bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term intensive fasting enhances the immune function of red blood cells in humans
Authors: Fang Yixuan , Qian Jiawei , Xu Li , Wei Wen , Bu Wenwen , Zhang Suping , Lv Yaqi , Li Lei , Zhao Chen , Gao Xueqin , Gu Yue , Wang Li , Chen Zixing , Wang Xiao , Zhang Ruizhi , Xu Youjia , Yang Yanjun , Lu Jie , Yan Zhanjun , Wang Mingyuan , Tang Longhai , Yuan Na , Wang Jianrong 
Published: August 2023

Abstract
Background
Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question.

Results
We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability.

Conclusion
STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.
Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway
Authors: Xiao Yaosheng , Zhang Shanshan , Ye Yongjun , Chen Jincai , Xu Youjia 
Published: August 2023

Abstract
Background
Osteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation.

Methods
The rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays.

Results
A high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN’s protection.

Conclusion
GEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.
MUC16 stimulates neutrophils to an inflammatory and immunosuppressive phenotype in ovarian cancer
Authors: Wu Yuliang , Liu Qi , Xie Yan , Zhu Jihui , Zhang Sai , Ge Yao , Guo Jing , Luo Ning , Huang Wei , Xu Runping , Liu Shupeng , Cheng Zhongping 
Published: August 2023

Abstract
Background
MUC16 (CA125) is a commonly used tumor marker for ovarian cancer screening and reported to be an immunosuppressive factor by acting on the sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on the surface of natural killer cells (NK cells), B cells, and monocytes. However, the role of MUC16 on neutrophils in the tumor microenvironment remains to be further explored.

Methods
The correlation between the proportion and count of peripheral blood cells, serum inflammatory-related factors and serum MUC16 (CA125) level in patients was constructed based on clinical samples. RNAseq data was obtained from TCGA and sequencing of ovarian cancer tissues, followed by TIMER immune cell infiltration and correlation analysis. Ovarian cancer organoid was constructed to stimulate neutrophils with immunophenotype identification by qPCR and flow cytometry. MUC16 protein stimulation to neutrophils validated the role of MUC16 under the analysis of RNA sequencing and inhibition of NK cytotoxicity in vitro.

Results
The serum MUC16 level was positively correlated with the proportion and count of peripheral blood neutrophils, neutrophil-to-lymphocyte ratio (NLR) and inflammatory factors IL-6, IL-8, IL-10 and IL-2R. Siglec-9, the receptor of MUC16, was expressed on neutrophils and was positively correlated to neutrophil infiltration in ovarian cancer. After the stimulation of ovarian cancer organoids and MUC16 respectively, the proportions of CD11b+, CD66b+, and ICAM-1+ neutrophils were significantly increased, while the proportion of CXCR4+ neutrophils was slightly decreased, with increasing of of inflammatory factors MMP9, IL-8, OSM, IL-1β, TNF-α, CXCL3, and ROS. RNA-sequencing analysis revealed that inflammatory response, TNFA signaling pathway, and IL6-related pathway were upregulated in MUC16-stimulated neutrophils, accompanied by high expression of immunosuppression-related factors HHLA2, IL-6, TNFRSF9, ADORA2A, CD274 (PD-L1), and IDO1. NK cytotoxicity was decreased when treated by supernanant of MUC16-stimulated neutrophils in vitro.

Conclusion
MUC16 acted on neutrophils by Siglec-9 leading to an inflammatory and immunosuppressive phenotype in ovarian cancer.
A pediatric case of Chlamydia psittaci caused severe Acute Respiratory Distress Syndrome (ARDS) in Italy
Authors: Marchese Serena , Marchese Giacomo , Paviglianiti Giuseppe , Lapi Maria , Ottoveggio Gaetano , Pipitone Giuseppe , Corsello Giovanni 
Published: August 2023

Abstract
Background
This case of psittacosis in children, is the first described in literature, in Italy. This respiratory infection can be transmitted to humans from the inhalation of respiratory secretions, feces and plumage aerosol of infected birds (and other animals). Usually it can have an asymptomatic or paucisymptomatic course, and the onset is often flu-like, but in this case the child risked his life for a severe respiratory failure. This report is unique because in children psittacosis is rare, and always misdiagnosed, or could cause a delayed diagnosis because of lack of awareness among the paediatricians and physicians. Furthermore, psittacosis enters a differential diagnosis with SARS-COV2 infection because both diseases may determine dyspnea and atypical pneumonia, up to acute respiratory failure.

Case presentation
This clinical case talks about a three-and-a-half-year-old male child affected by psittacosis (or ornithosis), with severe dyspnea and systemic symptoms who required oro-tracheal intubation for acute respiratory failure. The child had slept in a room at home, with some recently bought parrots affected by psittacosis. Initially the child was treated with empiric antibiotic therapy (i.v.ceftriaxone and teicoplanin), but after having isolated the DNA of the germ “Chlamydia psittaci” in both serological and through bronchoalveolar lavage (BAL), he was treated with targeted antibiotic therapy: tetracyclines (doxicillin).

Conclusions
Psittacosis is an extremely contagious disease, caused by an intracellular germ, called “Chlamydia psittaci”, a Gram-negative bacterium, transmitted to humans in particular by infected birds, responsible for atypical pneumonia, with acute and chronic respiratory symptoms, sometimes with multi-organ failure and disseminated intravascular coagulation. Even if it is a rare respiratory disease among children, a good doctor must think about psittacosis as cause of respiratory symptoms (and not only flu or SARS-COV2), above all through a correct medical history, in order to provide a targeted antibiotic therapy. An interesting case of psittacosis in a child is being reported here, which has been treated successfully with doxycillin.
Transcutaneous electrical diaphragmatic stimulation in mechanically ventilated patients: a randomised study
Authors: Medrinal Clément , Machefert Margaux , Lamia Bouchra , Bonnevie Tristan , Gravier Francis-Edouard , Hilfiker Roger , Prieur Guillaume , Combret Yann 
Published: August 2023

Abstract
Background
Few specific methods are available to reduce the risk of diaphragmatic dysfunction for patients under mechanical ventilation. The number of studies involving transcutaneous electrical stimulation of the diaphragm (TEDS) is increasing but none report results for diaphragmatic measurements, and they lack power. We hypothesised that the use of TEDS would decrease diaphragmatic dysfunction and improve respiratory muscle strength in patients in ICU.

Methods
We conducted a controlled trial to assess the impact of daily active electrical stimulation versus sham stimulation on the prevention of diaphragm dysfunction during the weaning process from mechanical ventilation. The evaluation was based on ultrasound measurements of diaphragm thickening fraction during spontaneous breathing trials. We also measured maximal inspiratory muscle pressure (MIP), peak cough flow (PEF) and extubation failure.

Results
Sixty-six patients were included and randomised using a 1:1 ratio. The mean number of days of mechanical ventilation was 10 ± 6.8. Diaphragm thickening fraction was > 30% at the SBT for 67% of participants in the TEDS group and 54% of the Sham group (OR1.55, 95% CI 0.47–5.1; p = 0.47). MIP and PEF were similar in the TEDS and Sham groups (respectively 35.5 ± 11.9 vs 29.7 ± 11.7 cmH20; p = 0.469 and 83.2 ± 39.5 vs. 75.3 ± 34.08 L/min; p = 0.83). Rate of extubation failure was not different between groups.

Conclusion
TEDS did not prevent diaphragm dysfunction or improve inspiratory muscle strength in mechanically ventilated patients.
Trial registration: Prospectively registered on the 20th November 2019 on ClinicalTrials.gov Identifier NCT04171024.
Phenotypically sorted highly and weakly migratory triple negative breast cancer cells exhibit migratory and metastatic commensalism
Authors: Hapach Lauren A. , Wang Wenjun , Schwager Samantha C. , Pokhriyal Devika , Fabiano Emily D. , Reinhart-King Cynthia A. 
Published: August 2023

Abstract
Background
Intratumor heterogeneity is a well-established hallmark of cancer that impedes cancer research, diagnosis, and treatment. Previously, we phenotypically sorted human breast cancer cells based on migratory potential. When injected into mice, highly migratory cells were weakly metastatic and weakly migratory cells were highly metastatic. The purpose of this study was to determine whether these weakly and highly migratory cells interact with each other in vitro or in vivo.

Methods
To assess the relationship between heterogeneity in cancer cell migration and metastatic fitness, MDA-MB-231 and SUM159PT triple negative breast cancer cells were phenotypically sorted into highly migratory and weakly migratory subpopulations and assayed separately and in a 1:1 mixture in vitro and in vivo for metastatic behaviors. Unpaired, two-tailed Student’s t-tests, Mann–Whitney tests, ordinary, one-way ANOVAs, and Kruskal–Wallis H tests were performed as appropriate with p < 0.05 as the cutoff for statistical significance.

Results
When highly and weakly migratory cells are co-seeded in mixed spheroids, the weakly migratory cells migrated farther than weakly migratory only spheroids. In mixed spheroids, leader–follower behavior occurred with highly migratory cells leading the weakly migratory cells in migration strands. When cell suspensions of highly migratory, weakly migratory, or a 1:1 mixture of both subpopulations were injected orthotopically into mice, both the mixed cell suspensions and weakly migratory cells showed significant distal metastasis, but the highly migratory cells did not metastasize significantly to any location. Notably, significantly more distal metastasis was observed in mice injected with the 1:1 mixture compared to either subpopulation alone.

Conclusions
This study suggests that weakly migratory cells interact with highly migratory cells in a commensal fashion resulting in increased migration and metastasis. Together, these findings indicate that cancer cell subpopulation migration ability does not correlate with metastatic potential and that cooperation between highly migratory and weakly migratory subpopulations can enhance overall metastatic fitness.
Correlations between IL-36 family cytokines in peripheral blood and subjective and objective assessment results in patients with allergic rhinitis
Authors: Gu Jia , Qin Gang , Jiang Liang , Xu Wei , Wang Yuanyuan , Liao Jiangxue , Pan Hongzhu , Liang Zhuoping 
Published: August 2023

Abstract
Background
Interleukin (IL)-36 family cytokines have received increasing attention, especially in the fields of inflammation and immunity research. However, whether IL-36 family cytokine levels are correlated with the results of the assessment of allergic rhinitis (AR) and affect the severity of AR remains unknown. Therefore, this study aimed to investigate the correlations between IL-36 family cytokine levels and subjective and objective assessment results and to further analyze the possible mechanisms of IL-36 family cytokines in the development of AR.

Methods
An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of the IL-36 family cytokines IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 in the peripheral blood of patients with AR. The condition of patients with AR was assessed by 22-item sino-nasal outcome test (SNOT-22) score, visual analogue scale (VAS) scores for disease severity, and serum inhalant allergen immunoglobulin E (IgE) detection. Correlations between IL-36 family cytokine levels and subjective and objective assessment results in patients with AR were analyzed.

Results
The concentration of IL-36α in the peripheral blood of patients with AR was the highest, and the concentration of IL-36β was the lowest. The concentration of IL-36α was higher in juvenile patients than in adult patients, and there was a difference in the IL-36Ra level between the perennial allergen group and the seasonal allergen group. There was a positive correlation between IL-36α level and IL-36γ level, IL-36γ level and IL-36Ra level, and IL-36Ra level and IL-38 level, and IL-36β level was positively correlated with IL-36Ra and IL-38 levels, respectively. IL-36α level was positively correlated with VAS score for nasal congestion symptom. IL-36β level was positively correlated with the total VAS score for ocular symptoms and VAS scores for ocular itching and eye pain symptoms. However, there was no correlation between the levels of all cytokines in IL-36 family and SNOT-22 score, the number of positive inhaled allergens, or the highest positive intensity of allergen specific immunoglobulin E (sIgE).

Conclusion
Peripheral blood IL-36 family cytokines play an important role in AR, and the concentrations of IL-36α and IL-36β were related to the severity of symptoms in patients with AR.
Umbilical cord-derived mesenchymal stem cells cultured in the MCL medium for aplastic anemia therapy
Authors: He Chuan , Yang Chao , Zeng Qiang , Liu Zhigang , Wang Fangfang , Chen Qiang , Liu Ting 
Published: August 2023

AbstractBackgroundMesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential that may be a treatment for aplastic anemia (AA).MethodUmbilical cord-derived MSCs were cultured in three media (Mesencult-XF, MCL, and StemPro MSC SFM CTS). HGF, PGE2, ANG-1, TGF-β1, IFN-γ, and TNF-α were detected using ELISA. The AA mouse model was built via post-irradiation lymphocyte infusion. After different treatments, routine blood, VEGF, and Tregs were detected every week. On day 28, all mice were killed, and their femurs were stained with HE.ResultsUmbilical cord-derived MSCs cultured in the three media all conformed to the general characteristics of MSCs. HGF secreted by MSCs in the Mesencult-XF, and MCL was greater than that in the StemPro MSC SFM CTS; ANG-1 and TGF-β1 in the MCL were more than that in Mesencult-XF and StemPro MSC SFM CTS; PGE2 in the MCL and StemPro MSC SFM CTS was more than that in the Mesencult-XF. MSCs in the MCL and StemPro MSC SFM CTS inhibited IFN-γ and TNF-α more than those in the Mesencult-XF. The peripheral blood cell in the AA groups was at a low level while that in the MSC group recovered rapidly. The Treg ratio and VEGF level in the MSC group were higher than those in the AA group. The bone marrow (BM) recovered significantly after MSC infusion.ConclusionMSCs in the MCL were advantageous in supporting hematopoiesis and modulating immunity and had the potential for effective treatment of AA.
Single-cell RNA sequencing of human non-hematopoietic bone marrow cells reveals a unique set of inter-species conserved biomarkers for native mesenchymal stromal cells
Authors: Fiévet Loïc , Espagnolle Nicolas , Gerovska Daniela , Bernard David , Syrykh Charlotte , Laurent Camille , Layrolle Pierre , De Lima Julien , Justo Arthur , Reina Nicolas , Casteilla Louis , Araúzo-Bravo Marcos J. , Naji Abderrahim , Pagès Jean-Christophe , Deschaseaux Frédéric 
Published: August 2023

Abstract
Background
Native bone marrow (BM) mesenchymal stem/stromal cells (BM-MSCs) participate in generating and shaping the skeleton and BM throughout the lifespan. Moreover, BM-MSCs regulate hematopoiesis by contributing to the hematopoietic stem cell niche in providing critical cytokines, chemokines and extracellular matrix components. However, BM-MSCs contain a heterogeneous cell population that remains ill-defined. Although studies on the taxonomy of native BM-MSCs in mice have just started to emerge, the taxonomy of native human BM-MSCs remains unelucidated.

Methods
By using single-cell RNA sequencing (scRNA-seq), we aimed to define a proper taxonomy for native human BM non-hematopoietic subsets including endothelial cells (ECs) and mural cells (MCs) but with a focal point on MSCs. To this end, transcriptomic scRNA-seq data were generated from 5 distinct BM donors and were analyzed together with other transcriptomic data and with computational biology analyses at different levels to identify, characterize and classify distinct native cell subsets with relevant biomarkers.

Results
We could ascribe novel specific biomarkers to ECs, MCs and MSCs. Unlike ECs and MCs, MSCs exhibited an adipogenic transcriptomic pattern while co-expressing genes related to hematopoiesis support and multilineage commitment potential. Furthermore, by a comparative analysis of scRNA-seq of BM cells from humans and mice, we identified core genes conserved in both species. Notably, we identified MARCKS, CXCL12, PDGFRA, and LEPR together with adipogenic factors as archetypal biomarkers of native MSCs within BM. In addition, our data suggest some complex gene nodes regulating critical biological functions of native BM-MSCs together with a preferential commitment toward an adipocyte lineage.

Conclusions
Overall, our taxonomy for native BM non-hematopoietic compartment provides an explicit depiction of gene expression in human ECs, MCs and MSCs at single-cell resolution. This analysis helps enhance our understanding of the phenotype and the complexity of biological functions of native human BM-MSCs.
Effects of Dopamine on stem cells and its potential roles in the treatment of inflammatory disorders: a narrative review
Authors: Liu Guan-qiao , Liu Zi-xian , Lin Ze-xin , Chen Peng , Yan Yu-chi , Lin Qing-rong , Hu Yan-jun , Jiang Nan , Yu Bin 
Published: August 2023

AbstractInflammation is the host's protective response against harmful external stimulation that helps tissue repair and remodeling. However, excessive inflammation seriously threatens the patient's life. Due to anti-inflammatory effects, corticosteroids, immunosuppressants, and monoclonal antibodies are used to treat various inflammatory diseases, but drug resistance, non-responsiveness, and severe side effect limit their development and application. Therefore, developing other alternative therapies has become essential in anti-inflammatory therapy. In recent years, the in-depth study of stem cells has made them a promising alternative drug for the treatment of inflammatory diseases, and the function of stem cells is regulated by a variety of signals, of which dopamine signaling is one of the main influencing factors. In this review, we review the effects of dopamine on various adult stem cells (neural stem cells, mesenchymal stromal cells, hematopoietic stem cells, and cancer stem cells) and their signaling pathways, as well as the application of some critical dopamine receptor agonists/antagonists. Besides, we also review the role of various adult stem cells in inflammatory diseases and discuss the potential anti-inflammation function of dopamine receptors, which provides a new therapeutic target for regenerative medicine in inflammatory diseases.
Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells
Authors: Arkenberg Matthew R. , Ueda Yoshitomo , Hashino Eri , Lin Chien-Chi 
Published: August 2023

Abstract
Background
Induced pluripotent stem cells (iPSC) can be differentiated to cells in all three germ layers, as well as cells in the extraembryonic tissues. Efforts in iPSC differentiation into pancreatic progenitors in vitro have largely been focused on optimizing soluble growth cues in conventional two-dimensional (2D) culture, whereas the impact of three-dimensional (3D) matrix properties on the morphogenesis of iPSC remains elusive.

Methods
In this work, we employ gelatin-based thiol-norbornene photo-click hydrogels for in situ 3D differentiation of human iPSCs into pancreatic progenitors (PP). Molecular analysis and single-cell RNA-sequencing were utilized to elucidate on the distinct identities of subpopulations within the 2D and 3D differentiated cells.

Results
We found that, while established soluble cues led to predominately PP cells in 2D culture, differentiation of iPSCs using the same soluble factors led to prominent branching morphogenesis, ductal network formation, and generation of diverse endoderm populations. Through single-cell RNA-sequencing, we found that 3D differentiation resulted in enrichments of pan-endodermal cells and ductal cells. We further noted the emergence of a group of extraembryonic cells in 3D, which was absent in 2D differentiation. The unexpected emergence of extraembryonic cells in 3D was found to be associated with enrichment of Wnt and BMP signaling pathways, which may have contributed to the emergence of diverse cell populations. The expressions of PP signature genes PDX1 and NKX6.1 were restored through inhibition of Wnt signaling at the beginning of the posterior foregut stage.

Conclusions
To our knowledge, this work established the first 3D hydrogel system for in situ differentiation of human iPSCs into PPs.