bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulating CXCR7 accelerates endothelial progenitor cell-mediated endothelial repair by activating Akt/Keap-1/Nrf2 signaling in diabetes mellitus
Authors: Jiang Chunyu , Li Ruiting , Xiu Chaoyang , Ma Xu , Hu Hui , Wei Liming , Tang Yihan , Tao Mingyang , Zhao Jungong 
Published: May 2021

AbstractBackgroundEndothelial progenitor cell (EPC) dysfunction contributes to vascular disease in diabetes mellitus. However, the molecular mechanism underlying EPC dysfunction and its contribution to delayed reendothelialization in diabetes mellitus remain unclear. Our study aimed to illustrate the potential molecular mechanism underlying diabetic EPC dysfunction in vivo and in vitro. Furthermore, we assessed the effect of EPC transplantation on endothelial regeneration in diabetic rats.MethodsLate outgrowth EPCs were isolated from the bone marrow of rats for in vivo and in vitro studies. In vitro functional assays and Western blotting were conducted to reveal the association between C-X-C chemokine receptor type 7 (CXCR7) expression and diabetic EPC dysfunction. To confirm the association between cellular CXCR7 levels and EPC function, CXCR7 expression in EPCs was upregulated and downregulated via lentiviral transduction and RNA interference, respectively. Western blotting was used to reveal the potential molecular mechanism by which the Stromal-Derived Factor-1 (SDF-1)/CXCR7 axis regulates EPC function. To elucidate the role of the SDF-1/CXCR7 axis in EPC-mediated endothelial regeneration, a carotid artery injury model was established in diabetic rats. After the model was established, saline-treated, diabetic, normal, or CXCR7-primed EPCs were injected via the tail vein.ResultsDiabetic EPC dysfunction was associated with decreased CXCR7 expression. Furthermore, EPC dysfunction was mimicked by knockdown of CXCR7 in normal EPCs. However, upregulating CXCR7 expression reversed the dysfunction of diabetic EPCs. The SDF-1/CXCR7 axis positively regulated EPC function by activating the AKT-associated Kelch-like ECH-associated protein 1 (keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis, which was reversed by blockade of AKT and Nrf2. Transplantation of CXCR7-EPCs accelerated endothelial repair and attenuated neointimal hyperplasia in diabetes mellitus more significantly than transplantation of diabetic or normal EPCs. However, the therapeutic effect of CXCR7-EPC transplantation on endothelial regeneration was reversed by knockdown of Nrf2 expression.ConclusionsDysfunction of diabetic EPCs is associated with decreased CXCR7 expression. Furthermore, the SDF-1/CXCR7 axis positively regulates EPC function by activating the AKT/keap-1/Nrf2 axis. CXCR7-primed EPCs might be useful for endothelial regeneration in diabetes-associated vascular disease.
Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells
Authors: Kowal Justyna Magdalena , Möller Sören , Ali Dalia , Figeac Florence , Barington Torben , Schmal Hagen , Kassem Moustapha 
Published: May 2021

Abstract
Background
Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity.

Methods
We collected hBMSCs from 58 patients undergoing surgery for bone fracture. Clinical profile of the donors and in vitro characteristics of cultured hBMSCs were included in uni- and multivariable analysis to determine their predictive value for osteoblastic versus adipocytic differentiation capacity assessed by quantification of mineralized matrix and mature adipocyte formation, respectively.

Results
We identified a signature that explained > 50% of variation in osteoblastic differentiation outcome which included the following positive predictors: donor sex (male), absence of osteoporosis diagnosis, intake of vitamin D supplements, higher fraction of CD146+, and alkaline phosphate (ALP+) cells. With the exception of vitamin D and ALP+ cells, these variables were also negative predictors of adipocytic differentiation.

Conclusions
Using a combination of clinical and cellular criteria, it is possible to predict differentiation outcome of hBMSCs. This signature may be helpful in selecting donor cells in clinical trials of bone regeneration.
A novel strategy for isolation of mice bone marrow endothelial cells (BMECs)
Authors: Smith Alhaji Osman , Adzraku Seyram Yao , Ju Wen , Qiao Jianlin , Xu Kailin , Zeng Lingyu 
Published: May 2021

Abstract
Background
In the bone marrow microenvironment (BM), endothelial cells are individual cells that form part of the sinusoidal blood vessels called the “bone marrow endothelial-vascular niche.” They account for less than 2% of the bone marrow cells. They play essential functions by generating growth and inhibitory factors that promote the hematopoietic stem cells (HSCs) regulation. In response to inflammatory stimuli, the BMECs increase in proliferation to maintain the blood vessels’ integrity within the BM. The inflammatory response releases cytokines such as tumor necrosis factor-alpha (TNF-α) that promote vascular endothelial cells’ expansion and upregulation of adhesion molecules (ICAM-1 and VCAM-1, respectively) in the BM. However, the evaluation of mouse BMECs in the bone marrow microenvironment is scared by a lack of mouse bone marrow endothelial cell primary culture

Methods
Two steps approach for isolation of bone marrow endothelial cells (BMECs) from mice. In brief, the bone marrow cells extracted from the mice long bones were cultured overnight with Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 20% fetal bovine serum (FBS) and antibiotics to separate between marrow-derived adherent and non-adherent cells. The floating cells were discarded, and the adhered section detached with accutase and BMECs selected using CD31 microbeads. The isolated BMECs were cultured in a dish pre-coated with rat-tail collagen type 1 with endothelial cells medium supplement with growth factors. The cells were verified by confocal microscopy for morphology and tube formation by matrigel assay. We validate the cells’ purity by flow cytometry, RT-qPCR, immunofluorescence staining, and immunoblotting by established BMEC markers, PECAM-1, VE-cadherin, vascular endothelial cell growth factor receptor-2 (VEGFR2), CD45, E-selectin, and endothelial selectin adhesion molecule (ESAM). Lastly, we characterize BMEC activation with recombinant TNF-α.

Results
Our method clearly defined the cells isolated have the characteristics of BMECs with the expression of CD31, VE-cadherin, E-selectin, VEGFR-2, and ESAM. The cells’ response to TNF-α indicates its inflammatory function by increasing proliferation and upregulation of adhesion molecules.

Conclusions
This study outline a simple new technique of isolating mouse BMEC primary culture and a suitable method to evaluate the function and dysregulation of BMEC in in vitro studies using mouse models.
Clinical-grade human dental pulp stem cells suppressed the activation of osteoarthritic macrophages and attenuated cartilaginous damage in a rabbit osteoarthritis model
Authors: Li Pei-Lin , Wang Yu-Xing , Zhao Zhi-Dong , Li Zhi-Ling , Liang Jia-Wu , Wang Qian , Yin Bo-Feng , Hao Rui-Cong , Han Meng-Yue , Ding Li , Wu Chu-Tse , Zhu Heng 
Published: May 2021

Abstract
Background
Although increasing evidence has demonstrated that human dental pulp stem cells (hDPSCs) are efficacious for the clinical treatment of skeletal disorders, the underlying mechanisms remain incompletely understood. Osteoarthritis (OA) is one of the most common degenerative disorders in joints and is characterized by gradual and irreversible cartilaginous tissue damage. Notably, immune factors were newly identified to be closely related to OA development. In this study, we explored the modulatory effects of clinical-grade hDPSCs on osteoarthritic macrophages and their protective effects on cartilaginous tissues in OA joints.

Methods
The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages were explored by phase contrast microscope, transmission electron microscopy, immunostaining, flow cytometry, quantitative polymerase chain reaction, and enzyme linked immunosorbent assay, respectively. Additionally, the factors and signaling pathways that suppressed macrophage activation by hDPSCs were determined by enzyme-linked immunosorbent assay and western-blotting. Furthermore, hDPSCs were administered to a rabbit knee OA model via intra-articular injection. Macrophage activation in vivo and cartilaginous tissue damage were also evaluated by pathological analysis.

Results
We found that hDPSCs markedly inhibited osteoarthritic macrophage activation in vitro. The cell morphology, immunophenotype, and inflammatory factor expression of osteoarthritic macrophages changed into less inflammatory status in the presence of hDPSCs. Mechanistically, we observed that hDPSC-derived hepatocyte growth factor and transforming growth factor β1 mediated the suppressive effects on osteoarthritic macrophages. Moreover, phosphorylation of MAPK pathway proteins contributed to osteoarthritic macrophage activation, and hDPSCs suppressed their activation by partially inactivating those pathways. Most importantly, injected hDPSCs inhibited macrophage activation in osteochondral tissues in a rabbit knee OA model in vivo. Further histological analysis showed that hDPSCs alleviated cartilaginous damage to knee joints.

Conclusions
In summary, our findings reveal a novel function for hDPSCs in suppressing osteoarthritic macrophages and suggest that macrophages are efficient cellular targets of hDPSCs for alleviation of cartilaginous damage in OA.

Graphical abstract
hDPSCs treat OA via an osteoarthritic macrophages-dependent mechanisms. hDPSCs suppress the activation of osteoarthritic macrophages in vitro and in vivo and alleviate cartilaginous lesions in OA models.
Sex differences in soluble prorenin receptor in patients with type 2 diabetes
Authors: Visniauskas Bruna , Arita Danielle Y. , Rosales Carla B. , Feroz Mohammed A. , Luffman Christina , Accavitti Michael J. , Dawkins Gabrielle , Hong Jennifer , Curnow Andrew C. , Thethi Tina K. , Lefante John J. , Jaimes Edgar A. , Mauvais-Jarvis Franck , Fonseca Vivian A. , Prieto Minolfa C. 
Published: May 2021

Abstract
Background
The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes.

Methods
Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction.

Results
Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI.

Conclusions
In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.
Sex differences associated with adverse drug reactions resulting in hospital admissions
Authors: Hendriksen L. C. , van der Linden P. D. , Lagro-Janssen A. L. M. , van den Bemt P. M. L. A. , Siiskonen S. J. , Teichert M. , Kuiper J. G. , Herings R. M. C. , Stricker B. H. , Visser L. E. 
Published: May 2021

Abstract
Background
Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5–1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission.

Methods
ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged ≥ 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated.

Results
A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men.

Conclusions
There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.
Dynamics in a ratio-dependent Lotka–Volterra competitive-competitive-cooperative system with feedback controls and delays
Authors: Muhammadhaji Ahmadjan , Halik Azhar , Li Hong-Li 
Published: May 2021

AbstractThis study investigates the dynamical behavior of a ratio-dependent Lotka–Volterra competitive-competitive-cooperative system with feedback controls and delays. Compared with previous studies, both ratio-dependent functional responses and time delays are considered. By employing the comparison method, the Lyapunov function method, and useful inequality techniques, some sufficient conditions on the permanence, periodic solution, and global attractivity for the considered system are derived. Finally, a numerical example is also presented to validate the practicability and feasibility of our proposed results.
Preliminary development of a bystander intervention scale for depression and the examination of socio-demographic correlates amongst Singapore university students
Authors: Ong Wei Jie , Lau Jue Hua , Abdin Edimansyah , Shahwan Shazana , Goh Janrius Chong Min , Tan Gregory Tee Hng , Samari Ellaisha , Kwok Kian Woon , Subramaniam Mythily , Chong Siow Ann 
Published: April 2021

Abstract
Background
Despite peer involvement having a positive impact on help-seeking behavior, there is a lack of a scale quantifying the possibility of an individual intervening upon noticing peers who show signs of depression. The aims of this study were to (1) develop a bystander intervention scale for depression that assesses the likelihood of university students intervening when a peer shows signs of depression based on the theory of bystander intervention, (2) identify the underlying factors contributing to the behavior, and (3) explore the socio-demographic correlates of the scale.

Methods
The proposed scale, the Bystander Intervention Scale for Depression (BISD), is a 17-item self-reported questionnaire that was developed based on existing bystander intervention theory and inputs from mental health experts. Data was collected as part of a larger study to evaluate the effectiveness of an anti-stigma intervention amongst university students from a local university. A total of 392 participants were recruited. Exploratory factor analyses were performed to identify the underlying factor structure. Multiple linear regressions were conducted to explore the socio-demographic correlates of the scale.

Result
Four key factors were identified for the proposed scale: (1) Awareness of depression among peers; (2) Vigilance towards possible symptoms of depression; (3) Knowledge on how to intervene; (4) Acceptance of responsibility to intervene. Having experience in the mental health field was associated with all factors while having family members or friends with mental illness was associated with all factors except for knowledge on how to intervene. Students of older age were associated with higher vigilance towards possible symptoms of depression and knowledge on how to intervene. Those of non-Chinese ethnicity were associated with acceptance of responsibility to intervene.

Conclusion
This study provides a preliminary tool to assess bystander intervention in depression amongst university students. This study identifies sub-groups of the student population that require more education to intervene with depressed peers and also informs the development of future strategies.
Robust α-synuclein pathology in select brainstem neuronal populations is a potential instigator of multiple system atrophy
Authors: Hass Ethan W. , Sorrentino Zachary A. , Lloyd Grace M. , McFarland Nikolaus R. , Prokop Stefan , Giasson Benoit I. 
Published: May 2021

AbstractMultiple system atrophy (MSA) is an insidious middle age-onset neurodegenerative disease that clinically presents with variable degrees of parkinsonism and cerebellar ataxia. The pathological hallmark of MSA is the progressive accumulation of glial cytoplasmic inclusions (GCIs) in oligodendrocytes that are comprised of α-synuclein (αSyn) aberrantly polymerized into fibrils. Experimentally, MSA brain samples display a high level of seeding activity to induce further αSyn aggregation by a prion-like conformational mechanism. Paradoxically, αSyn is predominantly a neuronal brain protein, with only marginal levels expressed in normal or diseased oligodendrocytes, and αSyn inclusions in other neurodegenerative diseases, including Parkinson’s disease and Dementia with Lewy bodies, are primarily found in neurons. Although GCIs are the hallmark of MSA, using a series of new monoclonal antibodies targeting the carboxy-terminal region of αSyn, we demonstrate that neuronal αSyn pathology in MSA patient brains is remarkably abundant in the pontine nuclei and medullary inferior olivary nucleus. This neuronal αSyn pathology has distinct histological properties compared to GCIs, which allows it to remain concealed to many routine detection methods associated with altered biochemical properties of the carboxy-terminal domain of αSyn. We propose that these previously underappreciated sources of aberrant αSyn could serve as a pool of αSyn prion seeds that can initiate and continue to drive the pathogenesis of MSA.
Spatiotemporal distribution of potentially toxic elements in the lower Gangetic delta and their implications for non-carcinogenic health risk management
Authors: Ghosh Somdeep , Bakshi Madhurima , Mahanty Shouvik , Gaine Tanushree , Bhattacharyya Subarna , Biswas Jayanta Kumar , Chaudhuri Punarbasu 
Published: May 2021

AbstractRiver Hooghly, a tributary of river Ganges is one of the major rivers of Asia having traditional, social, economic, religious, and spiritual values. Water samples were collected from 18 sampling locations of river Hooghly during summer (dry), monsoon (wet), and winter (cold) seasons. The samples are analysed for basic physicochemical properties and abundance of selected potentially toxic elements (PTEs) are measured. Several PTEs, e.g., Al, Fe, Ni, and Pb, were found to be above the permissible limits, prescribed by national and international guidelines for safe human consumption. The trend of variation in the mean PTE concentrations showed the following order: Cd < Pb < Co < Cr < Ni < Cu < Zn < Mn < Fe. Due to the presence of high total dissolve solid (TDS) and PTE contents, the water quality of river Hooghly is not suitable for direct human consumption. The evaluated Water Quality Index (WQI) value showed a distinct spatio-temporal variation indicating very severe condition of water quality, which is deteriorating gradually from upstream to downstream. In summer, monsoon, and winter, the highest WQI values were observed in Maushuni Island (S15), Petuaghat (S18), and Tapoban (S17), respectively. However, the non-carcinogenic human health risk in terms of Hazard Quotient and Hazard Index values of PTEs indicates no immediate adverse impact on human health due to exposure of PTE contaminated water from river Hooghly through ingestion or dermal route. Though, these risk values for children were higher than adults warranting the adoption of a long-term management plan to cope with potential human health risks. The result suggests implementation of a combination of stringent socio-legal regulations and numerical models for sustainable water related health risk management in river Hooghly.
Enhanced student perceptions of learning and performance using concept-point-recovery teaching sessions: a mixed-method approach
Authors: Cho Hyun Jin , Melloch Michael R. , Levesque-Bristol Chantal 
Published: May 2021

Abstract
Background
Active learning pedagogy has recently received a great deal of attention, and many universities have attempted to create student-centered learning environments to improve students’ academic success. The purpose of this study is to explore the impact of concept-point-recovery (CPR) teaching sessions as an active learning strategy on students’ perceptions of the learning environment, motivation, and academic learning outcomes in an electrical engineering course. To investigate the effectiveness of CPR sessions, students’ perceptions of learning and their performance were compared to those of students in a control classroom. Finally, students’ written comments on the course and instructor were explored in further analysis.

Results
The quantitative findings revealed that there was a significant change in students’ perceptions of learning after the CPR teaching sessions, and there was an increase in students’ perceptions and learning outcomes compared with those of the control group. In addition, the qualitative findings from students’ written feedback demonstrated that students felt that the instructor cared about students’ learning and success and that they had a positive learning environment.

Conclusions
CPR teaching sessions can be an alternative model for instructors to connect with students and create supportive environments to help students achieve academic success, which in turn promotes the satisfaction of students’ basic psychological needs and self-determined motivation. Therefore, increasing students’ engagement in their learning processes and making connections with students through CPR teaching sessions can facilitate improvements in students’ motivation and academic success. How this new active learning technique can be applied to higher education is discussed.