findings indicated that ireA, 0007, 0008, and 2235 indeed encode TBDRs, with ireA having the most important role in iron uptake. These results should help future studies explore the mechanisms underlying the TonB-dependent iron uptake pathway.
On weak solutions to a generalized Camassa–Holm equation with solitary wave
Authors: Guo Yunxi
Published: January 2020

A generalized Camassa–Holm equation proposed by Novikov is considered. The existence and uniqueness of a positive weak solution for the equation is established by using a classical method.
Dynamical analysis of a fractional-order eco-epidemiological model with disease in prey population
Authors: Moustafa Mahmoud , Mohd Mohd Hafiz , Ismail Ahmad Izani , Abdullah Farah Aini
Published: January 2020

A fractional-order eco-epidemiological model with disease in the prey population is formulated and analyzed. Mathematical analysis and numerical simulations are performed to clarify the characteristics of the proposed fractional-order model. The existence, uniqueness, non-negativity and boundedness of the solutions are proved. The local and global asymptotic stability of all equilibrium points are investigated. Finally, numerical simulations are conducted to illustrate the analytical results. The occurrence of Hopf bifurcations and transcritical bifurcations for the fractional-order eco-epidemiological model are demonstrated. It is observed that the fractional order has a stabilization effect and it may help to control the coexistence between susceptible prey, infected prey and predator populations.
Existence and global exponential stability of anti-periodic solutions for quaternion-valued cellular neural networks with time-varying delays
Authors: Li Yongkun , Xiang Jianglian
Published: January 2020

In this paper, we are concerned with a class of quaternion-valued cellular neural networks with time-varying transmission delays and leakage delays. By applying a continuation theorem of coincidence degree theory and the Wirtinger inequality as well as constructing a suitable Lyapunov functional, sufficient conditions are derived to ensure the existence and global exponential stability of anti-periodic solutions via direct approaches. Our results are completely new. Finally, numerical examples are also provided to show the effectiveness of our results.
The politics of energy landscapes: the influence of local anti-wind initiatives on state policies in Saxony, Germany
Authors: Lintz Gerd , Leibenath Markus
Published: January 2020

Background

In recent years, landscapes in many countries have been transformed by efforts to fight global warming, specifically the shift towards renewable energies such as wind power. This development has been met by growing opposition from local citizens and their initiatives. There is an ongoing debate about whether and how such protests have a real impact on the development of energy landscapes.

Methods

Drawing on the rare case of a state government scaling back ambitious targets for the expansion of renewables, the authors were able to analyse the impact of protests in the context of regional spatial planning and, particularly, state policy-making on energy. Conceptually drawing on the Advocacy Coalition Framework and using the method of causal-process tracing, the qualitative study investigates related interactions and decision-making processes in the federal state of Saxony, Germany, between 2011—when targets were increased—and 2013—when targets were scaled back.

Results

The findings show that the protests grew significantly when the raised expansion targets for renewables were translated into a higher number of potential wind farm sites. The protests, which primarily referred to landscapes, were well-organised and creative. Activists worked through a range of channels across various contexts and several levels of the politico-administrative system, in particular approaching regional spatial planners and a wide range of politicians. In the end, the protests (along with other factors) significantly contributed to the readjustment by the Saxon coalition government of its energy and climate policy and thus to a slowdown of energy-related landscape change.

Conclusions

The study confirms that the influence of protesters can greatly exceed the previously studied participation in the planning of sites and the approval process for individual wind farms. Also highlighting other relevant co-influential factors, the paper contributes to the development of a middle-range theory of the impact of local opposition to wind power in the context of energy landscapes.
Mechanical and physio-biological properties of peptide-coated stent for re-endothelialization
Authors: Bae In-Ho , Jeong Myung Ho , Park Dae Sung , Lim Kyung Seob , Shim Jae Won , Kim Mun Ki , Park Jun-Kyu
Published: January 2020

Background

The aim of this study was to characterize the mechanical and physio-biological properties of peptide-coated stent (PCS) compared to commercialized drug-eluting stents (DESs).

Methods

WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met), a stimulating peptide for homing endothelial colony-forming cell was specially synthesized and coated to bare metal stent (BMS) by dopamine-derived coordinated bond. Biological effects of PCS were investigated by endothelial cell proliferation assay and pre-clinical animal study. And mechanical properties were examined by various experiment.

Results

The peptide was well-coated to BMS and was maintained and delivered to 21 and 7 days in vitro and in vivo, respectively. Moreover, the proliferation of endothelial cell in PCS group was increased (approximately 36.4 ± 5.77%) in PCS group at 7 day of culture compare to BMS. Although, the radial force of PCS was moderated among study group. The flexibility of PCS was (0.49 ± 0.082 N) was greatest among study group. PCS did not show the outstanding performance in recoil and foreshortening test (3.1 ± 0.22% and 2.1 ± 0.06%, respectively), which was the reasonable result under the guide line of FDA (less than 7.0%). The nominal pressure (3.0 mm in a diameter) of PCS established by compliance analysis was 9 atm. The changing of PCS diameter by expansion was similar to other DESs, which is less than 10 atm of pressure for the nominal pressure.

Conclusions

These results suggest that the PCS is not inferior to commercialized DES. In addition, since the PCS was fabricated as polymer–free process, secondary coating with polymer-based immunosuppressive drugs such as –limus derivatives may possible.
First confirmed record of Sparid Pagellus bogaraveo (Brünnich, 1768) in the Syrian marine waters (Levantine Basin)
Authors: Saad Adib , Masri Mai , Sabour Waad
Published: January 2020

This paper aims to present the first record of Pagellus bogaraveo (Brünnich, 1768) from Syria marine waters. One specimen was caught by trawl nets at about 300 m depth in Rass Albassit, north of Lattakia, on 25 February 2019, and 6 additional specimens were caught by gill nets at a depth of 120 m off Jablah coast on 7 April 2019. This record represents the first sighting of this immigrant Atlantic species introduced in the Eastern Mediterranean (Levantine Basin). These specimens were found mixing in the same net haul with populations other Sparidae species such as: Pagellus acarne and Dentex macrophthalmus.
A scoping review and mapping exercise comparing the content of patient-reported outcome measures (PROMs) across heart disease-specific scales
Authors:   on behalf of the Collaboration and Exchange in Swedish cardiovascular caring Academic Research (CESAR) group, Algurén Beatrix , Coenen Michaela , Malm Dan , Fridlund Bengt , Mårtensson Jan , Årestedt Kristofer
Published: January 2020

Background

Over the past decade, the importance of person-centered care has led to increased interest in patient-reported outcome measures (PROMs). In cardiovascular care, selecting an appropriate PROM for clinical use or research is challenging because multimorbidity is often common in patients. The aim was therefore to provide an overview of heart-disease specific PROMs and to compare the content of those outcomes using a bio-psycho-social framework of health.

Methods

A scoping review of heart disease-specific PROMs, including arrhythmia/atrial fibrillation, congenital heart disease, heart failure, ischemic heart disease, and valve diseases was conducted in PubMed (January 2018). All items contained in the disease-specific PROMs were mapped to WHO’s International Classification of Functioning, Disability and Health (ICF) according to standardized linking rules.

Results

A total of 34 PROMs (heart diseases in general n = 5; cardiac arrhythmia n = 6; heart failure n = 14; ischemic heart disease n = 9) and 147 ICF categories were identified. ICF categories covered Body functions (n = 61), Activities & Participation (n = 69), and Environmental factors (n = 17). Most items were about experienced problems of Body functions and less often about patients’ daily activities, and most PROMs were specifically developed for heart failure and no PROM were identified for valve disease or congenital heart disease.

Conclusions

Our results motivate and provide information to develop comprehensive PROMs that consider activity and participation by patients with various types of heart disease.
Free fatty acid-based low-impedance liver image: a characteristic appearance in nonalcoholic steatohepatitis (NASH)
Authors: Maruyama Hitoshi , Kobayashi Kazufumi , Kiyono Soichiro , Chiba Tetsuhiro , Kato Naoya , Ohtsuka Masayuki , Ito Kazuyo , Yamaguchi Tadashi , Shiina Shuichiro
Published: January 2020

Background

To examine in vitro acoustic property of nonalcoholic fatty disease in mouse and human liver to identify nonalcoholic steatohepatitis (NASH).

Methods

The acoustic impedance (× 106 kg/m2/s) was measured in 35 free fatty acids (FFAs, 500 mmol/L) and histologically-diagnosed liver samples of twelve mice (four control, four simple steatosis [SS], and four NASH) and eight humans (two control, three SS, and three NASH), using 80-MHz acoustic microscopy. The sum of percentage (SP) composition of FFAs (SP-FFAs) was also assessed.

Results

Median impedance of all FFAs was 0.7 (5 FFAs with impedance 0.7); 17 FFAs with impedance < 0.7 were classified as low-impedance group; and, 13 FFAs with impedance > 0.7 were classified as high-impedance group. The median impedance of the mouse liver decreased from control (1.715), to SS (1.68), to NASH (1.635) (control versus NASH, p = 0.039 without significant differences for the other comparisons, p ≥ 0.1). Similarly, the median impedance of human liver showed decreased from control (1.825), to SS (1.788), to NASH (1.76) (control versus SS, p = 0.023; control versus NASH, p = 0.003; SS versus NASH, p = 0.050). The ratio of SP-FFAs between the low-impedance and high-impedance groups showed an increase in both mice and humans, with significant differences in mice (control versus SS, p < 0.001; control versus NASH, p < 0.001; SS versus NASH, p = 0.003), without significant differences in humans (p ≥ 0.671).

Conclusion

Lower acoustic impedance based on the intrahepatic composition of FFAs may be characteristic of NASH.
Competencies and training of radiographers and technologists for PET/MR imaging - a study from the UK MR-PET network
Authors: Mada Marius Ovidiu , Hindmarch Paula , Stirling James , Davies James , Brian David , Barnes Anna , Hammers Alexander , Gulliver Nick , Herholz Karl , O’Brien John , Taylor John-Paul
Published: January 2020

Background

After the success of PET/CT as a clinical diagnostic tool, the introduction of PET/MRI is a natural development aimed at further improving combined diagnostic imaging and reduced ionising radiation dose for half-body imaging. As with PET and CT, the combination of PET and MRI presents a series of issues that need to be addressed regarding workforce training and education. At present, there is a lack of agreement over the competencies, training requirements and educational pathways needed for PET/MRI operation. In the UK, following the establishment of the MR-PET imaging network, a task force was created to investigate the status of the workforce training, identify gaps and make recommendations regarding staff training. To do this, we ran a national survey on the status of the workforce training and the local practices across the UK’s seven PET/MRI sites, reviewed the literature, and convened a panel of experts, to assess all the evidence and make recommendations regarding PET/MRI competencies and training of nuclear medicine technologists and radiographers.

Results

There is limited literature available specifically on competencies and training for technologists and radiographers. The recommendations on the topic needed revisiting and adapting to the UK MR-PET network. The online survey confirmed the need for developing PET/MRI competencies and training pathways. Local organisational structures and practices were shared across the seven sites, based on models derived from experience outside the UK. The panel of experts agreed on the need for PET/MRI competencies and training strategies. Professional organisations started collaborative discussions with partners from both Nuclear Medicine and Radiography to set training priorities. Multidisciplinary collaboration and partnership were suggested as a key to a successful implementation of competencies and training.

Conclusions

The report identified the need for establishing competencies for the PET/MRI workforce, particularly for technologists and radiographers. It also helped defining these competencies as well as identifying the demand for bespoke training and the development of local and national courses to be implemented to fulfil this new training need.
Leveraging Multiple Analytic Frameworks to Assess the Stability of Students’ Knowledge in Physiology
Authors: Lira Matthew , Gardner Stephanie M.
Published: January 2020

When a student explains a biological phenomenon, does the answer reflect only the product of retrieving knowledge or does it also reflect a dynamic process of constructing knowledge? To gain insight into students’ dynamic knowledge, we leveraged three analytic frameworks—structures–behaviors–functions (SBF), mental models (MM), and conceptual dynamics (CD). To assess the stability of student knowledge, we asked undergraduate students to explain the same physiological phenomenon three times—once verbally, once after drawing, and once after interpreting a diagram. The SBF analysis illustrated fine-grained dynamic knowledge between tasks. The MM analysis suggested global stability between tasks. The CD analysis demonstrated local instability within tasks. The first two analyses call attention to differences between students’ knowledge about the parts of systems and their organization. The CD analysis, however, calls attention to similar learning mechanisms that operate differently vis-à-vis external representations. Students with different mental models deliberated localization or where to locate the structures and mechanisms that mediate physiological responses, but students made these deliberations during different tasks and arrived at different conclusions. These results demonstrate the utility of incorporating dynamic approaches to complement other analytic approaches and motivate future research agendas in biology education research.
Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths: A Longitudinal Study
Authors: Galderisi Alfonso , Tricò Domenico , Dalla Man Chiara , Santoro Nicola , Pierpont Bridget , Groop Leif , Cobelli Claudio , Caprio Sonia
Published: January 2020

Context

The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak.

Methods

We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of time-to-glucose-peak on glucose tolerance change.

Results

Participants were grouped into early (<30 minutes) and late (≥30 minutes) glucose peakers. A delayed glucose peak was featured by a decline in φstatic (P < .001) in the absence of a difference in φdynamic. The prevalence of T-risk allele for TCF7L2 rs7903146 variant significantly increased in the late peak group. A lower DI was correlated with higher glucose concentration at 1 and 2 hours, whereas SI was inversely associated with 1-hour glucose. Glucose peak <30 minutes was protective toward worsening of glucose tolerance overtime (odds ratio 0.35 [0.15–0.82]; P = .015), with no subjects progressing to NGT or persisting IGT, in contrast to the 40% of progressor in those with late glucose peak.

Conclusion

The prevalence of T-risk allele for the TCF7L2 rs7903146 prevailed in the late time-to-glucose peak group, which in turn is associated with impaired β-cell responsiveness to glucose (φ), thereby predisposing to prediabetes and diabetes in obese youths.