A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy.

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway.

Xenogeneic extracellular matrices (xECM) for cell support have emerged as a potential strategy for addressing the scarcity of donor matrices for allotransplantation. However, the poor survival rate or failure of xECM-based organ transplantation is due to the negative impacts of high-level oxidative stress and inflammation on seed cell viability and stemness. Herein, we constructed xenogeneic bioengineered tooth roots (bio-roots) and used extracellular vesicles from human adipose-derived mesenchymal stem cells (hASC-EVs) to shield bio-roots from oxidative damage. Pretreatment with hASC-EVs reduced cell apoptosis, reactive oxygen species generation, mitochondrial changes, and DNA damage. Furthermore, hASC-EV treatment improved cell proliferation, antioxidant capacity, and odontogenic and osteogenic differentiation, while significantly suppressing oxidative damage by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) nuclear translocation via p62-associated Kelch-like ECH-associated protein 1 (KEAP1) degradation. Inhibition of PI3K/Akt and Nrf2 knockdown reduced antioxidant capacity, indicating that the PI3K/Akt/NRF2 pathway partly mediates these effects. In subcutaneous grafting experiments using Sprague-Dawley rats, hASC-EV administration significantly enhanced the antioxidant effect of the bio-root, improved the regeneration efficiency of periodontal ligament-like tissue, and maximized xenograft function. Conclusively, therefore, hASC-EVs have the potential to be used as an immune modulator and antioxidant for treating oxidative stress-induced bio-root resorption and degradation, which may be utilized for the generation and restoration of other intricate tissues and organs.

Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study.

OBJECTIVES: To investigate the clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement of ameloblastoma with mucous cell differentiation. MATERIALS AND METHODS: Five cases of ameloblastoma with mucous cell differentiation were retrospectively studied. Clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement were analyzed. Follow-up information was available for all cases. RESULTS: Of five cases, two cases were male and three were female, aged 18-55 years. Four cases were located in the mandible and one case in the maxilla. Histologically, four of the five cases (80%) presented with cystic features and three of the five cases (60%) with varying degrees of squamous metaplasia. The mucous cells were located in the epithelial islands or the luminal aspect of the cystic cavities. The BRAF V600E mutation was found in three of five cases (60%). All the cases showed no MAML2 rearrangement. Two cases were recurrent lesions, and one case had a local recurrence during the follow-up. CONCLUSIONS: Ameloblastoma with mucous cell differentiation is closely related to the cystic features, squamous metaplasia, and shows a high prevalence of BRAF V600E mutation. The absence of MAML2 rearrangement reveals that ameloblastoma with mucous cell differentiation and central mucoepidermoid carcinoma (MEC) are two distinct tumor entities.

CeO2@PAA-LXW7 Attenuates LPS-Induced Inflammation in BV2 Microglia.

Microglia are the inherent immune effector cells in the central nervous system (CNS), are activated rapidly when the CNS is stimulated by ischaemia, infection, injury, etc. and participate in and aggravate the development of inflammatory reactions in the CNS. During the process of microglial activation, inflammatory factors such as TNF-α and IL-1ß and an abundance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), are released by damaged nerve cells. LXW7 is a small molecule peptide and specifically binds with integrin αvß3. Cerium oxide nanoparticles (nanoceria) are strong free radical scavengers and are widely used in many studies. In this research, a model of inflammation was established using lipopolysaccharide (LPS) to induce BV2 microglia activation, and the effects of CeO2@PAA (synthetic nanoscale cerium oxide particles), LXW7 and CeO2@PAA-LXW7 were evaluated. We detected the expression level of inflammatory factors, the release of NO in BV2 cells and the generation of intracellular ROS. The expression levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) and their phosphorylated proteins were detected in BV2 microglia. We found that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 all effectively inhibited the activation of BV2 microglia, reduced the production of cytokines and the release of NO and reduced the production of intracellular ROS. The three treatments all inhibited the phosphorylation of FAK and STAT3 in BV2 microglia. Regarding these effects, CeO2@PAA-LXW7 was more effective than the other two monotherapies. Our data indicate that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 can exert a neuroprotective function by inhibiting the inflammatory response of LPS-induced BV2 microglia. LXW7 may inhibit the activation of FAK and STAT3 signals in combination with integrin αvß3 to restrain neuroinflammation and the antioxidative stress effect of cerium oxide; hence, CeO2@PAA-LXW7 can exert a more robust anti-inflammatory and neuroprotective effect via synergistically suppressing the ability of LXW7 to influence the integrin pathway and the free radical-scavenging ability of CeO2@PAA.

A fast nucleic acid extraction system for point-of-care and integration of digital PCR.

Digital PCR is a powerful amplification method for absolute quantification of nucleic acids. The systems that integrated the nucleic acid extraction and amplification can reduce detection time, improve accuracy, and reduce labor costs. However, current nucleic acid extraction systems cannot be integrated well with integrated fluidic circuit (IFC) dPCR or droplet digital PCR chips perfectly and limit the application of digital PCR. In this study, a polytetrafluoroethylene (PTFE)-based nucleic acid extraction (PNE) system, which was able to achieve fully closed extraction for micro samples and was able to be integrated with IFC dPCR or droplet digital dPCR (ddPCR) chips perfectly is proposed. For this system, PTFE tubing with an inner diameter of 1 mm was used to load the reagents and superparamagnetic particles (PMPs) were used to extract nucleic acids. The system can extract nucleic acids from cells and blood in 5 minutes. Meanwhile, when nucleic acid extraction was completed, PNE was able to be directly combined with IFC dPCR or ddPCR chips without any intermediate steps. Therefore, the PNE system can realize sample-in-digital-answer-out. It will be highly useful in point-of-care (POC) and promote the development and application of dPCR.

Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells.

CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvß3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2@PAA-LXW7, a new compound that couples CeO2@PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2O2-induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO2@PAA, and CeO2@PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H2O2-induced injury. We used H2O2-induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO2@PAA-LXW7. In this study, LXW7, CeO2@PAA, and CeO2@PAA-LXW7 inhibit H2O2-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H2O2-induced NGF-differentiated PC12 cells, whereas LXW7, CeO2@PAA, and CeO2@PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO2@PAA-LXW7 on H2O2-induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO2@PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H2O2-induced NGF-differentiated PC12 cells. LXW7, CeO2@PAA, and CeO2@PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H2O2 in NGF-differentiated PC12 cells. CeO2@PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO2@PAA.

Improved Cancer Immunochemotherapy via Optimal Co-delivery of Chemotherapeutic and Immunomodulatory Agents.

It is highly demanded and still a big challenge to develop an effective formulation for immunochemotherapy against advanced tumors. We have previously reported a PEG-NLG-based immunostimulatory nanocarrier (PEG2k-Fmoc-NLG919) for co-delivery of an IDO1 inhibitor (NLG919) and a chemotherapeutic agent (paclitaxel, PTX). Although antitumor immune responses were enhanced with a PTX-loaded nanocarrier, the accumulation of myeloid-derived suppressor cells (MDSCs) was also significantly increased, which may limit the overall efficacy of therapy. In the present work, we developed an improved dual-functional nanocarrier (PEG5k-Fmoc-NLG2) to co-load PTX and sunitinib (SUN, a multitarget receptor tyrosine kinase inhibitor) for improved cancer immunochemotherapy. We found that the recruited MDSCs negatively impacted the overall antitumor activity of the PTX-loaded PEG-NLG nanocarrier. Mechanistic study suggests that this is likely attributed to the PTX-mediated induction of a number of chemokines that are involved in the recruitment of MDSCs. We have further shown that the induction of these chemokines was drastically blocked by SUN. Co-delivery of PTX and SUN via the PEG5k-Fmoc-NLG9192 nanocarrier led to a further improvement in the therapeutic efficacy with a concomitant reduction in MDSCs.

Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization.

Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based cationic lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of "lipid-raft-mediated endocytosis→lysosome→cell nucleic localization" was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application.

Lymphoma Immunochemotherapy: Targeted Delivery of Doxorubicin via a Dual Functional Nanocarrier.

Chemotherapy drug (paclitaxel, PTX) incorporated in a dual functional polymeric nanocarrier, PEG-Fmoc-NLG, has shown promise as an immunochemotherapy in a murine breast cancer model, 4T1.2. The formulation is composed of an amphiphilic polymer with a built-in immunotherapy drug NLG919 that exhibits the immunostimulatory ability through the inhibition of indoleamine 2,3-dioxygenase 1 (IDO-1) in cancer cells. This work evaluates whether the PEG-derivatized NLG polymer can also be used for delivery of doxorubicin (Dox) in treatment of leukemia. The Dox-loaded micelles were self-assembled from PEG-Fmoc-NLG conjugate, which have a spherical shape with a uniform size of ∼120 nm. In cultured murine lymphocytic leukemia cells (A20), Dox-loaded PEG-Fmoc-NLG micelles showed a cytotoxicity that was comparable to that of free Dox. For in vivo studies, significantly improved antitumor activity was observed for the Dox/PEG-Fmoc-NLG group compared to Doxil or the free Dox group in an A20 lymphoma mouse model. Flow cytometric analysis showed that treatment with Dox/PEG-Fmoc-NLG micelles led to significant increases in the numbers of both total CD4+/CD8+ T cells and the functional CD4+/CD8+ T cells with concomitant decreases in the numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Treg). Dox/PEG-Fmoc-NLG may represent a promising immunochemotherapy for lymphoma, which warrants more studies in the future.

Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier.

To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles). DOX/PSSN10 micelles displayed spherical morphology with a size of ∼170 nm. DOX was effectively loaded into PSSN10 micelles with a loading efficiency of 84.0%. In vitro DOX release studies showed that rapid drug release could be achieved in the highly redox environment after intracellular uptake by tumor cells. In 4T1.2 tumor-bearing mice, DOX/PSSN10 micelles exhibited greater accumulation of DOX and NLG in the tumor tissues compared with other organs. The PSSN10 carrier dose-dependently enhanced T-cell immune responses in the lymphocyte-Panc02 co-culture experiments, and significantly inhibited tumor growth in vivo. DOX/PSSN10 micelles showed potent cytotoxicity in vitro against 4T1.2 mouse breast cancer cells and PC-3 human prostate cancer cells comparable to that of DOX. In 4T1.2 tumor-bearing mice, DOX/PSSN10 mixed micelles (5 mg DOX/kg, iv) was more effective than DOXIL (a clinical formulation of liposomal DOX) or free DOX in inhibiting the tumor growth and prolonging the survival of the treated mice. In addition, a more immunoactive tumor microenvironment was observed in the mice treated with PSSN10 or DOX/PSSN10 micelles compared with the other treatment groups. In conclusion, systemic delivery of DOX via PSSN10 nanocarrier results in synergistic anti-tumor activity.

Cells isolated from cryopreserved dental follicle display similar characteristics to cryopreserved dental follicle cells.

Dental follicle tissue is a promising resource of mesenchymal stem cells for cytotherapeutic approaches and tissue engineering applications. There are two procedures for banking of human dental follicle stem cells have been reported. Conventional method requires cell isolation, expansion and immediate cryopreservation. Whereas dental follicle stem cells can be isolated from cryopreserved dental follicle fragments. The aim of this study was to compare the characteristics of dental follicle cells isolated from cryopreserved fragments (DFCs-CF) with dental follicle cells recovered from cryopreserved cells (DFCs-CC). Dental follicle fragments obtained after mechanical disaggregation were divided into two parts, with one part maintained in culture, while another part underwent cryopreservation. Dental follicle fragments and dental follicle cells from fresh tissue were stored in liquid nitrogen for 3 months. After thawing, the isolation, morphology, proliferation, cell cycle, colony-forming-unit ability, stemness-related marker expression, apoptosis, and multi-lineage differentiation potential of DFCs-CF were tested compared with DFCs-CC. DFCs-CF expressed mesenchymal stem cells marker, proliferated well, showed similar levels of mRNA for stemness- and apoptosis-related genes and exhibited the capacity of multi-lineage differentiation similar to those of DFCs-CC. These results imply that cryopreservation of dental follicle fragments is an effective banking method for isolation of dental follicle cells.

Amphiphilic Diblock Terpolymer PMAgala-b-P(MAA-co-MAChol)s with Attached Galactose and Cholesterol Grafts and Their Intracellular pH-Responsive Doxorubicin Delivery.

In this work, a series of diblock terpolymer poly(6-O-methacryloyl-D-galactopyranose)-b-poly(methacrylic acid-co-6-cholesteryloxy hexyl methacrylate) amphiphiles bearing attached galactose and cholesterol grafts denoted as the PMAgala-b-P(MAA-co-MAChol)s were designed and prepared, and these terpolymer amphiphiles were further exploited as a platform for intracellular doxorubicin (DOX) delivery. First, employing a sequential RAFT strategy with preliminarily synthesized poly(6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose) (PMAIpGP) macro-RAFT initiator and a successive trifluoroacetic acid (TFA)-mediated deprotection, a series of amphiphilic diblock terpolymer PMAgala-b-P(MAA-co-MAChol)s were prepared, and were further characterized by NMR, Fourier transform infrared spectrometer (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and a dynamic contact angle testing instrument (DCAT). In aqueous media, spontaneous micellization of the synthesized diblock terpolymer amphiphiles were continuously examined by critical micellization concentration assay, dynamic light scattering (DLS), and transmission electron microscopy (TEM), and the efficacies of DOX loading by these copolymer micelles were investigated along with the complexed nanoparticle stability. Furthermore, in vitro DOX release of the drug-loaded terpolymer micelles were studied at 37 °C in buffer under various pH conditions, and cell toxicities of as-synthesized diblock amphiphiles were examined by MTT assay. Finally, with H1299 cells, intracellular DOX delivery and localization by the block amphiphile vectors were investigated by invert fluorescence microscopy. As a result, it was revealed that the random copolymerization of MAA and MAChol comonomers in the second block limited the formation of cholesterol liquid-crystal phase and enhanced DOX loading efficiency and complex nanoparticle stability, that ionic interactions between the DOX and MAA comonomer could be exploited to trigger efficient DOX release under acidic condition, and that the diblock terpolymer micellular vector could alter the DOX trafficking in cells. Hence, these suggest the pH-sensitive PMAgala-b-P(MAA-co-MAChol)s might be further exploited as a smart nanoplatform toward efficient antitumor drug delivery.

Bio and nanomaterials based on Fe3O4.

During the past few years, nanoparticles have been used for various applications including, but not limited to, protein immobilization, bioseparation, environmental treatment, biomedical and bioengineering usage, and food analysis. Among all types of nanoparticles, superparamagnetic iron oxide nanoparticles, especially Fe3O4, have attracted a great deal of attention due to their unique magnetic properties and the ability of being easily chemical modified for improved biocompatibility, dispersibility. This review covers recent advances in the fabrication of functional materials based on Fe3O4 nanoparticles together with their possibilities and limitations for application in different fields.

A biocompatible pea protein isolate-derived bioink for 3D bioprinting and tissue engineering.

Three-dimensional bioprinting is a potent biofabrication technique in tissue engineering but is limited by inadequate bioink availability. Plant-derived proteins are increasingly recognized as highly promising yet underutilized materials for biomedical product development and hold potential for use in bioink formulations. Herein, we report the development of a biocompatible plant protein bioink from pea protein isolate. Through pH shifting, ethanol precipitation, and lyophilization, the pea protein isolate (PPI) transformed from an insoluble to a soluble form. Next, it was modified with glycidyl methacrylate to obtain methacrylate-modified PPI (PPIGMA), which is photocurable and was used as the precursor of bioink. The mechanical and microstructural studies of the hydrogel containing 16% PPIGMA revealed a suitable compress modulus and a porous network with a pore size over 100 µm, which can facilitate nutrient and waste transportation. The PPIGMA bioink exhibited good 3D bioprinting performance in creating complex patterns and good biocompatibility as plenty of viable cells were observed in the printed samples after 3 days of incubation in the cell culture medium. No immunogenicity of the PPIGMA bioink was identified as no inflammation was observed for 4 weeks after implantation in Sprague Dawley rats. Compared with methacrylate-modified gelatin, the PPIGMA bioink significantly enhanced cartilage regeneration in vitro and in vivo, suggesting that it can be used in tissue engineering applications. In summary, the PPIGMA bioink can be potentially used for tissue engineering applications.

Unveiling the residual plastics and produced toxicity during biodegradation of polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) microplastics by mealworms (Larvae of Tenebrio molitor).

Evidence for plastic degradation by mealworms has been reported. However, little is known about the residual plastics derived from incomplete digestion during mealworm-mediated plastic biodegradation. We herein reveal the residual plastic particles and toxicity produced during mealworm-mediated biodegradation of the three most common microplastics, i.e., polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC). All three microplastics are effectively depolymerized and biodegraded. We discover that the PVC-fed mealworms exhibit the lowest survival rate (81.3 ± 1.5%) and the highest body weight reduction (15.1 ± 1.1%) among the experimental groups by the end of the 24-day experiment. We also demonstrate that the residual PVC microplastic particles are more difficult to depurate and excrete for the mealworms compared to the residual PE and PS particles by using laser direct infrared spectrometry. The levels of oxidative stress responses, including reactive oxygen species, antioxidant enzyme activities, and lipid peroxidation, are also highest in the PVC-fed mealworms. Sub-micron microplastics and small microplastics are found in the frass of mealworms fed with PE, PS, and PVC, with the smallest particles detected at diameters of 5.0, 4.0, and 5.9 µm, respectively. Our findings provide insights into the residual microplastics and microplastic-induced stress responses in macroinvertebrates under micro(nano)plastics exposure.

Biomimetic, biodegradable and osteoinductive treated dentin matrix/α-calcium sulphate hemihydrate composite material for bone tissue engineering.

It is still a huge challenge for bone regenerative biomaterial to balance its mechanical, biological and biodegradable properties. In the present study, a new composite material including treated dentin matrix (TDM) and α-calcium sulphate hemihydrate (α-CSH) was prepared. The optimal composition ratio between TDM and α-CSH was explored. The results indicate that both components were physically mixed and structurally stable. Its compressive strength reaches up to 5.027 ± 0.035 MPa for 50%TDM/α-CSH group, similar to human cancellous bone tissues. Biological experiments results show that TDM/α-CSH composite exhibits excellent biocompatibility and the expression of osteogenic related genes and proteins (ALP, RUNX2, OPN) is significantly increased. In vivo experiments suggest that the addition of TDM for each group (10%, 30%, 50%) effectively promotes cell proliferation and osteomalacia. In addition, 50% of the TDM/α-CSH combination displays optimal osteoconductivity. The novel TDM/α-CSH composite is a good candidate for certain applications in bone tissue engineering.

GLI1 amplified/fused mesenchymal tumor: A case report and review of the literature.

Glioma-associated oncogene homologue 1 (GLI1) is an important transcription factor downstream of Hedgehog (HH) signaling pathway, and can be used as a marker of HH signaling pathway activation. GLI1 gene translocations have been reported in several tumor types, including those associated with t(7;12) translocated dermatocytoma, plexus fibromyxoma, and gastroblastoma and other types of malignant soft tissue tumors, whereas GLI1 amplification is actually very rare in tumors. In this case report, we describe for the first time a tumor in the right mandibular gingiva, which is consistent with GLI1 amplified/fused mesenchymal tumor. The tumor cells are elliptic, polygonal and spindle tumor cells growing into nests and segments, lobulated and occasionally mitotic. The identification of these pathological features can help guide pathologists to make appropriate diagnosis and, if necessary, follow-up molecular tests. Our case has been treated with surgical resection. To date, no recurrence or metastasis has occurred and the prognosis is good.

As(III) oxidation and kinetic analysis by Herminiimonas arsenicoxydans-loaded electrospinning activated carbon fiber biofilms.

In this study, an integrated and assembled recyclable biofilm material was prepared by loading Herminiimonas arsenicoxydans (H. arsenicoxydans) onto electrospun biomass-activated carbon nanofibers (denoted as H. arsenicoxydans-BACFs films). The H. arsenicoxydans-BACFs biofilms showed an approximately 50% increase in As(III) removal rate for 50 mg/L during a 48-h incubation. Furthermore, the biofilms demonstrated satisfactory biocompatibility, ideal catalytic As(III) oxidation and excellent recyclability in cyclic reactions (at least 5 runs). The improved catalytic efficiency is mainly due to a large amount of biomass accumulation and biofilms formation on the surface of the BACF films. More important, the BACF films as an electron transport medium from an oxidized state to a reduced state promote the electron transfer of As(III) oxidation of H. arsenicoxydans. The dual factors can synergistically promote As(III) oxidation efficiency. The oxidation process of As(III) in the H. arsenicoxydans-BACFs composite biofilm reactor was more in line with the first-order kinetic equation, and the oxidation rate of As(III) by H. arsenicoxydans-BACF0.4 was the fastest. The H. arsenicoxydans-BACF films outperformed conventional catalytic materials and could represent biomaterials for the remediation of As(III)-contaminated wastewater.

Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/ß-catenin signaling.

Treated dentin matrix (TDM) is an ideal scaffold material containing multiple extracellular matrix factors. The canonical Wnt signaling pathway is necessary for tooth regeneration. Thus, this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and determined the potential role of Wnt/ß-catenin signaling in this process. Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile, the expression of GSK3ß was decreased. Of note, the expression of the Wnt/ß-catenin pathway-related genes changed significantly in the context of TDM induction, as per RNA sequencing (RNA seq) data. In addition, the experiment showed that new dentin was visible in rat mandible cultured with TDM, and the thickness was significantly thicker than that of the control group. In addition, immunohistochemical staining showed lower GSK3ß expression in new dentin. Consistently, the GSK3ß knockdown hDPSCs performed enhanced odotogenesis compared with the control groups. However, GSK3ß overexpressing could decrease odotogenesis of TDM-induced hDPSCs. These results were confirmed in immunodeficient mice and Wistar rats. These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3ß and activating the canonical Wnt/ß-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.

Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells.

BACKGROUND: shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV) receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells. RESULTS: Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 10(6) TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 10(2) TCID(50) of FMDV. CONCLUSIONS: Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.