bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary conserved relocation of chromatin remodeling complexes to the mitotic apparatus
Authors: Messina Giovanni , Prozzillo Yuri , Monache Francesca Delle , Santopietro Maria Virginia , Dimitri Patrizio 
Published: August 2022

Abstract
Background
ATP-dependent chromatin remodeling complexes are multi-protein machines highly conserved across eukaryotic genomes. They control sliding and displacing of the nucleosomes, modulating histone-DNA interactions and making nucleosomal DNA more accessible to specific binding proteins during replication, transcription, and DNA repair, which are processes involved in cell division. The SRCAP and p400/Tip60 chromatin remodeling complexes in humans and the related Drosophila Tip60 complex belong to the evolutionary conserved INO80 family, whose main function is promoting the exchange of canonical histone H2A with the histone variant H2A in different eukaryotic species. Some subunits of these complexes were additionally shown to relocate to the mitotic apparatus and proposed to play direct roles in cell division in human cells. However, whether this phenomenon reflects a more general function of remodeling complex components and its evolutionary conservation remains unexplored.

Results
We have combined cell biology, reverse genetics, and biochemical approaches to study the subcellular distribution of a number of subunits belonging to the SRCAP and p400/Tip60 complexes and assess their involvement during cell division progression in HeLa cells. Interestingly, beyond their canonical chromatin localization, the subunits under investigation accumulate at different sites of the mitotic apparatus (centrosomes, spindle, and midbody), with their depletion yielding an array of aberrant outcomes of mitosis and cytokinesis, thus causing genomic instability. Importantly, this behavior was conserved by the Drosophila melanogaster orthologs tested, despite the evolutionary divergence between fly and humans has been estimated at approximately 780 million years ago.

Conclusions
Overall, our results support the existence of evolutionarily conserved diverse roles of chromatin remodeling complexes, whereby subunits of the SRCAP and p400/Tip60 complexes relocate from the interphase chromatin to the mitotic apparatus, playing moonlighting functions required for proper execution of cell division.
Effect of radiant catalytic ionization on environmental conditions in rodent rooms and the haematological status of mice
Authors: Niemiec Tomasz , Skowron Krzysztof , Świderek Wiesław , Kwiecińska-Piróg Joanna , Gryń Grzegorz , Wójcik-Trechcińska Urszula , Gajewska Marta , Zglińska Klara , Łozicki Andrzej , Koczoń Piotr 
Published: August 2022

AbstractHigh stocking densities, closed animal houses, and elevated concentrations of bacteria, fungi, and the products of their activity, including ammonia and hydrogen sulphide, have adverse health effects. Active techniques used to reduce unfavourable environmental conditions, such as ventilation, sprinkling, bedding sorbents, and nutritional treatments, are not always sufficient to improve the animals’ living environment. The current paper aims to evaluate the effect of radiant catalytic ionization (RCI) on airborne microorganisms, cage microbiological status, gaseous ammonia concentrations, and the haematological status of mice in animal houses. After one week of operation of an RCI system, the number of airborne bacteria and fungi in the experimental room decreased in comparison to the first day of the experiment (p < 0.05 and p < 0.05 respectively), as did the concentrations of ammonia (p < 0.01) and dust. At the same time, the basic health parameters of the mice, determined in the blood, were very similar between the control and experimental room. RCI seems to be an ideal solution to ensure high hygiene standards in animal rooms and houses with limited use of disinfectants or antibiotic treatment of sick animals. An additional, environmental benefit is the limited amount of nitrogen released.
Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease
Authors: Di Stefano Antonino , Dossena Francesca , Gnemmi Isabella , D’Anna Silvestro Ennio , Brun Paola , Balbi Bruno , Piraino Alessio , Spanevello Antonio , Nucera Francesco , Carriero Vitina , Bertolini Francesca , Maniscalco Mauro , Adcock Ian M. , Caramori Gaetano , Ricciardolo Fabio L. M. 
Published: August 2022

Abstract
Background
Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons.

Objective
To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners.

Methods
In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, − 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, − 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation “in vitro”.

Results
The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. “In vitro” stimulation of 16HBE cells with LPS (10 μg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 μM) significantly decreased pIgR epithelial expression.

Conclusion
These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD.
Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke
Authors: Veldema Jitka , Gharabaghi Alireza 
Published: August 2022

Abstract
Objectives
This systematic review and meta-analysis aim to summarize and analyze the available evidence of non-invasive brain stimulation/spinal cord stimulation on gait, balance and/or lower limb motor recovery in stroke patients.

Methods
The PubMed database was searched from its inception through to 31/03/2021 for randomized controlled trials investigating repetitive transcranial magnetic stimulation or transcranial/trans-spinal direct current/alternating current stimulation for improving gait, balance and/or lower limb motor function in stroke patients.

Results
Overall, 25 appropriate studies (including 657 stroke subjects) were found. The data indicates that non-invasive brain stimulation/spinal cord stimulation is effective in supporting recovery. However, the effects are inhomogeneous across studies: (1) transcranial/trans-spinal direct current/alternating current stimulation induce greater effects than repetitive transcranial magnetic stimulation, and (2) bilateral application of non-invasive brain stimulation is superior to unilateral stimulation.

Conclusions
The current evidence encourages further research and suggests that more individualized approaches are necessary for increasing effect sizes in stroke patients.
Salvianolic acid B activates chondrocytes autophagy and reduces chondrocyte apoptosis in obese mice via the KCNQ1OT1/miR-128-3p/SIRT1 signaling pathways
Authors: Sun Tianwen , Wang Fei , Hu Gaojian , Li Zhizhou 
Published: August 2022

Abstract
Purpose
Salvianolic acid B (Sal B) possesses strong anti-inflammatory and antioxidant activity. This study aims to explore the underlying mechanism of Sal B to improve the obesity-related osteoarthritis (OA).

Methods
C57BL/6 J male mice were fed with a normal control diet (NCD), a high fat diet (HFD), or HFD with Sal B (25 mg/kg), and mouse body weights and osteoarticular inflammatory factor levels were examined. Mouse chondrogenic cell line ATDC5 were transfected with lncRNA KCNQ1 overlapping transcript 1 small hairpin RNA (KCNQ1OT1 shRNA), miR-128-3p mimic or Sirtuin-1 small interfering RNA (SIRT1 siRNA), then stimulated with Palmitic acid (PA) followed by the treatment of Sal B. Then, inflammatory response, apoptosis, and autophagy of ATDC5 cells in different groups were detected.

Results
Sal B reduced the body weight, decreased the levels of inflammatory markers, and improved cartilage damage in OA mice fed with HFD. KCNQ1OT1 was downregulated in OA mice fed with HFD, and PA-stimulated ATDC5 cells. Sal B protected ATDC5 cells against PA-mediated inflammation, apoptosis, and the inhibition of autophagy, while knockdown of KCNQ1OT1 reversed these results. KCNQ1OT1 was found to be functioned as a ceRNA to bind and downregulate the expression of miR-128-3p that was upregulated in PA-induced cells. Furthermore, SIRT1 was verified as a target of miR-128-3p. MiR-128-3p overexpression reversed the effects of Sal B on inflammatory response, apoptosis, and autophagy in PA-stimulated cells, and knockdown of SIRT1 displayed the similar results.

Conclusion
Sal B exerted a chondroprotective effect by upregulating KCNQ1OT1, which indicates Sal B can used for a therapeutic agent in obesity-related OA.
Macrophage-mediated tissue response evoked by subchronic inhalation of lead oxide nanoparticles is associated with the alteration of phospholipases C and cholesterol transporters
Authors: Smutná Tereza , Dumková Jana , Kristeková Daniela , Laštovičková Markéta , Jedličková Adriena , Vrlíková Lucie , Dočekal Bohumil , Alexa Lukáš , Kotasová Hana , Pelková Vendula , Večeřa Zbyněk , Křůmal Kamil , Petráš Jiří , Coufalík Pavel , Všianský Dalibor , Záchej Samuel , Pinkas Dominik , Vondráček Jan , Hampl Aleš , Mikuška Pavel , Buchtová Marcela 
Published: August 2022

Abstract
Background
Inhalation of lead oxide nanoparticles (PbO NPs), which are emitted to the environment by high-temperature technological processes, heavily impairs target organs. These nanoparticles pass through the lung barrier and are distributed via the blood into secondary target organs, where they cause numerous pathological alterations. Here, we studied in detail, macrophages as specialized cells involved in the innate and adaptive immune response in selected target organs to unravel their potential involvement in reaction to subchronic PbO NP inhalation. In this context, we also tackled possible alterations in lipid uptake in the lungs and liver, which is usually associated with foam macrophage formation.

Results
The histopathological analysis of PbO NP exposed lung revealed serious chronic inflammation of lung tissues. The number of total and foam macrophages was significantly increased in lung, and they contained numerous cholesterol crystals. PbO NP inhalation induced changes in expression of phospholipases C (PLC) as enzymes linked to macrophage-mediated inflammation in lungs. In the liver, the subchronic inhalation of PbO NPs caused predominantly hyperemia, microsteatosis or remodeling of the liver parenchyma, and the number of liver macrophages also significantly was increased. The gene and protein expression of a cholesterol transporter CD36, which is associated with lipid metabolism, was altered in the liver. The amount of selected cholesteryl esters (CE 16:0, CE 18:1, CE 20:4, CE 22:6) in liver tissue was decreased after subchronic PbO NP inhalation, while total and free cholesterol in liver tissue was slightly increased. Gene and protein expression of phospholipase PLCβ1 and receptor CD36 in human hepatocytes were affected also in in vitro experiments after acute PbO NP exposure. No microscopic or serious functional kidney alterations were detected after subchronic PbO NP exposure and CD68 positive cells were present in the physiological mode in its interstitial tissues.

Conclusion
Our study revealed the association of increased cholesterol and lipid storage in targeted tissues with the alteration of scavenger receptors and phospholipases C after subchronic inhalation of PbO NPs and yet uncovered processes, which can contribute to steatosis in liver after metal nanoparticles exposure.

Graphical abstract
Oral eltanexor treatment of patients with higher-risk myelodysplastic syndrome refractory to hypomethylating agents
Authors: Lee Sangmin , Mohan Sanjay , Knupp Jessica , Chamoun Kamal , de Jonge Adrienne , Yang Fan , Baloglu Erkan , Shah Jatin , Kauffman Michael G. , Shacham Sharon , Bhatnagar Bhavana 
Published: August 2022

AbstractPatients with higher-risk myelodysplastic syndromes (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and an expected overall survival (OS) of 3–5 months. Eltanexor is an investigational oral selective inhibitor of nuclear export with low central nervous system penetrance and an acceptable tolerability profile. Preclinical studies suggest that myeloid malignancies are sensitive to nuclear export inhibition. Eltanexor exhibited efficacy in hematologic models, supporting exploration in a clinical trial. This phase 1/2 study (NCT02649790) assessed single-agent activity of eltanexor in patients with higher-risk MDS and 5–19% myeloblasts. Two starting doses of eltanexor were evaluated: 20 mg (n = 15), 10 mg (n = 5), both administered on days 1–5 each week of a 28-day cycle. Twenty patients with primary HMA-refractory MDS, with a median age of 77 years (range 62–89), and a median of two prior treatment regimens (range 1–4) were enrolled. Of these, 15 were evaluated for efficacy and 20 for safety. The overall response rate (ORR) was 53.3%, with seven patients (46.7%) achieving marrow complete remission (mCR) and one additional patient achieving hematologic improvement (HI). In the 10 mg group, three patients (60%) reached mCR and two (40%) stable disease (SD), while for 20 mg, four patients (40%) had mCR and two (20%) SD. A total of three patients (20%) had HI and became transfusion independent ≥ 8 weeks. Median OS for the efficacy-evaluable patients (n = 15) was 9.86 months (7.98, NE). Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS.
Muscular myostatin gene expression and plasma concentrations are decreased in critically ill patients
Authors: Grunow Julius J. , Reiher Katja , Carbon Niklas M. , Engelhardt Lilian Jo , Mai Knut , Koch Susanne , Schefold Joerg C. , Z’Graggen Werner , Schaller Stefan J. , Fielitz Jens , Spranger Joachim , Weber-Carstens Steffen , Wollersheim Tobias 
Published: August 2022

Abstract
Background
The objective was to investigate the role of gene expression and plasma levels of the muscular protein myostatin in intensive care unit-acquired weakness (ICUAW). This was performed to evaluate a potential clinical and/or pathophysiological rationale of therapeutic myostatin inhibition.

Methods
A retrospective analysis from pooled data of two prospective studies to assess the dynamics of myostatin plasma concentrations (day 4, 8 and 14) and myostatin gene (MSTN) expression levels in skeletal muscle (day 15) was performed. Associations of myostatin to clinical and electrophysiological outcomes, muscular metabolism and muscular atrophy pathways were investigated.

Results
MSTN gene expression (median [IQR] fold change: 1.00 [0.68–1.54] vs. 0.26 [0.11–0.80]; p = 0.004) and myostatin plasma concentrations were significantly reduced in all critically ill patients when compared to healthy controls. In critically ill patients, myostatin plasma concentrations increased over time (median [IQR] fold change: day 4: 0.13 [0.08/0.21] vs. day 8: 0.23 [0.10/0.43] vs. day 14: 0.40 [0.26/0.61]; p < 0.001). Patients with ICUAW versus without ICUAW showed significantly lower MSTN gene expression levels (median [IQR] fold change: 0.17 [0.10/0.33] and 0.51 [0.20/0.86]; p = 0.047). Myostatin levels were directly correlated with muscle strength (correlation coefficient 0.339; p = 0.020) and insulin sensitivity index (correlation coefficient 0.357; p = 0.015). No association was observed between myostatin plasma concentrations as well as MSTN expression levels and levels of mobilization, electrophysiological variables, or markers of atrophy pathways.

Conclusion
Muscular gene expression and systemic protein levels of myostatin are downregulated during critical illness. The previously proposed therapeutic inhibition of myostatin does therefore not seem to have a pathophysiological rationale to improve muscle quality in critically ill patients.
Trial registration: ISRCTN77569430—13th of February 2008 and ISRCTN19392591 17th of February 2011.

Graphical abstract
Topical administration of the secretome derived from human amniotic epithelial cells ameliorates psoriasis-like skin lesions in mice
Authors: Yang Mengbo , Wang Lanqi , Chen Zhimin , Hao Weijie , You Qian , Lin Jianhua , Tang Jingzhi , Zhao Xin , Gao Wei-Qiang , Xu Huiming 
Published: August 2022

AbstractBackgroundPsoriasis is a chronic inflammatory skin disease. Tissue stem cells have exhibited a therapeutic effect on psoriatic mice. However, the therapeutic effect of topical administration of the secretome derived from tissue stem cells on psoriasis has not been reported.MethodsThe secretome from human amniotic epithelial cells (AEC-SC) and human umbilical cord mesenchymal stem cells (UMSC-SC) was topically administrated on the back of imiquimod-induced psoriasis-like mice. Subsequently, we observed the skin lesions and skin inflammation of psoriasis-like mice. Next, we further analyzed the paracrine factors in AEC-SC and UMSC-SC by protein chips. Lastly, the effect of the crucial paracrine factor was investigated by imiquimod-induced psoriasis-like mice.ResultsWe found that AEC-SC had a better therapeutic effect on attenuating psoriasis-like skin lesions including skin scales, skin redness and skin thickness than UMSC-SC, and it had a better regulatory effect on keratinocyte hyperproliferation and altered differentiation. Thus, we focused on AEC-SC. Further study showed that AEC-SC reduced the infiltration of neutrophils and interleukin-17-producing T cells. Next, the analysis of AEC-SC with protein chip revealed that the levels of anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) were much higher in AEC-SC compared to that in UMSC-SC. More importantly, the beneficial effect of AEC-SC on psoriasis-like skin lesions and skin inflammation of mice were significantly impaired when neutralizing with IL-1ra antibody, while the recombinant human IL-1ra showed a less protective effect than AEC-SC.ConclusionsThe present study demonstrated that AEC-SC could efficiently ameliorate psoriasis-like skin lesions and skin inflammation and IL-1ra plays an essential role. Therefore, topical administration of AEC-SC may provide a novel strategy for treating psoriasis-like inflammatory skin diseases.
Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis
Authors: Chen Taiqiu , Peng Yan , Hu Wenjun , Shi Huihong , Li Pengfei , Que Yichen , Qiu Jincheng , Qiu Xianjian , Gao Bo , Zhou Hang , Chen Yanbo , Zhu Yuanxin , Li Shaoguang , Liang Anjing , Gao Wenjie , Huang Dongsheng 
Published: August 2022

Abstract
Background
Human mesenchymal stem cells (hMSCs) have been proven to have inherent chondrogenic differentiation potential, which appears to be used in cartilage regeneration. Increasing evidence suggests that irisin enhances osteoblast differentiation of MSCs, but little is known about its potential on chondrogenic differentiation.

Methods
In the study, we investigated the effects of irisin on chondrogenic differentiation of hMSCs using a high-density pellet culture system. The cartilage pellets were evaluated by morphology, and the metabolism of cartilage matrix was detected by qPCR, western blot and immunohistochemistry. Next, RNA-seq was performed to explore the underlying mechanism. Furthermore, using the transduction of plasmid, miRNAs mimics and inhibitor, the activation of Rap1/PI3K/AKT axis, the expression level of SIPA1L2, and the functional verification of miR-125b-5p were detected on day 7 of chondrogenic differentiation of hMSCs.

Results
Compared with the controls, we found that irisin treatment could significantly enhance the chondrogenic differentiation of hMSCs, enlarge the induced-cartilage tissue and up-regulate the expression levels of cartilage markers. RNA-seq indicated that irisin activated the Rap1 and PI3K/AKT signaling pathway, and the lower expression level of SIPA1L2 and the higher expression level of miR-125b-5p were found in irisin-treated group. Further, we found that irisin treatment could up-regulate the expression level of miR-125b-5p, targeting SIPA1L2 and consequently activating the Rap1/PI3K/AKT axis on the process of chondrogenic differentiation of hMSCs.

Conclusions
Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.
Transmission and innovation on gold granulation: the application of tin for soldering techniques in ancient China
Authors: Shi Yong , Wen Yadi , Li Xiaojun , Liu Zhaojian , Huang Yumin , He Bei 
Published: August 2022

Abstract
Granulation, an ancient metal processing technique mainly applied to gold, has originated from West Asia, and later appeared at many different archaeological sites across the Eurasia. The distribution of granulated gold ornaments bearing diverse soldering techniques reveal the long-distance human interaction across the Eurasia. This paper presents the scientific analysis of the surface morphology and elemental composition of two granulated gold ornaments from Tushan Tomb No.2 pit in Xuzhou, Jiangsu Province, which approximately dated to the first century CE of Han Dynasty. Multiple non-destructive analytical methods including Ultra-Depth Three-Dimensional Microscope, Energy dispersive X-ray fluorescence spectrometer (XRF) and Scanning electron microscope with energy dispersive X-Ray spectrometer (SEM-EDS) were conducted to obtain analytical data. The result indicates that tin-participated soldering technique has been adopted to accomplish the granulation. Although the usage of tin has been mentioned in a former study as “a secret of Etruscan granulation”, the lack of quantitative analyses leaves this assumption unconvinced. Our findings on Tushan ornaments throw light on this issue by illustrating the regular distribution pattern of the tin content at the joints, which appears to be intentionally added for certain amount. Although tiny in size, the gold granules record the secret of soldering techniques used in China and many other regions across the Eurasia during the ancient time, complementing the study of granulation techniques and reflecting the transmission and innovation along with the technological and cultural contacts.