bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascorbic acid can promote the generation and expansion of neuroepithelial-like stem cells derived from hiPS/ES cells under chemically defined conditions through promoting collagen synthesis
Authors: Bai Rui , Chang Yun , Saleem Amina , Wu Fujian , Tian Lei , Zhang Siyao , Li Ya’nan , Ma Shuhong , Dong Tao , Guo Tianwei , Jiang Youxu , You Yi , Lu Wen-Jing , Jiang Hong Feng , Lan Feng 
Published: January 2021

AbstractIntroductionSpinal cord injury (SCI) is a neurological, medically incurable disorder. Human pluripotent stem cells (hPSCs) have the potential to generate neural stem/progenitor cells (NS/PCs), which hold promise in the treatment of SCI by transplantation. In our study, we aimed to establish a chemically defined culture system using serum-free medium and ascorbic acid (AA) to generate and expand long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) differentiated from hPSCs effectively and stably.MethodsWe induced human embryonic stem cells (hESCs)/induced PSCs (iPSCs) to neurospheres using a newly established in vitro induction system. Moreover, lt-NES cells were derived from hESC/iPSC-neurospheres using two induction systems, i.e., conventional N2 medium with gelatin-coated plates (coated) and N2+AA medium without pre-coated plates (AA), and were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis and immunocytochemistry staining. Subsequently, lt-NES cells were induced to neurons. A microelectrode array (MEA) recording system was used to evaluate the functionality of the neurons differentiated from lt-NES cells. Finally, the mechanism underlying the induction of lt-NES cells by AA was explored through RNA-seq and the use of inhibitors.ResultsHESCs/iPSCs were efficiently induced to neurospheres using a newly established induction system in vitro. lt-NES cells derived from hESC/iPSC-neurospheres using the two induction systems (coated vs. AA) both expressed the neural pluripotency-associated genesPAX6,NESTIN,SOX1, andSOX2. After long-term cultivation, we found that they both exhibited long-term expansion for more than a dozen generations while maintaining neuropluripotency. Moreover, the lt-NES cells retained the ability to differentiate into general functional neurons that express β-tubulin at high levels. We also demonstrated that AA promotes the generation and long-term expansion of lt-NES cells by promoting collagen synthesis via the MEK-ERK1/2 pathway.ConclusionsThis new chemically defined culture system was stable and effective regarding the generation and culture of lt-NES cells induced from hESCs/iPSCs using serum-free medium combined with AA. The lt-NES cells induced under this culture system maintained their long-term expansion and neural pluripotency, with the potential to differentiate into functional neurons.Graphical abstract
Human foreskin-derived dermal stem/progenitor cell-conditioned medium combined with hyaluronic acid promotes extracellular matrix regeneration in diabetic wounds
Authors: Xin Yu , Xu Peng , Wang Xiangsheng , Chen Yunsheng , Zhang Zheng , Zhang Yixin 
Published: January 2021

AbstractBackgroundDiabetic wounds remain a challenging clinical problem, which requires further treatment development. Published data showed that dermis-derived stem/progenitor cells (DSPCs) display superior wound healing in vitro. The beneficial effects of DSPCs are mediated through paracrine secretion, which can be obtained from conditioned medium (CM). Hyaluronic acid (HA) is especially suitable for skin regeneration and delivering bioactive molecules in CM. This study investigated the effect of human foreskin-derived dermal stem/progenitor cell (hFDSPC)-CM combined with HA on a diabetic mouse model and relevant mechanism in vitro.MethodshFDSPCs and human adipose-derived stem cells (hADSCs) were identified, and the respective CM was prepared. PBS, HA, hFDSPC-CM combined with HA, or hADSC-CM combined with HA was topically applied to mice. HE, CD31, CD68, CD86, and CD206 staining was performed to evaluate gross wound condition, angiogenesis, and inflammation, respectively. Masson and Picrosirius red staining was performed to evaluate collagen deposition and maturation. The effects of hFDSPC-CM and hADSC-CM on human keratinocyte cells (HaCaT) and fibroblasts were evaluated in vitro using CCK-8 and EdU assays to determine cell viability and proliferation, respectively. The scratch assay was performed to evaluate cell migration. Tube formation assay was performed on human umbilical vein endothelial cells (HUVECs) to confirm angiogenesis. Extracellular matrix (ECM) metabolic balance-related genes and proteins, such as collagen I (COL 1), collagen III (COL 3), fibronectin (FN), α-SMA, matrix metalloproteinases 1 (MMP-1), matrix metalloproteinases 3 (MMP-3), and transforming growth factor-beta 1 (TGF-β1), were analysed.ResultshFDSPC-CM combined with HA showed superior wound closure rate over hADSC-CM. Histologically, the hFDSPC-CM combined with HA group showed significantly improved re-epithelialisation, angiogenesis, anti-inflammation, collagen regeneration, and maturation compared to hADSC-CM combined with HA group. In vitro assays revealed that hFDSPC-CM displayed significant advantages on cell proliferation, migration, and ECM regeneration through a TGF-β/Smad signalling pathway compared with hADSC-CM.ConclusionshFDSPC-CM combined with HA was superior for treating diabetic wounds. The underlying mechanism may promote proliferation and migration of epidermal cells with fibroblasts, thus leading to ECM deposition and remodelling. Reduced inflammation may be due to the above-mentioned mechanism.
Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis
Authors: Zhang Shengchao , Fang Jiankai , Liu Zhanhong , Hou Pengbo , Cao Lijuan , Zhang Yuyan , Liu Rui , Li Yanan , Shang Qianwen , Chen Yongjing , Feng Chao , Wang Guan , Melino Gerry , Wang Ying , Shao Changshun , Shi Yufang 
Published: January 2021

Abstract
Background
Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored.

Methods
The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression.

Results
hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR).

Conclusion
Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.
Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomesticle
Authors: Li Wen , Wang Shanshan , He Hui , Qin Jianbing , Cheng Xiang , Zhao Heyan , Tian Meiling , Zhang Xinhua , Jin Guohua 
Published: January 2021

Abstract
Background
In the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiation.

Methods
Hippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly upregulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses.

Results
Our results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 was significantly upregulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate neural stem cell differentiation by targeting Ndel1.

Conclusions
Our results revealed that deafferentation of the hippocampal exosomes co-cultured with neural stem cells could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate neural stem cells differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after fimbria fornix transection in vivo. These findings set the stage for a better understanding of neurogenesis, a process that 1 day may inspire new treatments for central nervous system diseases.
Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa
Authors: Tuekprakhon Aekkachai , Sangkitporn Siripakorn , Trinavarat Adisak , Pawestri Aulia Rahmi , Vamvanij Visit , Ruangchainikom Monchai , Luksanapruksa Panya , Pongpaksupasin Phitchapa , Khorchai Areerat , Dambua Acharaporn , Boonchu Patcharaporn , Yodtup Chonlada , Uiprasertkul Mongkol , Sangkitporn Somchai , Atchaneeyasakul La-ongsri 
Published: January 2021

Abstract
Background
Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP.

Methods
This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences.

Results
During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3.

Conclusion
Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention.

Trial registration
ClinicalTrials.gov, NCT01531348. Registered on February 10, 2012
Application of a roller conveyor type plasma disinfection device with fungus-contaminated citrus fruits
Authors: Sakudo Akikazu , Yagyu Yoshihito 
Published: January 2021

AbstractEfficient methods to achieve the safe decontamination of agricultural products are needed. Here, we investigated the decontamination of citrus fruits to test the antifungal potential of a novel non-thermal gas plasma apparatus, termed a roller conveyer plasma instrument. This instrument generates an atmospheric pressure dielectric barrier discharge (APDBP) plasma on a set of rollers. Penicillium venetum was spotted onto the surface of the fruit or pericarps, as well as an aluminium plate to act as a control, before performing the plasma treatment. The results showed that viable cell number of P. venetum decreased with a decimal reduction time (D value or estimated treatment time required to reduce viable cell number by 90%) of 0.967 min on the aluminium plate, 2.90 min and 1.88 min on the pericarps of ‘Kiyomi’ (Citrus unshiu × C. sinensis) and ‘Kawano-natsudaidai’ (C. natsudaidai) respectively, and 2.42 min on the surface of ‘Unshu-mikan’ (C. unshiu). These findings confirmed a fungicidal effect of the plasma not only on an abiotic surface (aluminium plate) but also on a biotic surface (citrus fruit). Further development of the instrument by combining sorting systems with the plasma device promises an efficient means of disinfecting citrus fruits during food processing.
ATPIF1 maintains normal mitochondrial structure which is impaired by CCM3 deficiency in endothelial cells
Authors: Wang Kang , Chen Haixuan , Zhou Zhongyang , Zhang Haifeng , Zhou Huanjiao Jenny , Min Wang 
Published: January 2021

Abstract
Background
Numerous signaling pathways have been demonstrated experimentally to affect the pathogenesis of cerebral cavernous malformations (CCM), a disease that can be caused by CCM3 deficiency. However, the understanding of the CCM progression is still limited. The objective of the present work was to elucidate the role of CCM3 by RNA-seq screening of CCM3 knockout mice.

Results
We found that ATPIF1 was decreased in siCCM3-treated Human Umbilical Vein Endothelial Cells (HUVECs), and the overexpression of ATPIF1 attenuated the changes in cell proliferation, adhesion and migration caused by siCCM3. The probable mechanism involved the conserved ATP concentration in mitochondria and the elongated morphology of the organelles. By using the CRISPR-cas9 system, we generated CCM3-KO Endothelial Progenitor Cells (EPCs) and found that the knockout of CCM3 destroyed the morphology of mitochondria, impaired the mitochondrial membrane potential and increased mitophagy. Overexpression of ATPIF1 contributed to the maintenance of normal structure of mitochondria, inhibiting activation of mitophagy and other signaling proteins (e.g., KLF4 and Tie2). The expression of KLF4 returned to normal in CCM3-KO EPCs after 2 days of re-overexpression of CCM3, but not other signaling proteins.

Conclusion
ATPIF1 maintains the normal structure of mitochondria, inhibiting the activation of mitophagy and other signaling pathway in endothelial cells. Loss of CCM3 leads to the destruction of mitochondria and activation of signaling pathways, which can be regulated by KLF4.
Decrease of peripheral blood mucosal‐associated invariant T cells and impaired serum Granzyme-B production in patients with gastric cancer
Authors: Shao Chunyan , Zhu Chenwen , Zhu Yun , Hao Jiqing , Li Yongxiang , Hu Huaqing , Si Li , Zhong Fei , Wang Xuefu , Wang Hua 
Published: January 2021

AbstractMucosal-associated invariant T (MAIT) cells are an invariant T cell subset, which have been reported to play an antimicrobial role in infectious diseases. However, little is known about it in malignant diseases and tumors, especially in gastric cancer (GC). So in this study, we aim to examine the frequency, phenotype, partial functional capacity and clinical relevance of this cells from GC patients’ peripheral blood by flow cytometry. It was shown that the frequency of peripheral blood MAIT cells was negatively correlated with their increasing age in healthy adults. Importantly, comparing to the healthy controls (HC), the frequency and the absolute number of MAIT cells from GC patients’ peripheral blood with or without chemotherapy were both significantly lower than those. For the phenotype, the proportion of CD4−MAIT cell subset in GC patients without chemotherapy was lower than in HC, but higher than in GC patients with chemotherapy. Whereas, the proportion of CD4−CD8+MAIT cell subset in GC patients without chemotherapy was significantly lower than that in HC. Finally, the level of Granzyme-B (GrB), a molecule associated with MAIT cells was markedly lower in GC patients. But the correlation between the serum levels of GC-associated tumor antigens and the percentages of MAIT cells in GC patients was not observed. In conclusion, our study shows the decreased frequency, changed phenotypes and partial potentially impaired function of MAIT cells in GC patients, suggesting a possible MAIT cell-based immunological surveillance of GC.
The views of health guideline developers on the use of automation in health evidence synthesis
Authors: Arno Anneliese , Elliott Julian , Wallace Byron , Turner Tari , Thomas James 
Published: January 2021

Abstract
Background
The increasingly rapid rate of evidence publication has made it difficult for evidence synthesis—systematic reviews and health guidelines—to be continually kept up to date. One proposed solution for this is the use of automation in health evidence synthesis. Guideline developers are key gatekeepers in the acceptance and use of evidence, and therefore, their opinions on the potential use of automation are crucial.

Methods
The objective of this study was to analyze the attitudes of guideline developers towards the use of automation in health evidence synthesis. The Diffusion of Innovations framework was chosen as an initial analytical framework because it encapsulates some of the core issues which are thought to affect the adoption of new innovations in practice. This well-established theory posits five dimensions which affect the adoption of novel technologies: Relative Advantage, Compatibility, Complexity, Trialability, and Observability. Eighteen interviews were conducted with individuals who were currently working, or had previously worked, in guideline development. After transcription, a multiphase mixed deductive and grounded approach was used to analyze the data. First, transcripts were coded with a deductive approach using Rogers’ Diffusion of Innovation as the top-level themes. Second, sub-themes within the framework were identified using a grounded approach.

Results
Participants were consistently most concerned with the extent to which an innovation is in line with current values and practices (i.e., Compatibility in the Diffusion of Innovations framework). Participants were also concerned with Relative Advantage and Observability, which were discussed in approximately equal amounts. For the latter, participants expressed a desire for transparency in the methodology of automation software. Participants were noticeably less interested in Complexity and Trialability, which were discussed infrequently. These results were reasonably consistent across all participants.

Conclusions
If machine learning and other automation technologies are to be used more widely and to their full potential in systematic reviews and guideline development, it is crucial to ensure new technologies are in line with current values and practice. It will also be important to maximize the transparency of the methods of these technologies to address the concerns of guideline developers.
Mapping evidence of nurses’ attitudes toward older adults in Africa: a scoping review protocol
Authors: Wanko Keutchafo Esther L. , Kerr Jane , Jarvis Mary A. , Kuupiel Desmond 
Published: January 2021

Abstract
Background
Culture influences nurses’ attitudes towards caring for older adults. Additionally, nursing students’ perceptions and attitudes towards older adults affect their behavior, possibly their career choices and/or the quality of care provided to older adults after graduation. In the context of lower–middle-income countries with a faster growing older adults population compared to upper income countries, the improvement of the quality care, inclusive of nurses’ attitudes towards older adults, is one of the strategies for strengthening nursing and midwifery in Africa. Furthermore, examining nurses and nursing students’ attitudes towards older adults will answer the United Nations’ call for more data to understand the needs and the status of older adults in Africa.

Methods
This scoping review will be guided by Arksey and O’Malley’s framework. The search will be performed using Scopus, PubMed databases, Academic search complete, CINAHL with full text, Education source, Health source: Nursing/Academic Edition, with words related to the topic. The reviewers will also use Google Scholar and the reference lists of the relevant articles. Primary studies and grey literature addressing the research question will be included. The search process will include a first stage where two reviewers will perform the title screening and the removal of duplicates, followed by a parallel abstract screening according to eligibility criteria. The second stage will involve the reading of full articles and the exclusion of articles, in accordance with the eligibility criteria. Data will be collated by two reviewers independently and parallel, using a predetermined data extraction form. Discrepancies will involve a third reviewer. The Mixed Methods Appraisal Tool, version 2018 will be used to assess the quality of the data of eligible articles. A narrative approach containing summary tables and graphs will facilitate synthesis.

Discussion
The review will provide insight into nurses' and nursing students’ attitudes towards older adults in African countries. The outcomes will guide future research, practice, and education in nursing.