bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial repair of bioengineered cardiac patches with decellularized placental scaffold and human-induced pluripotent stem cells in a rat model of myocardial infarction
Authors: Jiang Yu , Sun Si-Jia , Zhen Zhe , Wei Rui , Zhang Nannan , Liao Song-Yan , Tse Hung-Fat 
Published: January 2021

Abstract
Background
The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown.

Objective
We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair.

Methods and results
A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor-1, basic fibroblast growth factor, angiogenin, and angiopoietin-2. In vitro optical mapping showed that the BCP exhibited organized mechanical contraction and synchronized electrical propagation. RNA sequencing showed that DP enhanced the maturation of hiPSC-CMs compared with the monolayer of cultured hiPSC-CMs. At 4 weeks follow-up, the BCP significantly improved left ventricular (LV) function, as determined by LV ejection fraction, fractional shortening, + dP/dtmax, and end-systolic pressure-volume relationship, compared with the MI, MI + DP, and MI + CM groups. Moreover, histological examination revealed that engraftment of the BCP at the infarct zone decreased infarct size and increased cell retention and neovascularization compared with the MI, MI + DP, and MI + CM groups.

Conclusions
Our results demonstrate that a DP scaffold contains multiple growth and angiogenic factors that enhance the maturation and survival of seeded hiPSC-CMs. Transplantation of a BCP is superior to DP or hiPSC-CMs alone in reducing infarct size and improving cell retention and neovascularization, thus providing a novel therapy for myocardial repair following MI.
The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C) priming through promoting the expression of indoleamine 2,3-dioxygenase
Authors: Lim Ji-Young , Kim Byung-Su , Ryu Da-Bin , Kim Tae Woo , Park Gyeongsin , Min Chang-Ki 
Published: January 2021

Abstract
Background
Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner.

Methods
To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9.

Results
Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC.

Conclusions
The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.
Efficacy of stem cells therapy for Crohn’s fistula: a meta-analysis and systematic review
Authors: Cao Yantian , Su Qi , Zhang Bangjie , Shen Fangfang , Li Shaoshan 
Published: January 2021

Abstract
Background
Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn’s fistula.

Methods
Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn’s fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0.

Results
Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn’s fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 107 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14).

Conclusions
Our study has highlighted that stem cells was a promising method in the treatment of Crohn’s fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.
GDF-5 promotes epidermal stem cells proliferation via Foxg1-cyclin D1 signaling
Authors: Zhao Xiaohong , Bian Ruyu , Wang Fan , Wang Ying , Li Xue , Guo Yicheng , Zhang Xiaorong , Luo Gaoxing , Zhan Rixing 
Published: January 2021

AbstractObjectiveEpidermal stem cells (EpSCs) can self-renew, which are responsible for the long-term maintenance of the skin, and it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. GDF-5, also known as BMP-14, is a member of the BMP family and can be used as a self-renewal supporter. Here, we studied the effects of GDF-5 on mouse EpSCs proliferation mechanism in wound healing.MethodsFirstly, the effects of GDF-5 on EpSCs proliferation was tested by using CCK8 reagent and PCNA expression was analyzed by Western blotting. Secondly, we screened genes that promote EpSCs proliferation in the FOX and cyclin family by qPCR, and then the protein expression level of the selected genes was further analyzed by Western blotting. Thirdly, siRNA plasmids and pAdEasy adenovirus were transfected or infected, respectively, into mouse EpSCs to detect the effect of target genes on GDF-5-induced cell proliferation. Furthermore, we injected GDF-5 to a deep partial thickness burn mouse model for finding out whether EpSCs proliferation can be detected by immunohistochemical. Finally, the relevant target genes were analyzed by qPCR, immunoblotting, and dual-luciferase reporter gene detection.ResultsWe discovered that 100 ng/ml recombinant mouse GDF-5 was the optimal concentration for promoting mouse EpSCs proliferation. Through preliminary screened by qPCR, we found that Foxg1 and cyclin D1 could be the downstream molecules of GDF-5, and the results were confirmed by Western blotting. And the effect of GDF-5 on mouse EpSCs proliferation was adjusted by Foxg1/cyclin D1 in vitro and in vivo. Besides, GDF-5-induced transcription of cyclin D1 was regulated by Foxg1-mediated cyclin D1 promoter activity.ConclusionThis paper showed that GDF-5 promotes mouse EpSCs proliferation via Foxg1-cyclin D1 signal pathway. It is suggested that GDF-5 may be a new approach to make EpSCs proliferation which can be used in wound healing.
Sex-dependent differences in the secretome of human endothelial cells
Authors: Cattaneo Maria Grazia , Banfi Cristina , Brioschi Maura , Lattuada Donatella , Vicentini Lucia M. 
Published: January 2021

Abstract
Background
Cellular sex has rarely been considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and “omics” approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.

Methods
We performed proteomic and Gene Ontology (GO) analyses of the secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and Western blot techniques and efferocytosis through the ability of the macrophage cell line RAW 264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR.

Results
Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison with female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggested that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seemed to be independent on PTX3 expression.

Conclusions
Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke
Authors: Manwani Bharti , Fall Pamela , Zhu Liang , O’Reilly Meaghan Roy , Conway Sarah , Staff Ilene , McCullough Louise D. 
Published: January 2021

Abstract
Background
Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.

Methods
Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17β-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression.

Results
We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04).

Conclusions
Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
New insights into the taxonomy and evolution of Jurassic planktonic foraminifera
Authors: Gradstein Felix , Waskowska Anna 
Published: January 2021

AbstractGlobuligerina glinskikhae nov. sp. Gradstein & Waskowska and Globuligerina waskowskae nov. sp. Gradstein are new species of Jurassic planktonic foraminifera from the Middle Jurassic of Dagestan and Poland. G. glinskikhae nov. sp. with its remarkable ‘protoglobigerine’ test may be an early evolutionary offshoot of Globuligerina oxfordiana (Grigelis). It may be an index taxon for upper Bajocian through Bathonian strata in Eastern Europe and Southwest Asia, and might be recognizable also in thin sections. We consider G. waskowskae nov. sp. to be a possible forerunner of Conoglobigerina helvetojurassica (Haeusler), the first planktonic foraminiferal species with a reticulate wall texture. Currently, is only known from Poland. In some localities, specimens of G. oxfordiana and of G. glinskikhae nov. sp. posses an additional apertural opening, often lacking a rim; its function is enigmatic. The postulated lineage from Jurassic Globuligerina balakhmatovae (Morozova) to Cretaceous Clavihedbergella eocretacea Neagu is refined with the description of Petaloglobigerina simmonsi nov. gen., nov. sp. Gradstein from the Kimmeridgian of Portugal. The evolutionary transition from G. balakhmatovae to P. simmonsi occurs by means of the ontogenic development of a petaloid test, with a pronounced flattening of the whorl with ovate chambers, the last ones often offset and twisted. Jurassic planktonic foraminifera, now known to consist of three genera and 12+ species underwent long periods of stasis, interrupted by late Bajocian, mid-Oxfordian and early Kimmeridgian evolution. The three ‘stasis and root’ taxa G. oxfordiana, G. bathoniana and G. balakhmatovae are geographically widespread in lower to mid palaeo-latitudes, and stratigraphically long ranging within the Middle and Late Jurassic. Modern digital microscopes, with co-axial and side LED lighting and excellent image stacking software are important tools in the study of Jurassic planktonic foraminifera, and fast and cost-effective communication tools in modern micropalaeontology.ZooBank LSID: urn:lsid:zoobank.org:pub:A2927FFD-8C2B-4712-A06F-EE9D45ACA481.
Biological properties and roles of a Trichinella spiralis inorganic pyrophosphatase in molting and developmental process of intestinal larval stages
Authors: Hu Chen Xi , Zeng Jie , Hao Hui Nan , Xu Yang Xiu Yue , Liu Fang , Liu Ruo Dan , Long Shao Rong , Wang Zhong Quan , Cui Jing 
Published: January 2021

AbstractInorganic pyrophosphatase (PPase) participates in energy cycle and plays a vital role in hydrolysis of inorganic pyrophosphate (PPi) into inorganic phosphate (Pi). The aim of this study was to investigate the biological properties of a Trichinella spiralis PPase (TsPPase) and its role in larval molting and developmental process. The predicted TsPPase consisted of 367 amino acids with a molecular mass of 41.48 kDa and a pI of 5.76. Amino acid sequence alignment and phylogenetic analysis showed that the TsPPase gene encodes a functional family I soluble PPase with the same characteristics as prokaryotic, plant and animal/fungal soluble PPase. The rTsPPase was expressed and purified, it has the activity to catalyze the hydrolysis of PPi to Pi, and the activity was dependent on Mg2+, pH and temperature. The enzymatic activity of rTsPPase was significantly inhibited after its metal binding sites mutation. TsPPase was transcribed and expressed in all T. spiralis phases, especially in muscle larvae (ML) and intestinal infective larvae (IIL). Immunofluorescence assay (IFA) revealed that TsPPase was mainly located in cuticle and stichosome. When the ML and IIL were treated with TsPPase-specific siRNA-279, TsPPase expression and enzymatic activity were obviously reduced, the larval molting and development were also impeded. Intestinal IIL as well as AW burden, IIL molting rates from mice infected with siRNA-treated ML were obviously suppressed. The results indicated that rTsPPase possesses the enzymatic activity of native inorganic pyrophosphatase, and TsPPase plays an important role in development and molting process of intestinal T. spiralis larval stages.
Microbial keratinase and the bio-economy: a three-decade meta-analysis of research exploit
Authors: Nnolim Nonso E. , Nwodo Uchechukwu U. 
Published: January 2021

AbstractMicrobial keratinase research has been on an upward trajectory due to the robustness and efficiency of the enzyme toward various green technological processes that promote economic development and environmental sustainability. A compendium of research progression and advancement within the domain was achieved through a bibliometric study to understand the trend of research productivity, scientific impacts, authors' involvement, collaboration networks, and the advancement of knowledge gaps for future research endeavours. A three-decade (1990 to 2019) scholarly published articles were retrieved from the web of science database using a combination of terms "keratinas* or keratinolytic proteas* or keratinolytic enzym*", and subsequently analyzed for bibliometric indicators. A collection of 330 peer-reviewed, research, articles were retrieved for the survey period and authored by 1063 researchers with collaboration index of 3.27. Research productivity was most in 2013 with total research output of 28 articles. The top three authors' keywords were keratinase, keratin and protease with a respective frequency of 188, 26 and 22. India, China and Brazil ranked top in terms of keratinase research outputs and total citation with respective article productivity (total citations) of 85 (1533), 57 (826), and 36 (764). This study evaluated the trend of keratinase research outputs, scientific impact, collaboration networks and biotechnology innovations. It has the potentials to influence positively decision making on future research direction, collaborations and development of products for the bio-economy.
Acceleration of emergence of E. coli antibiotic resistance in a simulated sublethal concentration of copper and tetracycline co-contaminated environment
Authors: Li Jinmei , Phulpoto Irfan Ali , Zhang Guilong , Yu Zhisheng 
Published: January 2021

AbstractAn environment co-contaminated with metals and antibiotics ultimately exposes bacteria to these metals and antibiotics simultaneously. This study aims to explore the efficacy of sublethal concentrations of copper ions contaminated with tetracycline regarding antibiotic resistance in a sensitive strain of E. coli K12. The study proved that a copper ions and tetracycline co-contaminated environment could considerably enhance the mutation frequencies of chloramphenicol and polymyxin B resistance in antibiotic susceptible E. coli; however, the equivalent copper ions and tetracycline alone showed weaker effects. Results also demonstrated that an environment co-contaminated with relatively high sublethal concentrations of copper ion and tetracycline co-contaminated environment could induce much higher antibiotic resistance than the low sublethal and control groups. Whole-genome characterization results indicated that variability existed within the genotype and phenotype involved in antibiotic resistance. Additionally, the evolved resistant strains displayed hereditary resistance after 5 round culture cycles in LB broth over 5 days. Results implied that co-contamination with metals and antibiotics environment could strengthen resistance and contribute to the induction and dissemination of antibiotic resistance in metal and antibiotic co-contaminated environment.
Selonsertib, a potential drug for liver failure therapy by rescuing the mitochondrial dysfunction of macrophage via ASK1–JNK–DRP1 pathway
Authors: Lou Guohua , Li Aichun , Cen Yelei , Yang Qin , Zhang Tianbo , Qi Jinjin , Chen Zhi , Liu Yanning 
Published: January 2021

Abstract
Background
Acute liver failure (ALF) is associated with a high mortality rate, and there are still no effective treatments except liver transplantation and artificial liver therapies. This study aimed to determine the effects, therapeutic window and mechanisms of selonsertib, a selective inhibitor of ASK1, for ALF therapy.

Results
Lipopolysaccharide and d-galactosamine (LPS/GalN) were used to simulate ALF. We found that selonsertib pretreatment significantly ameliorated ALF, as determined by reduced hepatic necrosis and serum alanine aminotransferase, aspartate aminotransferase and inflammatory cytokine levels. However, selonsertib is only effective early after LPS/GalN administration, and the limited therapeutic window is related to the activation and mitochondrial translocation of JNK and DRP1. Further experiments revealed that selonsertib could alleviate LPS-induced mitochondrial damage in macrophages by evaluating the mitochondrial membrane potential and mitochondrial permeability transition pore opening in macrophages. Selonsertib also suppressed the release of inflammatory cytokines from macrophages by reducing DRP1-mediated mitochondrial dysfunction, which was confirmed by using mdivi, a specific DRP1 inhibitor.

Conclusions
Selonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and may have therapeutic potential for early ALF patients.