Efficacy of autogenous particulated dentin graft for alveolar ridge preservation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Autogenous particulate dentin (APD) has been used as a bone graft material for bone augmentation, but the specifics of its effect on alveolar ridge preservation (ARP) are uncertain. The aim of this study was to investigate the clinical and histomorphometric performance of APD compared with blood clot healing or other grafted materials in ARP. METHODS: MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library and citation databases were searched until August 2, 2023 to identify randomized controlled trials that employed APD for ARP. Two independent meta-analyses were performed based on the different control groups (Group I: blood clot healing; Group II: other grafted materials). Weighted or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were calculated. The protocol was prospectively registered with PROSPERO (CRD42023409339). RESULTS: A total of 238 records were identified, of which ten studies with 182 participants were included. The meta-analysis indicated that APD resulted in fewer changes in horizontal ridge width (Group I: MD = 1.61, 95% CI 0.76-2.46; Group II: MD = 1.28, 95% CI 1.08-1.48) and labial bone height (Group I: MD = 1.75, 95% CI 0.56-2.94; Group II: P < .05) than the control treatments. Regarding histomorphometry, APD yielded a satisfactory proportion of vital bone area (MD = 10.51, 95% CI 4.70-16.32) and residual material area (MD = -8.76, 95% CI -12.81 to -4.71) in Group II, while there was no significant difference in Group I. Moreover, none of the secondary outcomes were significantly differed between groups. CONCLUSION: Within this study limitations, APD effectively maintained the horizontal and vertical dimensions of the extraction sockets and exhibited favorable osteogenic properties and degradation capacity. Further well-designed randomized controlled trials with larger samples and longer follow-up periods are needed to evaluate whether APD is superior to other substitutes for ARP.

Role of Intraoperative Imaging in Improving Closed Reduction of Zygomatic Arch Fractures: A Systematic Review and Meta-analysis.

PURPOSE: The use of intraoperative imaging (IOI) to improve the reduction adequacy of zygomatic arch (ZMA) fractures has been reported, but few systematic reviews have examined this topic. The aim of this review was to investigate and compare the value of IOI with conventional methods without IOI (N-IOI) for the closed reduction of ZMA fractures. METHODS: Electronic retrieval of MEDLINE, Embase, Cochrane Library, Web of Science, Scopus, and citation search until December 2, 2022, was used to identify controlled clinical trials that employed IOI for improving adequacy in closed reduction of ZMA fractures. The predictor variable was the use of IOI-yes/no (IOI vs N-IOI). The covariates included imaging technique (ultrasound, C-arm, and cone beam computed tomography) and ZMA fracture type (M-shape fracture, mechanistic force in 1 direction; variable fracture, mechanistic force in 2 directions). The primary outcome variables were the reduction adequacy of ZMA fractures (the remaining cortical step and dislocation angle) compared with the ideal mirrored position. Weighted or mean differences, risk ratios, and corresponding 95% confidence intervals were calculated, where P >.05 and I2＜50% fixed effect model was adopted, and a vice versa random effect model was adopted. RESULTS: A total of 1250 studies were identified, of which 6 studies with 259 participants were included. The meta-analysis results indicated that compared with N-IOI, IOI yielded fewer cortical steps (-1.76 [-2.42, 1.10], P ＜.00001, fixed model) and dislocation angles (-5.60 [-8.08, 3.12], P＜.00001, fixed model) in patients with variable ZMA fractures, while no significant difference was detected in the M-shape ZMA fracture (-0.72, [-2.93, 1.48], P = .52; -1.48, [-3.51, 0.55], P = .15). Although there was no significant difference in postoperative correction (0.35, [0.06, 2.01] P = .24, fixed model), all secondary revision cases occurred in the N-IOI group. Descriptive analysis showed that IOI yielded better symmetry and appearance satisfaction. CONCLUSION: IOI improved the adequacy of the procedure and led to a better postoperative appearance, especially for patients with variable ZMA fractures. Furthermore, the use of IOI avoided the risk of secondary surgery. In future studies, researchers should standardize the scale and outcomes to facilitate the intuitive evaluation of reduction adequacy.

Efficacy of autogenous tooth block for lateral ridge augmentation compared with autogenous bone block: A systematic review and meta-analysis.

BACKGROUND: Autogenous tooth block (ATB) has been used as an alternative material for bone regeneration, but its efficacy compared with autogenous bone block (ABB) remains uncertain. The aim of this systematic review was to investigate and compare the clinical and histological performance of ATB and ABB grafts in lateral alveolar ridge augmentation (LARA). METHODS: Electronic retrieval of MEDLINE, Embase, Cochrane Library (CENTRAL), Scopus, Web of Science, China national knowledge infrastructure, Wanfang data, SinoMed, and manual searching until July 2023 were used to identify controlled clinical trials employing ATB grafts in LARA. The identified reports included at least one of the following outcome variables: ridge width gain, graft resorption, postoperative complications, histology, and histomorphometry. Weighted or mean differences (MD), relative risk, and corresponding 95% confidence intervals (CI) were calculated. Descriptive analysis was applied to the qualitative statistics. The protocol followed the preferred reporting items for systematic reviews and meta-analyses statement and was prospectively registered in PROSPERO (CRD42023399611). RESULTS: Four controlled clinical trials with 77 participants each using ATB and ABB grafts were included. Meta-analysis indicated that ATB grafts resulted in greater bone width (MD = 1.31, 95% CI [0.92, 1.71], P < .00001) and less graft resorption (MD = -0.71, 95% CI [-1.22, -0.21], P = .005) than ABB grafts on LARA. There was no statistical difference in postoperative complications between ATB and ABB grafts (relative risk = 0.81, 95% CI [0.32, 2.04], P = .66). Furthermore, the ATB grafts exhibited positive replacement resorption with alveolar bone for favorable signs of new bone activity on histology and histomorphometry. CONCLUSION: Within the limitations of this study, ATB grafts could serve as an alternative material for ABB to support LARA. Further research with a longer follow-up period is required to verify these findings.

Successful Management of Peri-Implant Infection from the Endodontic Lesion of Adjacent Natural Tooth.

Recently, dental implants have had the most important role in oral rehabilitation. Peri-implantitis is considered a common complication of dental implants. Adjacent natural teeth with untreated endodontic pathology may be a potential risk for implant placement. Retrograde/periapical peri-implantitis (RPI), the inverting of the progress direction of peri-implantitis. Radiographically, it is characterized by signs of periapical bone loss and normal coronal osteointegration of the implant; and its prevalence is closely associated with endodontic lesions of adjacent teeth. Another novel separate disease entity is known as the endodontic peri-implant defects (endo-implant defects), manifesting as the peri-implant marginal bone loss due to endodontic pathology of adjacent teeth, to which endodontists and implantologists are supposed to attach great importance. This current study presented two cases of different types of peri-implant infection in which conducting proper intervention to the endodontic lesions of adjacent teeth resulted in full radiographic and clinical resolution of peri-implant defects.

A novel histopathological classification of implant periapical lesion: A systematic review and treatment decision tree.

BACKGROUND: Implant periapical lesion (IPL), as a peri-implant disease originating from implant apex, maintains coronal osseointegration in the early stage. With the understanding to IPL increasingly deepened, IPL classification based on different elements was proposed although there still lacks an overall classification system. This study, aiming to systematically integrate the available data published in the literature on IPL associated with histopathology, proposed a comprehensive classification framework and treatment decision tree for IPL. METHODS AND FINDINGS: English articles on the topic of "implant periapical lesion", "retrograde peri-implantitis" and "apical peri-implantitis" were searched on PubMed, Embase and Web of Science from 1992 to 2021, and citation retrieval was performed for critical articles. Definite histopathology and radiology of IPL are indispensable criteria for including the article in the literature. The protocol was registered in PROSPERO (CRD42022378001). A total of 509 papers identified, 28 studies were included in this review. In only one retrospective study, 37 of 39 IPL were reported to be at the inflammatory or abscess stage. 27 cases (37 implants) were reported, including acute non-suppurative (1/37, developed to chronic granuloma), chronic granuloma (5/37), acute suppurated (2/37), chronic suppurated-fistulized (6/37), implant periapical cyst (21/37), poor bone healing (2/37), foreign body reaction (1/37). Antibiotics alone did not appear to be effective, and the consequence of surgical debridement required cautious interpretation because of the heterogeneity of lesion course and operation. Implant apicoectomy and marsupialization were predictable approaches in some cases. CONCLUSIONS: The diversiform nature of IPL in the case reports confirms the need for such histopathological classification, which may enhance the comparison and management of different category.

The Current Status and Prevention of Antibiotic Pollution in Groundwater in China.

The problem of environmental pollution caused by the abuse of antibiotics has received increasing attention. However, only in recent years have antibiotic pollution and its risk assessment to the environment been deeply studied. Although there has been a large number of reports about the input, occurrence, destination, and influence of antibiotics in the past 10 years, systemic knowledge of antibiotics in the groundwater environment is still lacking. This review systematically expounds the sources, migration and transformation, pollution status, and potential risks to the ecological environment of antibiotics in groundwater systems, by integrating 10 years of existing research results. The results showed that 47 kinds of antibiotics in four categories, mainly sulfonamides and fluoroquinolones, have been detected; antibiotics in groundwater species will induce the production of resistance genes and cause ecological harm. In view of the entire process of antibiotics entering groundwater, the current antibiotic control methods at various levels are listed, including the control of the discharge of antibiotics at source, the removal of antibiotics in water treatment plants, and the treatment of existing antibiotic contamination in groundwater. Additionally, the future research direction of antibiotics in groundwater is pointed out, and suggestions and prospects for antibiotic control are put forward.

Clinical Efficacy and Safety of Different Dental Prosthetic Membranes in Guided Bone Regeneration during Dental Implants: A Meta-Analysis.

Objective. To evaluate clinical efficacy and safety of absorbable and non-absorbable dental restorative membranes in guided bone regeneration (GBR). Articles concerning absorbable and non-absorbable prosthetic membrane-related studies of GBR were screened from multiple databases. In the end, 526 postoperative patients who met eligibility criteria were screened for the study from eight trials. The results showed that the repair success rate of the experimental group (absorbable dental restorative membrane) was higher than that of the control group (non-absorbable dental restorative membrane) (RR = 1.18, 95% CI [1.11,1.26], and the total physical therapy effect was P < 0.0001, I 2 = 0%), and the height of bone graft in the experimental group was higher than that in the control group (MD = 0.67, 95% CI [0.11, 1.23]). The thickness of bone graft in the experimental group was higher than that in the control group (MD = 0.43, 95% CI [0.30,0.56], P < 0.00001, I 2 = 61%), and the adverse events in the experimental group were less than those in the control group (RR = 0.31, 95% CI [0.18, 0.51], P < 0.00001, I 2 = 13%). Absorbable prosthetic membrane is superior to non-absorbable prosthetic membrane in clinical efficacy and safety.

Novel core-shell CHX/ACP nanoparticles effectively improve the mechanical, antibacterial and remineralized properties of the dental resin composite.

OBJECTIVE: The core-shell chlorhexidine/amorphous calcium phosphate (CHX/ACP) nanoparticles were synthesized and used to modify the dental resin composite, aiming to improve its remineralized and antibacterial properties. METHODS: The core-shell CHX/ACP nanoparticles were synthesized by vesicle-templating technology and characterized, and their sustained release and antibacterial properties were also evaluated. Subsequently, the synthesized nanoparticles were incorporated into the dental resin composite at 1 wt.%, 5 wt.% or 10 wt.% to obtain different experimental groups. The physical properties, including curing depth, double bond conversion rate, water absorption and solubility, the sustained-release effects, and mechanical properties of the modified resin composite were evaluated. The remineralization ability was also measured by SEM. The antibacterial experiment of the modified resin composite with fresh preparation or aging in water for 28 days was carried out by a plate count method. RESULTS: The physical and chemical characterizations showed that the synthesized nanoparticles presented a core-shell structure, and their diameter was about 98.5 nm. The shell was composed of ACP with the core full of CHX. These nanoparticles had a release effect on calcium, phosphate ions, and CHX. The nanoparticles could effectively inhibit the growth of S. mutan at a lower concentration (≥50 µg/mL). The curing depth, the double bond conversion, the water absorption, the solubility, the flexural strength, the flexural modulus, and the compressive strength of the modified resin composite were 3.86-4.88 mm, 62.32-73.61%, 1.47-2.84%, 0.21-0.48%, 45.83-109.46 MPa, 2.57-4.91 GPa, and 66.43-160.38 MPa, respectively. The modified resin composite containing 5 wt.% and above CHX/ACP nanoparticles could effectively inhibit the growth of S. mutans regardless of aging in water, with immediate and aging antibacterial rate of more than 92%. In addition, the modified resin composite had a certain remineralization property in the SBF solution verified by SEM. SIGNIFICANCE: The core-shell CHX/ACP nanoparticles were successfully prepared and used to modify the resin composite. The modified dental resin composite with 5 wt.% CHX/ACP nanoparticles had excellent mechanical, antibacterial, and remineralization properties. It is expected to be an ideal restorative filling material for clinical application.

Nna1 gene deficiency triggers Purkinje neuron death by tubulin hyperglutamylation and ER dysfunction.

Posttranslational glutamylation/deglutamylation balance in tubulins influences dendritic maturation and neuronal survival of cerebellar Purkinje neurons (PNs). PNs and some additional neuronal types degenerate in several spontaneous, independently occurring Purkinje cell degeneration (pcd) mice featuring mutant neuronal nuclear protein induced by axotomy (Nna1), a deglutamylase gene. This defective deglutamylase allows glutamylases to form hyperglutamylated tubulins. In pcd, all PNs die during postnatal "adolescence." Neurons in some additional brain regions also die, mostly later than PNs. We show in laser capture microdissected single PNs, in cerebellar granule cell neuronal clusters, and in dissected hippocampus and substantia nigra that deglutamase mRNA and protein were virtually absent before pcd PNs degenerated, whereas glutaminase mRNA and protein remained normal. Hyperglutamylated microtubules and dimeric tubulins accumulated in pcd PNs and were involved in pcd PN death by glutamylase/deglutamylase imbalance. Importantly, treatment with a microtubule depolymerizer corrected the glutamylation/deglutamylation ratio, increasing PN survival. Further, before onset of neuronal death, pcd PNs displayed prominent basal polylisosomal masses rich in ER. We propose a "seesaw" metamorphic model summarizing mutant Nna1-induced tubulin hyperglutamylation, the pcd's PN phenotype, and report that the neuronal disorder involved ER stress, unfolded protein response, and protein synthesis inhibition preceding PN death by apoptosis/necroptosis.

Comprehensive analysis of differential expression profiles reveals potential biomarkers associated with the cell cycle and regulated by p53 in human small cell lung cancer.

Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database. Furthermore, microarray data was analyzed by using the clustering analysis tool GoMiner. Protein-protein interaction (PPI) networks of DEGs were constructed using the STRING online database. Protein expression was determined from the Human Protein Atlas, and SCLC gene expression was determined using Oncomine. In total, 153 DEGs were obtained. Functional enrichment analysis suggested that the majority of DEGs were associated with the cell cycle. CCNB1, CCNB2, MAD2L1 and CDK1 were identified to contribute to the progression of SCLC through combined use of GO, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and a PPI network. mRNA and protein expression were also validated in an integrative database. The present study indicated that the formation of SCLC may be associated with cell cycle regulation. In addition, the four crucial genes CCNB1, CCNB2, MAD2L1 and CDK1, which are downstream of p53, may have important roles in the occurrence and progression of SCLC, and thus may be promising potential biomarkers and therapeutic targets.

Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis.

The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in polygenic diseases is generally challenging. However, hiPSCs from BPD patients responsive to lithium offered unique opportunities to discern lithium's target and hence gain molecular insight into BPD. By profiling the proteomics of BDP-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2). Active nonphosphorylated CRMP2, which binds cytoskeleton, is present throughout the neuron; inactive phosphorylated CRMP2, which dissociates from cytoskeleton, exits dendritic spines. CRMP2 elimination yields aberrant dendritogenesis with diminished spine density and lost lithium responsiveness (LiR). The "set-point" for the ratio of pCRMP2:CRMP2 is elevated uniquely in hiPSC-derived neurons from LiR BPD patients, but not with other psychiatric (including lithium-nonresponsive BPD) and neurological disorders. Lithium (and other pathway modulators) lowers pCRMP2, increasing spine area and density. Human BPD brains show similarly elevated ratios and diminished spine densities; lithium therapy normalizes the ratios and spines. Consistent with such "spine-opathies," human LiR BPD neurons with abnormal ratios evince abnormally steep slopes for calcium flux; lithium normalizes both. Behaviorally, transgenic mice that reproduce lithium's postulated site-of-action in dephosphorylating CRMP2 emulate LiR in BPD. These data suggest that the "lithium response pathway" in BPD governs CRMP2's phosphorylation, which regulates cytoskeletal organization, particularly in spines, modulating neural networks. Aberrations in the posttranslational regulation of this developmentally critical molecule may underlie LiR BPD pathogenesis. Instructively, examining the proteomic profile in hiPSCs of a functional agent-even one whose mechanism-of-action is unknown-might reveal otherwise inscrutable intracellular pathogenic pathways.

Cerebellar Pathways in Mouse Model of Purkinje Cell Degeneration Detected by High-Angular Resolution Diffusion Imaging Tractography.

Cerebellar MR imaging has several challenging aspects, due to the fine, repetitive layered structure of cortical folia with underlying axonal pathways. In this MR study, we imaged with high-angular resolution diffusion imaging (HARDI) abnormal cerebellar cortical structure (gray matter) and myelinated axonal pathways (white matter) of a mouse spontaneous mutation, Purkinje cell degeneration (pcd), in which almost all Purkinje neurons degenerate, mainly between postnatal days 20 and 35. Mouse brains at postnatal day 20 (P20) and at 8 months were scanned, and known or expected abnormalities, such as reduction of the white matter volume, disorganized pathways likely linked to parallel fibers, mossy fibers, and other fibers running from/to the cerebellar cortex were observed in mutant mice. Such abnormalities were detected at both an early and a fully advanced degeneration stage. These results suggest that our diffusion MR tractography is useful for early detection and tracking of neuropathology in the cerebellum.

Reduced-representation Phosphosignatures Measured by Quantitative Targeted MS Capture Cellular States and Enable Large-scale Comparison of Drug-induced Phenotypes.

Profiling post-translational modifications represents an alternative dimension to gene expression data in characterizing cellular processes. Many cellular responses to drugs are mediated by changes in cellular phosphosignaling. We sought to develop a common platform on which phosphosignaling responses could be profiled across thousands of samples, and created a targeted MS assay that profiles a reduced-representation set of phosphopeptides that we show to be strong indicators of responses to chemical perturbagens.To develop the assay, we investigated the coordinate regulation of phosphosites in samples derived from three cell lines treated with 26 different bioactive small molecules. Phosphopeptide analytes were selected from these discovery studies by clustering and picking 1 to 2 proxy members from each cluster. A quantitative, targeted parallel reaction monitoring assay was developed to directly measure 96 reduced-representation probes. Sample processing for proteolytic digestion, protein quantification, peptide desalting, and phosphopeptide enrichment have been fully automated, making possible the simultaneous processing of 96 samples in only 3 days, with a plate phosphopeptide enrichment variance of 12%. This highly reproducible process allowed ∼95% of the reduced-representation phosphopeptide probes to be detected in ∼200 samples.The performance of the assay was evaluated by measuring the probes in new samples generated under treatment conditions from discovery experiments, recapitulating the observations of deeper experiments using a fraction of the analytical effort. We measured these probes in new experiments varying the treatments, cell types, and timepoints to demonstrate generalizability. We demonstrated that the assay is sensitive to disruptions in common signaling pathways (e.g. MAPK, PI3K/mTOR, and CDK). The high-throughput, reduced-representation phosphoproteomics assay provides a platform for the comparison of perturbations across a range of biological conditions, suitable for profiling thousands of samples. We believe the assay will prove highly useful for classification of known and novel drug and genetic mechanisms through comparison of phosphoproteomic signatures.

Prefabrication of axially vascularized bone by combining ß-tricalciumphosphate, arteriovenous loop, and cell sheet technique.

The repair of bone defects poses a great challenge for reconstructive surgeons. Although the development of tißsue engineering has exhibited promise in replacing damaged bone, the fabrication of large constructs with functional blood veßsels remains an obstacle. From the orthopedic surgeon's point of view, the generation of axially vascularized bone, which can anastomose with the recipient vessel, might be a solution to this medical problem. In this study, we aimed to prefabricate an axially vascularized bone by combining a ß-TCP scaffold, arteriovenous loop (AVL), and cell sheet in a bioreactor in vivo. Twelve rabbits were randomly allocated into two groups: the experimental group (presence of AVL) and the control group (absence of AVL). The constructs were explanted at 8 weeks postoperatively. The histomorphometric results showed 42.8±5.9% of the bone area in the AVL group and 26.6±3.5% in the control group. Similarly, vessel analysis revealed the average vessel density in the AVL group (12.5±3.3) was significantly more than that in the control group (6.1±1.5, p<0.05). Our research indicated that the combination of a ß-TCP scaffold, AVL and cell sheet might engineer vascularized bone. This prefabrication strategy might facilitate clinical translation of bone tissue engineering in reconstructing large bone defects.

The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease.

Blood vessel growth from preexisting vessels (angiogenesis) underlies many severe diseases including major blinding retinal diseases such as retinopathy of prematurity (ROP) and aged macular degeneration (AMD). This observation has driven development of antibody inhibitors that block a central factor in AMD, vascular endothelial growth factor (VEGF), from binding to its receptors VEGFR-1 and mainly VEGFR-2. However, some patients are insensitive to current anti-VEGF drugs or develop resistance, and the required repeated intravitreal injection of these large molecules is costly and clinically problematic. We have evaluated a small cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys) [D(CLPRC)], and hereafter named Vasotide, that inhibits retinal angiogenesis by binding selectively to the VEGF receptors VEGFR-1 and neuropilin-1 (NRP-1). Delivery of Vasotide via either eye drops or intraperitoneal injection in a laser-induced monkey model of human wet AMD, a mouse genetic knockout model of the AMD subtype called retinal angiomatous proliferation (RAP), and a mouse oxygen-induced model of ROP decreased retinal angiogenesis in all three animal models. This prototype drug candidate is a promising new dual receptor inhibitor of the VEGF ligand with potential for translation into safer, less-invasive applications to combat pathological angiogenesis in retinal disorders.

Non-surgical treatment of an Angle Class III malocclusion in adults.

OBJECTIVE: To examine the application of a modified fixed reverse twin-block appliance (TBA) in adults with an Angle Class III malocclusion and anterior crossbite. PARTICIPANTS: Thirty-two adults with an Angle III malocclusion were recruited. An associated temporomandibular disorder (TMD) was found in 18 patients, laterognathism in 21, and both conditions in the remaining 12 patients. METHODS: A modified fixed reverse TBA was used to posture the mandible back, divert bite force and centre the dentition. The malocclusion, laterognathism and temporomandibular disorders were concurrently treated. The outcome was evaluated radiographically and the findings were analyzed via Electronic Measurement Scale software. RESULTS: Treatment was shown to be effective and could significantly shorten the course of treatment and avoid orthognathic surgery. The average course of treatment was 14 months, during which time, the mandible was postured back and the dentition was successfully aligned and levelled. Most patients achieved an edge-to-edge occlusion of the anterior teeth after 7-10 days of appliance wear. Most symptoms of TMD were relieved after 1 month and the laterognathism resolved in 4-5 months. CONCLUSION: A modified fixed reverse TBA was an effective non-surgical strategy for the treatment of selected Angle Class III malocclusions with an anterior crossbite in adults.

Tissue plasminogen activator regulates Purkinje neuron development and survival.

The cerebellar cortex is centrally involved in motor coordination and learning, and its sole output is provided by Purkinje neurons (PNs). Growth of PN dendrites and their major synaptic input from granule cell parallel fiber axons takes place almost entirely in the first several postnatal weeks. PNs are more vulnerable to cell death than most other neurons, but the mechanisms remain unclear. We find that the homozygous nervous (nr) mutant mouse's 10-fold-increased cerebellar tissue plasminogen activator (tPA), a part of the tPA/plasmin proteolytic system, influences several different molecular mechanisms, each regulating a key aspect of postnatal PN development, followed by selective PN necrosis, as follows. (i) Excess endogenous or exogenous tPA inhibits dendritic growth in vivo and in vitro by activating protein kinase Cγ and phosphorylation of microtubule-associated protein 2. (ii) tPA/plasmin proteolysis impairs parallel fiber-PN synaptogenesis by blocking brain-derived neurotrophic factor/tyrosine kinase receptor B signaling. (iii) Voltage-dependent anion channel 1 (a mitochondrial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen) promotes pathological enlargement and rounding of PN mitochondria, reduces mitochondrial membrane potential, and damages plasma membranes. These abnormalities culminate in young nr PN necrosis that can be mimicked in wild-type PNs by exogenous tPA injection into cerebellum or prevented by endogenous tPA deletion in nr:tPA-knockout double mutants. In sum, excess tPA/plasmin, through separate downstream molecular mechanisms, regulates postnatal PN dendritogenesis, synaptogenesis, mitochondrial structure and function, and selective PN viability.

Multimodal actions of neural stem cells in a mouse model of ALS: a meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a lethal disease characterized by the unremitting degeneration of motor neurons. Multiple processes involving motor neurons and other cell types have been implicated in its pathogenesis. Neural stem cells (NSCs) perform multiple actions within the nervous system to fulfill their functions of organogenesis and homeostasis. We test the hypothesis that transplanted, undifferentiated multipotent migratory NSCs may help to ameliorate an array of pathological mechanisms in the SOD1(G93A) transgenic mouse model of ALS. On the basis of a meta-analysis of 11 independent studies performed by a consortium of ALS investigators, we propose that transplanted NSCs (both mouse and human) can slow both the onset and the progression of clinical signs and prolong survival in ALS mice, particularly if regions sustaining vital functions such as respiration are rendered chimeric. The beneficial effects of transplanted NSCs seem to be mediated by a number of actions including their ability to produce trophic factors, preserve neuromuscular function, and reduce astrogliosis and inflammation. We conclude that the widespread, pleiotropic, modulatory actions exerted by transplanted NSCs may represent an accessible therapeutic application of stem cells for treating ALS and other untreatable degenerative diseases.

Use of autologous chondrocytes and bioinert perforated chambers to tissue engineer cartilage in vivo.

OBJECTIVE: To explore the potential applications of a chamber for in vivo tissue engineering, and to establish a novel model for in vivo tissue-engineered cartilage. METHODS: Four experimental groups were included in this study: (A) chambers + chondrocytes/collagen gel; (B) chambers + chondrocytes/PLGA gel; (C) chondrocytes/collagen gel alone; and (D) chondrocytes/PLGA gel alone. Groups C and D served as controls. The samples were implanted subcutaneously in the donor rabbit, and the contents were harvested at 8 wk after implantation. RESULTS: Histologic and immunohistochemical staining and RT-PCR results revealed regenerated cartilage-like tissue in group B and small, irregularly shaped islands of opalescent tissue in group A. In contrast, the control groups displayed vascular invasion and inflammatory reaction, which eventually led to fibrosis and absorption. CONCLUSIONS: Reproduced cartilages were obtained in an immunocompetent animal model through the use of a bioinert perforated chamber.

Self-renewal induced efficiently, safely, and effective therapeutically with one regulatable gene in a human somatic progenitor cell.

In the field of induced potency and fate reprogramming, it remains unclear what the best starting cell might be and to what extent a cell need be transported back to a more primitive state for translational purposes. Reprogramming a committed cell back to pluripotence to then instruct it toward a particular specialized cell type is demanding and may increase risks of neoplasia and undesired cell types. Precursor/progenitor cells from the organ of therapeutic concern typically lack only one critical attribute--the capacity for sustained self-renewal. We speculated that this could be induced in a regulatable manner such that cells proliferate only in vitro and differentiate in vivo without the need for promoting pluripotence or specifying lineage identity. As proof-of-concept, we generated and tested the efficiency, safety, engraftability, and therapeutic utility of "induced conditional self-renewing progenitor (ICSP) cells" derived from the human central nervous system (CNS); we conditionally induced self-renewal efficiently within neural progenitors solely by introducing v-myc tightly regulated by a tetracycline (Tet)-on gene expression system. Tet in the culture medium activated myc transcription and translation, allowing efficient expansion of homogeneous, clonal, karyotypically normal human CNS precursors ex vivo; in vivo, where Tet was absent, myc was not expressed, and self-renewal was entirely inactivated (as was tumorigenic potential). Cell proliferation ceased, and differentiation into electrophysiologically active neurons and other CNS cell types in vivo ensued upon transplantation into rats, both during development and after adult injury--with functional improvement and without neoplasia, overgrowth, deformation, emergence of non-neural cell types, phenotypic or genomic instability, or need for immunosuppression. This strategy of inducing self-renewal might be applied to progenitors from other organs and may prove to be a safe, effective, efficient, and practical method for optimizing insights gained from the ability to reprogram cells.