Role In Regeneration Research Articles

Repositing honey incorporated electrospun nanofiber membranes to provide anti-oxidant, anti-bacterial and anti-inflammatory microenvironment for wound regeneration.

Topical application of honey for tissue regeneration, has recently regained attention in clinical practice with controlled studies affirming its efficacy and indicating its role in regeneration over repair. Parallely, to overcome difficulties of applying raw honey, several product development studies like nanofibrous matrices have been reported. However, one approach concentrated on achieving highest possible honey loading in the nanofiber membranes while other studies have found that only specific honey dilutions result in differential cellular responses on wound healing and re-epithelization. From these results, it can be suggested that high honey loading provides optimum external microenvironment, low-loaded membranes could provide a more conducive internal microenvironment for tissue regeneration. With this hypothesis, this paper sought to evaluate ability of low-honey loaded nanofibers to modulate the anti-oxidant, anti-biofilm and anti-inflammatory properties which are important to be maintained in wound micro-environment. A loading-dependent reduction of biofilm formation and anti-oxidant activity was noted in different concentration ranges investigated. After scratch assay, a certain honey loading (0.5%) afforded the maximum re-epithelization. Since there is lack of methods to determine anti-inflammatory properties of nanofiber membranes during epithelial healing process, we performed anti-inflammatory assessment of nano-fibers by evaluating the expressions of pro-inflammatory markers-Cycloxygenase-2 (COX-2) and Interleukin-6 (IL-6) and to confirm the optimized concentration. Considering the role of COX-2 and IL-6, the novel methodology used in this study can also be developed as an assay for anti-inflammatory matrices for wound healing.

InForm software: a semi-automated research tool to identify presumptive human hepatic progenitor cells, and other histological features of pathological significance

Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists’ reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer’s “InForm” software package to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist’s assessment. We examined a cohort of eleven acute hepatitis samples and three non-alcoholic fatty liver disease (NAFLD) samples, stained with HPC markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red to detect collagen and haematoxylin/eosin for general histology. InForm was configured to identify presumptive HPCs, CD45+ve inflammatory cells, areas of necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then evaluated both by a pathologist using the Ishak-Knodell scoring system, and by InForm through customised algorithms. Necroinflammation as evaluated by a pathologist, correlated with InForm outputs (r2 = 0.8192, p < 0.05). This study demonstrates that the InForm software package provides a useful tool for liver disease research, allowing rapid, and objective quantification of the presumptive HPCs and identifies histological features that assist with assessing liver disease severity, and potentially can facilitate diagnosis.

Distinct role of nuclear receptor corepressor 1 regulated de novo fatty acids synthesis in liver regeneration and hepatocarcinogenesis in mice.

NCoR1 functions as a negative modulator for hepatic de novo FAS and mitochondria energy adaptation, playing distinct roles in regeneration or carcinogenesis. (Hepatology 2018;67:1071-1087).

An optimised protocol for platelet-rich plasma preparation to improve its angiogenic and regenerative properties

Although platelet-rich plasma (PRP) is used as a source of growth factors in regenerative medicine, its effectiveness remains controversial, partially due to the absence of PRP preparation protocols based on the regenerative role of platelets. Here, we aimed to optimise the protocol by analysing PRP angiogenic and regenerative properties. Three optimising strategies were evaluated: dilution, 4 °C pre-incubation, and plasma cryoprecipitate supplementation. Following coagulation, PRP releasates (PRPr) were used to induce angiogenesis in vitro (HMEC-1 proliferation, migration, and tubule formation) and in vivo (chorioallantoic membrane), as well as regeneration of excisional wounds on mouse skin. Washed platelet releasates induced greater angiogenesis than PRPr due to the anti-angiogenic effect of plasma, which was decreased by diluting PRPr with saline. Angiogenesis was also improved by both PRP pre-incubation at 4 °C and cryoprecipitate supplementation. A combination of optimising variables exerted an additive effect, thereby increasing the angiogenic activity of PRPr from healthy donors and diabetic patients. Optimised PRPr induced faster and more efficient mouse skin wound repair compared to that induced by non-optimised PRPr. Acetylsalicylic acid inhibited angiogenesis and tissue regeneration mediated by PRPr; this inhibition was reversed following optimisation. Our findings indicate that PRP pre-incubation at 4 °C, PRPr dilution, and cryoprecipitate supplementation improve the angiogenic and regenerative properties of PRP compared to the obtained by current methods.

Characteristics of a Bottomland Hardwood Forest at Arcadia Lake, Edmond, Oklahoma, with Special Emphasis on Green Ash (Fraxinus pennsylvanica Marshall)

We characterized the structure and tree species composition of bottomland hardwood forest at Arcadia Lake, Oklahoma County, Oklahoma. Additionally, we quantified the age structure of Fraxinus pennsylvanica Marshall (green ash) at the study site in order to establish a baseline dataset in the event that Agrilus planipennis (emerald ash borer) invades F. pennsylvanica stands in central Oklahoma. Three species, Salix nigra Marshall (black willow), F. pennsylvanica , and Populus deltoides W. Bartram ex Marshall (cottonwood) accounted for over 98% of importance values. These three species were also common in the understory. We found that 95% of F. pennsylvanica established following Arcadia Lake reaching pool conservation status in 1987. Arcadia Lake has experienced five sustained flooding events since 1995 that have likely played a role in regeneration at the study site. In particular, we showed that the 1995 event resulted in reduced radial growth in seedlings of F. pennsylvanica . Two biotic stressors appear to be influencing F. pennsylvanica overstory trees, Castor canadensis (American beaver) and Hylesinus spp. (ash bark beetle), which will likely enhance the establishment of A. planipennis at the study site. We recommend expanding the study of Fraxinus spp. forest stands in Oklahoma. Baseline data on Fraxinus species prior to an A. planipennis range expansion to central Oklahoma can enhance strategies for control and management of this invasive insect by identifying the traits of surviving ash following the invasion.

Detection of Apoptotic Cells in Planarians by Whole-Mount TUNEL.

Planarians have gained a well-deserved reputation as an excellent model organism for research on the biology of adult stem cells and their role in regeneration. Though less widely recognized, these animals also offer many advantages for investigating mechanisms and functions of programmed cell death in self-renewing tissues. Apoptosis complements stem cell division during physiological cell turnover and constitutes a prominent feature of the tissue remodeling process that restores anatomical scale and proportion during regeneration. One technical advantage to studying apoptosis in planarians is the availability of a whole-mount TUNEL assay for visualizing dying cells throughout the animal. Here, we provide a detailed protocol for this assay that is likely to benefit researchers investigating planarian cell death in either physiological or pathological contexts.

A growing field: The regulation of axonal regeneration by Wnt signaling.

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.

The Role of Magnetic Resonance Imaging in the Management of Diabetic Foot

Background: Novel therapies are urgently needed to address the rising incidence and prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD). Mesenchymal stem cells (MSCs) can generate extracellular micro vesicles (EVs) with intrinsic protective or regenerative capacity. Objectives: Studying the possible role of EVs generated from bone marrow-derived mesenchymal stem cells (BM MSCs) in regeneration of kidney tissue in acetaminophen-induced renal failure (RF). Patients and Methods: Twenty four adult male albino rats of a local strain were chosen as an animal model for this study. They were divided into 4 equal groups: control, RF, RF received culture media, and RF received MSCs-derived EVs. Renal failure (RF) was induced by oral administration of acetaminophen. At the end of the experiment (24 days), blood samples were obtained for serum creatinine, urea, malodialdehyde (MDA) and tumor necrosis factor alpha (TNF-α). Animals were sacrificed, and kidney tissue was obtained for histopathological examination and immunohistochemical examination for BAX protein expression, in addition to BCL2 gene expression by real time (RT) PCR. Results: There was a significant decrease in BCL2 gene expression in addition to significant increases in serum creatinine, urea, MDA and TNF-α in acetaminophen- treated group. There was an increased BAX protein expression by immunohistochemistry in acetaminophen- treated group. There were significant increase in BCL2 gene expression, and significant decreases in serum creatinine, urea, MDA and TNF-α in MSCs-derived EVs - treated group. There was a decrease in BAX protein expression by immunohistochemistry in MSCs derived EVs - treated group. Conclusion: BM MSCs-derived (EVs) have a role in regeneration of kidney tissue in acetaminophen-induced renal failure through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

DjhnRNPA2/B1-like gene is required for planarian regeneration and tissue homeostasis

The hnRNPs play important roles in physiological processes in eukaryotic organisms by regulation of pre-mRNA after transcription, including pre-mRNA splicing, mRNA stability, DNA replication and repair and telomere maintenance and so on. However, it remains unclear about the specific functions of these genes. In this study, the full-length cDNA sequence of hnRNPA2/B1-like was first cloned from Dugesia japonica, and its roles were investigated by WISH and RNAi. The results showed that: (1) DjhnRNPA2/B1-like was highly conserved during animal evolution; (2) DjhnRNPA2/B1-like mRNA was mainly distributed each side of the body in intact worms and regenerative blastemas, and its expression levels were up-regulated on days 0 and 5 after amputation; (3) the intact and regenerating worms gradually lysed or lost regeneration capacity after DjhnRNPA2/B1-like RNAi; and (4) DjhnRNPA2/B1-like expression is induced by temperature and heavy metal ion stress. The data suggests that DjhnRNPA2/B1-like is a multiple functional gene, it plays important roles in regeneration and homeostatic maintenance and it is also involved in stress responses in planarians. Our work provides basic data for the study of regenerative mechanism and stress responses in freshwater planarians.

The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.

Regenerating tissue must initiate the signaling that drives regenerative growth, and sustain that signaling long enough for regeneration to complete. How these key signals are sustained is unclear. To gain a comprehensive view of the changes in gene expression that occur during regeneration, we performed whole-genome mRNAseq of actively regenerating tissue from damaged Drosophila wing imaginal discs. We used genetic tools to ablate the wing primordium to induce regeneration, and carried out transcriptional profiling of the regeneration blastema by fluorescently labeling and sorting the blastema cells, thus identifying differentially expressed genes. Importantly, by using genetic mutants of several of these differentially expressed genes we have confirmed that they have roles in regeneration. Using this approach, we show that high expression of the gene moladietz (mol), which encodes the Duox-maturation factor NIP, is required during regeneration to produce reactive oxygen species (ROS), which in turn sustain JNK signaling during regeneration. We also show that JNK signaling upregulates mol expression, thereby activating a positive feedback signal that ensures the prolonged JNK activation required for regenerative growth. Thus, by whole-genome transcriptional profiling of regenerating tissue we have identified a positive feedback loop that regulates the extent of regenerative growth.

Long-term persistence of Velloziaceae species in the soil seed bank in campo rupestre vegetation, Brazil

Background: Soil seed banks play an important role in regeneration in many ecosystems and contribute to ecosystem resilience in disturbed environments. This is especially true for the Brazilian campo rupestre, a fire-prone ecosystem that harbours a large number of endangered endemic species.Aims: We aimed to determine the persistence in the soil seed bank, through the evaluation of the in situ longevity, of seeds from four species of Velloziaceae, an endemic-rich and dominant family in the campo rupestre vegetation.Methods: Seeds of four sympatric and common Vellozia species were collected and placed in bags, which were buried in their natural area of occurrence. The germination capacity of the buried seeds was regularly evaluated under controlled light and temperature conditions over a 5-year period.Results: No in situ establishment was observed for any of the buried seeds. All species retained high germinability throughout the burial, except for V. glandulifera, whose germinability was reduced by 60%. The reduction in germinability of V. glandulifera was positively correlated with seed size and mass.Conclusions: Seeds of the studied species of Vellozia are capable of persisting in soil over time while maintaining high germinability. Seed traits appear to be important for seed bank persistence.

Decreased myoblast differentiation in chronic binge alcohol-administered simian immunodeficiency virus-infected male macaques: role of decreased miR-206.

Skeletal muscle stem cells play a critical role in regeneration of myofibers. We previously demonstrated that chronic binge alcohol (CBA) markedly attenuates myoblast differentiation potential and myogenic gene expression. Muscle-specific microRNAs (miRs) are implicated in regulation of myogenic genes. The aim of this study was to determine whether myoblasts isolated from asymptomatic CBA-administered simian immunodeficiency virus (SIV)-infected macaques treated with antiretroviral therapy (ART) showed similar impairments and, if so, to elucidate potential underlying mechanisms. Myoblasts were isolated from muscle at 11 mo after SIV infection from CBA/SIV macaques and from time-matched sucrose (SUC)-treated SIV-infected (SUC/SIV) animals and age-matched controls. Myoblast differentiation and myogenic gene expression were significantly decreased in myoblasts from SUC/SIV and CBA/SIV animals compared with controls. SIV and CBA decreased muscle-specific miR-206 in plasma and muscle and SIV decreased miR-206 expression in myoblasts, with no statistically significant changes in other muscle-specific miRs. These findings were associated with a significant increase in histone deacetylase 4 (HDAC4) and decrease in myogenic enhancer factor 2C (MEF2C) expression in CBA/SIV muscle. Transfection with miR-206 inhibitor decreased myotube differentiation, increased expression of HDAC4, and decreased MEF2C, suggesting a critical role of miR-206 in myogenesis. Moreover, HDAC4 was confirmed to be a direct miR-206 target. These results support a mechanistic role for decreased miR-206 in suppression of myoblast differentiation resulting from chronic alcohol and SIV infection. The parallel changes in skeletal muscle and circulating levels of miR-206 warrant studies to establish the possible use of plasma miR-206 as an indicator of impaired muscle function.

Checklist of root-sprouters in the Czech flora: mapping the gaps in our knowledge

The production of shoots from roots (adventitious bud and shoot formation, root sprouting) first attracted attention in the 19th century as a morphological rarity. At that time, the first checklists of plants capable of root sprouting were compiled. Since then, experiments have proven that the ability to produce buds on roots serves the purpose of bud bank formation or represents a mode of clonal growth. The former enables resprouting after injury whereas the latter facilitates foraging for nutrients and vegetative multiplication. However, only a small proportion of root-sprouters have been studied so far, and for most of them we lack detailed data on the anatomy, morphology, ecology and physiology of adventitious shoot formation. These knowledge gaps hinder further understanding of their ecology and evolution. To support researchers interested in adventitious bud and shoot formation in any field of plant science, we compiled a list of plants considered capable of root sprouting based on the literature and the CLO-PLA database for the flora of the Czech Republic. Here we provide basic comparisons concerning the distribution of root sprouting ability among life history types, plants differing in rarity and invasive status, and taxonomic groups. Altogether 342 plant species are reported to be root-sprouters, i.e. 10% of the Czech flora. Root-sprouters are most commonly found among woody plants, less so among non-clonal perennial herbs, biennials and clonal herbs, and least commonly among annuals. Root-sprouters are more common among alien plants (especially woody ones) than among red-listed plants. Root sprouting usually plays a supplementary (facultative) or regenerative role in the plant life cycle. Root-sprouters occur in 64 families, mostly of dicots. The greatest number of root-sprouters belong to the Asteraceae and Rosaceae families (41). We have only rudimentary information on 145 species out of the 342 (42%) species that are regarded as root-sprouters.

Sonic Hedgehog and TDP-43 Participate in the Spontaneous Locomotor Recovery in a Mouse Model of Spinal Motoneuron Disease

Several studies have attempted to repair the damaged spinal cord (SC) by stimulating neurogenesis or neuroplasticity, with limited success. Sonic hedgehog (Shh) is involved in neural induction and stem cell functioning, but recent findings also suggest its role in regeneration and functional recovery. Transactive response DNA-binding protein of 43 kDa (TDP-43) is a nuclear DNA/RNA binding protein involved in transcription and RNA processing. Recent findings have reported cytoplasmic inclusions containing TDP-43 in amyotrophic lateral sclerosis. Although substantial attention has been given to the toxic effects of this protein, the functional role of TDP-43 remains largely unclear. We used a mouse model of neurotoxic motoneuron depletion to study the role of the above-described factors in the compensatory changes occurring after the lesion. The injection of cholera toxin-B saporin into the gastrocnemius muscle caused a partial motoneuron death accompanied by an impairment of locomotion. Interestingly, motor activity was significantly restored as soon as one month later. Moreover, we observed an activity-dependent modification of Shh and synaptic proteins: synapsin-I and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. Notably, the motor performance of lesioned animals correlated with the expression of synapsin-I and Shh. Conversely, the expression of Shh significantly correlated with the levels of synapsin-I, GluR2, and TDP-43. The results suggest that Shh and TDP-43 are crucial parts of a complex mechanism of neuroplasticity in a mouse model of SC motoneuron disease.

10 Macrophage-derived wnts are required for scar-free regeneration of the neonatal mouse myocardium

Objective In contrast to the adult, neonatal mice regenerate their myocardium following injury, at least during the first week after birth. 1 Macrophages (Mx) contribute to vessel formation and scar removal following neonatal myocardial infarction (MI) 2 . In the kidney 3 liver 4,7 and gut 5 Mx-derived WNTs are required for scar free regeneration following injury. Secretion of WNTs is dependent on acylation by Porcupine (PORCN). In the present study it was hypothesised that neonatal cardiac regeneration would be impaired in mice with Csf1r-Cre driven Mx specific Porcn deletion. 5 Methods Csf1r-EGFP(MacGreen), Porcn fl/ Csf1r Cre-ve and Porcn fl /Csf1r Cre+ve mice underwent coronary artery ligation at post-natal day 1 (P1). Functional loss 1 day after MI, and recovery by P21 were assessed by high-resolution ultrasound. Heart sections were stained with isolectin B4 (vessel density) and picrosirius res (fibrosis). Myocardial gene expression was determined by PCR array in wild-type (WT) mice after injury. Results At day 1 and day 7 post-MI, Csf1r-expressing cells accumulated within the injured myocardium, consistent with a role in regeneration. 2 At day 1 post-MI, fractional area change (FAC) decreased from 40.9% ± 1.6 to 18.0% ± 2.4% (p Porcn fl/ Csf1r Cre-ve and Porcnfl/Csf1rCre-ve mice respectively. By 21 days after MI, FAC had recovered to 47.4% ± 2.5% (p Porcn fl/ Csf1r Cre-ve and 45.8% ± 1.9% (p Porcn fl/ Csf1r Cre-ve littermates. Coronary vascularisation was restored in the infarct area by 21 days in both lines, but interstitial fibrosis was significantly higher in Porcn fl/ Csf1r Cre-ve (6.0 ± 0.9% LV) compared to Porcn fl/ Csf1r Cre-ve (3.8 ± 0.5% LV, p Wnt5b and Fzd2 , genes associated with regulation of fibrosis. 8 Conclusion Mx-derived WNTs are not required for re-vascularisation or restoration of myocardial function after neonatal myocardial injury, but are necessary for scar removal during regeneration. References Porrello et al . PNAS 2013; 110 :p187–92. Aurora et al . JCI 2014; 124 :p1382–92. Lin et al . PNAS 2010; 107 :p4194–99. Boulter et al . Nat Med 2012; 18 :572–9. Saha et al . Nat Com 2016; 7 :1–16. Derlindati et al . PLoS ONE 2015; 10 :1–17. Irvine et al . Fibrogenesis Tissue Repair 2015; 8 :19–32. Laeremans et al . Cardiovascular Research 2010; 87 :514–523.

Increasing Calcium Level Limits Schwann Cell Numbers In Vitro following Peripheral Nerve Injury

Background After peripheral nerve injury, there is an increase in calcium concentration in the injured nerves. Our previous publications have shown that increase in calcium concentration correlated well with degree of nerve injury and that local infusion of calcitonin has a beneficial effect on nerve recovery. Schwann cells play a pivotal role in regeneration and recovery. We aim to examine cultured Schwann cell survivals in various concentrations of calcium-containing growth media and the effect of calcitonin in such media. Methods To establish baseline in postinjury state, crush injury was induced in male Sprague-Dawley rats' sciatic nerves. Extra- and intraneural calcium concentrations were measured. To study Schwann cell survival, uninjured sciatic nerve segment was harvested and cultured in media containing various amounts of calcium. To study the effect of calcitonin, nerve harvest and culture were done in four additional media: (1) normal control, (2) normal control with calcitonin, (3) high calcium medium, and (4) high calcium medium with calcitonin. Schwann cells were studied and analyzed under fluorescent conditions. Results With increasing calcium concentration, there was a significant decrease in the number of Schwann cells. For the experimental groups, in which calcitonin had been added to the growth medium, there were similar amounts of Schwann cells present in both high and low calcium-containing medium. Conclusion Schwann cells are sensitive to increasing calcium concentration. Calcitonin counteracts the detrimental effects of high calcium on Schwann cell survival. This can have significant future clinical implications for patients with peripheral nerve injuries.

Autophagy is the key process in the re-establishment of the epitheloid phenotype during mesenchymal-epithelial transition (MET)

In previous studies we showed that during Freund's adjuvant induced inflammation rat mesenteric mesothelial cells undergo epithelial-mesenchymal transition type II (EMT). This process was characterized by a dramatic increase of the number of cell organelles and volume of mesothelial cells. After the inflammation reached its maximum, the mesenchymal-like cells gradually regained their epithelial phenotype (mesenchymal-epithelial transition, MET). During the recovery process, the decrease of the number of cell organelles was accompanied by an increasing number of autophagic structures in the cytoplasm, indicating that autophagy might play crucial role in MET. Morphometric data of this study showed that the number of the autophagic organelles increased by the time of inflammation and was the highest at day 7–8, when regeneration started. These morphological observations were supported by immunocytochemistry and Western blot analyses with various markers, directly or indirectly involved in this process. Endocytic markers were expressed at high level during both EMT and MET, while the expression of factors regulating autophagy simultaneously changed with the morphology: p-Akt and p-mTOR level was high at day 3–5 and significantly decreased when autophagy speeded up. The Beclin-1, which is the key factor of initiating autophagy, was expressed at the early time of inflammation. These results strongly suggest that autophagy plays important role in regeneration (MET), and it is regulated and synchronized by various signalling events during inflammation.

Expressions Profiles of the Proteins Associated with Carbohydrate Metabolism in Rat Liver Regeneration.

Liver has a very amazing ability to regenerate from the remnant liver after injury or partial hepatectomy (PH). Carbohydrate metabolism plays a critical role in regeneration. Many signaling pathways are involved in the metabolism process. We analyzed the changes of proteins at 0–36 h after PH in rats using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS-based quantitative proteomics strategy. The results showed that 110 proteins and 5 signaling pathways related to carbohydrate metabolism in rat LR changed significantly. Based on a motif discovery method performed by iRegulon, we identified for the first time that the transcription factor SPIB whose motif was enriched among the differentiated genes associated with carbohydrate metabolism may play an important role in liver regeneration for the first time. The findings of this research provide a molecular basis for further unrevealing the mechanism of regeneration at priming stage (0–6 h) and proliferation stage (6–36 h) of LR in rats. At the same time, our studies provide more novel evidence for the signaling pathways which regulate carbohydrate metabolism from proteomics level. This study can provide some new thinking of liver regeneration and treatment of diseases associated with glucose metabolism.

Different Roles of Microglia/Macrophage in Ischemic Stroke and Alzheimer's Disease

Neuroinflammation is a double edge sword: it plays both destructive and regenerative roles in a variety of neurological diseases, such stroke and Alzheimer’s disease (AD). In the central nervous system, these inflammatory changes are restricted exclusively to microglia. Ischemic stroke causes an acute cascade of events, including excitotoxicity, inflammatory responses, oxidative stress and apoptosis, whereas AD is a chronic progressive process. As the blood–brain barrier separates the central nervous system and the peripheral immune system, the brain is used to be considered an immune-privileged organ. However, accumulating evidence reveals mononuclear phagocytes and the resident microglia play a key role in modulating the development and progression of brain pathology. In this mini review, we summarize the role of microglia in the brain and in disease states. Microglia serves different roles at different stages of the diseases. We emphasize the regulatory role of CX3CR1, which may provide a novel and effective means for therapy.

Biodegradable mesoporous delivery system for biomineralization precursors.

Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation. Because both amorphous calcium phosphate (ACP) and silica are osteoinductive, a biodegradable, nonfunctionalized, expanded-pore mesoporous silica nanoparticle carrier was developed for loading, storage, and sustained release of a novel, biosilicification-inspired, polyamine-stabilized liquid precursor phase of ACP for collagen biomineralization and for release of orthosilicic acid, both of which are conducive to bone growth. Positively charged poly(allylamine)-stabilized ACP (PAH-ACP) could be effectively loaded and released from nonfunctionalized expanded-pore mesoporous silica nanoparticles (pMSN). The PAH-ACP released from loaded pMSN still retained its ability to infiltrate and mineralize collagen fibrils. Complete degradation of pMSN occurred following unloading of their PAH-ACP cargo. Because PAH-ACP loaded pMSN possesses relatively low cytotoxicity to human bone marrow-derived mesenchymal stem cells, these nanoparticles may be blended with any osteoconductive scaffold with macro- and microporosities as a versatile scaffold supplement to enhance bone regeneration.