bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polysaccharides from Ganoderma Sinense - rice bran fermentation products and their anti-tumor activities on non-small-cell lung cancer
Authors: Han Wei , Chen Hongjuan , Zhou Lin , Zou Haijie , Luo Xiaohong , Sun Bo , Zhuang Xuhui 
Published: June 2021

Abstract
Background
Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo.

Method
Polysaccharides (GSRBPs) were extracted from Ganoderma sinense – full-fat rice bran (GS-FRB) and Ganoderma sinense – defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice.

Result
All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1.

Conclusion
GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer.
Mechanisms of impact and experiences of a person-centred transition programme for adolescents with CHD: the Stepstones project
Authors: Saarijärvi Markus , Wallin Lars , Moons Philip , Gyllensten Hanna , Bratt Ewa-Lena 
Published: June 2021

Abstract
Background
During the past decade there has been some evaluation of transition programmes for adolescents with chronic conditions. However, this has rarely involved process evaluations focusing on mechanisms leading to outcomes, thus hampering implementation of these complex interventions. Our aim was to (I) describe adolescents’ and parents’ experiences of participating in a person-centred transition programme aiming to empower them in transition to adulthood and (II) explore the mechanisms of impact.

Methods
A qualitative process evaluation was performed, embedded in a randomized controlled trial evaluating the effectiveness of a transition programme for adolescents with congenital heart disease in Sweden. A purposive sample of 14 adolescents and 12 parents randomized to the intervention group were interviewed after participation in the programme. Data were analysed deductively and inductively in NVivo v12.

Results
Experiences of participation in the transition programme were generally positive. Meeting a transition coordinator trained in person-centred care and adolescent health and embarking on an educational process based on the adolescents’ prerequisites in combination with peer support were considered key change mechanisms. However, support to parents were not sufficient for some participants, resulting in ambivalence about changing roles and the unmet needs of parents who required additional support.

Conclusions
Participants experienced increased empowerment in several dimensions of this construct, thus demonstrating that the transition programme was largely implemented as intended and the evidence-based behaviour-change techniques used proved effective in reaching the outcome. These findings can inform future implementation of transition programmes and illuminate challenges associated with delivering a complex intervention for adolescents with chronic conditions.
A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection
Authors: Huang Shenglan , Li Dan , Zhuang LingLing , Sun Liying , Wu Jianbing 
Published: June 2021

Abstract
Background
Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery.

Methods
The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model.

Results
In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59–0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54–0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68–0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (< 1%).

Conclusions
This meta-analysis demonstrated that adjuvant sorafenib therapy after resection in patients with hepatocellular carcinoma could prolong overall survival and recurrence-free survival and reduce recurrence rates without intolerable side effects. However, more evidence is needed before reaching a definitive conclusion.
Val50Met hereditary transthyretin amyloidosis: not just a medical problem, but a psychosocial burden
Authors: González-Moreno Juan , Gaya-Barroso Aina , Losada-López Inés , Rodríguez Adrián , Bosch-Rovira Teresa , Ripoll-Vera Tomás , Usón Mercedes , Figuerola Antoni , Descals Cristina , Montalà Carles , Ferrer-Nadal María Asunción , Cisneros-Barroso Eugenia 
Published: June 2021

Abstract
Background
Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a heterogeneous disease with a clinical presentation that varies according to geographical area and TTR mutation. The symptoms of Val50Met-ATTRv are mainly neuropathic and progress to complete disability and death in most untreated patients within 10 to 15 years of diagnosis. The neurological effects may also be accompanied by gastrointestinal impairment, cardiomyopathy, nephropathy and/or ocular deposition. The disease is thus associated with a high degree of patient disability. Accordingly, we aimed to describe the psychosocial burden associated with ATTRv in a group of patients, asymptomatic Val50Met carriers, relatives and caregivers in the endemic focus of the disease in Majorca via a survey addressing various aspects related to psychosocial burden. We performed a an observational, descriptive, cross-sectional and multicentre study in order to analyze the prevalence of self-reported impact of ATTRv disease upon their daily life. In addition to the self-knowledge, fear and burden related to the disease. The survey was disseminated during the regular follow up at the outpatient clinic of the Hospital Universitario Son Llàtzer and during the meetings organized by the Andrade’s Disease patients’ advocacy group from the Balearic Islands. These meetings were attended also by subjects followed up by the Hospital Universitario Son Espases and their caregivers and relatives. Survey was self-administrated. No intervention was done by the investigators. 85 subjects completed the survey: 61 carrying the TTR-V50M variant and 24 caregivers or relatives.

Results
Our study revealed that, although most of the population studied had had prior contact with ATTRv through affected relatives, there was still a lack of information regarding disease diagnosis. Fear of the genetic test result and psychological issues were common in our population. Moreover, the disease had a stronger impact on the daily life of our patients than that of our asymptomatic carriers. Autonomic symptoms were the main source of burden for relatives and caregivers.

Conclusion
Our survey results show high psychosocial burden associated with Val50Met-ATTRv in our area.
Kinetic modeling of phosphorylase-catalyzed iterative β-1,4-glycosylation for degree of polymerization-controlled synthesis of soluble cello-oligosaccharides
Authors: Klimacek Mario , Zhong Chao , Nidetzky Bernd 
Published: June 2021

Abstract
Background
Cellodextrin phosphorylase (CdP; EC 2.4.1.49) catalyzes the iterative β-1,4-glycosylation of cellobiose using α-d-glucose 1-phosphate as the donor substrate. Cello-oligosaccharides (COS) with a degree of polymerization (DP) of up to 6 are soluble while those of larger DP self-assemble into solid cellulose material. The soluble COS have attracted considerable attention for their use as dietary fibers that offer a selective prebiotic function. An efficient synthesis of soluble COS requires good control over the DP of the products formed. A mathematical model of the iterative enzymatic glycosylation would be important to facilitate target-oriented process development.

Results
A detailed time-course analysis of the formation of COS products from cellobiose (25 mM, 50 mM) and α-d-glucose 1-phosphate (10–100 mM) was performed using the CdP from Clostridium cellulosi. A mechanism-based, Michaelis–Menten type mathematical model was developed to describe the kinetics of the iterative enzymatic glycosylation of cellobiose. The mechanistic model was combined with an empirical description of the DP-dependent self-assembly of the COS into insoluble cellulose. The hybrid model thus obtained was used for kinetic parameter determination from time-course fits performed with constraints derived from initial rate data. The fitted hybrid model provided excellent description of the experimental dynamics of the COS in the DP range 3–6 and also accounted for the insoluble product formation. The hybrid model was suitable to disentangle the complex relationship between the process conditions used (i.e., substrate concentration, donor/acceptor ratio, reaction time) and the reaction output obtained (i.e., yield and composition of soluble COS). Model application to a window-of-operation analysis for the synthesis of soluble COS was demonstrated on the example of a COS mixture enriched in DP 4.

Conclusions
The hybrid model of CdP-catalyzed iterative glycosylation is an important engineering tool to study and optimize the biocatalytic synthesis of soluble COS. The kinetic modeling approach used here can be of a general interest to be applied to other iteratively catalyzed enzymatic reactions of synthetic importance.
Stem cells in the treatment of renal fibrosis: a review of preclinical and clinical studies of renal fibrosis pathogenesis
Authors: Liu Yiping , Su Yan-Yan , Yang Qian , Zhou Tianbiao 
Published: June 2021

AbstractRenal fibrosis commonly leads to glomerulosclerosis and renal interstitial fibrosis and the main pathological basis involves tubular atrophy and the abnormal increase and excessive deposition of extracellular matrix (ECM). Renal fibrosis can progress to chronic kidney disease. Stem cells have multilineage differentiation potential under appropriate conditions and are easy to obtain. At present, there have been some studies showing that stem cells can alleviate the accumulation of ECM and renal fibrosis. However, the sources of stem cells and the types of renal fibrosis or renal fibrosis models used in these studies have differed. In this review, we summarize the pathogenesis (including signaling pathways) of renal fibrosis, and the effect of stem cell therapy on renal fibrosis as described in preclinical and clinical studies. We found that stem cells from various sources have certain effects on improving renal function and alleviating renal fibrosis. However, additional clinical studies should be conducted to confirm this conclusion in the future.
Intra-iliac bone marrow injection as a novel alternative to intra-tibial inoculation in rat model
Authors: Khattab Marwa S. , AbuBakr Huda O. , El Iraqi Kassem G. , AbdElKader Naglaa A. , Kamel Mervat M. , Salem Khaled Hamed , Steitz Julia , Afify Mamdouh 
Published: June 2021

AbstractBackgroundIntra-bone marrow injection (IBMI) in rats is adopted in many studies for stem cell and hematopoietic cell transplantation. IBMI in the tibia or the femur results in severe distress to the animal. Therefore, this study aims to evaluate intra-iliac injections as an alternative approach for IBMI.MethodsTwenty-seven Sprague Dawley rats were assigned into 3 groups, 9 rats each, for 4 weeks. The control group rats were not injected. Tibia group rats were injected intra-tibial and the iliac group rats were injected intra-iliac with saline. Behavioral, radiological, histopathological, and stress evaluation was performed. Total bilirubin, cortisol, and insulin-like growth factor-1 (IGF1) were measured.ResultsBehavioral measurements revealed deviation compared to control, in both injected groups, on the 1st and 2nd week. By the 3rd week, it was equivalent to control in the iliac group only. Bilirubin and cortisol levels were increased by intra-tibial injection compared to intra-iliac injection. The IGF-1 gene expression increased compared to control at 1st and 2nd weeks in intra-iliac injection and decreased by intra-tibial injection at 2nd week. The thickness of the iliac crest was not different from the control group, whereas there were significant differences between the control and tibia groups. Healing of the iliac crest was faster compared to the tibia. In the 3rd week, the tibia showed fibrosis at the site of injection whereas the iliac crest showed complete bone reconstruction.ConclusionIntra-iliac injections exert less distress on animals, and by 3 weeks, they regained their normal activity in comparison to intra-tibial injections.
One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study
Authors: Lu Jing , Shen Shan-mei , Ling Qing , Wang Bin , Li Li-rong , Zhang Wei , Qu Duo-duo , Bi Yan , Zhu Da-long 
Published: June 2021

Abstract
Background
The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D.

Methods
This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses.

Results
After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed.

Conclusion
One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone.

Trial registration
ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/
Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway
Authors: Lin Zhixiao , Zhao Congying , Lei Zhanjun , Zhang Yuheng , Huang Rong , Lin Bin , Dong Yuchen , Zhang Hao , Li Jinqing , Li Xueyong 
Published: June 2021

Abstract
Background
Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application.

Methods
To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied.

Results
In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models.

Conclusions
Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.
The effect of reproductive hormones on women’s daily smoking across the menstrual cycle
Authors: Ethier Ashley R. , McKinney Ty L. , Tottenham Laurie Sykes , Gordon Jennifer L. 
Published: June 2021

Abstract
Background
Women attempt to quit smoking less often than men and are less likely to maintain abstinence. Reproductive hormones have been postulated as a reason for this sex difference, though this remains to be clarified. Research suggests that estradiol and progesterone may influence nicotine addiction, though various methodologies have led to inconsistent findings. The current study aimed to directly examine the effect of reproductive hormones on women’s smoking behavior.

Methods
Over the course of one menstrual cycle, twenty-one female smokers recorded the number of cigarettes smoked in a day, as well as their perceived need for and enjoyment of cigarettes smoked. Additionally, they provided 12 urine samples for the measurement of the urinary metabolites of estradiol (estrone-3-glucuronide, E1G) and progesterone (pregnanediol glucuronide, PdG). Multilevel modeling was used to examine the effects of hormone levels as well as hormone change on smoking outcomes.

Results
When PdG levels were low, they were inversely associated with daily cigarettes smoked. Furthermore, E1G level was negatively associated with both self-reported need for and enjoyment of cigarettes smoked but not the number of cigarettes smoked. Examining the effect of hormonal change on smoking outcomes revealed a significant interaction between change in PdG and E1G on number of cigarettes smoked such that only a simultaneous drop or increase in both hormones was associated with a greater number of cigarettes. Hormonal change effects on need for and enjoyment of cigarettes were not significant.

Conclusions
The present study suggests that (1) elevated progesterone levels lessen the propensity to smoke in women, (2) estrogen levels influence women’s subjective experience of smoking, and (3) simultaneous drops or increases in these hormones are associated with increased smoking.