bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired activation of STAT5 upon IL-2 stimulation in Tregs and elevated sIL-2R in Sjögren’s syndrome
Authors: Keindl Magdalena , Davies Richard , Bergum Brith , Brun Johan G. , Hammenfors Daniel , Jonsson Roland , Lyssenko Valeriya , Appel Silke 
Published: May 2022

AbstractBackgroundInterleukin-2 (IL-2) and the high-affinity IL-2 receptor (IL-2R) are essential for the survival of regulatory T cells (Tregs) which are the main players in immune tolerance and prevention of autoimmune diseases. Sjögren’s syndrome (SS) is a chronic autoimmune disease predominantly affecting women and is characterised by sicca symptoms including oral and ocular dryness. The aim of this study was to investigate an association between IL-2R and Treg function in patients with SS of different severity defined by the salivary flow rate.MethodsIn a cross-sectional study, we determined plasma soluble IL-2R (sIL-2R) levels in women with SS (n=97) and healthy females (n=50) using ELISA. A subset of those (n=51) was screened for Treg function measured by the STAT5 signalling response to IL-2 using phospho-flow cytometry.ResultsWe found that elevated plasma levels of sIL-2R were positively associated with the severity of SS reflected by a pathologically low salivary flow. Phospho-flow analysis revealed that patients with SS have a significantly lower frequency of pSTAT5+Tregs upon IL-2 stimulation compared with healthy individuals, while the frequency of Tregs and pSTAT5 in conventional T cells remained unchanged. In addition, we observed more pSTAT5+Tregs at baseline in patients with SS, which is significantly associated with seropositivity and elevated sIL-2R.ConclusionsOur data indicates that Tregs have a weakened immunosuppressive function in patients with SS due to impaired IL-2/IL-2R signalling capacity. This could mediate lymphocytic infiltration into salivary glands inducing sicca symptoms. We believe that sIL-2R could act as a useful indicator for SS and disease severity.
Impact of type and dose of oral polyunsaturated fatty acid supplementation on disease activity in inflammatory rheumatic diseases: a systematic literature review and meta-analysis
Authors: Sigaux Johanna , Mathieu Sylvain , Nguyen Yann , Sanchez Pauline , Letarouilly Jean-Guillaume , Soubrier Martin , Czernichow Sébastien , Flipo René-Marc , Sellam Jérémie , Daïen Claire 
Published: May 2022

Abstract
Background
Polyunsaturated fatty acid (PUFA) supplementation has been reported to improve disease activity in inflammatory rheumatic diseases (IRDs). However, data are often conflicting and studies insufficiently large to draw conclusions. This systematic literature review and meta-analysis aimed to better estimate the effect of oral supplementation with omega (n)-3 and n-6 PUFA on IRD activity in terms of duration, dose, type, and source.

Methods
The literature was searched in PubMed, EMBASE, and Cochrane Library databases up to October 2020. Studies were reviewed in accordance with PRISMA guidelines. The effect of PUFA supplementation on disease activity was expressed as the standardized mean difference (95% CI). Metaregression and subgroup analyses involved type of IRD, Jadad score, PUFA source (animal or vegetable), and doses.

Results
We obtained 42 references; 30 randomized controlled studies were included comparing the effects of PUFA versus control on disease activity (710 IRD patients receiving PUFA supplementation and 710 controls, most with rheumatoid arthritis). We found a significant improvement in pain, swollen and tender joint count, Disease Activity Score in 28 joints, and Health Assessment Questionnaire score in IRD patients receiving PUFA supplementation as compared with controls, with a significant decrease in erythrocyte sedimentation rate but not C-reactive protein level. Although meta-regression revealed no difference by IRD type or source or dose of PUFA supplementation, subgroup analysis revealed more parameters significantly improved with animal- than vegetable-derived PUFAs and 3- to 6-month supplementation. Most studies examined high-dose supplementation (>2 g/day).

Conclusion
PUFA consumption, especially omega-3 from animal source >2 g/day, may improve IRD activity and might be an adjuvant therapy in rheumatoid arthritis.

Trial registration
The protocol was registered at PROSPERO (CRD42021253685).
The Salzburg 10/7 HIIT shock cycle study: the effects of a 7-day high-intensity interval training shock microcycle with or without additional low-intensity training on endurance performance, well-being, stress and recovery in endurance trained athletes—study protocol of a randomized controlled trial
Authors: Stöggl Thomas Leonhard , Blumkaitis Julia C. , Strepp Tilmann , Sareban Mahdi , Simon Perikles , Neuberger Elmo W. I. , Finkenzeller Thomas , Nunes Natalia , Aglas Lorenz , Haller Nils 
Published: May 2022

AbstractBackgroundPerforming multiple high-intensity interval training (HIIT) sessions in a compressed period of time (approximately 7–14 days) is called a HIIT shock microcycle (SM) and promises a rapid increase in endurance performance. However, the efficacy of HIIT-SM, as well as knowledge about optimal training volumes during a SM in the endurance-trained population have not been adequately investigated. This study aims to examine the effects of two different types of HIIT-SM (with or without additional low-intensity training (LIT)) compared to a control group (CG) on key endurance performance variables. Moreover, participants are closely monitored for stress, fatigue, recovery, and sleep before, during and after the intervention using innovative biomarkers, questionnaires, and wearable devices.MethodsThis is a study protocol of a randomized controlled trial that includes the results of a pilot participant. Thirty-six endurance trained athletes will be recruited and randomly assigned to either a HIIT-SM (HSM) group, HIIT-SM with additional LIT (HSM + LIT) group or a CG. All participants will be monitored before (9 days), during (7 days), and after (14 days) a 7-day intervention, for a total of 30 days. Participants in both intervention groups will complete 10 HIIT sessions over 7 consecutive days, with an additional 30 min of LIT in the HSM + LIT group. HIIT sessions consist of aerobic HIIT, i.e., 5 × 4 min at 90–95% of maximal heart rate interspersed by recovery periods of 2.5 min. To determine the effects of the intervention, physiological exercise testing, and a 5 km time trial will be conducted before and after the intervention.ResultsThe feasibility study indicates good adherence and performance improvement of the pilot participant. Load monitoring tools, i.e., biomarkers and questionnaires showed increased values during the intervention period, indicating sensitive variables.ConclusionThis study will be the first to examine the effects of different total training volumes of HIIT-SM, especially the combination of LIT and HIIT in the HSM + LIT group. In addition, different assessments to monitor the athletes' load during such an exhaustive training period will allow the identification of load monitoring tools such as innovative biomarkers, questionnaires, and wearable technology.Trial Registration: clinicaltrials.gov, NCT05067426. Registered 05 October 2021—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT05067426.Protocol VersionIssue date: 1 Dec 2021. Original protocol. Authors: TLS, NH.
Comparison of physical workload and physical work capacity among municipality cleaners in Shiraz to determine number of workers needed to counterbalance physical workload
Authors: Bagherifard Farnaz , Daneshmandi Hadi , Ziaei Mansour , Ghaem Haleh , Khoshbakht Ruhollah , Jaberi Omid , Choobineh Alireza 
Published: May 2022

Abstract
Background
Assessing physical workload is the most important step in deciding whether a workload is high and adopting appropriate control strategies to reduce physical workload. This study aimed to compare physical workload and Physical Work Capacity (PWC) among municipality cleaners in Shiraz to determine the number of workers needed to counterbalance physical workload.

Methods
The present cross-sectional study was performed on 97 municipality cleaners in Shiraz. In the first step, the participants' maximum aerobic capacity (VO2-max) was estimated in the laboratory using an ergometer bicycle and the Young Men’s Christian Association (YMCA) protocol, based on which the PWC was estimated. Secondly, energy expenditure and heart rate during work were measured using a POLAR400 device in an eight-hour shift. At the end of the work shift, the workers’ perceived physical exertion was assessed using a Rating of Perceived Exertion 6–20 (RPE 6–20) Borg scale. In the final stage, the physical workload was assessed based on the results of the two steps.

Results
The mean VO2-max of the cleaners and PWC were estimated to be 2.6 ± 0.66 l min−1 and 4.3 ± 1.088 kcal min−1, respectively. The average energy consumed during work was 4.122 ± 1.016 kcal min−1. The overall results of this study showed that physical workload was greater than PWC in 46% of the municipality cleaners. In addition, it was found that 12.45% workforce was required to be added to the street cleaners of Shiraz municipality to reduce the physiological workload on the employed workforce.

Conclusions
With respect to the high level of physical activity in a significant proportion of the cleaners, measures such as increasing the workforce are suggested.
Effect of nitrogen addition on the carbon metabolism of soil microorganisms in a Calamagrostis angustifolia wetland of the Sanjiang Plain, northeastern China
Authors: Weng Xiaohong , Sui Xin , Liu Yingnan , Yang Libin , Zhang Rongtao 
Published: May 2022

AbstractPurposeSoil microorganisms are important mediators of land ecosystem functions and stability. However, carbon sources in different amounts of nitrogen addition are known to affect the function of soil microbial communities. Thus, this study sought to evaluate the effects of nitrogen addition on the carbon utilization capacity of soil microorganisms in the Sanjiang Plain wetland, northeastern China.MethodsThree nitrogen treatments (CK, 0 kg N ha−1a−1; N40, 40 kg N ha−1a−1; and N80 kg N ha−1a−1) were evaluated in the Honghe National Nature Reserve of the Sanjiang Plain. The carbon metabolism capacity of soil microorganisms in theC. angustifoliawetland was investigated after five consecutive year’s nitrogen addition treatment using the Bio-Eco technique.ResultsDifferent amounts of nitrogen addition conditions resulted in significant differences in pH, ammonium nitrogen (NH4+), dissolved organic carbon (DOC), and soil microbial alpha diversity. The average well-color development (AWCD) in the Bio-Eco Plate assay increased gradually with incubation time, and different nitrogen levels significantly affected these AWCD values (P< 0.05), with the N40 treatment exhibiting the highest value. Furthermore, the N80 treatment had significantly lower Shannon and Pielou diversity indices (P< 0.05). N40 significantly promoted carbohydrate, amino acid, and ester utilization rates by soil microorganisms, whereas N80 significantly inhibited carbohydrate, amino acid, alcohol, amine, and organic acids utilization. Redundancy analysis (RDA) showed that the three treatments had remarkable differences in soil microbial community metabolism, and the cumulative variance contribution was 72.86%. In addition, RDA revealed that the N80 treatment was positively correlated with the TN, SMC, DON, and TOC but negatively correlated with DOC, NH4+, pH, and NO3−.ConclusionLong-term nitrogen addition leads to changes in soil microbial community structure and significantly alters the ability of soil microorganisms to utilize carbon sources in theCalamagrostis angustifoliawetland.
Molecular regulation of trophoblast stem cell self-renewal and giant cell differentiation by the Hippo components YAP and LATS1
Authors: Basak Trishita , Ain Rupasri 
Published: May 2022

Abstract
Background
Trophoblast stem cells (TSCs), the precursors of trophoblast cells of placenta, possess the potential to differentiate into various trophoblastic subtypes in vitro. Establishment of extraembryonic trophoblastic lineage is preceded by the “outside versus inside” positional information in preimplantation embryos, critically synchronized by the Hippo components. Abundant expression of Hippo effector YAP in TSCs and differentiated cells with paucity of information on Hippo regulation of TSC proliferation/differentiation led us test the hypothesis that Hippo dynamics is one of the regulators of TSC proliferation/differentiation.

Methods
Blastocyst-derived murine TSCs were used. Dynamics of Hippo components were analyzed using immunofluorescence, western blotting, immunoprecipitation, qRT-PCR. Interaction studies were performed using full-length and deletion constructs. BrdU incorporation assay, flow cytometry-based polyploidy analysis and confocal microscopy were used to decipher the underlying mechanism.

Results
YAP translocates to the nucleus in TSCs and utilizes its WW2 domain to interact with the PPQY motif of the stemness factor, CDX2. YAP limits TSC proliferation with associated effect on CDX2 target CyclinD1. Trophoblast giant cells (TGC) differentiation is associated with cytoplasmic retention of YAP, heightened pYAPSer127, decrease in the level of the core Hippo component, LATS1, which thereby impedes LATS1-LIMK2 association. Decreased LATS1-LIMK2 complex formation in TGCs was associated with elevated pLIMK2Thr505 as well as its target pCOFILINSer3. Precocious overexpression of LATS1 during trophoblast differentiation decreased TGC marker, Prl2c2, diminished pLIMK2Thr505 and inactive COFILIN (pCOFILINSer3) while COFILIN-phosphatase, CHRONOPHIN remained unchanged. LATS1 overexpression inhibited trophoblast endoreduplication with smaller-sized TGC-nuclei, lower ploidy level and disintegrated actin filaments. Inhibition of LIMK2 activity recapitulated the effects of LATS1 overexpression in trophoblast cells.

Conclusion
These results unveil a multilayered regulation of trophoblast self-renewal and differentiation by the Hippo components.
Intrarenal arterial administration of human umbilical cord-derived mesenchymal stem cells effectively preserved the residual renal function of diabetic kidney disease in rat
Authors: Yue Ya , Yeh Jui-Ning , Chiang John Y. , Sung Pei-Hsun , Chen Yi-Ling , Liu Fanna , Yip Hon-Kan 
Published: May 2022

Abstract
Background
This experimental study was designed as a preclinical study for testing the hypothesis that intrarenal arterial (IRA) transfusion of human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy preserved the residual renal function of diabetic kidney disease (DKD) in rat [induction by 5/6 nephrectomy of left kidney and right nephrectomy, followed by intraperitoneal administration of aminoguanidine (180 mg/kg) and streptozotocin (30 mg/kg)].

Methods
Animals (n = 24) were categorized into group 1 (sham-operated control), group 2 (DKD), group 3 [DKD + HUCDMSCs (2.1 × 105/IRA injection at day 28 after CKD induction)] and group 4 [(DKD + HUCDMSCs (6.3 × 105/IRA injection)].

Results
By day 60 after DKD induction, the kidneys were harvested and the result showed that the creatinine level, ratio of urine protein/urine creatinine and kidney injury score were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p < 0.0001). The protein expressions of apoptotic (cleaved caspase-3/cleaved PARP/mitochondrial Bax), fibrotic (TGF-ß/p-Smad3), autophagic (ratio of LC3B-II/LC3B-I, Atg5/Beclin-1), oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), mitochondrial/DNA-damaged (cytosolic-cytochrome-C/DRP1/γ-H2AX) and inflammatory (MMP-9/TNF-α/p-NF-κB) biomarkers exhibited an identical pattern, whereas the protein expressions of angiogenesis factors (CD31/vWF/vascularity) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). Histopathological findings demonstrated the renal tubular-damaged (KIM-1)/kidney fibrosis area/oxidative stress (8-OHdG + cells) expressed an identical pattern, whereas the podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). No tumorigenesis or immune rejection event was identified.

Conclusion
IRA injection of xenogeneic MSCs was safe and effectively protected the residual renal function and architectural integrity in DKD rat.
Endothelial nitric oxide synthase (eNOS)-NO signaling axis functions to promote the growth of prostate cancer stem-like cells
Authors: Gao Weijie , Wang Yuliang , Yu Shan , Wang Zhu , Ma Taiyang , Chan Andrew Man-Lok , Chiu Peter Ka-Fung , Ng Chi-Fai , Wu Dinglan , Chan Franky Leung 
Published: May 2022

Abstract
Background
Accumulating evidence supports that prostate cancer stem-like cells (PCSCs) play significant roles in therapy resistance and metastasis of prostate cancer. Many studies also show that nitric oxide (NO) synthesized by NO synthases can function to promote tumor progression. However, the exact roles of NOSs and NO signaling in the growth regulation of PCSCs and castration-resistant prostate cancer (CRPC) are still not fully understood.

Methods
The regulatory functions of NOS-NO signaling were evaluated in prostate cancer cells, especially in PCSCs enriched by 3D spheroid culture and CD133/CD44 cell sorting. The molecular mechanisms of NOS-NO signaling in PCSCs growth regulation and tumor metastasis were investigated in PCSCs and mice orthotopic prostate tumor model.

Results
Endothelial NOS (eNOS) exhibited a significant upregulation in high-grade prostate cancer and metastatic CRPC. Xenograft models of CRPC exhibited notable increased eNOS expression and higher intracellular NO levels. PCSCs isolated from various models displayed significant enhanced eNOS-NO signaling. Functional analyses demonstrated that increased eNOS expression could promote in vivo tumorigenicity and metastatic potential of prostate cancer cells. Characterization of eNOS-NO involved downstream pathway which confirmed that enhanced eNOS signaling could promote the growth of PCSCs and antiandrogen-resistant prostate cancer cells via an activated downstream NO-sGC-cGMP-PKG effector signaling pathway. Interestingly, eNOS expression could be co-targeted by nuclear receptor ERRα and transcription factor ERG in prostate cancer cells and PCSCs.

Conclusions
Enhanced eNOS-NO signaling could function to promote the growth of PCSCs and also the development of metastatic CRPC. Besides eNOS-NO as potential targets, targeting its upstream regulators (ERRα and ERG) of eNOS-NO signaling could also be the therapeutic strategy for the management of advanced prostate cancer, particularly the aggressive cancer carrying with the TMPRSS2:ERG fusion gene.
Mesh-like electrospun membrane loaded with atorvastatin facilitates cutaneous wound healing by promoting the paracrine function of mesenchymal stem cells
Authors: Xiang Jieyu , Zhou Ling , Xie Yuanlong , Zhu Yufan , Xiao Lingfei , Chen Yan , Zhou Wei , Chen Danyang , Wang Min , Cai Lin , Guo Liang 
Published: May 2022

Abstract
Background
Functional electrospun membranes are promising dressings for promoting wound healing. However, their microstructure and drug loading capacity need further improvements. It is the first time to design a novel mesh-like electrospun fiber loaded with atorvastatin (ATV) and investigated its effects on paracrine secretion by bone marrow-derived mesenchymal stem cells (BMSCs) and wound healing in vivo.

Methods
We fabricated a mesh-like electrospun membrane using a copper mesh receiver. The physical properties of the membranes were evaluated by SEM, FTIR spectroscopy, tensile strength analysis, and contrast angle test. Drug release was measured by plotting concentration as a function of time. We tested the effects of conditioned media (CM) derived from BMSCs on endothelial cell migration and angiogenesis. We used these BMSCs and performed RT-PCR and ELISA to evaluate the expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) genes and proteins, respectively. The involvement of FAK and AKT mechanotransduction pathways in the regulation of BMSC secretion by material surface topography was also investigated. Furthermore, we established a rat model of wound healing, applied ATV-loaded mesh-like membranes (PCL/MAT) seeded with BMSCs on wounds, and assessed their efficacy for promoting wound healing.

Results
FTIR spectroscopy revealed successful ATV loading in PCL/MAT. Compared with random electrospun fibers (PCL/R) and mesh-like electrospun fibers without drug load (PCL/M), PCL/MAT induced maximum promotion of human umbilical vein endothelial cell (HUVEC) migration. In the PCL/MAT group, the cell sheet scratches were nearly closed after 24 h. However, the cell sheet scratches remained open in other treatments at the same time point. The PCL/MAT promoted angiogenesis and led to the generation of longer tubes than the other treatments. Finally, the PCL/MAT induced maximum gene expression and protein secretion of VEGF and b-FGF. As for material surface topography effect on BMSCs, FAK and AKT signaling pathways were shown to participate in the modulation of MSC morphology and its paracrine function. In vivo, PCL/MAT seeded with BMSCs significantly accelerated healing and improved neovascularization and collagen reconstruction in the wound area compared to the other treatments.

Conclusions
The mesh-like topography of fibrous scaffolds combined with ATV release creates a unique microenvironment that promotes paracrine secretion of BMSCs, thereby accelerating wound healing. Hence, drug-loaded mesh-like electrospun membranes may be highly efficacious for wound healing and as artificial skin. It is a promising approach to solve the traumatic skin defect and accelerate recovery, which is essential to developing functional materials for future regenerative medicine.