bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gold nanoparticles loaded chitosan encapsulate 6-mercaptopurine as a novel nanocomposite for chemo-photothermal therapy on breast cancer
Authors: Faid Amna H. , Shouman Samia A. , Badr Yehia A. , Sharaky Marwa , Mostafa Elham M. , Sliem Mahmoud A. 
Published: November 2022

Abstract
Background
As a promising strategy to overcome the therapeutic disadvantages of 6-mercaptopurine (6MP), we proposed the encapsulation of 6MP in chitosan nanoparticles (CNPs) to form the 6MP-CNPs complexes. The encapsulation was followed by the loading of complexes on gold nanoparticles (AuNPs) to generate a novel 6MP-CNPs-AuNPs nanocomposite to facilitate the chemo-photothermal therapeutic effect.

Methods
CNPs were produced based on the ionic gelation method of tripolyphosphate (TPP). Moreover, 6MP-CNPs composite were prepared by the modified ionic gelation method and then loaded on AuNPs which were synthesized according to the standard wet chemical method using trisodium citrate as a reducing and capping agent. The synthesized nanocomposites were characterized by UV–VIS spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscopy. The potential cytotoxicity of the prepared nanocomposites on MCF7 cell line was carried out using Sulphorhodamine-B (SRB) assay.

Results
Optimization of CNPs, 6MP-CNPs, and 6MP-CNPs-AuNPs revealed 130 ± 10, 200 ± 20, and 25 ± 5 nm particle size diameters with narrow size distributions and exhibited high stability with zeta potential 36.9 ± 4.11, 37, and 44.4 mV, respectively. The encapsulation efficiency of 6MP was found to be 57%. The cytotoxicity of 6MP-CNPs and 6MP-CNPs-AuNPs on breast cell line MCF7 was significantly increased and reached IC50 of 9.3 and 8.7 µM, respectively. The co-therapeutic effect of the nanocomposites resulted in an improvement of the therapeutic efficacy compared to the individual effect of chemo- and photothermal therapy. Irradiation of 6MP-CNPs and 6MP-CNPs-AuNPs with a diode laser (DPSS laser, 532 nm) was found to have more inhibition on cell viability with a decrease in IC50 to 5 and 4.4 µM, respectively.

Conclusion
The Chemo-Photothermal co-therapy treatment with novel prepared nanocomposite exhibits maximum therapeutic efficacy and limits the dosage-related side effects of 6MP.

Graphical Abstract
Arabinan saccharification by biogas reactor metagenome-derived arabinosyl hydrolases
Authors: Liu Yajing , Angelov Angel , Feiler Werner , Baudrexl Melanie , Zverlov Vladimir , Liebl Wolfgang , Vanderhaeghen Sonja 
Published: November 2022

AbstractBackgroundPlant cell walls represent the most plentiful renewable organic resource on earth, but due to their heterogeneity, complex structure and partial recalcitrance, their use as biotechnological feedstock is still limited.ResultsIn order to identify efficient enzymes for polysaccharide breakdown, we have carried out functional screening of metagenomic fosmid libraries from biogas fermenter microbial communities grown on sugar beet pulp, an arabinan-rich agricultural residue, or other sources containing microbes that efficiently depolymerize polysaccharides, using CPH (chromogenic polysaccharide hydrogel) or ICB (insoluble chromogenic biomass) labeled polysaccharide substrates. Seventy-one depolymerase-encoding genes were identified from 55 active fosmid clones by using Illumina and Sanger sequencing and dbCAN CAZyme (carbohydrate-active enzyme) annotation. An around 56 kb assembled DNA fragment putatively originating fromXylanivirga thermophilastrain or a close relative was analyzed in detail. It contained 48 ORFs (open reading frames), of which 31 were assigned to sugar metabolism. Interestingly, a large number of genes for enzymes putatively involved in degradation and utilization of arabinose-containing carbohydrates were found. Seven putative arabinosyl hydrolases from this DNA fragment belonging to glycoside hydrolase (GH) families GH51 and GH43 were biochemically characterized, revealing two with endo-arabinanase activity and four with exo-α-l-arabinofuranosidase activity but with complementary cleavage properties. These enzymes were found to act synergistically and can completely hydrolyze SBA (sugar beet arabinan) and DA (debranched arabinan).ConclusionsWe screened 32,776 fosmid clones from several metagenomic libraries with chromogenic lignocellulosic substrates for functional enzymes to advance the understanding about the saccharification of recalcitrant lignocellulose. Seven putativeX. thermophilaarabinosyl hydrolases were characterized for pectic substrate degradation.The arabinosyl hydrolases displayed maximum activity and significant long-term stability around 50 °C. The enzyme cocktails composed in this study fully degraded the arabinan substrates and thus could serve for arabinose production in food and biofuel industries.
Promising therapeutic aspects in human genetic imprinting disorders
Authors: Chao Yunqi , Qin Yifang , Zou Xinyi , Wang Xiangzhi , Hu Chenxi , Xia Fangling , Zou Chaochun 
Published: November 2022

AbstractGenomic imprinting is an epigenetic phenomenon of monoallelic gene expression pattern depending on parental origin. In humans, congenital imprinting disruptions resulting from genetic or epigenetic mechanisms can cause a group of diseases known as genetic imprinting disorders (IDs). Genetic IDs involve several distinct syndromes sharing homologies in terms of genetic etiologies and phenotypic features. However, the molecular pathogenesis of genetic IDs is complex and remains largely uncharacterized, resulting in a lack of effective therapeutic approaches for patients. In this review, we begin with an overview of the genomic and epigenomic molecular basis of human genetic IDs. Notably, we address ethical aspects as a priority of employing emerging techniques for therapeutic applications in human IDs. With a particular focus, we delineate the current field of emerging therapeutics for genetic IDs. We briefly summarize novel symptomatic drugs and highlight the key milestones of new techniques and therapeutic programs as they stand today which can offer highly promising disease-modifying interventions for genetic IDs accompanied by various challenges.
Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer
Authors: Shozu Kanto , Kaneko Syuzo , Shinkai Norio , Dozen Ai , Kosuge Hirofumi , Nakakido Makoto , Machino Hidenori , Takasawa Ken , Asada Ken , Komatsu Masaaki , Tsumoto Kouhei , Ohnuma Shin-Ichi , Hamamoto Ryuji 
Published: November 2022

Abstract
Background
Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a member of the small leucine-rich proteoglycan family of extracellular matrix proteins, which is markedly suppressed in the majority of early-stage epithelial cancers and plays a role in regulating the epithelial–mesenchymal transition by altering cell–cell adhesion. Although PRELP is an important factor in the development and progression of bladder cancer, the mechanism of PRELP gene repression remains unclear.

Results
Here, we show that repression of PRELP mRNA expression in bladder cancer cells is alleviated by HDAC inhibitors (HDACi) through histone acetylation. Using ChIP-qPCR analysis, we found that acetylation of lysine residue 5 of histone H2B in the PRELP gene promoter region is a marker for the de-repression of PRELP expression.

Conclusions
These results suggest a mechanism through which HDACi may partially regulate the function of PRELP to suppress the development and progression of bladder cancer. Some HDACi are already in clinical use, and the findings of this study provide a mechanistic basis for further investigation of HDACi-based therapeutic strategies.
Budget impact analysis of the use of Souvenaid in patients with prodromal Alzheimer’s Disease in Spain
Authors: Mar Javier , Ibarrondo Oliver , Larrañaga Igor , Mar-Barrutia Lorea , Soto-Gordoa Myriam 
Published: November 2022

AbstractIntroductionThe effectiveness, safety, and cost-effectiveness of the use of Souvenaid for Alzheimer’s disease (AD) have been previously evidenced. To complete the economic analysis, there is a need to assess whether society can afford it. The objective of this study was to carry out a budget impact analysis of the use of Souvenaid in Spain under the conditions of the LipiDidiet clinical trial from a societal perspective.MethodsWe built a population model that took into account all the cohorts of individuals with AD, their individual progression, and the potential impact of Souvenaid treatment on their trajectories. Patient progression data were obtained from mixed models. The target population was estimated based on the population forecast for 2020–2035 and the incidence of dementia. Individual progression to dementia measured by the Clinical Dementia Rating-Sum of Boxes was reproduced using mixed models. Besides the costs of treatment and diagnosis, direct costs of medical and non-medical care and indirect costs were included.ResultsThe epidemiological indicators and the distribution of life expectancy by stages validated the model. From the third year (2022), the differences in the cost of dementia offset the incremental cost of diagnosis and treatment. The costs of dependency reached €500 million/year while those of the intervention were limited to €40 million.ConclusionsSouvenaid, with modest effectiveness in delaying dementia associated with AD, achieved a positive economic balance between costs and savings. Its use in the treatment of prodromal AD would imply an initial cost that would be ongoing, but this would be offset by savings in the care system for dependency associated with dementia from the third year. These results were based on adopting a societal perspective taking into account the effect of treatment on the use of health, social, and family resources.
Non-suicidal self-injury and its relation to suicide through acquired capability: investigating this causal mechanism in a mainly late-diagnosed autistic sample
Authors: Moseley Rachel L. , Gregory Nicola J. , Smith Paula , Allison Carrie , Cassidy Sarah , Baron-Cohen Simon 
Published: November 2022

AbstractBackgroundNon-suicidal self-injury (NSSI) has been linked with a higher risk of suicide attempts in autistic and non-autistic people. In the general population, NSSI may confer acquired capability for suicide by eroding one’s fear and avoidance of pain and death. The present study aimed to explore acquired capability as the mediator of increased suicide risk conferred by NSSI in autistic and non-autistic adults.MethodsAutistic and non-autistic adults (n = 314,n = 312) completed an online survey exploring lifetime suicide attempts, experience with NSSI, and acquired capability for suicide. We explored relationships between lifetime incidence of NSSI and lifetime suicide attempts via three facets of acquired capability (pain tolerance, reduced fear of death, and mental rehearsal of suicide). In self-harming participants (224 autistic and 156 non-autistic), we explored whether particular types and features of NSSI might be especially associated with capability and through that with suicide: namely engagement in scratching, cutting, and self-hitting, and engaging in more numerous forms of NSSI.ResultsWhile a higher frequency of NSSI was associated with all three facets of acquired capability, only reduced fear of death and mental rehearsal of suicide mediated an indirect relationship with lifetime suicide attempts. NSSI also directly predicted more numerous suicide attempts. Autistic people tended towards reduced fear of death and mental rehearsal regardless of NSSI status. Among self-harming autistic and non-autistic participants, cutting and an increased number of NSSI behaviours were associated with lifetime suicide attempts directly and indirectly via acquired capability. In both groups, self-hitting was associated with lifetime suicide attempts only via acquired capability.LimitationsOur cross-sectional methodology negates inferences of directionality. While we controlled for age, our samples were poorly matched, with the autistic group two times older on average. The autistic sample, predominantly late-diagnosed, female and highly qualified, were unrepresentative of the whole autistic community.ConclusionsOur data suggest that acquired capability, as measured herein, is an incomplete explanation for the association between NSSI and suicide risk. A broader construct with stable and transient facets may offer greater explanatory power, but it is probable that other variables explain or provide additional means through which this association arises.
Maternal vitamin D during pregnancy and offspring autism and autism-associated traits: a prospective cohort study
Authors: Madley-Dowd Paul , Dardani Christina , Wootton Robyn E. , Dack Kyle , Palmer Tom , Thurston Rupert , Havdahl Alexandra , Golding Jean , Lawlor Deborah , Rai Dheeraj 
Published: November 2022

AbstractBackgroundThere has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive.MethodsWe used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference.ResultsNo strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis.LimitationsOur study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data.ConclusionsThe present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.
The use of artificial intelligence and machine learning monitoring to safely administer a fluid-restrictive goal-directed treatment protocol to minimize the risk of transfusion during major spine surgery of a Jehovah’s Witness: a case report
Authors: Denn Sara , Schneck Emmanuel , Jablawi Fidaa , Bender Michael , Schmidt Götz , Habicher Marit , Uhl Eberhard , Sander Michael 
Published: November 2022

Abstract
Background
The Hypotension Prediction Index (HPI) displays an innovative monitoring tool which predicts intraoperative hypotension before its onset.

Case presentation
We report the case of an 84-year-old Caucasian woman undergoing major spinal surgery with no possibility for the transfer of blood products given her status as a Jehovah’s Witness. The hemodynamic treatment algorithm we employed was based on HPI and resulted in a high degree of hemodynamic stability during the surgical procedure. Further, the patient was not at risk for either hypo- or hypervolemia, conditions which might have caused dilution anemia. By using HPI as a tool for patient blood management, it was possible to reduce the incidence of intraoperative hypotension to a minimum.

Conclusions
In sum, this HPI-based treatment algorithm represents a useful application for the treatment of complex anesthesia and perioperative patient blood management. It is a simple but powerful extension of standard monitoring for the prevention of intraoperative hypotension.
Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation
Authors: Wang Kuo-Chuan , Yang Ling-Yu , Lee Jing-Er , Wu Vicent , Chen Te-Fu , Hsieh Sung-Tsang , Kuo Meng-Fai 
Published: November 2022

AbstractObjectiveEndothelial progenitor cells (EPCs) contribute to the recovery of neurological function after ischemic stroke. Indirect revascularization has exhibited promising effects in the treatment of cerebral ischemia related to moyamoya disease and intracranial atherosclerotic disease. The role of EPCs in augmenting the revascularization effect is not clear. In this study, we investigated the therapeutic effects of indirect revascularization combined with EPC transplantation in rats with chronic cerebral ischemia.MethodsChronic cerebral ischemia was induced by bilateral internal carotid artery ligation (BICAL) in rats, and indirect revascularization by encephalo-myo-synangiosis (EMS) was performed 1 week later. During the EMS procedure, intramuscular injection of EPCs and the addition of stromal cell-derived factor 1 (SDF-1), and AMD3100, an SDF-1 inhibitor, were undertaken, respectively, to investigate their effects on indirect revascularization. Two weeks later, the cortical microcirculation, neuronal damage, and functional outcome were evaluated according to the microvasculature density and partial pressure of brain tissue oxygen (PbtO2), regional blood flow, expression of phosphorylated Tau (pTau), TUNEL staining and the rotarod performance test, respectively.ResultsThe cortical microcirculation, according to PbtO2and regional blood flow, was impaired 3 weeks after BICAL. These impairments were improved by the EMS procedure. The regional blood flow was further increased by the addition of SDF-1 and decreased by the addition of AMD3100. Intramuscular injection of EPCs further increased the regional blood flow as compared with the EMS group. The rotarod test results showed that the functional outcome was best in the EMS combined with EPC injection group. Western blot analysis showed that the EMS combined with EPC treatment group had significantly decreased expressions of phosphorylated Tau and phosphorylated glycogen synthase kinase 3 beta (Y216 of GSK-3β). pTau and TUNEL-positive cells were markedly increased at 3 weeks after BICAL induction. Furthermore, the groups treated with EMS combined with SDF-1 or EPCs exhibited marked decreases in the pTau expression and TUNEL-positive cells, whereas AMD3100 treatment increased TUNEL-positive cells.ConclusionThe results of this study suggested that indirect revascularization ameliorated the cerebral ischemic changes. EPCs played a key role in augmenting the effect of indirect revascularization in the treatment of chronic cerebral ischemia.
Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model
Authors: Shi Ying , Yang Xiaoguang , Wang Shuyue , Wu Yulun , Zheng Lihua , Tang Yufang , Gao Yanhang , Niu Junqi 
Published: November 2022

Abstract
Background and aims
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are increasingly being studied in clinical trials of end-stage liver disease because of their good tissue repair and anti-inflammatory effects. hUC-MSC exosomes are vesicles with spherical structures secreted by cells that produce them. The diameter of exosomes is much smaller than that of hUC-MSCs, suggesting that exosomes might be a novel and safer therapeutic product of mesenchymal stem cells. As exosomes have been suggested to have biochemical functions similar to those of hUC-MSCs, this study investigated the efficiency of hUC-MSC-derived exosomes in protecting against nonalcoholic steatohepatitis using an MCD-induced mouse model.

Methods
Human umbilical cord mesenchymal stem cell-derived exosomes were extracted and purified. The effect of these exosomes on disease progression in an MCD-induced nonalcoholic steatohepatitis mouse model was investigated.

Results
The results showed that UC-MSC exosomes intravenously transplanted into mice with MCD-induced NASH improved MCD-induced body weight loss and liver damage in a mouse model. Additionally, the inflammatory cytokines in liver tissue were reduced, which may be caused by exosome-induced macrophage anti-inflammatory phenotypes both in vitro and in vivo. In addition, UC-MSC exosomes reversed PPARα level in ox-LDL-treated hepatocytes in vitro and in NASH mouse liver, which had been downregulated.

Conclusions
UC-MSC exosomes alleviate MCD-induced NASH in mice by regulating the anti-inflammatory phenotype of macrophages and by reversing PPARα protein expression in liver cells, which holds great potential in NASH therapy.
Establishment of a human pluripotent stem cell-derived MKX-td Tomato reporter system
Authors: Fujisawa Yuki , Ming Lu , Yamada Daisuke , Takao Tomoka , Takarada Takeshi 
Published: November 2022

AbstractTendon regeneration is difficult because detailed knowledge about tendon progenitor cells (TPCs), which produce tenocytes to repair tendon tissue, has not been revealed. Mohawk homeobox (MKX) is a marker of TPCs or tenocytes, but a human pluripotent stem cell (hPSC)-based reporter system that visualizes MKX+ cells has not been developed. Here, we established an hPSC-derived MKX-tdTomato reporter cell line and tested the induction ratio of MKX-tdTomato+ cells using our stepwise/xeno-free differentiation protocol. MKX-tdTomato+ cells were generated with high efficiency and expressed tendon-specific markers, including MKX, SCX, TNMD, and COL1A1. Our MKX-tdTomato hPSC line would be a useful tool for studying the development or regeneration of tendon tissue.
Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways
Authors: Ahmadi Armin , Mazloomnejad Radman , Kasravi Mohammadreza , Gholamine Babak , Bahrami Soheyl , Sarzaeem Mohammad Mahdi , Niknejad Hassan 
Published: November 2022

AbstractBone-related diseases are major contributors to morbidity and mortality in elderly people and the current treatments result in insufficient healing and several complications. One of the promising areas of research for healing bone fractures and skeletal defects is regenerative medicine using stem cells. Differentiating stem cells using agents that shift cell development towards the preferred lineage requires activation of certain intracellular signaling pathways, many of which are known to induce osteogenesis during embryological stages. Imitating embryological bone formation through activation of these signaling pathways has been the focus of many osteogenic studies. Activation of osteogenic signaling can be done by using small molecules. Several of these agents, e.g., statins, metformin, adenosine, and dexamethasone have other clinical uses but have also shown osteogenic capacities. On the other hand, some other molecules such as T63 and tetrahydroquinolines are not as well recognized in the clinic. Osteogenic small molecules exert their effects through the activation of signaling pathways known to be related to osteogenesis. These pathways include more well-known pathways including BMP/Smad, Wnt, and Hedgehog as well as ancillary pathways including estrogen signaling and neuropeptide signaling. In this paper, we review the recent data on small molecule-mediated osteogenic differentiation, possible adjunctive agents with these molecules, and the signaling pathways through which each small molecule exerts its effects.

Graphical Abstract