bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF
Authors: Li Rui , Li Dize , Wang Huanan , Chen Kaiwen , Wang Si , Xu Jie , Ji Ping 
Published: April 2022

Abstract
Objectives
Bone defects caused by diseases and trauma are usually accompanied by inflammation, and the implantation of biomaterials as a common repair method has also been found to cause inflammatory reactions, which affect bone metabolism and new bone formation. This study investigated whether exosomes from adipose-derived stem cells (ADSC-Exos) plays an immunomodulatory role in traumatic bone defects and elucidated the underlying mechanisms.

Methods
ADSC-Exos were loaded by a biomaterial named gelatine nanoparticles (GNPs), physical and chemical properties were analysed by zeta potential, surface topography and rheology. A rat model of skull defect was used for our in vivo studies, and micro-CT and histological staining were used to analyse histological changes in the bone defect area. RT-qPCR and western blotting were performed to verify that ADSC-Exos could regulate M1/M2 macrophage polarization. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of ADSC-Exos. After macrophages were treated with a miR-451a mimic, miR-451a inhibitor and ISO-1, the relative expression of genes and proteins was measured by RT-qPCR and western blotting.

Results
In vivo, micro-CT and histological staining showed that exosome-loaded GNPs (GNP-Exos) hydrogel, with good biocompatibility and strong mechanical adaptability, exhibited immunomodulatory effect mainly by regulating macrophage immunity and promoting bone tissue healing. Immunofluorescence further indicated that ADSC-Exos reduced M1 marker (iNOS) expression and increased M2 marker (CD206) expression. Moreover, in vitro studies, western blotting and RT-qPCR showed that ADSC-Exos inhibited M1 macrophage marker expression and upregulated M2 macrophage marker expression. MiR-451a was enriched in ADSC-Exos and targeted macrophage migration inhibitory factor (MIF). Macrophages treated with the miR-451a mimic showed lower expression of M1 markers. In contrast, miR-451a inhibitor treatment upregulated the expression of M1 markers and downregulated the expression of M2 markers, while ISO-1 (a MIF inhibitor) treatment upregulated miR-451a expression and downregulated M1 macrophage marker expression.

Conclusion
GNP-Exos can effectively regulate bone immune metabolism and further promote bone healing partly through immune regulation of miR-451a, which may provide a therapeutic direction for bone repair.
Extracellular vesicles from hair follicle-derived mesenchymal stromal cells: isolation, characterization and therapeutic potential for chronic wound healing
Authors: Las Heras Kevin , Royo Félix , Garcia-Vallicrosa Clara , Igartua Manoli , Santos-Vizcaino Edorta , Falcon-Perez Juan M. , Hernandez Rosa Maria 
Published: April 2022

Abstract
Background
Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have demonstrated to elicit immunomodulatory and pro-regenerative properties that are beneficial for the treatment of chronic wounds. Thanks to different mediators, MSC-EVs have shown to play an important role in the proliferation, migration and cell survival of different skin cell populations. However, there is still a big bid to achieve the most effective, suitable and available source of MSC-EVs.

Methods
We isolated, characterized and compared medium-large EVs (m-lEVs) and small EVs (sEVs) obtained from hair follicle-derived MSCs (HF-MSCs) against the gold standard in regenerative medicine, EVs isolated from adipose tissue-derived MSCs (AT-MSCs).

Results
We demonstrated that HF-EVs, as well as AT-EVs, expressed typical MSC-EVs markers (CD9, CD44, CD63, CD81 and CD105) among other different functional markers. We showed that both cell types were able to increase human dermal fibroblasts (HDFs) proliferation and migration. Moreover, both MSC-EVs were able to increase angiogenesis in human umbilical vein endothelial cells (HUVECs) and protect HDFs exposed to a hyperglycemic environment from oxidative stress and cytotoxicity.

Conclusions
Taken together, HF-EVs demonstrated to exhibit comparable potential to that of AT-EVs as promising candidates in the treatment of chronic wounds.
Immune evader cancer stem cells direct the perspective approaches to cancer immunotherapy
Authors: Dianat-Moghadam Hassan , Mahari Amir , Salahlou Reza , Khalili Mostafa , Azizi Mehdi , Sadeghzadeh Hadi 
Published: April 2022

AbstractExploration of tumor immunity leads to the development of immune checkpoint inhibitors and cell-based immunotherapies which improve the clinical outcomes in several tumor types. However, the poor clinical efficacy of these treatments observed for other tumors could be attributed to the inherent complex tumor microenvironment (TME), cellular heterogeneity, and stemness driven by cancer stem cells (CSCs). CSC-specific characteristics provide the bulk tumor surveillance and resistance to entire eradication upon conventional therapies. CSCs-immune cells crosstalk creates an immunosuppressive TME that reshapes the stemness in tumor cells, resulting in tumor formation and progression. Thus, identifying the immunological features of CSCs could introduce the therapeutic targets with powerful antitumor responses. In this review, we summarized the role of immune cells providing CSCs to evade tumor immunity, and then discussed the intrinsic mechanisms represented by CSCs to promote tumors’ resistance to immunotherapies. Then, we outlined potent immunotherapeutic interventions followed by a perspective outlook on the use of nanomedicine-based drug delivery systems for controlled modulation of the immune system.
Stem cell-derived exosomes in the treatment of acute myocardial infarction in preclinical animal models: a meta-analysis of randomized controlled trials
Authors: Zheng Yan-li , Wang Wan-da , Cai Ping-yu , Zheng Feng , Zhou Yi-fan , Li Mei-mei , Du Jing-ru , Lin Shu , Lin Hui-li 
Published: April 2022

Abstract
Background
Exosomes (EXOs) derived from stem cells have become a potential new treatment for acute myocardial infarction (AMI). However, their impact is still not fully understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EXOs on AMI in preclinical animal models.

Methods
We searched PubMed, EMBASE, and the Web of Science from September 1, 1980 to September 1, 2021, to retrieve the studies reporting the therapeutic effects of EXOs on AMI animal models. Secondary endpoints include the fractional shortening (FS), infarct size (IS), fibrosis area (FA), the TNF-α, IL-6 and IL-10 levels, the apoptosis rate and the number of autophagic vesicles. Two authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were conducted using Stata14.0.

Results
Ten studies satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of LVEF (WMD = 3.67%; 95% CI 2.28–5.07%; P = 0.000), FS (WMD = 3.69%; 95% CI 2.06–5.33%; P = 0.000), IS (WMD = −4.52%, 95% CI − 7.14 to − 1.9%; P = 0.001), and FA (WMD = −7.04%, 95% CI − 8.74 to − 5.34%; P = 0.000), TNF-α (WMD = −3.09, 95% CI − 5.47 to − 0.72; P = 0.011), TL-6 (WMD = −6.34, 95% CI − 11.2 to − 1.49; P < 0.01), TL-10 (WMD = 6.37, 95% CI 1.53–11.21; P = 0.01), the apoptosis rate (WMD = −8.23, 95% CI − 15.29 to − 1.17; P = 0.000), and the number of autophagic vesicles (WMD = −4.52, 95% CI − 7.43 to − 1.62; P = 0.000). Subgroup analysis showed that the EXOs were derived from HMSCs. Subgroup analysis showed that the EXOs derived from HMSCs, and that exosome therapy immediately after myocardial infarction can better improve the LVEF. Conclusions: EXOs therapy has the potential to improve cardiac function, fibrogenesis, and inflammatory response, as well as reducing cell apoptosis and autophagy in preclinical AMI animal models. This can inform future human clinical trials of EXOs.
General decay for a viscoelastic von Karman equation with delay and variable exponent nonlinearities
Authors: Park Sun-Hye 
Published: April 2022

AbstractIn this paper, we consider a viscoelastic von Karman equation with damping, delay, and source effects of variable exponent type. Firstly, we show the global existence of solution applying the potential well method. Then, by making use of the perturbed energy method and properties of convex functions, we derive general decay results for the solution under more general conditions of a relaxation function. General decay results of solutions for viscoelastic von Karman equations with variable exponent nonlinearities have not been discussed before. Our results extend and complement many results for von Karman equations in the literature.
Collaboration Leading to Addiction Treatment and Recovery from Other Stresses (CLARO): process of adapting collaborative care for co-occurring opioid use and mental disorders
Authors: Osilla Karen Chan , Dopp Alex R. , Watkins Katherine E. , Ceballos Venice , Hurley Brian , Meredith Lisa S. , Leamon Isabel , Jacobsohn Vanessa , Komaromy Miriam 
Published: April 2022

Abstract
Background
Opioid use disorders (OUD), co-occurring with either depression and/or PTSD, are prevalent, burdensome, and often receive little or low-quality care. Collaborative care is a service delivery intervention that uses a team-based model to improve treatment access, quality, and outcomes in primary care patients, but has not been evaluated for co-occurring OUD and mental health disorders. To address this treatment and quality gap, we adapted collaborative care for co-occurring OUD and mental health disorders.

Methods
Our adapted model is called Collaboration Leading to Addiction Treatment and Recovery from Other Stresses (CLARO). We used the five-step Map of Adaptation Process (McKleroy in AIDS Educ Prev 18:59–73, 2006) to develop the model. For each step, our stakeholder team of research and clinical experts, primary care partners, and patients provided input into adaptation processes (e.g., adaptation team meetings, clinic partner feedback, patient interviews and beta-testing). To document each adaptation and our decision-making process, we used the Framework for Reporting Adaptations and Modifications-Enhanced (Wiltsey Stirman in Implement Sci 14:1–10, 2019).

Results
We documented 12 planned fidelity-consistent adaptations to collaborative care, including a mix of content, context, and training/evaluation modifications intended to improve fit with the patient population (co-occurring disorders) or the New Mexico setting (low-resource clinics in health professional shortage areas). Examples of documented adaptations include use of community health workers as care coordinators; an expanded consultant team to support task-shifting to community health workers; modified training protocols for Problem-Solving Therapy and Written Exposure Therapy to incorporate examples of treating patients for depression or PTSD with co-occurring OUD; and having care coordinators screen for patients’ social needs.

Conclusions
We completed the first three steps of the Map of Adaptation Process, resulting in a variety of adaptations that we believe will make collaborative care more acceptable and feasible in treating co-occurring OUD and mental health disorders. Future steps include evaluating the effectiveness of CLARO and documenting reactive and/or planned adaptations to the model that occur during its implementation and delivery.
Trial registration NCT04559893, NCT04634279. Registered 08 September 2020, https://clinicaltrials.gov/ct2/show/NCT04559893
Gut health benefit and application of postbiotics in animal production
Authors: Zhong Yifan , Wang Shanshan , Di Hanqiu , Deng Zhaoxi , Liu Jianxin , Wang Haifeng 
Published: April 2022

AbstractGut homeostasis is of importance to host health and imbalance of the gut usually leads to disorders or diseases for both human and animal. Postbiotics have been applied in manipulating of gut health, and utilization of postbiotics threads new lights into the host health. Compared with the application of probiotics, the characteristics such as stability and safety of postbiotics make it a potential alternative to probiotics. Studies have reported the beneficial effects of components derived from postbiotics, mainly through the mechanisms including inhibition of pathogens, strengthen gut barrier, and/or regulation of immunity of the host. In this review, we summarized the characteristics of postbiotics, main compounds of postbiotics, potential mechanisms in gut health, and their application in animal production.
The Pandemic Stressor Scale: factorial validity and reliability of a measure of stressors during a pandemic
Authors: Lotzin Annett , Ketelsen Ronja , Zrnic Irina , Lueger-Schuster Brigitte , Böttche Maria , Schäfer Ingo 
Published: April 2022

Abstract
Background
This study aimed to assess the factorial validity and reliability of the Pandemic Stressor Scale (PaSS), a new measure to assess the severity of distress for different stressors relevant during a pandemic or epidemic.

Methods
The PaSS was administered in N = 2760 German participants. Exploratory factor analysis was used to extract factors. The factor structure obtained in the German sample was examined in N = 1021 Austrian participants using confirmatory factor analysis. χ2, RMSEA, SRMR, CFI, TLI were assessed as global goodness of fit indices for two models (Model 1: nine-factor model; Model 2: nine-factor model combined with a second-order general factor). We additionally assessed factor loadings, communalities, factor reliability, discriminant validity as local fit indices. Internal consistency, item discrimination, and item difficulty were assessed as additional test quality criteria.

Results
The results of the exploratory factor analysis suggested a nine-factor solution with factor loadings accounting for 50.4% of the total variance (Factor 1 ‘Problems with Childcare’, Factor 2 ‘Work-related Problems’, Factor 3 ‘Restricted Face-to-Face Contact’, Factor 4 ‘Burden of Infection ‘, Factor 5 ‘Crisis Management and Communication’, Factor 6 ‘Difficult Housing Condition’, Factor 7 ‘Fear of Infection’, Factor 8 ‘Restricted Access to Resources’, Factor 9 ‘Restricted Activity’). The confirmatory factor analysis showed a sufficient global fit for both tested models (Model 1: χ2 (369, N = 1021) = 1443.28, p < .001, RMSEA = .053, SRMR = .055, CFI = .919, TLI = .904; Model 2: χ2 (396, N = 1021) = 1948.51, p < .001, RMSEA = .062, SRMR = .074, CFI = .883, TLI = .871). The results of the chi-square difference test indicated a significantly better model-fit of Model 1 compared to Model 2 (∆χ2 (27, N = 1021) = 505.23, p < .001). Local goodness of fit indices were comparable for both tested models. We found good factor reliabilities for all factors and moderate to large factor loadings of the items as indicators. In Model 2, four first-order factors showed small factor loadings on the second-order general factor.

Conclusion
The Pandemic Stressor Scale showed sufficient factorial validity for the nine measured domains of stressors during the current COVID-19 pandemic.
TGF-β induced reprogramming and drug resistance in triple-negative breast cells
Authors: Wu Guoyu , Li Yuchao 
Published: April 2022

Abstract
Background
The development of drug resistance remains to be a major cause of therapeutic failure in breast cancer patients. How drug-sensitive cells first evade drug inhibition to proliferate remains to be fully investigated.

Methods
Here we characterized the early transcriptional evolution in response to TGF-β in the human triple-negative breast cells through bioinformatical analysis using a published RNA-seq dataset, for which MCF10A cells were treated with 5 ng/ml TGF-β1 for 0 h, 24 h, 48 h and 72 h, and the RNA-seq were performed in biological duplicates. The protein-protein interaction networks of the differentially expressed genes were constructed. KEGG enrichment analysis, cis-regulatory sequence analysis and Kaplan-Meier analysis were also performed to analyze the cellular reprograming induced by TGF-β and its contribution to the survival probability decline of breast cancer patients.

Result
Transcriptomic analysis revealed that cell growth was severely suppressed by TGF-β in the first 24 h but this anti-proliferate impact attenuated between 48 h and 72 h. The oncogenic actions of TGF-β happened within the same time frame with its anti-proliferative effects. In addition, sustained high expression of several drug resistance markers was observed after TGF-β treatment. We also identified 17 TGF-β induced genes that were highly correlated with the survival probability decline of breast cancer patients.

Conclusion
Together, TGF-β plays an important role in tumorigenesis and the development of drug resistance, which implies potential therapeutic strategies targeting the early-stage TGF-β signaling activities.
Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening
Authors: Yu James , Lee Somin , Song Jiyoung , Lee Seung-Ryeol , Kim Suryong , Choi Hyeri , Kang Habin , Hwang Yunchan , Hong Young-Kwon , Jeon Noo Li 
Published: April 2022

AbstractMicrofluidic organ-on-a-chip technologies have enabled construction of biomimetic physiologically and pathologically relevant models. This paper describes an injection molded microfluidic platform that utilizes a novel sequential edge-guided patterning method based on spontaneous capillary flow to realize three-dimensional co-culture models and form an array of micro-vascularized tissues (28 per 1 × 2-inch slide format). The MicroVascular Injection-Molded Plastic Array 3D Culture (MV-IMPACT) platform is fabricated by injection molding, resulting in devices that are reliable and easy to use. By patterning hydrogels containing human umbilical endothelial cells and fibroblasts in close proximity and allowing them to form vasculogenic networks, an array of perfusable vascularized micro-tissues can be formed in a highly efficient manner. The high-throughput generation of angiogenic sprouts was quantified and their uniformity was characterized. Due to its compact design (half the size of a 96-well microtiter plate), it requires small amount of reagents and cells per device. In addition, the device design is compatible with a high content imaging machine such as Yokogawa CQ-1. Furthermore, we demonstrated the potential of our platform for high-throughput phenotypic screening by testing the effect of DAPT, a chemical known to affect angiogenesis. The MV-IMPACT represent a significant improvement over our previous PDMS-based devices in terms of molding 3D co-culture conditions at much higher throughput with added reliability and robustness in obtaining vascular micro-tissues and will provide a platform for developing applications in drug screening and development.
Biodegradation of plastic polymers by fungi: a brief review
Authors: Srikanth Munuru , Sandeep T. S. R. S. , Sucharitha Kuvala , Godi Sudhakar 
Published: April 2022

AbstractPlastic polymers are non-degradable solid wastes that have become a great threat to the whole world and degradation of these plastics would take a few decades. Compared with other degradation processes, the biodegradation process is the most effective and best way for plastic degradation due to its non-polluting mechanism, eco-friendly nature, and cost-effectiveness. Biodegradation of synthetic plastics is a very slow process that also involves environmental factors and the action of wild microbial species. In this plastic biodegradation, fungi play a pivotal role, it acts on plastics by secreting some degrading enzymes, i.e., cutinase`, lipase, and proteases, lignocellulolytic enzymes, and also the presence of some pro-oxidant ions can cause effective degradation. The oxidation or hydrolysis by the enzyme creates functional groups that improve the hydrophilicity of polymers, and consequently degrade the high molecular weight polymer into low molecular weight. This leads to the degradation of plastics within a few days. Some well-known species which show effective degradation on plastics are Aspergillus nidulans, Aspergillus flavus, Aspergillus glaucus, Aspergillus oryzae, Aspergillus nomius, Penicillium griseofulvum, Bjerkandera adusta, Phanerochaete chrysosporium, Cladosporium cladosporioides, etc., and some other saprotrophic fungi, such as Pleurotus abalones, Pleurotus ostreatus, Agaricus bisporus and Pleurotus eryngii which also helps in degradation of plastics by growing on them. Some studies say that the degradation of plastics was more effective when photodegradation and thermo-oxidative mechanisms involved with the biodegradation simultaneously can make the degradation faster and easier. This present review gives current knowledge regarding different species of fungi that are involved in the degradation of plastics by their different enzymatic mechanisms to degrade different forms of plastic polymers.
Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study
Authors: Heesterbeek Catharina J. , Aukema Sietse M. , Galjaard Robert-Jan H. , Boon Elles M.J. , Srebniak Malgorzata I. , Bouman Katelijne , Faas Brigitte H.W. , Govaerts Lutgarde C.P. , Hoffer Mariëtte J.V. , den Hollander Nicolette S. , Lichtenbelt Klaske D. , van Maarle Merel C. , van Prooyen Schuurman Lisanne , van Rij Maartje C. , Schuring-Blom G. Heleen , Stevens Servi J.C. , Tan-Sindhunata Gita , Zamani Esteki Masoud , de Die-Smulders Christine E.M. , Tjan-Heijnen Vivianne C.G. , Henneman Lidewij , Sistermans Erik A. , Macville Merryn V.E. ,   The Dutch NIPT Consortium
Published: April 2022

PURPOSE: Noninvasive prenatal testing (NIPT) for fetal aneuploidy screening using cell-free DNA derived from maternal plasma can incidentally raise suspicion for cancer. Diagnostic routing after malignancy suspicious–NIPT faces many challenges. Here, we detail malignancy suspicious–NIPT cases, and describe the clinical characteristics, chromosomal aberrations, and diagnostic routing of the patients with a confirmed malignancy. Clinical lessons can be learned from our experience. METHODS: Patients with NIPT results indicative of a malignancy referred for tumor screening between April 2017 and April 2020 were retrospectively included from a Dutch nationwide NIPT implementation study, TRIDENT-2. NIPT profiles from patients with confirmed malignancies were reviewed, and the pattern of chromosomal aberrations related to tumor type was analyzed. We evaluated the diagnostic contribution of clinical and genetic examinations. RESULTS: Malignancy suspicious–NIPT results were reported in 0.03% after genome-wide NIPT, and malignancies confirmed in 16 patients (16/48, 33.3%). Multiple chromosomal aberrations were seen in 23 of 48 patients with genome-wide NIPT, and a malignancy was confirmed in 16 patients (16/23, 69.6%). After targeted NIPT, 0.005% malignancy suspicious–NIPT results were reported, in 2/3 patients a malignancy was confirmed. Different tumor types and stages were diagnosed, predominantly hematologic malignancies (12/18). NIPT data showed recurrent gains and losses in primary mediastinal B-cell lymphomas and classic Hodgkin lymphomas. Magnetic resonance imaging and computed tomography were most informative in diagnosing the malignancy. CONCLUSION: In 231,896 pregnant women, a low percentage (0.02%) of NIPT results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high. Referral for extensive oncologic examination is recommended, and may be guided by tumor-specific hallmarks in the NIPT profile.