Model Of Regeneration Research Articles

Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration

BackgroundThe remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration.MethodsThe model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1).ResultsTet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly.ConclusionOur findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function.Graphical Tet2 interacts with Stat1 in the cytoplasm and suppresses IFN-γ-induced macrophage activation. Tet2 inhibitor decreases the combination of Stat1 and Tet2, activating the macrophages through the Jak-Stat pathway. The activation of macrophages increases the transcription and translation of the IL-6 and promotes liver regeneration.BnQa2gdaXkcfesAu78GqfXVideo

Enhancing Sustainability and Yield in Maritime Pine Forests: Evaluating Silvicultural Models for Natural Regeneration

The maritime pine (Pinus pinaster Ait.) forest is an essential element of the Portuguese forest landscape due to its social, economic, and environmental importance. The sustainability of these forests in the Mediterranean region faces challenges due to recurrent forest fires and the absence of or delayed management. The species has a high capacity for regeneration, but the perpetuation of pine forests in sustainable conditions depends on adequate management to achieve high biomass production and assure fire resilience. This study aimed to analyse four management scenarios (C1 to C4) for the natural regeneration of maritime pine in six areas with stand ages ranging from 6 to 16 years and densities varying from 15,000 to circa 93,000 trees per ha. The same four scenarios were implemented in each of the six areas. The scenarios considered the evolution of forest growth according to different management prescriptions and were simulated using Modispinaster and PiroPinus models. Scenario C1 considered no intervention, with only the final cut. Scenario C2 considered a thinning schedule to maintain the stand within the 50–60% range of the Stand Density Index (SDI). Scenario C3 followed the area’s Forest Management Plan (PGF), which typically includes two or three thinning operations throughout the cycle. Scenario C4 was adapted from the MS1 silvicultural model of the National Institute for Nature Conservation and Forests—ICNF, which involves opening strips at earlier ages (3 and 6 years), with the selection of trees to remain in the wooded area carried out between 4 and 10 years of age and performing thinning whenever the Wilson Spacing Factor (FW) reaches 0.21. The final cutting age was assumed to be 45 years but could be lowered to 35 years in Scenario 3 if defined in the plan. Based on the indicators generated by the simulators, the results showed variations in the total volume of timber produced at the time of harvest depending on the silvicultural guidelines. Scenario C4 was the most effective in generating the highest individual tree volume at the end of the cycle and the total volume of timber collected throughout the cycle. The ability of the forest to resist fire was evaluated before and after the first treatment for density reduction. The treatments performed did not decrease the resistance to fire control.

Big data analysis and evaluation for vitality factors of public space of regenerated industrial heritage in Luoyang

Abstract The regeneration of idle industrial heritage buildings needs to take into account many factors such as history, science, art, and social aspects. Current research on industrial heritage regeneration has not developed quantitative research in each factor of assessment, and cannot provide clear guidance and program reference for industrial building regeneration weighting ratios. In this study, we put forward a spatial vitality factor range prediction method based on big data analysis for the regeneration of an industrial heritage public space in Luoyang, aiming to establish a model for the regeneration of industrial heritage abandoned industrial buildings and to provide implementation and regeneration planning. The specific evaluation process and regeneration evaluation design scheme based on Luoyang’s industrial heritage were restored. The weights and percentages of the key domain indicators and branch indicators of the idle industrial building regeneration model were predicted, which provided clear guidance and reference for the planning of regeneration of public spaces of industrial heritage. The prediction accuracy of each key assessment factor was maintained above 90%, and the sequential ranking result of the assessment factors was given. The spatial regeneration prediction scheme provided an effective guide and indicator reference for the case design, highlighting the effectiveness of our approach.

CREG1 deficiency impaired myoblast differentiation and skeletal muscle regeneration.

CREG1 (cellular repressor of E1A-stimulated genes 1) is a protein involved in cellular differentiation and homeostasis regulation. However, its role in skeletal muscle satellite cells differentiation and muscle regeneration is poorly understood. This study aimed to investigate the role of CREG1 in myogenesis and muscle regeneration. RNA sequencing data (GSE8479) was analysed from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi). We generated Creg1 knockdown and skeletal muscle satellite cells specific Creg1 overexpression mice mediated by adeno-associated virus serotype 9 (AAV9), skeletal muscle mature myofibre Creg1 knockout mice (myoblast/Creg1MKO), and control mice Creg1flox/flox (Creg1fl/fl) as in vivo models. The mice were injected into tibialis anterior (TA) muscle with 100μL of 10μM cardiotoxin to establish a muscle regeneration model. Creg1fl/fl and Creg1MKO mice were treated with AAV-sh-C-Cbl (2×1010 genomic copies/mouse) to silence C-Cbl in the TA muscle. 293T and C2C12 cells were transfected with plasmids using lipofectamine RNAi MAX in vitro. Mass spectrometry analyses and RNA sequencing transcriptomic assay were performed. We analysed the transcriptional profiles of the skeletal muscle biopsies from healthy older (N=25) and younger (N=26) adult men and women in GSE8479 database, and the results showed that Creg1 was associated with human sarcopenia. We found that Creg1 knockdown mice regenerated less newly formed fibres in response to cardiotoxin injection (~30% reduction, P<0.01); however, muscle satellite cells specific Creg1 overexpression mice regenerated more newly formed fibres (~20% increase, P<0.05). AMPKa1 is known as a key mediator in the muscle regeneration process. Our results revealed that CREG1 deficiency inhibited AMPKa1 signalling through C-CBL E3-ubiquitin ligase-mediated AMPKa1 degradation (P<0.01). C-CBL-mediated AMPKa1 ubiquitination was attributed to the K48-linked polyubiquitination of AMPKa1 at K396 and that the modification played an important role in the regulation of AMPKa1 protein stability. We also found that Creg1MKO mice regenerated less newly formed fibres compared with Creg1fl/fl mice (~30% reduction, P<0.01). RNA-seq analysis showed that CREG1 deletion in impaired muscles led to the upregulation of inflammation and DKK3 expression. The TA muscles of Creg1MKO mice were injected with AAV-vector or AAV-shC-Cbl, silencing C-CBL (P<0.01) in the skeletal muscles of Creg1MKO mice significantly improved muscle regeneration induced by CTX injury (P<0.01). Our findings suggest that CREG1 may be a potential therapeutic target for skeletal muscle regeneration.

Flatworm Transcriptomes Reveal Widespread Parasitism by Histophagous Ciliates.

Unicellular ciliates like Tetrahymena are best known as free-living bacteriovores, but many species are facultative or obligate parasites. These "histophages" feed on the tissues of hosts ranging from planarian flatworms to commercially important fish and the larvae of imperiled freshwater mussels. Here, we developed a novel bioinformatics pipeline incorporating the nonstandard ciliate genetic code and used it to search for Ciliophora sequences in 34 publicly available Platyhelminthes EST libraries. From 2,615,036 screened ESTs, we identified nearly 6,000 high-confidence ciliate transcripts, supporting parasitism of seven additional flatworm species. We also cultured and identified Tetrahymena from nine terrestrial and freshwater planarians, including invasive earthworm predators from the genus Bipalium and the widely studied regeneration models Dugesia japonica and Schmidtea mediterranea. A co-phylogenetic reconstruction provides strong evidence for the coevolution of histophagous Ciliophora with their Platyhelminthes hosts. We further report the antiprotozoal aminoglycoside paromomycin expels Tetrahymena from S. mediterranea, providing new opportunities to investigate the effects of this relationship on planarian biology. Together, our findings raise the possibility that invasive flatworms constitute a novel dispersal mechanism for Tetrahymena parasites and position the Platyhelminthes as an ideal model phylum for studying the ecology and evolution of histophagous ciliates.

Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model

Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.

Interactions Between Silver Nanoparticles and Culture Medium Biomolecules with Dose and Time Dependencies.

The interaction between silver nanoparticles (AgNPs) and molecules producing coronas plays a key role in cytotoxicity mechanisms. Once adsorbed coronas determine the destiny of nanomaterials in vivo, their effective deployment in the biomedical field requires a comprehensive understanding of the dynamic interactions of biomolecules with nanoparticles. In this work, we characterized 40nm AgNPs in three different nutritional cell media at different molar concentrations and incubation times to study the binding mechanism of molecules on surface nanoparticles. In addition, their cytotoxic effects have been studied in three cell lineages used as tissue regeneration models: FN1, HUV-EC-C, RAW 264.7. According to the data, when biomolecules from DMEM medium were in contact with AgNPs, agglomeration and precipitation occurred. However, FBS medium proteins indicated the formation of coronas over the nanoparticles. Nonetheless, little adsorption of molecules around the nanoparticles was observed when compared to DMEM supplemented with 10% FBS. These findings indicate that when nanoparticles and bioproteins from supplemented media interact, inorganic salts from DMEM contribute to produce large bio-coronas, the size of which varies with the concentration and time. The static quenching mechanism was shown to be responsible for the fluorescence quenching of the bioprotein aggregates on the AgNPs surface. The calculated bioprotein-nanoparticle surface binding constants were on the order of 105M-1 at 37°C, with hydrophobic interactions driven by enthalpy and entropy playing a role, as confirmed by thermodynamic analysis. Cytotoxicity data showed a systematic degrowth in the viable cell population as the number of nanoparticles increased and the diameter of coronas decreased. Cytotoxic intervals associated with half decrease of cell population were established for AgNPs molar concentration of 75µM for 24h and 50µM for 48h. In summary, through the cytotoxicity mechanism of bio-coronas we are able to manipulate cells' expansion rates to promote specific processes, such inflammatory mechanisms, at different time instants.

Three-dimensional bioprinting for musculoskeletal regeneration and disease modeling

Musculoskeletal disease and injury are highly prevalent disorders that impose tremendous medical and socioeconomic burdens. Tissue engineering has attracted increasing attention as a promising technique of regenerative medicine to restore degenerative or damaged tissues and is used to produce functional disease models. As a revolutionary technology, three-dimensional (3D) bioprinting has demonstrated a considerable potential in enhancing the versatility of tissue engineering. 3D bioprinting allows for the rapid and accurate spatial patterning of cells, growth factors, and biomaterials to generate biomimetic tissue constructs. Meanwhile, 3D-bioprinted in vitro models also offer a viable option to enable precise pharmacological interventions in various diseases. This review provides an overview of 3D bioprinting methods and bioinks for therapeutic applications and describes their potential for musculoskeletal tissue regeneration. We also highlight the fabrication of 3D-bioprinted models for drug development targeting musculoskeletal disease. Finally, the existing challenges and future perspectives of 3D bioprinting for musculoskeletal regeneration and disease modeling are discussed.

Regeneration in the dorids exemplified by Onchidoris muricata (Gastropoda, Nudibranchia)

Regenerative capabilities vary among different groups of invertebrates and despite being a highly abundant and diverse group of invertebrates with significant commercial and scientific value, gastropods remain relatively understudied in this respect. This work presents the first investigation of post–traumatic regeneration in the nudibranch mollusc Doridina, specifically focusing on Onchidoris muricata. Dorids have unique subepidermal calcite spicules that form a complex network inside the body. However, their capacity for complete or partial recovery, as well as the impact on regeneration of organs containing these spicules, has never been studied. We examined the regeneration of chemosensory organs (rhinophores) and dorsal body outgrowths (tubercle), both containing spicules and having different innervation. Our investigation explores three models of rhinophore regeneration: 1) after the removal of the apex and three lamellae of the rhinophore, 2) when the entire metameric lammelae part is removed, and 3) when the rhinophore is entirely excised. Additionally, two series of experiments were conducted to examine tubercle regeneration in the peribranchial region and in the rhinophore region. The study reveals varying regenerative abilities of these organs, likely linked to their different innervation patterns. Notably, we observed that the presence of the apex and spicules de novo synthesis influence the formation of the first rhinophore lamellae. The search for new patterns and mechanisms underlying the restoration of elements in the nervous system, muscular system, and solid skeleton can significantly contribute to our understanding of regenerative biology. This research expands our knowledge of nudibranch molluscs regeneration and the unique restoration of the subepidermal spicule complex. Furthermore, the regeneration of spicule-containing organs can be a model for studying the formation and structure of biomineralized structures, including their organic component.

Cross-linking manipulation of waterborne biodegradable polyurethane for constructing mechanically adaptable tissue engineering scaffolds.

Mechanical adaptation of tissue engineering scaffolds is critically important since natural tissue regeneration is highly regulated by mechanical signals. Herein, we report a facile and convenient strategy to tune the modulus of waterborne biodegradable polyurethanes (WBPU) via cross-linking manipulation of phase separation and water infiltration for constructing mechanically adaptable tissue engineering scaffolds. Amorphous aliphatic polycarbonate and trifunctional trimethylolpropane were introduced to polycaprolactone-based WBPUs to interrupt interchain hydrogen bonds in the polymer segments and suppress microphase separation, inhibiting the crystallization process and enhancing covalent cross-linking. Intriguingly, as the crosslinking density of WBPU increases and the extent of microphase separation decreases, the material exhibits a surprisingly soft modulus and enhanced water infiltration. Based on this strategy, we constructed WBPU scaffolds with a tunable modulus to adapt various cells for tissue regeneration and regulate the immune response. As a representative application of brain tissue regeneration model in vivo, it was demonstrated that the mechanically adaptable WBPU scaffolds can guide the migration and differentiation of endogenous neural progenitor cells into mature neurons and neuronal neurites and regulate immunostimulation with low inflammation. Therefore, the proposed strategy of tuning the modulus of WBPU can inspire the development of novel mechanically adaptable biomaterials, which has very broad application value.

COTiR: Molecular Communication Model for Synthetic Exosome-Based Tissue Regeneration.

Mesenchymal stem cell (MSC)-derived exosomes are recognized as an unparalleled therapy for tissue damage rendered by COVID-19 infection and subsequent hyper-inflammatory immune response. However, the natural targeting mechanism of exosomes is challenging to detect the damaged tissue over long diffusion distances efficiently. The coordinated movement of exosomes is desired for successful identification of target sites. In this work, we propose a molecular communication model, CoTiR, with a bio-inspired directional migration strategy (DMS) for guided propagation of exosomes to target the damaged tissues. The model includes directional propagation, reception, and regeneration of tissue. The proposed model has the potential to be used in designing efficient communication systems in the nanodomain. We compare the proposed model to the basic random propagation model and show the efficacy of our model regarding the detection of multiple targets and the detection time required. Simulation results indicate that the proposed model requires a shorter period of time for a similar number of exosomes to detect the targets compared to the basic random propagation model. Furthermore, the results reveal a 99.96% decrease in the collagen concentration in the absence of inflammatory cytokine molecules compared to the collagen concentration in the presence of inflammatory cytokine molecules.

Evaluation of in vitro osteoblast and osteoclast differentiation from stem cell: a systematic review of morphological assays and staining techniques.

Understanding human stem cell differentiation into osteoblasts and osteoclasts is crucial for bone regeneration and disease modeling. Numerous morphological techniques have been employed to assess this differentiation, but a comprehensive review of their application and effectiveness is lacking. Guided by the PRISMA framework, we conducted a rigorous search through the PubMed, Web of Science and Scopus databases, analyzing 254 articles. Each article was scrutinized against pre-defined inclusion criteria, yielding a refined selection of 14 studies worthy of in-depth analysis. The trends in using morphological approaches were identified for analyzing osteoblast and osteoclast differentiation. The three most used techniques for osteoblasts were Alizarin Red S (mineralization; six articles), von Kossa (mineralization; three articles) and alkaline phosphatase (ALP; two articles) followed by one article on Giemsa staining (cell morphology) and finally immunochemistry (three articles involved Vinculin, F-actin and Col1 biomarkers). For osteoclasts, tartrate-resistant acid phosphatase (TRAP staining) has the highest number of articles (six articles), followed by two articles on DAPI staining (cell morphology), and immunochemistry (two articles with VNR, Cathepsin K and TROP2. The study involved four stem cell types: peripheral blood monocyte, mesenchymal, dental pulp, and periodontal ligament. This review offers a valuable resource for researchers, with Alizarin Red S and TRAP staining being the most utilized morphological procedures for osteoblasts and osteoclasts, respectively. This understanding provides a foundation for future research in this rapidly changing field.

Hierarchical double-layer microneedles accomplish multicenter skin regeneration in diabetic full-thickness wounds

IntroductionManaging large chronic wounds presents significant challenges because of inadequate donor sites, infection, and lack of structural support from dermal substitutes. Hydrogels are extensively used in various forms to promote chronic wound healing and provide a three-dimensional spatial structure, through growth factors or cell transport. ObjectivesWe present a novel multicenter regenerative model that is capable of regenerating and merging simultaneously to form a complete layer of skin. This method significantly reduces wound healing time compared to the traditional centripetal healing model. We believe that our model can improve clinical outcomes and pave the way for further research into regenerative medicine. MethodsWe prepared a novel multi-island double-layer microneedle (MDMN) using gelatin-methacryloylchitosan (GelMA-CS). The MDMN was loaded with keratinocytes (KCs) and dermal fibroblasts (FBs). Our aim in this study was to explore the therapeutic potential of MDMN in a total skin excision model. ResultsThe MDMN model replicated the layered structure of full-thickness skin and facilitated tissue regeneration and healing via dual omni-bearing. Multi-island regeneration centres accomplished horizontal multicentric regeneration, while epidermal and dermal cells migrated synchronously from each location. This produced a healing area approximately 4.7 times greater than that of the conventional scratch tests. The MDMN model exhibited excellent antibacterial properties, attributed to the chitosan layer. During wound healing in diabetic mice, the MDMN achieved earlier epidermal coverage and faster wound healing through multi-island regeneration centres and the omnidirectional regeneration mode. The MDMN group displayed an accelerated wound healing rate upon arrival at the destination (0.96 % ± 0.58 % vs. 4.61 % ± 0.32 %). Additionally, the MDMN group exhibited superior vascularization and orderly collagen deposition. ConclusionThe present study presents a novel skin regeneration model using microneedles as carriers of autologous keratinocytes and dermal fibroblasts, which allows for omni-directional, multi-center, and full-thickness skin regeneration.

Nanotube topography rejuvenates the senescence of mesenchymal stem cells by activating YAP signalling.

Improving the regenerative ability of senescent stem cells is a critical issue in combating aging. The destiny and function of senescent stem cells are controlled by the niche, including the physical architecture of the surface of the extracellular matrix (ECM). In this study, we explored the functions of TiO2 nanotube topography on mesenchymal stem cells (MSCs) under senescence, as well as its mechanical effects on senescence. First, we created different nanotube topographies on the titanium samples. Next, we cultured senescent mesenchymal stem cells (S-MSCs) on samples with various nanotube topographies to determine suitable parameters. We found nanotube with a diameter of 10 nm significantly alleviated the cellular senescence of S-MSCs and improved the osteogenic differentiation of S-MSCs in vitro. Using an ectopic periodontium regeneration model, we confirmed that specific nanotube topography could promote tissue regeneration of S-MSCs in vivo. Moreover, we demonstrated that nanotube topography activated YAP in S-MSCs and reformed nuclear-cytoskeletal morphology to inhibit senescence. Taken together, our study establishes a bridge linking between nano-topography, mechanics, and senescence, suggesting a potential strategy to improve tissue regeneration in aged individuals by providing optimized surface topography on biomaterials.

The Kyai’s Strategy to Develop Cadres with Islamic Characters

This article aims to explain the Islamic character regeneration model in Islamic boarding schools and the strategy of the kyai as the highest leader in developing Islamic character regeneration for students. The location of this research, namely Arrisalah Modern Islamic Boarding School Ponorogo, is unique from other sites because of the curriculum or general subjects at the Islamic boarding school, which is famous for its salaf curriculum, which is integrated with Islamic values typical of Islamic boarding schools. This study uses an interpretive paradigm through a qualitative approach, a case study type. The primary data were obtained from caregivers, madrasa heads, teachers, students, and other parties involved, using data collection techniques such as in-depth interviews, observation, and documentation. The analysis technique used is the Miles and Huberman data reduction models, data display, and verification. Checking data validity using triangulation: credibility, transferability, dependability, and confirmability. The study results show that the cadre model at Arrisalah Modern Islamic Boarding School is a reduction or transfer of the Islamic boarding school's Islamic character and values. The kyai's strategy in creating cadres with Islamic character is actualized in several aspects, including the kyai's example, curriculum, 'Ala Manhaj Rabbaniy education system, organization, Pondok discipline, and compulsory service. So, this research provides a lot of valuable insights into the cadre model in Islamic boarding schools, and it cannot be denied that there are still various opportunities for more in-depth and broad future research.

Freezing Injury in Mouse Masseter Muscle to Establish an Orofacial Muscle Fibrosis Model.

Orofacial muscle constitutes a subset of skeletal muscle tissue, with a distinct evolutionary trajectory and development origin. Unlike the somite-derived limb muscles, the orofacial muscles originate from the branchial arches, with exclusive contributions from the cranial neural crest. A recent study has revealed that regeneration is also different in the orofacial muscle group. However, the underlying regulatory mechanism remains to be uncovered. Current skeletal muscle regeneration models mainly focus on the limb and trunk muscle. In this protocol, dry ice was used to induce freezing injury in the mouse masseter muscle and tibialis anterior muscle to create an orofacial muscle fibrosis model. The temporal dynamics of muscle satellite cells and fibro-adipogenic progenitors were different between the two muscles, leading to impaired myofiber regeneration and excessive extracellular matrix deposition. With the help of this model, a deeper investigation into muscle regeneration in the orofacial area could be carried out to develop therapeutic approaches for patients with orofacial diseases.

Generation of a Transgenic Zebrafish Model for Pancreatic Beta Cell Regeneration

Background: Diabetes is a major worldwide health problem. It is widely accepted that the beta cell mass decreases in type I diabetes (T1D). Accordingly, beta cell regeneration is a promising approach to increase the beta cell mass in T1D patients. However, the underlying mechanisms of beta cell regeneration have yet to be elucidated. One promising avenue is to create a relevant animal model to explore the underlying molecular and cellular mechanisms of beta cell regeneration. The zebrafish can be considered a model in beta cell regeneration studies because the pancreas structure and gene expression pattern are highly conserved between human and zebrafish. Materials and Methods: In this study, the Tol2 transposase was exploited to generate a Tg(Ins:egfp-nfsB) zebrafish model that expressed a fusion protein composed of enhanced green fluorescent protein (EGFP) and nitroreductase (NTR) under control of the Ins promoter. Results: Metronidazole (MTZ) treatment of Tg(ins:egfp-nfsB) zebrafish larvae led to selective ablation of beta cells. Proof-of-concept evidence for beta cell regeneration in the transgenic larvae was observed two days after withdrawal of MTZ. Conclusion: This study suggests that the Tg(ins:egfp-nfsB) zebrafish can be used as a disease model to study beta cell regeneration and elucidate underlying mechanisms during the regeneration process. [GMJ.2019;8:e1056]

Continuous tooth replacement: what can teleost fish teach us?

Most tooth-bearing non-mammalian vertebrates have the capacity to replace their teeth throughout life. This capacity was lost in mammals, which replace their teeth only once at most. Not surprisingly, continuous tooth replacement has attracted much attention. Classical morphological studies (e.g. to analyse patterns of replacement) are now being complemented by molecular studies that investigate the expression of genes involved in tooth formation. This review focuses on ray-finned fish (actinopterygians), which have teeth often distributed throughout the mouth and pharynx, and more specifically on teleost fish, the largest group of extant vertebrates. First we highlight the diversity in tooth distribution and in tooth replacement patterns. Replacement tooth formation can start from a distinct (usually discontinuous and transient) dental lamina, but also in the absence of a successional lamina, e.g. from the surface epithelium of the oropharynx or from the outer dental epithelium of a predecessor tooth. The relationship of a replacement tooth to its predecessor is closely related to whether replacement is the result of a prepattern or occurs on demand. As replacement teeth do not necessarily have the same molecular signature as first-generation teeth, the question of the actual trigger for tooth replacement is discussed. Much emphasis has been laid in the past on the potential role of epithelial stem cells in initiating tooth replacement. The outcome of such studies has been equivocal, possibly related to the taxa investigated, and the permanent or transient nature of the dental lamina. Alternatively, replacement may result from local proliferation of undifferentiated progenitors, stimulated by hitherto unknown, perhaps mesenchymal, factors. So far, the role of the neurovascular link in continuous tooth replacement has been poorly investigated, despite the presence of a rich vascularisation surrounding actinopterygian (as well as chondrichthyan) teeth and despite a complete arrest of tooth replacement after nerve resection. Lastly, tooth replacement is possibly co-opted as a process to expand the number of teeth in a dentition ontogenetically whilst conserving features of the primary dentition. That neither a dental lamina, nor stem cells appear to be required for tooth replacement places teleosts in an advantageous position as models for tooth regeneration in humans, where the dental lamina regresses and epithelial stem cells are considered lost.

Building a “reservoir of social resilience:” A strategy for social infrastructure regeneration in shrinking cities based on social network analysis

Northeast China is generally experiencing a shrinkage phenomenon similar to that in other old industrial regions worldwide. Large-scale growth-oriented regeneration programs by the government over the long term have led to the decline of social infrastructure in inner cities, thereby causing a structural crisis at the social level, and exacerbating the negative effects of shrinkage. This study investigated Hegang as a typical shrinking city in northeastern China. Coupling analysis was conducted based on network indexes and two categories of social resilience indexes to identify the key social infrastructure that provides residents with resilience to help cope with shrinkage. Our results demonstrate the centralizing effect of large-scale retail sites, and large green spaces and squares on social resilience. We also found that these categories of social infrastructure had effects across different areas of the city, which then provided social resilience to a wider range of residents. Our results also provide evidence for inequalities in the ability of residents to cope with shrinkage. Based on these findings, we characterize China's urban shrinkage and future development trends, and discuss the limitations of the regeneration model that has long been adopted by local governments. We suggest that local governments should consider incorporating investment in resilience to shrinkage into regeneration policies. They should also consider regenerating social infrastructure and deploying funds to a holistic network to build “reservoirs” of social resilience in shrinking cities. In addition, we highlight our methodological contributions and argue that social resilience monitoring should be integrated into China's urban physical examination framework to enhance dynamic planning and the sustainable regeneration capacity of shrinking urban local governments.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats

BackgroundThis animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). MethodsWistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. ResultsIn ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DiscussionThis study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.