bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy modulation altered differentiation capacity of CD146+ cells toward endothelial cells, pericytes, and cardiomyocytes
Authors: Hassanpour Mehdi , Rezaie Jafar , Darabi Masoud , Hiradfar Amirataollah , Rahbarghazi Reza , Nouri Mohammad 
Published: February 2020

Abstract
Background: To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis whether an autophagy modulation could induce/reduce CD146+ cells differentiation into mature pericyte, endothelial and cardiomyocyte lineage. Methods In this study, CD146+ cells were enriched from human bone marrow aspirates and trans-differentiated into mature EC, PC and CM after exposure to autophagy stimulator (50 µM Met)/inhibitor (15 µM HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. The fatty acid change was determined by gas chromatography. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The exosome secretion capacity was assessed by AChE activity and real-time PCR assay. Result Data revealed the modulation of autophagy factors, Beclin-1, P62 and LC3 II/I ratio in differentiating CD146+ cells after exposure to Met and HCQ (p<0.05). The inhibition of autophagy increased released NO content and decreased intracellular NO content compared to the Met-treated cells (p<0.05). Real-time PCR analysis showed that the treatment of CD146+ cells with autophagy modulators altered the expression of VE-cadherin, cTnI and α-SMA. Our data demonstrated that the stimulation of autophagy signaling in CD146+ cells with Met increased the expression of VE-cadherin, α-SMA, and cTnI compared to HCQ-treated cells (p<0.05) while western blotting revealed the protein synthesis of all lineage-specific proteins in under the stimulation and inhibition of autophagy. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p<0.05). None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1 and VEGFR-2 after autophagy modulation. The treatment of cells with HCQ increased the levels of TNF-α and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p<0.05).ConclusionsIn summary, autophagy modulation could be altered differentiation potency of CD146+ cells and could be novel and applicable cardiac cell therapy in the cardiac regeneration field.
Circulating Tumor Cell Subtypes may Predict Responses to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
Authors: Ma Ge , Wang Jingyi , Wang Xingmeng , Zeng Hanling , Li Minghui , Han Xu , Mao Xinrui , Jiang Yi , Xia Tiansong , Liu Xiaoan , wang shui 
Published: February 2020

Abstract
Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). However, the predictive value of circulating tumor cells (CTCs) with different molecular subtypes in NCT response has not yet been determined, which was, therefore, the aim of this study.
Methods: All patients were staged as LABC and received an EC×4 –T×4 NCT regimen. Blood samples were collected from patients at the time of biopsy, and after the first and eighth NCT courses. Patients were divided into High responders (High-R) and Low responders (Low-R) according to Miller-Payne system and changes in Ki-67 levels after NCT treatment. A novel SE-i•FISH strategy was applied to detect CTCs. Subtypes were successfully analyzed in LABC patients undergoing NCT, for the first time.
Results: Total CTCs increased continuously and were higher for Low-R patients; while in the High-R group, total CTCs increased slightly during NCT before returning to baseline levels. Triploid and tetraploid chromosome 8 as well as the proportion of each, increased for Low-R but not High-R patients. The number of small CTCs in the Low-R group increased significantly until the last sample, however, remained constant in the High-R group. The patients with more CTCs had shorter PFS and OS than those with less CTCs after the 8th course of NCT.
Conclusions: Total CTCs as well as individual subtypes within peripheral blood following NCT were predictive of patient responses to NCT. More detailed characterization of CTC blood profiles may improve predictive capacity and lead to improved LABC treatments.
Proactive community case management in Senegal 2014-2016: a case study in maximizing the impact of community case management of malaria
Authors: Gaye Seynabou , Kibler Janelle , Ndiaye Jean Louis , Diouf Mame Birame , Linn Annē , Gueye Alioune Badara , Fall Fatou Ba , Ndiop Medoune , Diallo Ibrahima , Cisse Moustapha , Ba Mady , Thwing Julie 
Published: February 2020

Abstract
The Senegal National Malaria Control Program (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2000 villages nationwide by 2014. With prise en charge à domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61, and 43 patients with malaria per CHW in 2014, 2015, and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results, and lessons learned from Senegal’s implementation of PECADOM Plus, as well as guidance for other programs considering introduction of this innovative strategy.
A Family of Fuchs Endothelial Corneal Dystrophy and Anterior Polar Cataract with An Analysis of Whole Exome Sequencing
Authors: Jiang Xue , Jin Xin , Zhang Nan , Zhang Hong 
Published: February 2020

Abstract
Background Our aim was to introduce a family affected by this rare phenotype, and perform the whole exome sequencing (WES) to explore the potential candidate genes causing the disorders.Methods A five-generation family including 5 patients affected by FECD with APC, and 9 patients suffered from only FECD was recruited from the First Affiliated Hospital of Harbin Medical University. All participants received ophthalmic examinations. 8 family members were selected to perform WES with a bioinformatics analysis.Results Patients in this family had FECD as the common feature. The proband (a 65-year-old female) was affected by FECD and APC in both eyes, with epithelial bullae in the left eye of the. Slit-lamp, specular and confocal microscope and OCT images showed guttae more serious in the central cornea than the peripheral area, confirming the diagnosis of FECD. In this family, most corneal guttae were bilateral with almost equal degree of progression in Descemet membrane, APC was found around the age of 10, perhaps even earlier. Bioinformatics analysis showed that 83 potential candidate genes in total may cause this condition in this family. No known causative gene of this phenotype or FECD was found by WES.Conclusion We introduced a family of FECD with APC, with no known causative gene found by WES, inferring that there may be a novel gene-locus associated with this condition. Further study will be engaged on candidate gene screening and variants validation with corresponding functional aspects to clarify the relationship between genotype and phenotype.
Impact on Early Discharge After Emergency Department-Based Treatment Pathway in Nonperforated Appendicitis: A Retrospective Study
Authors: Ojakäär Artur , Purdy Martin , Kechagias Aristotelis , Järvelin Ulla , Palomäki Ari 
Published: February 2020

Abstract
Background Acute appendicitis is a global disease and a very common indication for emergency surgery worldwide. The need for hospital resources is therefore constantly high. The administration in Kanta-Häme Central Hospital, southern Finland, called for an urgent reorganisation due to shortage of hospital beds at the department of general surgery. Treatment pathway of nonperforated acute appendicitis was moved into Emergency Department (ED). The aim of this study was to assess whether it affected the length of in-hospital stay (LOS) and the 30-day complication rate.MethodsThis is a retrospective pre- and post- intervention analysis. After the reorganisation, most postoperative patients with nonperforated appendicitis were followed at the 24-hour observation unit of the ED instead of the surgical ward. Patients operated during the first three months after the reorganisation were compared to those operated during the three months before it. A case met inclusion criteria if there were no signs of appendiceal perforation during surgery. Exclusion criteria comprised age <18 years and perforated disease. ResultsDuring the study period, appendicectomy was performed on 112 patients, of whom 62 were adults with nonperforated appendicitis. Twenty-seven of the included patients were treated before the reorganisation, and 35 after it. Twenty of the latter were followed only at the ED. LOS decreased significantly after the reorganisation. Median postoperative time till discharge was 15.67 hrs for all patients after the reorganisation and 13.13 hrs for those exclusively followed at the ED, compared to 24.42 hrs before the reorganisation (standard error 6.2 hrs, 95% confidence interval 2.3–15.2 hrs, p < 0.01). There were no more complications in the group treated postoperatively in the ED. ConclusionsEarly discharge from the ED observation unit after appendicectomy for nonperforated appendicitis in adults is safe and feasible. Shifting the postoperative monitoring and the discharge policy of such patients to the ED – instead of the surgical ward – occurred in the majority of the cases after the reorganisation. This change may spare resources as in this series it resulted in a significantly shorter LOS without any increase in the 30-day complication rate.
HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple negative breast cancer cells
Authors: Oba Takaaki , Ono Mayu , Matoba Hisanori , Uehara Takeshi , Hasegawa Yoshie , Ito Ken-ichi 
Published: February 2020

Abstract
Background: Improved prognosis for triple-negative breast cancer (TNBC) has currently plateaued and the development of novel therapeutic strategies is required. This study aimed to explore the anti-tumor effect of combined eribulin and HDAC inhibitor (vorinostat: VOR, pan-HDAC inhibitor and ricolinostat: RICO, selective HDAC6 inhibitor) treatment for TNBC. Methods: The effect of eribulin in combination with VOR or RICO was tested based on both concurrent and sequential administration to three TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157) and their eribulin-resistant derivatives. The expression of acetylated α-tubulin was analyzed by western blotting. Immunohistochemical analyses of clinical specimens obtained from breast cancer patients who underwent neoadjuvant chemotherapy with eribulin were also examined. Results: The simultaneous administration of low concentrations of VOR (0.2 μM) or RICO (0.2 μM) enhanced the anti-tumor effect of eribulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. Meanwhile, pre-treatment with 5 μM of VOR or RICO enhanced sensitivity to eribulin in MDA-MB-231, Hs578T, and MDA-MB-157 cells. VOR or RICO increased acetylated α-tubulin expression in MDA-MB-231 and Hs578T cells in a dose-dependent manner (0.2 μM to 5 μM). In contrast, whereas 5 μM of VOR or RICO increased the expression of acetylated α-tubulin in MDA-MB-157 cells, low concentrations (0.2 μM or 0.5 μM) did not. Treatment with eribulin also increased the expression of acetylated α-tubulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. These phenomena were also observed in eribulin-resistant cells. Based on immunohistochemical analyses of clinical specimens, the expression of acetylated α-tubulin was increased after eribulin treatment in TNBC. Conclusions: HDAC6 inhibition enhances the anti-tumor effect of eribulin through the acetylation of α-tubulin. This combination therapy could represent a novel therapeutic strategy for TNBC.
MYB44 competitively inhibits the formation of the MYB340-bHLH2-NAC56 complex to regulate anthocyanin biosynthesis in purple-fleshed sweet potato
Authors: Wei Zeng-Zheng , Hu Kang-Di , Zhao Dong-Lan , Tang Jun , Huang Zhong-Qin , Jin Peng , Li Yan-Hong , Han Zhuo , Hu Lan-Ying , Yao Gai-Fang , Zhang Hua 
Published: February 2020

Abstract
Background: Anthocyanins, which have important biological functions and have a beneficial effect on human health, notably account for pigmentation in purple-fleshed sweet potato tuberous roots. Individual regulatory factors of anthocyanin biosynthesis have been identified; however, the regulatory network of anthocyanin biosynthesis in purple-fleshed sweet potato is unclear. Results: We functionally determined that IbMYB340 cotransformed with IbbHLH2 in tobacco and strawberry receptacles induced anthocyanin accumulation, and the addition of IbNAC56a or IbNAC56b caused increased pigmentation. Furthermore, we confirmed the interaction of IbMYB340 with IbbHLH2 and IbNAC56a or IbNAC56b via yeast two-hybrid and firefly luciferase complementation assays; these proteins could form a MYB340-bHLH2-NAC56a or MYB340-bHLH2-NAC56b transcriptional complex to regulate anthocyanin biosynthesis by binding to the IbANS promoter rather than the IbUFGT promoter. Furthermore, it was found by a transient expression system in tobacco leaves that IbMYB44 could decrease anthocyanin accumulation. Moreover, the interaction of IbMYB44 with IbMYB340 and IbNAC56a or IbNAC56b was verified. This result suggested that IbMYB44 acts as a repressor of anthocyanin in sweet potato.Conclusions: The repressor IbMYB44 affected anthocyanin biosynthesis by competitively inhibiting the IbMYB340-IbbHLH2-IbNAC56a or IbMYB340-IbbHLH2-IbNAC56b regulatory complex formation. Overall, the present study proposed a novel regulatory network whereby several vital TFs play key roles in regulating anthocyanin biosynthesis, and it provides strong insight into the potential mechanism underlying anthocyanin biosynthesis in sweet potato tuberous roots with purple color.
Ambient sulfur dioxide could have an impact on testicular volume from an observational study on a population of infertile male
Authors: Chen Yuan , Chang Yi-Kai , Su Yann-Rong , Chang Hong Chiang 
Published: February 2020

Abstract
Background The present retrospective study investigates the effect of environmental pollutants on male reproductive health. Methods Male patients with primary infertility (n = 282) from a single center (National Taiwan University Hospital, Taipei, Taiwan), between January 2016 and December 2017, were identified. Patients were physically examined for the presence of varicocele, and the volume of both testicles. Semen quality was measured in terms of total sperm count (millions), sperm concentration (millions/ml), and the percentage of motile sperm cells and the sperm cells with normal morphology. Data on the concentration of SO 2 (ppb), O3 (ppb), NO and NO 2 (ppb), and PM2.5 concentrations (μg/m3), measured on daily and hourly basis, were acquired from the Environmental Protection Administration Executive Yuan, Taiwan. Individual exposure to pollutants was estimated based on the reported residential address of patients. Statistical analysis indicated the impact of each pollutant on the testicular volume and semen parameters. Results Mean ± SD of age was 36.7 ± 7.3 years. The average sperm count and concentration was 41.9 million/ml and 34.1 million/ml, respectively. Except for PM2.5, the mean concentration of all the particulate matters were within the reference value. NO2 and SO2 exposure were negatively associated with the sperm concentration and motility, and testicular volume, respectively. Conclusions NO2 and SO 2 exposure were negatively associated with the sperm concentration and motility, and testicular volume, respectively, in a population of infertile male. Nevertheless, studies are needed to ascertain the impact of different exposure levels of pollutants on the semen parameters.
Detection and Dynamics of Circulating Tumor Cells in Patients with High-Risk Prostate Cancer Treated with Radiotherapy and Hormones: A Prospective Phase II Study
Authors: Zapatero Almudena , Gómez-Caamaño Antonio , Rodriguez María Ángeles Cabeza , Muinelo-Romay Laura , de Vidales Carmen Martin , Abalo Alicia , Crespo Patricia Calvo , Mateos Luis León , Olivier Carlos , Piris Lorena Vega 
Published: February 2020

Abstract
Background: Circulating tumor cells (CTCs) are an established prognostic marker in castration-resistant prostate cancer but have received little attention in localized high-risk disease. We studied the detection rate of CTCs in patients with high-risk prostate cancer before and after androgen deprivation therapy and radiotherapy to assess its value as a prognostic and monitoring marker.Patients and Methods: We performed a prospective analysis of CTCs in the peripheral blood of 65 treatment-naïve patients with high-risk prostate cancer. EpCAM-positive CTCs were enumerated using the CELLSEARCH system at 4 timepoints. A cut off of 0 vs ≥ 1 CTC/7.5 ml blood was defined as a threshold for negative versus positive CTCs status.Results: CTCs were detected in 5/65 patients (7.5%) at diagnosis, 8/62 (12.9%) following neoadjuvant AD, and 11/59 (18.6%) at the end of radiotherapy, with a median CTC count/7.5 ml of 1 (range, 1-136). Only 1 patient presented a positive CTC result 9 months after radiotherapy. Positive CTC status was not significantly associated with any clinicopathologic factors. However, a significant association was observed between conversion of CTCs and stages T3 ( P = 0.044) and N1 ( P = 0.002). Detection of CTCs was not significantly associated with overall survival ( P > 0.40).Conclusions: We found a low detection rate for CTCs. De novo positive CTC counts after treatment are probably due to a passive mechanism associated with destruction of the tumor. Further studies with larger samples and more accurate assessment methods are needed to determine the prognostic and therapeutic potential of CTC detection.Trial registration: ClinicalTrials.gov ID: NCT01800058
Advanced glycation end products increased placental vascular permeability of human BeWo cells via RAGE/NF-kB signaling pathway
Authors: Shi Yuehua , Qian Jie , Zhang Qinfen , Hu Yan , Sun Dongdong , Jiang Li 
Published: February 2020

Abstract
Background: The placental barrier plays an important role in protecting the fetus from the maternal environment. Gestational diabetes mellitus (GDM), caused by placental permeability, is a serious pregnancy complication with a high incidence worldwide. This study aimed to investigate the effects of advanced glycation end products (AGEs) on cell tight conjunction, and explore underlying mechanisms of the dys-regulation of placental vascular permeability in BeWo cells. Methods: Monolayer permeability assay was employed to reveal the transformation of the placental vascular permeability in BeWo cells under different administrations. Transmission electron microscopy was utilized to evaluate cell tight conjunction of BeWo cells. Immunofluorescence, wetern blot and RT-qPCR were adopted to determine the protein and mRNA levels of ZO-1, Occludin, RAGE and NF-kB. In addition, anti-RAGE and NF-kB inhibitor (PDTC) were used to inactivate the RAGE/NF-kB signaling pathway. Results: AGEs significantly decreased trans-epithelial electrical resistance (TEER), while increased paracellular permeability (P < 0.05). TEM results showed that AGEs made the cell junction loose. Immunofluorescence, wetern blot and RT-qPCR analyses showed that AGEs significantly inhibited the expressions of ZO-1 and Occludin, while anti-RAGE or PDTC partially restored their levels. Besides, AGEs also significantly increased the expressions of mRNA RAGE and NF-kB in BeWo cells (P < 0.05), and their expressions were inhibited by anti-RAGEy or PDTC. Conclusion: AGEs could reduce the expressions of ZO-1 and Occludin by activating RAGE/NF-kB signaling pathway, thus increasing placental vascular permeability of BeWos cells. These findings would provide a novel sight for improving the development and prognosis of GDM.
Gestational vinclozolin exposure suppresses fetal Leydig cell development in rats
Authors: Wu Keyang , Li Yang , Pan Peipei , Li Zengqiang , Yu Yige , Ma Feifei , Tian Lili , Fang Yinghui , Wang Yiyan , Ge Ren-Shan 
Published: February 2020

Abstract
Background: Vinclozolin is not only a common dicarboximide fungicide used to protect crops against diseases but also an endocrine disruptor. This study aimed to investigate the effects of gestational vinclozolin exposure on the development of rat fetal Leydig cells.Methods: Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by oral gavage from gestational day 14 to 21.Results: Vinclozolin dose-dependently depressed serum testosterone levels at doses of 50 and 100 mg/kg and anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blot showed that vinclozolin down-regulated the expression of Nr5a1 , Sox9 , Lhcgr , Cyp11a1 , Hsd3b1 , Hsd17b3 , Amh , Pdgfa , and Dhh and their encoded proteins. Vinclozolin depressed NR2F2-positive stem Leydig cell number at a dose of 100 mg/kg and also enhanced autophagy in the testis.Conclusion: Vinclozolin disrupts fetal Leydig cell development via several pathways.