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Graphene-based materials represent advanced platforms for tissue engineering and implantable medical devices. From a clinical standpoint, it is essential that these materials are produced using non-toxic and non-hazardous methods, and have predictable properties and reliable performance under variable physiological conditions; especially when used with a cellular component. Here we describe such a biomaterial, namely smart graphene-cellulose (G-C) paper, and its suitability for traditional planar two-dimensional (2D) or three-dimensional (3D) human cell support, verified by adipose-derived stem cell (ADSC) culture and osteogenic differentiation. G-C paper is prepared using commercially available cellulose tissue paper as a substrate that is coated by immersion-deposition with graphene oxide (GO) followed by reduction to reduced graphene oxide (RGO) without the use of toxic organic solvents. The fabrication process is amenable to large scale production and the resultant papers have low electrical resistivity (up to ∼300 Ω/sq). Importantly, G-C papers can be configured to 3D constructs by lamination with alginate and further modified by folding and rolling for 3D "origami-inspired" cell-laden structures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: We investigated the applicability of single layer paper-based scaffolds for the three-dimensional (3D) growth and osteogenic differentiation of equine adipose-derived stem cells (EADSC), with comparison against conventional two-dimensional (2D) culture on polystyrene tissue culture vessels., Results: Viable culture of EADSC was achieved using paper-based scaffolds, with EADSC grown and differentiated in 3D culture retaining high cell viability (>94 %), similarly to EADSC in 2D culture. Osteogenic differentiation of EADSC was significantly enhanced in 3D culture, with Alizarin Red S staining and quantification demonstrating increased mineralisation (p < 0.0001), and an associated increase in expression of the osteogenic-specific markers alkaline phosphatase (p < 0.0001), osteopontin (p < 0.0001), and runx2 (p < 0.01). Furthermore, scanning electron microscopy revealed a spherical morphology of EADSC in 3D culture, compared to a flat morphology of EADSC in 2D culture., Conclusions: Single layer paper-based scaffolds provide an enhanced environment for the in vitro 3D growth and osteogenic differentiation of EADSC, with high cell viability, and a spherical morphology.

This article is a tribute to Lewis Wolpert and his ideas on the occasion of the recent 50th anniversary of the publication of his article 'Positional Information and the Spatial Pattern of Differentiation'. This tribute relates to another one of his ideas: his early 'Progress Zone' timing model for limb development. Recent evidence is reviewed showing a mechanism sharing features with this model patterning the main body axis in early vertebrate development. This tribute celebrates the golden era of Developmental Biology.

The aim of this study was to prepare cellulose nanowhiskers (CNWs) from wastepaper powder (WPP), as an environmentally friendly approach for obtaining the source material, which is a highly available and low-cost precursor for cellulose nanomaterial processing. Acid hydrolysis and calcification treatments were employed for extraction of CNWs and preparation of novel phospho-calcified cellulose nanowhiskers (PCCNWs). CNWs and PCCNWs were analyzed through optical microscopy (OM), scanning electron microscopy (SEM), Fourier-transformed infrared spectra (FTIR) and X-ray diffraction analysis (XRD). Cell behaviors in the presence of CNWs and PCCNWs were studied by MTT assay and live-dead staining. Finally, the effect of these particles on osteogenic differentiation of stem cells was evaluated based on alkaline phosphatase activity (ALP), calcium mineralization as well as von Kossa and alizarin red staining. Based on the results, PCCNWs had a positive effect on osteogenic differentiation of human mesenchymal stem cells (hMSCs) and can be used for developing new approaches for bone tissue engineering., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Impact: Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes. Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease. Methods: An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics. Results: Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value < 0.05 after multiple comparison testing. Endotype A consisted of neonates with a higher gestational age and birthweight. Endotypes B-D included neonates between 25 and 26 weeks and a birthweight range of 640 to 940 g. Endotype D appeared to have a protective role against BPD compared to Endotypes B and C (36% vs. 62% vs. 60%, respectively). The most significant pathway focused on T helper 17 cell differentiation. Conclusion: Bioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD. [ABSTRACT FROM AUTHOR]

A new study in the journal Development has found that many mRNAs enriched in germ granules in Caenorhabditis elegans are not involved in germline development. The researchers were surprised to find that most of the transcripts in germ granules encode general housekeeping functions and are degraded before the formation of primordial germ cells (PGCs). Only a small number of transcripts are maintained in PGCs and are required for germ cell fate. The researchers hypothesize that the majority of transcripts in germ granules function as structural scaffolds to support the condensation of the protein MEG-3, while only a minority of transcripts enrich in PGCs and play a role in germ cell fate determination. [Extracted from the article]

A new study in the journal Development has found that many mRNAs enriched in germ granules in Caenorhabditis elegans are not involved in germline development. The researchers were surprised to find that most of the transcripts in germ granules encode general housekeeping functions and are degraded before the formation of primordial germ cells (PGCs). Only a small number of transcripts are maintained in PGCs and are required for germ cell fate. The researchers hypothesize that the majority of transcripts in germ granules function as structural scaffolds to support the condensation of the protein MEG-3, while only a minority of transcripts enrich in PGCs and play a role in germ cell fate determination. [Extracted from the article]

Background: Mori Radicis Cortex (MRC) is the root bark of the mulberry family as Morus alba L. In Korea, it is known as "Sangbaegpi". Although MRC has demonstrated anti-inflammatory and antioxidant effects, its specific mechanisms of action and impact on osteoporosis remain poorly understood., Methods: To investigate the antiosteoporosis effect of MRC, we examined the level of osteoclast differentiation inhibition in receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced-RAW 264.7 cells and animal models of ovariectomy (OVX) with MRC. Serum analysis in OVX animals was investigated by enzyme-linked immunosorbent assay (ELISA), and bone density analysis was confirmed by micro-computed tomography (micro-CT). The expression analysis of nuclear factor of activated T cells 1 (NFATc1) was confirmed by immunohistochemistry (IHC) in femur tissue. In addition, osteoclast differentiation inhibition was measured using tartrate-resistant acid phosphatase (TRAP). mRNA analysis was performed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression analysis was investigated by western blot., Results: Micro-CT analysis showed that MRC effectively inhibited bone loss in the OVX-induced rat model. MRC also inhibited the expression of alkaline phosphatase (ALP) and TRAP in serum. Histological analysis showed that MRC treatment increased bone density and IHC analysis showed that MRC significantly inhibited the expression of NFATc1. In RANKL-induced-RAW 264.7 cells, MRC significantly reduced TRAP activity and actin ring formation. In addition, MRC significantly inhibited the expression of NFATc1 and c-Fos, and suppressed the mRNA expression., Conclusion: Based on micro-CT, serum and histological analysis, MRC effectively inhibited bone loss in an OVX-induced rat model. In addition, MRC treatment suppressed the expression of osteoclast differentiation, fusion, and bone resorption markers through inhibition of NFATc1/c-Fos expression in RANKL-induced RAW 264.7 cells, ultimately resulting in a decrease in osteoclast activity. These results demonstrate that MRC is effective in preventing bone loss through inhibiting osteoclast differentiation and activity., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

There is a growing interest in using paper as a biomaterial scaffold for cell-based applications. In this study, we made the first attempt to fabricate a paper-based array for the culture, proliferation, and direct differentiation of human induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues and create “a beating heart on paper.” This array was simply constructed by binding a cured multi-well polydimethylsiloxane (PDMS) mold with common, commercially available paper substrates. Three types of paper material (print paper, chromatography paper and nitrocellulose membrane) were tested for adhesion, proliferation and differentiation of human-derived iPSCs. We found that hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)-like morphology with a pluripotent property. The direct differentiation of human iPSCs into functional cardiac tissues on paper was also achieved using our modified differentiation approach. The cardiac tissue retained its functional activities on the coated print paper and chromatography paper with a beating frequency of 40–70 beats per min for up to three months. Interestingly, human iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose membrane under the conditions of cardiac-specific induction, indicating the potential roles of material properties and mechanical cues that are involved in regulating stem cell differentiation. Taken together, these results suggest that different grades of paper could offer great opportunities as bioactive, low-cost, and 3D in vitro platforms for stem cell-based high-throughput drug testing at the tissue/organ level and for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Several signaling pathways and transcription factors control the cell fate in its in vitro development and differentiation. The orchestrated use of these factors results in cell specification. In coculture methods, many of these factors secrete from host cells but control the process. Today, transcription factors required for retinal progenitor cells are well known, but the generation of these cells from mesenchymal stem cells is an ideal goal. The purpose of the paper is to review novel methods for retinal progenitor cell production and selecting a set of signaling molecules in the presence of adult retinal pigment epithelium and extraocular mesenchyme acting as inducers of retinal cell differentiation. [ABSTRACT FROM AUTHOR]

Glucosylceramides (GlcCer), glucose-conjugated sphingolipids, are major components of the endomembrane system and plasma membrane in most eukaryotic cells. Yet the quantitative significance and cellular functions of GlcCer are not well characterized in plants and other multi-organ eukaryotes. To address this, we examined Arabidopsis lines that were lacking or deficient in GlcCer by insertional disruption or by RNA interference (RNAi) suppression of the single gene for GlcCer synthase (GCS, At2g19880), the enzyme that catalyzes GlcCer synthesis. Null mutants for GCS (designated 'gcs-1') were viable as seedlings, albeit strongly reduced in size, and failed to develop beyond the seedling stage. Heterozygous plants harboring the insertion allele exhibited reduced transmission through the male gametophyte. Undifferentiated calli generated from gcs-1 seedlings and lacking GlcCer proliferated in a manner similar to calli from wild-type plants. However, gcs-1 calli, in contrast to wild-type calli, were unable to develop organs on differentiation media. Consistent with a role for GlcCer in organ-specific cell differentiation, calli from gcs-1 mutants formed roots and leaves on media supplemented with the glucosylated sphingosine glucopsychosine, which was readily converted to GlcCer independent of GCS. Underlying these phenotypes, gcs-1 cells had altered Golgi morphology and fewer cisternae per Golgi apparatus relative to wild-type cells, indicative of protein trafficking defects. Despite seedling lethality in the null mutant, GCS RNAi suppression lines with ≤2% of wild-type GlcCer levels were viable and fertile. Collectively, these results indicate that GlcCer are essential for cell-type differentiation and organogenesis, and plant cells produce amounts of GlcCer in excess of that required for normal development., (© 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.)

An appropriate physical support provided by scaffolds creates a supportive environment that directs proliferation and differentiation of stem cells. However, it is difficult to homogenously inoculate stem cells into the inner part of scaffolds at high cell densities. In this study, mesenchymal stem cells were seeded into a hydroxyapatite/poly (D, L-lactic-co-glycolic acid) (HAP/PLGA) scaffold that had enough mechanical strength and porous 3-D structure. With an aid of a filter paper placed under the bottom of a HAP/PLGA block, the cells suspended in a culture medium flowed from the top to the bottom through interconnected pores in the scaffold, and distributed almost homogenously, as compared to cell distribution near the surface of the block by the conventional method using centrifugation or reduced pressure. This simple method with a filter paper may be useful in preparation of cell-scaffold complexes for tissue engineering. [ABSTRACT FROM AUTHOR]

Nanocomposite (NC) papers using bifunctional nanoparticles are prepared for 3D cell growth experiments. Cells show better affinity to NC papers than to paper itself and differentiate the chemical group on the external surface of the nanoparticles. Cells possess spherical shaped morphology and form agglomerates onto the (NC) papers like as observed by cell growth in 3D materials. Furthermore, the preparation of “Janus” paper and the differentiation of its two distinct faces by cells is presented. [ABSTRACT FROM AUTHOR]

Tissue engineering research aims to repair the form and/or function of impaired tissues. Tissue engineering studies mostly rely on scaffold-based techniques. However, these techniques have certain challenges, such as the selection of proper scaffold material, including mechanical properties, sterilization, and fabrication processes. As an alternative, we propose a novel scaffold-free adipose tissue biofabrication technique based on magnetic levitation. In this study, a label-free magnetic levitation technique was used to form three-dimensional (3D) scaffold-free adipocyte structures with various fabrication strategies in a microcapillary-based setup. Adipogenic-differentiated 7F2 cells and growth D1 ORL UVA stem cells were used as model cells. The morphological properties of the 3D structures of single and cocultured cells were analyzed. The developed procedure leads to the formation of different patterns of single and cocultured adipocytes without a scaffold. Our results indicated that adipocytes formed loose structures while growth cells were tightly packed during 3D culture in the magnetic levitation platform. This system has potential for ex vivo modeling of adipose tissue for drug testing and transplantation applications for cell therapy in soft tissue damage. Also, it will be possible to extend this technique to other cell and tissue types., (© 2020 Wiley Periodicals LLC.)

The intestinal epithelium serves the unique and critical function of harvesting dietary nutrients, while simultaneously acting as a cellular barrier separating tissues from the luminal environment and gut microbial ecosystem. Two salient features of the intestinal epithelium enable it to perform these complex functions. First, cells within the intestinal epithelium achieve a wide range of specialized identities, including different cell types and distinct anterior-posterior patterning along the intestine. Second, intestinal epithelial cells are sensitive and responsive to the dynamic milieu of dietary nutrients, xenobiotics and microorganisms encountered in the intestinal luminal environment. These diverse identities and responsiveness of intestinal epithelial cells are achieved in part through the differential transcription of genes encoded in their shared genome. Here, we review insights from mice and other vertebrate models into the transcriptional regulatory mechanisms underlying intestinal epithelial identity and microbial responsiveness, including DNA methylation, chromatin accessibility, histone modifications and transcription factors. These studies are revealing that most transcription factors involved in intestinal epithelial identity also respond to changes in the microbiota, raising both opportunities and challenges to discern the underlying integrative transcriptional regulatory networks.

Summary: The International Collaboration for Transfusion Medicine Guidelines (ICTMG) has published guidance on transfusion for haemoglobinopathies. To give a UK perspective on this guidance, each of the recommendations in the ICTMG guideline were reviewed and the applicability for transfusion practice in the UK considered with reference to relevant published British Society for Haematology (BSH) guidelines and national standards. There was much consensus; however, there was disparity surrounding the recommendations for routinely extended matching in those with alloimmunisation. [ABSTRACT FROM AUTHOR]

The article presents several rules for restructuring papers to avoid losing readers. Authors are instructed to focus their papers on a central contribution and to concentrate on the context-content-conclusion (C-C-C) scheme. They are also advised to optimize a paper's logical flow by avoiding zig-zag and using parallelism and to include complete story in the abstract.

Early cell specification in mammalian preimplantation embryos is an intricate cellular process that leads to coordinated spatial and temporal expression of specific genes. Proper segregation into the first two cell lineages, the inner cell mass (ICM) and the trophectoderm (TE), is imperative for developing the embryo proper and the placenta, respectively. Somatic cell nuclear transfer (SCNT) allows the formation of a blastocyst containing both ICM and TE from a differentiated cell nucleus, which means that this differentiated genome must be reprogrammed to a totipotent state. Although blastocysts can be generated efficiently through SCNT, the full-term development of SCNT embryos is impaired mostly due to placental defects. In this review, we examine the early cell fate decisions in fertilized embryos and compare them to observations in SCNT-derived embryos, in order to understand if these processes are affected by SCNT and could be responsible for the low success of reproductive cloning., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Our previous study demonstrated that ultrasound is able to promote differentiation on neural stem cells (NSCs), and dual-frequency ultrasound promotes this effect due to enhanced acoustic cavitation compared with single-frequency ultrasound. However, the underlying biological reasons have not been well disclosed. The purpose of this study was to investigate the underlying bioeffects, mechanisms and signaling pathways of dual-frequency ultrasound on NSC differentiation. The morphology, neurite outgrowth, and differentiation percentages were investigated under various dual-frequency simulation parameters with exposure periods varying from 5 to 15 min. Morphological observations identified that dual-frequency ultrasound stimulation promoted ultrasound dose-dependent neurite outgrowth. In particular, cells exposed for 10 min/2 days showed optimal neurite outgrowth and neuron differentiation percentages. In addition, live cell calcium images showed that dual-frequency ultrasound enhanced the internal calcium content of the cells, and calcium ions entering cells from the extracellular environment could be observed. Dual frequency ultrasound exposure enhanced extracellular calcium influx and upregulated extracellular signal-regulated kinases 1/2 (ERK1/2) expression. Observations from immunostaining and protein expression examinations also identified that dual-frequency ultrasound promoted brain-derived neurotrophic factor (BDNF) secretion from astrocytes derived from NSCs. In summary, evidence supports that dual-frequency ultrasound effectively enhances functional neuron differentiation via calcium channel regulation via the downstream ERK1/2 pathway and promotes BDNF secretion to serve as feedback to cascade neuron differentiation. The results may provide an alternative for cell-based therapy in brain injury., (© 2022 Wiley Periodicals LLC.)

Fabrication of cardiac tissue from human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) has received great interest, but a major challenge facing researchers is the alignment of cardiomyocytes in the same direction to optimize force generation. We have developed a novel method of fabricating a cardiac tissue-like construct with aligned cells based on the unidirectional stretching of an hiPS-CM sheet. A square cell sheet was harvested from a temperature-responsive culture dish and placed on a silicone surface, and an extending force was imposed on the silicone to stretch the cell sheet along one direction. To enable evaluation of cardiomyocyte morphology in vitro, a cell sheet was constructed by coculture of hiPS-CMs and human adipose-derived stem cells. In separate experiments, a stretched double-layered cell sheet constructed from hiPS-CMs alone was transplanted onto the muscle of an athymic rat, and its features were compared with those of a nonstretched (control) cell sheet. Immediately after stretching, the stretched cell sheet was significantly longer than the control cell sheet. Immunohistological analysis revealed that the cardiomyocytes showed unidirectional alignment in the stretched cell sheet but random directionality in the control cell sheet. Two weeks after transplantation, immunohistology demonstrated that the stretched cell sheet had retained the unidirectionality of its myocardial fibers and had an orientation intensity that was higher than that of the control cell sheet after transplantation or the stretched cell sheet before transplantation. Our technique provides a simple method of aligning an hiPS-CM-derived cardiac tissue-like construct without the use of a scaffold., (© 2020 John Wiley & Sons, Ltd.)

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases., Competing Interests: The authors declare no conflict of interest.

How cells adopt different identities has long fascinated biologists. Signal transduction in response to environmental cues results in the activation of transcription factors that determine the gene-expression program characteristic of each cell type. Technological advances in the study of 3D chromatin folding are bringing the role of genome conformation in transcriptional regulation to the fore. Characterizing this role of genome architecture has profound implications, not only for differentiation and development but also for diseases including developmental malformations and cancer. Here we review recent studies indicating that the interplay between transcription and genome conformation is a driving force for cell-fate decisions.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague-Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results: In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, and promoting calcium nodule formation and collagen content. The authors also provide evidence regarding the involvement of the BMP-2/MAPKs/β-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, this study provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.

Background: The distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention., Aim: In this study, we produced porous nanofibrous scaffolds fabricated from random poly-L-lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain., Methods: The viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21 days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM., Results: The DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI-positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p < .05) increased (51 ± 19 on day 2 compared to 77 ± 25 cells on day 5). The results showed that the cell viability on PLLA scaffolds significantly increased compared to control groups. Moreover, cell viability was significantly increased 5 days after culturing (262.3 ± 50.2) as compared to 2 days culture in Vitro (174.2 ± 28.3, p < .05). Scanning electron micrographs also showed that the NSPCs adhered and differentiated on PLLA scaffolds. We found that the neural cell markers, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP), were expressed in NSPCs seeded on random PLLA scaffolds after 21 days of cultivation., Conclusion: These results suggest that the PLLA nano-scaffolds, due to their biocompatible property, are an appropriate structure for the proliferation, differentiation, and normal growth of NSPCs., (© 2021 International Society for Developmental Neuroscience.)

Background: Statins are 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors blocking cholesterol biosynthesis in hepatic cells, thereby causing an increase in low-density lipoprotein (LDL) receptors resulting in enhanced uptake and clearance of atherogenic LDL-cholesterol (LDL-C) from the blood. Accordingly, statins decrease the risk of developing atherosclerosis and its acute complications, such as acute myocardial infarction and ischaemic stroke. Besides the LDL-C-lowering impact, statins also have other so-called pleiotropic effects. Among them, the ability to modulate differentiation and function of bone cells and exert direct effects on osteosynthesis factors. Specifically, earlier studies have shown that statins cause in vitro and in vivo osteogenic differentiation., Design: The most relevant papers on the bone-related 'pleiotropic' effects of statins were selected following literature search in databases and were reveiwed., Results: Statins increase the expression of many mediators involved in bone metabolism including bone morphogenetic protein-2 (BMP-2), glucocorticoids, transforming growth factor-beta (TGF-β), alkaline phosphatase (ALP), type I collagen and collagenase-1. As a result, they enhance bone formation and improve bone mineral density by modulating osteoblast and osteoclast differentiation., Conclusion: This review summarizes the literature exploring bone-related 'pleiotropic' effects of statins and suggests an anabolic role in the bone tissue for this drug class. Accordingly, current knowledge encourages further clinical trials to assess the therapeutic potential of statins in the treatment of bone disorders, such as arthritis and osteoporosis., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

We have previously shown evidence that α-syntrophin plays an important role in myoblast differentiation. In this study, we focused on abnormal myotube formation of the α-syntrophin knockdown C2 cell line (SNKD). The overall amount of intracellular protein and muscle-specific proteins in SNKD cells were significantly lower than those in the control. Akt-mTOR signaling, an important pathway for protein synthesis and muscle hypertrophy, was downregulated. In addition, the levels of endoplasmic reticulum (ER) stress markers increased in SNKD cells. The decrease in intracellular protein synthesis and reduction in the myotube diameter in SNKD cells were restored by 4-phenylbutyric acid, a chemical chaperone, or overexpression of α-syntrophin. These results suggest a novel role for α-syntrophin in protein homeostasis during myoblast differentiation., (© 2021 Federation of European Biochemical Societies.)

Conduits that promote nerve regeneration are currently of great medical concern, particularly when gaps exist between nerve endings. To address this issue, our laboratory previously developed a nerve conduit from biodegradable poly(caprolactone fumarate) (PCLF) that supports peripheral nerve regeneration. The present study improves upon this work by further developing an electrically conductive, positively charged PCLF scaffold through the incorporation of graphene, carbon nanotubes (CNTs), and [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MTAC) (PCLF-Graphene-CNT-MTAC) using ultraviolet (UV) induced photocrosslinking. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy were used to assess the incorporation of CNTs and graphene into PCLF-Graphene-CNT-MTAC scaffolds, which displayed enhanced surface roughness and reduced electrochemical impedance when compared to neat PCLF. Scaffolds with these surface modifications also showed improved growth and differentiation of rat pheochromocytoma 12 cells in vitro, with enhanced cell growth, neurite extension, and cellular migration. Furthermore, an increased number of neurite protrusions were observed when the conduit was electrically stimulated. These results show that the electrically conductive PCLF-Graphene-CNT-MTAC nerve scaffolds presented here support the cellular behaviors that are critical for nerve regeneration, ultimately making this material an attractive candidate for regenerative medicine applications., (© 2020 Wiley Periodicals LLC.)