Quantitative Assessment of Tumor Contact with Neurogenic Zones and Its Effects on Survival: Insights beyond Traditional Predictors.

So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM's relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann-Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic.

Superoxide Dismutase-Mimetic Polyphenol-Based Carbon Dots for Multimodal Bioimaging and Treatment of Atopic Dermatitis.

Polyphenols have been investigated for their potential to mitigate inflammation in the context of atopic dermatitis (AD). In this study, epigallocatechin-3-gallate (EGCG)-based carbon dots (EGCG@CDs) were developed to enhance transdermal penetration, reduce inflammation, recapitulate superoxide dismutase (SOD) activity, and provide antimicrobial effects for AD treatment. The water-soluble EGCG@CDs in a few nanometers size exhibit a negative zeta potential, making them suitable for effective transdermal penetration. The fluorescence properties, including an upconversion effect, make EGCG@CDs suitable imaging probes for both in vitro and in vivo applications. By mimicking the SOD enzyme, EGCG@CDs scavenge reactive oxygen species (ROS) and actively produce hydrogen peroxide through a highly catalytic capability toward the oxygen reduction reaction, resulting in the inhibition of bacterial growth. The enhanced antioxidant properties, high charge mobility, and various functional groups of EGCG@CDs prove effective in reducing intracellular ROS in an in vitro AD model. In the mouse AD model, EGCG@CDs incorporated into a hydrogel actively penetrated the epidermal layer, leading to ROS scavenging, reduced mast cell activation, and histological recovery of skin barriers. This research represents the versatile potential of EGCG@CDs in addressing AD and advancing tissue engineering.

Regenerative Potential of Bone Morphogenetic Protein 7-Engineered Mesenchymal Stem Cells in Ligature-Induced Periodontitis.

Periodontitis is an oral disease caused by bacterial infection that has stages according to the severity of tissue destruction. The advanced stage of periodontitis presents irreversible destruction of soft and hard tissues, which finally results in loss of teeth. When conventional treatment modalities show limited results, tissue regeneration therapy is required in patients with advanced periodontitis. In the present study, we aimed to evaluate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) delivering bone morphogenetic protein 7 (BMP7) on tissue regeneration in a periodontitis model. BMP7 is a member of the BMP family that shows bone-forming ability; however, BMPs rapid clearing and degradation and unproven efficacy make it difficult to apply it in clinical dentistry. To overcome this, we established BMP7-expressing engineered BM-MSCs (BMP7-eBMSCs) that showed superior osteogenic differentiation potential when subcutaneously transplanted with a biphasic calcium phosphate scaffold into immunocompromised mice. Furthermore, the efficacy of BMP7-eBMSC transplantation for periodontal tissue regeneration was evaluated in a rat ligature-induced periodontitis model. Upon measuring two-dimensional and three-dimensional amounts of regenerated alveolar bone using microcomputed tomography, the amounts were found to be significantly higher in the BMP7-eBMSC transplantation group than in the eBMSC transplantation group. Most importantly, fibrous periodontal ligament (PDL) tissue regeneration was also achieved upon BMP7-eBMSC transplantation, which was evaluated by calculating the modified relative connective tissue attachment. The amount of connective tissue attachment in the BMP7-eBMSC transplantation group was significantly higher than that in the ligature-induced periodontitis group, although the increase was comparable between the BMP7-eBMSC and human PDL stem cell transplantation groups. Taken together, our results suggested that sustainable release of BMP7 induces periodontal tissue regeneration and that transplantation of BMP7-eBMSCs is a feasible treatment option for periodontal regeneration. Impact Statement Periodontitis is the second most common human dental disease affecting chronic systemic diseases. Despite the tremendous efforts trying to cure the damaged periodontal tissues using tissue engineering technologies, a definitive regenerative method has not been in consensus. Researchers are seeking more feasible and abundant source of mesenchymal stem cells (MSCs), and furthermore, how to use reliable growth factors under more efficient control are the issues to be solved. In this study, we aimed to evaluate the effect of bone morphogenetic protein 7 (BMP7) gene delivering bone marrow-derived MSCs on periodontal tissue regeneration to evaluate the efficacy of BMP7 and engineered BMSCs for periodontal tissue regeneration.

Penoscrotal defect reconstruction using loco-regional flaps in treatment of extramammary Paget's disease: Experience and suggestion of a simplified algorithm.

BACKGROUND: Reconstruction of penoscrotal defects resulted from margin-controlled excision of extramammary Paget's disease (EMPD) remains challenging, due to its unpredictably varying extents. The present study aimed to investigate outcomes of reconstruction of penoscrotal defects following radical excision of EMPD and to introduce a simplified algorithm for selecting reconstruction strategies. METHODS: Patients with penoscrotal EMPD who were treated with wide excision and subsequent reconstruction from 2009 to 2020 were reviewed. Their demographics, operation-related characteristics, and postoperative outcomes were evaluated. RESULTS: In total, 46 patients with a mean age of 64.9 years (range, 44-85 years) were analyzed. An average size of defects was 129.6 cm2 (range, 8-900 cm2 ). The most frequently involving anatomical subunit was scrotum, followed by suprapubic area and penile shaft. Twenty-six patients had defects spanning multiple subunits. The most commonly used reconstruction methods for each anatomical subunit were internal pudendal artery perforator (IPAP) flaps and/or scrotal flaps for scrotal defects, superficial external pudendal artery perforator (SEPAP) flaps for suprapubic defects, and skin grafts for penile defects. In all but four cases, successful reconstruction was achieved with combination of those reconstruction options. No major complications developed except for one case of marginal flap necrosis. All patients were satisfied with their aesthetic and functional results. CONCLUSIONS: Diverse penoscrotal defects following excision of EMPD could be solidly reconstructed with combination of several loco-regional options. A simplified algorithm using in combination of IPAP flap, SEPAP flap, scrotal flap, and skin graft may enable efficient and reliable reconstruction of penoscrotal EMPD defects.

Dual action of a tyrosinase-mesoporous silica nanoparticle complex for synergistic tissue adhesion.

Bridging biological tissues for immediate adhesion and long-term sustainability was accomplished using a combination of mesoporous silica nanoparticles (MSNs) and tyrosinase. Tyrosinase-loaded MSNs provided rapid physical adsorption, while tyrosinase within MSNs induced enzymatic chemical bond gluing of tissues. This synergistic strategy has robust potential in tissue adhesives for clinical settings.

Salvage of impending rhinostomy failure after dacryocystorhinostomy with office-based microdebrider treatment.

PURPOSE: This article is to introduce office-based salvage revision of impending rhinostomy failure after endoscopic dacryocystorhinostomy (EN-DCR), using a microdebrider. METHODS: The authors conducted retrospective medical chart review of 27 eyes of 26 patients who underwent microdebrider treatment for impending rhinostomy failure in an office setting. After local anesthesia, obstructive soft tissue, interfering with ostium function (granuloma, cicatrization, synechia), was treated with a microdebrider (Osseoduo s120, Bien-Air Surgery, Le Noirmont, Switzerland) within 6 months after primary EN-DCR. Anatomical improvement and functional relief of epiphora were evaluated after revision. RESULTS: The causes of impending rhinostomy failure were granuloma formation (17/27 eyes, 63.0%), cicatrization (8/27 eyes, 29.6%), and synechial formation (2/27 eyes, 7.4%). The surgery did not exceed 5 min in all cases, and partial damage to pre-placed silicone tubes occurred in the first two cases (7.4%). Salvage revision resulted in anatomical success in all eyes, based on patent syringing and a positive functional endoscopic dye test. All cases showed improvement of epiphora after revision surgery. CONCLUSIONS: Office-based salvage revision using a microdebrider provided effective management of impending rhinostomy failure during early follow-up period after primary EN-DCR. It enabled prompt management of excessive wound healing interfering with ostium function, while performing the routine postoperative nasal debridement.

Identification of stemness and differentially expressed genes in human cementum-derived cells.

PURPOSE: Periodontal treatment aims at complete regeneration of the periodontium, and developing strategies for periodontal regeneration requires a deep understanding of the tissues composing the periodontium. In the present study, the stemness characteristics and gene expression profiles of cementum-derived cells (CDCs) were investigated and compared with previously established human stem cells. Candidate marker proteins for CDCs were also explored. METHODS: Periodontal ligament stem cells (PDLSCs), pulp stem cells (PULPSCs), and CDCs were isolated and cultured from extracted human mandibular third molars. Human bone marrow stem cells (BMSCs) were used as a positive control. To identify the stemness of CDCs, cell differentiation (osteogenic, adipogenic, and chondrogenic) and surface antigens were evaluated through flow cytometry. The expression of cementum protein 1 (CEMP1) and cementum attachment protein (CAP) was investigated to explore marker proteins for CDCs through reverse-transcription polymerase chain reaction. To compare the gene expression profiles of the 4 cell types, mRNA and miRNA microarray analysis of 10 samples of BMSCs (n=1), PDLSCs (n=3), PULPSCs (n=3), and CDCs (n=3) were performed. RESULTS: The expression of mesenchymal stem cell markers with a concomitant absence of hematopoietic markers was observed in PDLSCs, PULPSCs, CDCs and BMSCs. All 4 cell populations also showed differentiation into osteogenic, adipogenic, and chondrogenic lineages. CEMP1 was strongly expressed in CDCs, while it was weakly detected in the other 3 cell populations. Meanwhile, CAP was not found in any of the 4 cell populations. The mRNA and miRNA microarray analysis showed that 14 mRNA genes and 4 miRNA genes were differentially expressed in CDCs vs. PDLSCs and PULPSCs. CONCLUSIONS: Within the limitations of the study, CDCs seem to have stemness and preferentially express CEMP1. Moreover, there were several up- or down-regulated genes in CDCs vs. PDLSCs, PULPSCs, and BMSCs and these genes could be candidate marker proteins of CDCs.

Effect of contralateral augmentation on postoperative complications after the second stage of tissue expander/implant breast reconstruction.

BACKGROUND: Contralateral augmentation mammoplasty in implant-based reconstruction could potentially lead to deterioration of the thickness of the mastectomy skin flap and increase postoperative complications of the reconstructed breast. We compared the complication rates of the reconstructed breast in the augmentation and no-augmentation groups among patients undergoing tissue expander/implant breast reconstruction. METHODS: Patients who underwent mastectomy followed by tissue expander/implant breast reconstruction between February 2010 and April 2018 were retrospectively reviewed. The primary outcome measures were complications and the need for a revision operation. The augmentation and no-augmentation groups underwent propensity score-matched analysis and the matched cases underwent multivariable logistic regression analysis. RESULTS: From the 234 patients in the augmentation group and 517 patients in the no-augmentation group, 200 propensity score-matched pairs were obtained. Analysis of the matched pairs revealed that the augmentation group as compared to the no-augmentation group showed a significantly higher overall complication rate (13.5 percent versus 6.5 percent; P=0.025) and revision operation rate (9.0 percent versus 3.0 percent; P=0.019). Multivariable conditional logistic regression analyses of the matched cases revealed that contralateral augmentation (odds ratio, 3.457; 95% confidence interval, 1.039-11.498; P=0.043) was associated with increased odds for a revision operation of the reconstructed breast. CONCLUSIONS: This study investigated the postoperative complications of the reconstructed breast associated with contralateral augmentation mammoplasty in patients who underwent mastectomy followed by tissue expander/implant breast reconstruction. The augmentation group had a higher revision operation rate than did the no-augmentation group. A clinical evaluation of the risks and benefits of contralateral augmentation and preoperative counseling may be indicated for patients who are undergoing implant-based breast reconstruction and are candidates for contralateral augmentation mammoplasty.

Abdominal wall reconstruction using anterolateral thigh flap with microsurgical pedicle lengthening technique: A case report.

Pedicled anterolateral thigh (ALT) flap has been employed for coverage of low abdominal wall defects. However, its use is limited for defects located more on the cranial side because of insufficient pedicle length. We present a case of successful reconstruction of mid-abdominal wall defect using pedicled ALT flap, overcoming the issue of pedicle length shortage with a microsurgical pedicle lengthening technique. A 75-year-old man suffered from a 12 × 8 cm full-thickness soft tissue defect on his mid-abdominal wall originated from colon anastomosis site leakage after ileostomy takedown surgery. A pedicled ALT flap was planned for the defect coverage. After we performed debridement to prepare the wound bed, a 14 × 8.5 cm sized ALT flap based on two lateral circumflex femoral artery (LCFA) perforators was elevated. During intramuscular dissection of perforators, we dissected the distal portion of the LCFA descending branch. After full dissection of the pedicle to source vessels, we attempted to transfer the flap, but still the flap had short pedicle. We transected the pedicle just distal to the bifurcating point and reconnected it to the distal end of the dissected descending LCFA branch with microsurgical anastomosis. We passed the flap through a subcutaneous tunnel and conducted smooth flap insetting without any tension on the lengthened pedicle. Postoperatively, the wound healed successfully without complications. The patient was discharged 2 weeks after surgery and followed up at postoperative 3 months without adverse events. A local ALT flap with pedicle lengthened might be a reliable option for reconstruction of supraumbilical abdominal defects.

Validation of a three-dimensional printed model for training of surgical extraction of supernumerary teeth.

INTRODUCTION: This study aimed to validate a three-dimensional (3D) printed model to provide training for supernumerary teeth (SNTs) extraction. MATERIALS AND METHODS: Each of the 30 participants, grouped as experienced and without experience, conducted two identically simulated surgeries on a 3D-printed replica of human mixed dentition with a SNT. The surgery time, area of bony window and volume of removed material were measured; subsequently, responses to a five-item questionnaire were recorded. The collected data were statistically analysed. RESULTS: The surgery time was 228.37 ± 141.53 seconds and 125.47 ± 53.03 seconds in the first and second surgery, respectively. The training significantly decreased the surgery time in the participants without experience (P = .000). However, there were no significant differences in the area of window opening (P = .271) and volume of removed material between the two surgeries (P = .075). The participants who perceived educational benefits accounted for more than 60% of the respondents for every question. Participants without experience in SNT extraction showed a tendency to rate a higher score than did those with experience. CONCLUSIONS: A 3D-printed model for surgical extraction of a SNT can improve surgical skill and, especially, shorten the learning curve in beginners.

Facilitated Transdermal Drug Delivery Using Nanocarriers-Embedded Electroconductive Hydrogel Coupled with Reverse Electrodialysis-Driven Iontophoresis.

We herein developed an iontophoretic transdermal drug delivery system for the effective delivery of electrically mobile drug nanocarriers (DNs). Our system consists of a portable and disposable reverse electrodialysis (RED) battery that generates electric power for iontophoresis through the ionic exchange. In addition, in order to provide a drug reservoir to the RED-driven iontophoretic system, an electroconductive hydrogel composed of polypyrrole-incorporated poly(vinyl alcohol) (PYP) was used. The PYP hydrogel facilitated electron transfer from the RED battery and accelerated the mobility of electrically mobile DNs released from the PYP hydrogel. In this study, we showed that fluconazole- or rosiglitazone-loaded DNs could be functionalized with charge-inducing agents, and DNs with charge modification resulted in facilitated transdermal transport via repulsive RED-driven iontophoresis. In addition, topical application and RED-driven iontophoresis of rosiglitazone-loaded DNs resulted in an effective antiobese condition displaying decreased bodyweight, reduced glucose level, and increased conversion of white adipose tissues to brown adipose tissues in vivo. Consequently, we highlight that this transdermal drug delivery platform would be extensively utilized for delivering diverse therapeutic agents in a noninvasive way.

Fabrication of polyphenol-incorporated anti-inflammatory hydrogel via high-affinity enzymatic crosslinking for wet tissue adhesion.

Epigallocatechin gallates (EGCGs), isolated from green tea, have intrinsic properties such as anti-oxidant, anti-inflammation, and radical scavenger effects. In this study, we report a tissue adhesive and anti-inflammatory hydrogel formed by high-affinity enzymatic crosslinking of polyphenolic EGCGs. A mixture of EGCG conjugated hyaluronic acids (HA_E) and tyramine conjugated hyaluronic acids (HA_T) was reacted with tyrosinase isolated from Streptomyces avermitillis (SA_Ty) to form that displayed fast enzyme kinetic to form a crosslinked adhesive hydrogel. A 1,2,3-trihydroxyphenyl group in EGCG displayed a high affinity to SA_Ty that allowed HA_E to be quickly oxidized and crosslinked with HA_T to form HA_T and HA_E mixed hydrogel (HA_TE). We then compared the HA_TE hydrogel with commercially available tissue adhesives, such as cyanoacrylate and fibrin glue. We report that the HA_TE exhibited the highest tissue adhesiveness both in wet and dry conditions. Furthermore, HA_TE successfully closed a skin wound and displayed insignificant host tissue responses. This demonstrates that polyphenol-incorporated anti-inflammatory hydrogel may provide a robust tissue adhesive platform for clinical applications.

Identifying genetic variants underlying medication-induced osteonecrosis of the jaw in cancer and osteoporosis: a case control study.

BACKGROUND: Bisphosphonate-induced osteonecrosis of the jaw (BRONJ) presents with a typical pattern of jaw necrosis in patients who have been prescribed bisphosphonates (BPs) and other antiangiogenetic drugs to treat osteoporosis or bone-related complications of cancer. METHODS: This study divided 38 patients with BRONJ into two groups according to the prescribing causes: cancer (n = 13) and osteoporosis (n = 25), and underwent whole exome sequencing and compared them with normal controls (n = 90). To identify candidate genes and variants, we conducted three analyses: a traditional genetic model, gene-wise variant score burden, and rare-variant analysis methods. RESULTS: The stop-gain mutation (rs117889746) of the PZP gene in the BRONJ cancer group was significantly identified in the additive trend model analysis. In the cancer group, ARIDS, HEBP1, LTBP1, and PLVAP were identified as candidate genes. In the osteoporosis group, VEGFA, DFFA, and FAM193A genes showed a significant association. No significant genes were identified in the rare-variant analysis pipeline. Biologically accountable functions related to BRONJ occurrence-angiogenesis-related signaling (VEGFA and PLVAP genes), TGF-ß signaling (LTBP1 and PZP genes), heme toxicity (HEBP1) and osteoblast maturation (ARIDS)-were shown in candidate genes. CONCLUSION: This study showed that the candidate causative genes contributing to the development of BRONJ differ according to the BP dose and background disease.

Dual-Channel Fluorescence Imaging of Hydrogel Degradation and Tissue Regeneration in the Brain.

The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despite promising results in pre-clinical studies, the translation of regenerative medicine to the clinic has many challenges due to the lack of reliable imaging systems to achieve accurate evaluation of the treatment efficacy. Methods: In this study, we developed a dual-channel fluorescence imaging technique to simultaneously monitor tissue ingrowth and scaffold disintegration. Enzymatically crosslinked gelatin-hyaluronic acid hydrogel was labeled with 800 nm fluorophore, ZW800-3a, while the regenerated tissue was highlighted with 700 nm brain-specific contrast agent, Ox1. Results: Using the multichannel fluorescence imaging system, tissue growth and degradation of the NIR hydrogel were simultaneously imaged in the brain of mice. Images were further analyzed and reconstructed to show both visual and quantitative information of each stage of a therapeutic period. Conclusion: Dual-channel in vivo imaging systems can provide highly accurate visual and quantitative information of the brain tissue ingrowth for the evaluation of the therapeutic effect of NIR hydrogel through a simple and fast operating procedure.

Antioxidant and anti-inflammatory activities of methanol extracts of Tremella fuciformis and its major phenolic acids.

Methanol extract subfractions of the edible white jelly mushroom (Tremella fuciformis), were assessed for the following antioxidant properties: ABTS(+) radical scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and inhibitory activity of human low-density lipoprotein (LDL) oxidation. Among the subfractions tested, the chloroform subfraction exhibited the strongest antioxidant activity, with the highest total phenolic content (66.31 µg CAE/mg extract) and flavonoids content (5.12 µg QE/mg extract). The ABTS(+) radical scavenging activity of the chloroform subfraction was 7.89 µmol trolox/mg extract, which was the highest among all subfractions. This subfraction also showed the highest DPPH radical scavenging activity and inhibitory activity of LDL oxidation. In addition, the chloroform subfraction demonstrated anti-inflammatory activity through inhibition of nitric oxide production and inducible nitric oxide synthase expression in RAW 264.7 cells. Major phenolic acids from the mushroom extract were identified as 4-hydroxybenzoic acid (323 mg/kg dry weight of mushroom), gentisic acid (174 mg/kg dry weight of mushroom), and 4-coumaric acid (30 mg/kg dry weight of mushroom).

Detection and identification of breast cancer volatile organic compounds biomarkers using highly-sensitive single nanowire array on a chip.

A single nanowire array on a chip with different materials of Palladium, Polypyrrole and Zinc Oxide has been fabricated using electrochemical deposition method. The fabricated single nanowire array has been demonstrated for highly sensitive and specific diagnosis of breast cancer by detecting four volatile organic compound biomarkers: Heptanal, Acetophenone, Isopropyl Myristate and 2-Propanol. The demonstrated sensing limits for Heptanal, Acetophenone, Isopropyl Myristate and 2-propanol using individual Palladium, Polypyrrole and Zinc Oxide nanowires were 8.982 ppm, 798 ppb, 134 ppm, and 129.5 ppm, respectively, and the corresponding sensitivities of resistance change were in the range of 0.3%-5% which indicated excellent sensing performance of the single nanowires. The response time for Palladium, Polypyrrole and Zinc Oxide nanowires to achieve maximum conductance change was less than 200 seconds while also illustrating excellent signal repeatability. With the principal component analysis of the resistance change versus time in each detection period of the nanowire array, the smell prints for the four volatile organic compounds biomarkers of Breast Cancer are discriminated in the 3-D plots.

Ex vivo bone morphogenetic protein-2 gene delivery using bone marrow stem cells in rabbit maxillary sinus augmentation in conjunction with implant placement.

BACKGROUND: This study evaluates the potential of bone morphogenetic protein 2 (BMP-2) gene-transduced bone marrow stem cells (BMSCs) to facilitate osseous healing after rabbit maxillary sinus augmentation in conjunction with implant placement. METHODS: Autologous BMSCs derived from New Zealand white rabbits were cultured and transduced with BMP-2 using an adenovirus vector. Transduced BMSCs (BMP-2/BMSCs) were then combined with a deproteinized bovine bone mineral (DBBM) scaffold. Twenty-seven animals were randomly allocated into three groups: 1) control, sinus grafted with DBBM alone; 2) BMSC, sinus grafted with non-transduced BMSCs and DBBM; and 3) BMP-2/BMSC, sinus grafted with BMP-2/BMSCs and DBBM. During these procedures, a mini-implant was placed in the floor of the sinus. Animals were sacrificed at 2, 4, and 8 weeks after surgery. New bone area and bone-to-implant contact (BIC) were evaluated histomorphometrically. RESULTS: At 2 and 4 weeks, the BMP-2/BMSC group showed more new bone area and higher BIC than the other two groups. BMP-2/BMSCs were detected with confocal microscopy for up to 4 weeks, which indicates that transduced cells contributed to new bone formation. However, at 8 weeks, there was no difference in new bone area or BIC among the three groups. CONCLUSIONS: These results suggest that BMP-2 delivery using BMSCs may result in earlier and increased bone formation in the maxillary sinus. This finding may offer more stable bone support to implants and reduce healing times. However, this study also revealed limitations in the stimulatory effect of BMP-2/BMSCs, such as diminished activity over time in later healing stages.

Simultaneous measurement of neural spike recordings and multi-photon calcium imaging in neuroblastoma cells.

This paper proposes the design and implementation of a micro-electrode array (MEA) for neuroblastoma cell culturing. It also explains the implementation of a multi-photon microscope (MPM) customized for neuroblastoma cell excitation and imaging under ambient light. Electrical signal and fluorescence images were simultaneously acquired from the neuroblastoma cells on the MEA. MPM calcium images of the cultured neuroblastoma cell on the MEA are presented and also the neural activity was acquired through the MEA recording. A calcium green-1 (CG-1) dextran conjugate of 10,000 D molecular weight was used in this experiment for calcium imaging. This study also evaluated the calcium oscillations and neural spike recording of neuroblastoma cells in an epileptic condition. Based on our observation of neural spikes in neuroblastoma cells with our proposed imaging modality, we report that neuroblastoma cells can be an important model for epileptic activity studies.

Effects of immunosuppressants, FK506 and cyclosporin A, on the osteogenic differentiation of rat mesenchymal stem cells.

PURPOSE: The purpose of this study was to investigate the effects of the immunosuppressants FK506 and cyclosporin A (CsA) on the osteogenic differentiation of rat mesenchymal stem cells (MSCs). METHODS: The effect of FK506 and CsA on rat MSCs was assessed in vitro. The MTT assay was used to determine the deleterious effect of immunosuppressants on stem cell proliferation at 1, 3, and 7 days. Alkaline phosphatase (ALP) activity was analyzed on days 3, 7, and 14. Alizarin red S staining was done on day 21 to check mineralization nodule formation. Real-time polymerase chain reaction (RT-PCR) was also performed to detect the expressions of bone tissue-specific genes on days 1 and 7. RESULTS: Cell proliferation was promoted more in the FK506 groups than the control or CsA groups on days 3 and 7. The FK506 groups showed increased ALP activity compared to the other groups during the experimental period. The ALP activity of the CsA groups did not differ from the control group in any of the assessments. Mineralization nodule formation was most prominent in the FK506 groups at 21 days. RT-PCR results of the FK506 groups showed that several bone-related genes-osteopontin, osteonectin, and type I collagen (Col-I)-were expressed more than the control in the beginning, but the intensity of expression decreased over time. Runx2 and Dlx5 gene expression were up-regulated on day 7. The effects of 50 nM CsA on osteonectin and Col-I were similar to those of the FK506 groups, but in the 500 nM CsA group, most of the genes were less expressed compared to the control. CONCLUSIONS: These results suggest that FK506 enhances the osteoblastic differentiation of rat MSCs. Therefore, FK506 might have a beneficial effect on bone regeneration when immunosuppressants are needed in xenogenic or allogenic stem cell transplantation to treat bone defects.

Integrating metal-oxide-decorated CNT networks with a CMOS readout in a gas sensor.

We have implemented a tin-oxide-decorated carbon nanotube (CNT) network gas sensor system on a single die. We have also demonstrated the deposition of metallic tin on the CNT network, its subsequent oxidation in air, and the improvement of the lifetime of the sensors. The fabricated array of CNT sensors contains 128 sensor cells for added redundancy and increased accuracy. The read-out integrated circuit (ROIC) was combined with coarse and fine time-to-digital converters to extend its resolution in a power-efficient way. The ROIC is fabricated using a 0.35 µm CMOS process, and the whole sensor system consumes 30 mA at 5 V. The sensor system was successfully tested in the detection of ammonia gas at elevated temperatures.