RESUMEN
Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.
Asunto(s)
Cognición/fisiología , Suturas Craneales/fisiopatología , Craneosinostosis/fisiopatología , Regeneración/fisiología , Cráneo/fisiopatología , Animales , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Craneosinostosis/genética , Duramadre/patología , Duramadre/fisiopatología , Gelatina/farmacología , Perfilación de la Expresión Génica , Fuerza de la Mano , Presión Intracraneal/efectos de los fármacos , Presión Intracraneal/fisiología , Locomoción/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Metacrilatos/farmacología , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Regeneración/efectos de los fármacos , Cráneo/patología , Proteína 1 Relacionada con Twist/metabolismo , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Nerves play important roles in organ development and tissue homeostasis. Stem/progenitor cells differentiate into different cell lineages responsible for building the craniofacial organs. The mechanism by which nerves regulate stem/progenitor cell behavior in organ morphogenesis has not yet been comprehensively explored. Here, we use tooth root development in mouse as a model to investigate how sensory nerves regulate organogenesis. We show that sensory nerve fibers are enriched in the dental papilla at the initiation of tooth root development. Through single cell RNA-sequencing analysis of the trigeminal ganglion and developing molar, we reveal several signaling pathways that connect the sensory nerve with the developing molar, of which FGF signaling appears to be one of the important regulators. Fgfr2 is expressed in the progenitor cells during tooth root development. Loss of FGF signaling leads to shortened roots with compromised proliferation and differentiation of progenitor cells. Furthermore, Hh signaling is impaired in Gli1-CreER;Fgfr2fl/fl mice. Modulation of Hh signaling rescues the tooth root defects in these mice. Collectively, our findings elucidate the nerve-progenitor crosstalk and reveal the molecular mechanism of the FGF-SHH signaling cascade during tooth root morphogenesis.
Asunto(s)
Diente , Animales , Ratones , Diente Molar , Morfogénesis/genética , Odontogénesis/genética , Raíz del DienteRESUMEN
The ubiquitous bacterial second messenger c-di-GMP is synthesized by diguanylate cyclase and degraded by c-di-GMP-specific phosphodiesterase. The genome of Pseudomonas putida contains dozens of genes encoding diguanylate cyclase/phosphodiesterase, but the phenotypical-genotypical correlation and functional mechanism of these genes are largely unknown. Herein, we characterize the function and mechanism of a P. putida phosphodiesterase named DibA. DibA consists of a PAS domain, a GGDEF domain, and an EAL domain. The EAL domain is active and confers DibA phosphodiesterase activity. The GGDEF domain is inactive, but it promotes the phosphodiesterase activity of the EAL domain via binding GTP. Regarding phenotypic regulation, DibA modulates the cell surface adhesin LapA level in a c-di-GMP receptor LapD-dependent manner, thereby inhibiting biofilm formation. Moreover, DibA interacts and colocalizes with LapD in the cell membrane, and the interaction between DibA and LapD promotes the PDE activity of DibA. Besides, except for interacting with DibA and LapD itself, LapD is found to interact with 11 different potential diguanylate cyclases/phosphodiesterases in P. putida, including the conserved phosphodiesterase BifA. Overall, our findings demonstrate the functional mechanism by which DibA regulates biofilm formation and expand the understanding of the LapD-mediated c-di-GMP signaling network in P. putida.
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Proteínas de Escherichia coli , Pseudomonas putida , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , GMP Cíclico/metabolismo , Biopelículas , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas Portadoras/metabolismo , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión GénicaRESUMEN
A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the bHLH transcription factors TWIST1 and TCF12. Although compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here, we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detected asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Craneosinostosis/metabolismo , Osteogénesis , Cráneo/embriología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Craneosinostosis/embriología , Craneosinostosis/genética , Células Madre Mesenquimatosas/metabolismo , Mesodermo/metabolismo , Ratones , Ratones Endogámicos C57BL , Cresta Neural/metabolismo , Cráneo/metabolismoRESUMEN
The control of size and shape is an important part of regulatory process during organogenesis. Tooth formation is a highly complex process that fine-tunes the size and shape of the tooth, which are crucial for its physiological functions. Each tooth consists of a crown and one or more roots. Despite comprehensive knowledge of the mechanism that regulates early tooth crown development, we have limited understanding of the mechanism regulating root patterning and size during development. Here, we show that Ror2-mediated non-canonical Wnt signaling in the dental mesenchyme plays a crucial role in cell proliferation, and thereby regulates root development size in mouse molars. Furthermore, Cdc42 acts as a potential downstream mediator of Ror2 signaling in root formation. Importantly, activation of Cdc42 can restore cell proliferation and partially rescue the root development size defects in Ror2 mutant mice. Collectively, our findings provide novel insights into the function of Ror2-mediated non-canonical Wnt signaling in regulating tooth morphogenesis, and suggest potential avenues for dental tissue engineering.
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Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Raíz del Diente/embriología , Raíz del Diente/metabolismo , Vía de Señalización Wnt , Proteína de Unión al GTP cdc42/metabolismo , Animales , Diferenciación Celular , Proliferación Celular , Femenino , Masculino , Mesodermo/embriología , Ratones , Ratones Mutantes , Morfogénesis , Odontoblastos/citología , Odontoblastos/metabolismo , Raíz del Diente/citologíaRESUMEN
The properties of single molecules and molecular aggregates can differ dramatically, leading to a long-standing interest in mesoscale aggregation processes. Herein, a series of acid-base molecular complexes is developed by using a tetraphenylethylene-backboned fluorophore, and investigated the photophysical properties and photochemical activities at different aggregation length scales. This fluorophore, with two basic diethylamine groups and two acidic tetrazole groups, exhibits sparse solubility due to multivalent interactions that cause infinite aggregation. The addition of a third acid leads to the formation of fluorophore/acid complexes with good dispersibility and colloidal stability. This assembly process can be controlled by the use of different acids and their stoichiometry, resulting in aggregates ranging in size from a few to hundreds of nanometers. A crystalline structure is obtained to illustrate the complex properties of the acid-base network. Unlike the single molecule, these complexes show a trend of size-related properties for photoluminescence efficiency and photochemical activity. As the amount of acid added increases, the size of the complexes decreases, the aggregation effect of the complexes on fluorescence emission increases, and the rates of the oxidative photocyclization and photodecomposition slow down. This work may help to understand size-controlled molecular materials at the mesoscale for functional design.
RESUMEN
As the prevalence of diabetes continues to increase, the number of individuals living with diabetes complications will reach an unprecedented magnitude. Continuous use of some synthetic agents to reduce blood glucose levels causes severe side effects, and thus, the demand for nontoxic, affordable drugs persists. Naturally occurring compounds, such as iminosugars derived from the mulberry (Morus spp.), have been shown to reduce blood glucose levels. In mulberry, 1-deoxynojirimycin (DNJ) is the predominant iminosugar. However, the mechanism underlying DNJ biosynthesis is not completely understood. Here, we showed that DNJ in mulberry is derived from sugar and catalyzed through 2-amino-2-deoxy-D-mannitol (ADM) dehydrogenase MnGutB1. Combining both targeted and nontargeted metabolite profiling methods, DNJ and its precursors ADM and nojirimycin (NJ) were quantified in mulberry samples from different tissues. Purified His-tagged MnGutB1 oxidized the hexose derivative ADM to form the 6-oxo compound DNJ. The mutant MnGutB1 D283N lost this remarkable capability. Furthermore, in contrast to virus-induced gene silencing of MnGutB1 in mulberry leaves that disrupted the biosynthesis of DNJ, overexpression of MnGutB1 in hairy roots and light-induced upregulation of MnGutB1 enhanced DNJ accumulation. Our results demonstrated that hexose derivative ADM, rather than lysine derivatives, is the precursor in DNJ biosynthesis, and it is catalyzed by MnGutB1 to form the 6-oxo compound. These results represent a breakthrough in producing DNJ and its analogs for medical use by metabolic engineering or synthetic biology.
Asunto(s)
1-Desoxinojirimicina , Morus , Humanos , Glucemia , Frutas , Oxidorreductasas , Hojas de la Planta/genéticaRESUMEN
Aggregation-induced emission (AIE) has revolutionized solid-state fluorescence by overcoming the limitations of aggregation-caused quenching. While extensively studied in solutions, AIE's potential on solid surfaces remains largely unexplored, which can be fundamentally interesting and practically useful. In this work, we demonstrate the successful dispersion of tetraphenylethylene (TPE), one of the most classical AIE luminogens, on solid surfaces coated with silicone nanofilaments (SNF). The high surface area of SNF enables the uniform immobilization of TPE luminogens, replicating their dispersal behavior in solutions. Compared to unmodified surfaces, TPE dispersed on SNF-coated surfaces exhibits significantly enhanced fluorescence intensity. Moreover, a fascinating dynamic blue shift in TPE emission on SNF-coated surfaces is observed, with the velocity controllable by the surface group of SNF by up to 4 orders of magnitude, showing that TPE can be applied to the judgment of the nanoscale morphology and surface free energy of the solid surface. Owing to the superhydrophobicity and self-cleaning properties of SNF, the on-surface fluorescence can be sustained underwater and is resistant to dust contamination and rain erosion, with potential applications of information encryption presented. Our approach of uniformly dispersing AIE luminogens on nanomaterials with high surface areas provides a general methodology for creating on-surface fluorescence and saving the usage of expensive AIE luminogens in applications.
RESUMEN
The asymmetric cycloaddition between N-2,2,2-trifluoroethylisatin ketimines and unsymmetrical dicarbonyl-activated alkenes catalyzed by a bifunctional squaramide has been discovered. The present study demonstrates an efficient approach for the regio-, diastereo-, and enantioselective synthesis of densely functionalized 5'-trifluoromethylated 3,2'-pyrrolidinyl spirooxindoles featuring three different types of carbonyl groups.
RESUMEN
Mammalian tooth crown formation has long served as a model for investigating how patterning and morphogenesis are orchestrated during development. However, the mechanism underlying root patterning and morphogenesis remains poorly understood. In this study, we find that Lhx6 labels a subpopulation of root progenitor cells in the apical dental mesenchyme, which is closely associated with furcation development. Loss of Lhx6 leads to furcation and root number defects, indicating that Lhx6 is a key root patterning regulator. Among the multiple cellular events regulated by Lhx6 is the odontoblast fate commitment of progenitor cells, which it controls in a cell-autonomous manner. Specifically, Lhx6 loss leads to elevated expression of the Wnt antagonist Sfrp2 and down-regulation of Wnt signaling in the furcation region, while overactivation of Wnt signaling in Lhx6+ progenitor cells partially restore the furcation defects in Lhx6-/- mice. Collectively, our findings have important implications for understanding organ morphogenesis and future strategies for tooth root regeneration.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Proteínas con Homeodominio LIM/genética , Células Madre Mesenquimatosas/metabolismo , Diente Molar/metabolismo , Morfogénesis/genética , Proteínas del Tejido Nervioso/genética , Raíz del Diente/metabolismo , Factores de Transcripción/genética , Vía de Señalización Wnt/genética , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Células Cultivadas , Femenino , Proteínas con Homeodominio LIM/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Genéticos , Diente Molar/citología , Diente Molar/crecimiento & desarrollo , Proteínas del Tejido Nervioso/metabolismo , Raíz del Diente/citología , Raíz del Diente/crecimiento & desarrollo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Virtual simulations (VSs) enhance clinical competencies and skills. However, a previous systematic review of 9 RCT studies highlighted a paucity of literature on the effects of haptic feedback in surgical VSs. An updated systematic and scoping review was conducted to encompass more studies and a broader range of study methodologies. METHODS: A systematic literature search was conducted on July 31, 2023, in MEDLINE, Embase, and Cochrane. English language studies comparing haptic vs non-haptic conditions and using VSs were included. Studies were evaluated and reported using PRISMA-ScR guidelines. RESULTS: Out of 2782 initial studies, 51 were included in the review. Most studies used RCT (21) or crossover (23) methodologies with medical residents, students, and attending physicians. Most used post-intervention metrics, while some used pre- and post-intervention metrics. Overall, 34 performance results from studies favored haptics, 3 favored non-haptics, and the rest showed mixed or equal results. CONCLUSION: This updated review highlights the diverse application of haptic technology in surgical VSs. Haptics generally enhances performance, complements traditional teaching methods, and offers personalized learning with adequate simulator validation. However, a sparsity of orienting to the simulator, pre-/post-study designs, and small sample sizes poses concerns with the validity of the results. We underscore the urgent need for standardized protocols, large-scale studies, and nuanced understanding of haptic feedback integration. We also accentuate the significance of simulator validation, personalized learning potential, and the need for researcher, educator, and manufacturer collaboration. This review is a guidepost for navigating the complexities and advancements in haptic-enhanced surgical VSs.
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Competencia Clínica , Entrenamiento Simulado , Humanos , Retroalimentación , Cirugía General/educación , Entrenamiento Simulado/métodos , Realidad VirtualRESUMEN
AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.
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Antineoplásicos , Neoplasias de la Mama , Neutropenia Febril , Neoplasias Pulmonares , Humanos , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Prospectivos , Polietilenglicoles , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Proteínas Recombinantes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tratamiento de Urgencia , Antineoplásicos/efectos adversos , Neutropenia Febril/inducido químicamenteRESUMEN
BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization. CASE PRESENTATION: We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge. CONCLUSIONS: GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.
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Enfermedades Autoinmunes , Enfermedad de Graves , Hiperinsulinismo , Hipoglucemia , Insulinas , Humanos , Estudios de Seguimiento , Alta del Paciente , Cadenas HLA-DRB1/genética , Metimazol , Enfermedades Autoinmunes/complicaciones , Enfermedad de Graves/complicaciones , Enfermedad de Graves/tratamiento farmacológico , Autoanticuerpos , Hipoglucemia/etiología , Compuestos de Sulfhidrilo , HipoglucemiantesRESUMEN
PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.
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Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Docetaxel/uso terapéutico , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Estudios Retrospectivos , Paclitaxel/uso terapéutico , Albúminas , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.
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Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/patología , Paclitaxel Unido a Albúmina/uso terapéutico , Terapia Neoadyuvante , Docetaxel/uso terapéutico , Lipopolisacáridos , Ciclofosfamida/uso terapéutico , Epirrubicina/uso terapéutico , Paclitaxel/uso terapéutico , Albúminas , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to investigate the root canal morphology and the thickness of crown and root of mandibular incisors in a Chinese subpopulation by micro-computed tomography (micro-CT). METHODS: In total, 208 mandibular incisors were scanned using micro-CT. The anatomical features of the canals (canal configuration, apical constriction, foramen-to-apex distance, accessory canal vertical distribution, and canal geometrical parameters) and the thickness of the crown and root 2/3 were evaluated. RESULTS: Three canal categories, labeled as Single (77.88%), Merged (15.87%), and Separated (6.25%), were summarized. The most frequent constriction type in main foramina was single constriction (42.53%). Wide and narrow diameters in a single main foramen were 0.37 ± 0.14 mm and 0.26 ± 0.07 mm, respectively. The distance from the anatomical foramen to the physiological foramen and the anatomical apex was 0.49 ± 0.20 mm and 0.36 ± 0.28 mm, respectively. During the virtual root-end resection, 97.12% of roots underwent successful resection at the 2-mm level, with the foramina visible on the resection surface. During 2-D cross-sectional analyses, the shape parameters of the root and canal showed significant positive correlation (P < 0.05). The thickest and thinnest walls were the incisal and proximal walls (P < 0.05) of the crown, respectively. The buccal walls were significantly thicker than the lingual walls on the crown (P < 0.05), whereas the lingual walls were thicker on the root 2/3 (P < 0.05). CONCLUSIONS: This study provides detailed information about the root canal morphology and thickness of the crown and root of mandibular incisors in a Chinese population. An understanding of morphology can benefit endodontic treatment. CLINICAL RELEVANCE: Adequate knowledge of the crown, root, and canal morphology, as well as the thickness distribution of the crown and root, is essential for successful root canal therapy and prevention of complications.
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Cavidad Pulpar , Incisivo , China , Estudios Transversales , Coronas , Cavidad Pulpar/diagnóstico por imagen , Humanos , Incisivo/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Tratamiento del Conducto Radicular , Raíz del Diente/diagnóstico por imagen , Microtomografía por Rayos XRESUMEN
CONTEXT: The traditional Chinese medicine formula Tao-Hong-Si-Wu decoction (TSD), used for treating ischaemic stroke, has the potential to treat depressive disorder (DD). OBJECTIVE: To explore the effective targets of TSD on DD animal models. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were modelled by inducing chronic unpredictable mild stress (CUMS) during 35 days and treated with three dosages of TSD (2.5, 5 and 10 g/kg) or fluoxetine (10 mg/kg) by oral gavage for 14 days. Bodyweight measurements and behavioural tests were performed to observe the effect of TSD on the CUMS animals. A gas chromatography coupled with mass spectrometry (GC-MS)-based metabolomic analysis was conducted to reveal the metabolic characteristics related to the curative effect of TSD. Levels of the proteins associated with the feature metabolites were analysed. RESULTS: Reduced immobile duration and crossed squares in the behavioural tests were raised by 48.6% and 32.9%, on average, respectively, by TSD treatment (ED50=3.2 g/kg). Antidepressant effects of TSD were associated with 13 decreased metabolites and the restorations of ornithine and urea in the serum. TSD (5 g/kg) raised serum serotonin by 54.1 mg/dL but suppressed arginase I (Arg I) by 47.8 mg/dL in the CUMS rats. Proteins on the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) axis that modulate the inhibition of Arg I were suppressed in the CUMS rats but reversed by the TSD intervention. DISCUSSION AND CONCLUSIONS: TSD improves depression-like symptoms in CUMS rats. Further study will focus on the antidepressant-like effects of effective compounds contained in TSD.
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Isquemia Encefálica , Accidente Cerebrovascular , Animales , Antidepresivos/farmacología , Arginasa/metabolismo , Arginasa/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Medicamentos Herbarios Chinos , Hipocampo , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismoRESUMEN
The present study utilized an in vitro dual-species biofilm model and an in vivo rat post-treatment endodontic disease (PTED) model to investigate whether co-infection of Candida albicans and Enterococcus faecalis would aggravate periapical lesions. The results showed that co-culturing yielded a thicker and denser biofilm more tolerant to detrimental stresses compared with the mono-species biofilm, such as a starvation-alkalinity environment, mechanical shear force and bactericidal chemicals. Consistently, co-inoculation of E. faecalis and C. albicans significantly increased the extent of in vivo periapical lesions compared with mono-species infection. Specifically, coexistence of both microorganisms increased osteoclastic bone resorption and suppressed osteoblastic bone formation. The synergistic effects also up-regulated inflammatory cytokines including TNF-α and IL-6. In summary, coexistence of C. albicans and E. faecalis increased periapical lesions by enhanced biofilm virulence.
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Candida albicans , Enterococcus faecalis , Animales , Antibacterianos , Biopelículas , Ratas , VirulenciaRESUMEN
BACKGROUND: Patients with connective tissue disease, such as dermatomyositis (DM), and positive anti-TIF1γ self-antibodies are commonly diagnosed with malignant tumors as a comorbidity. The relationship between anti-TIF1γ self-antibodies and existing malignant tumors has been confirmed by several reports. However, interstitial pneumonia with autoimmune features (IPAF) cases with a positive anti-TIF1γ self-antibody developing to solid malignant tumors are rarely reported now. CASE PRESENTATION: Herein, we presented an IPAF patient with anti-TIF1γ self-antibodies. No evidence of malignant tumors was found at the initial visit. However, the patient had developed stage IVB lung squamous cell carcinoma at the 1-year follow-up review. CONCLUSIONS: Altogether, this report described a rare case of IPAF patient with anti-TIF1γ self-antibodies developed to advanced lung squamous cell carcinoma in 1 year. The present case highlights more frequent imaging examinations to identify the occurrence of malignant tumors as early as possible in IPAF patients with positive anti-TIF1γ self-antibodies.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Neoplasias Pulmonares/diagnóstico , Anciano , Autoanticuerpos/sangre , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Factores de Tiempo , Tomografía Computarizada por Rayos X , Factores de Transcripción/inmunologíaRESUMEN
BACKGROUND: Erbium yttrium-aluminum-garnet (Er:YAG) laser have been shown to be suitable for decontamination of titanium surfaces at a wide range of energy settings, however, high intensity of laser irradiation destroy titanium surface and low intensity cannot remove enough microbial biofilm. The aim of this study was to investigate the optimal energy setting of Er:YAG laser for decontamination of sandblasted/acid-etched (SLA) and hydroxyapatite (HA) titanium surfaces. MATERIAL AND METHODS: After supragingival biofilm construction in vivo, SLA and HA titanium discs were divided into three groups: blank control (BC, clean discs), experimental control (EC, contaminated discs) and experimental groups (EP, contaminated discs irradiated by Er:YAG laser at 40, 70, and 100 mJ/pulse). Scanning electron microscopy (SEM), live/dead bacterial fluorescent detection, and colony counting assay were used to detect the efficacy of laser decontamination. To investigate the effect of laser decontamination on titanium surface biocompatibility, MC3T3-E1 cell adhesion and proliferation activity were examined by SEM and CCK-8 assay. RESULTS: Er:YAG laser irradiation at 100 mJ/pulse removed 84.1% of bacteria from SLA titanium surface; laser irradiation at 70 and 100 mJ/pulse removed 76.4% and 77.85% of bacteria from HA titanium surface respectively. Laser irradiation improved MC3T3-E1 cell adhesion on both titanium surfaces. For SLA titanium discs, 100 mJ/pulse group displayed excellent cellular proliferation activity higher than that in BC group (P < 0.01). For HA titanium discs, 70 mJ/pulse group showed the highest activity comparable to BC group (P > 0.05). CONCLUSIONS: With regards to efficient microbial biofilm decontamination and biocompatibility maintenance, Er:YAG laser at 100 mJ/pulse and 70 mJ/pulse are considered as the optimal energy settings for SLA titanium and HA titanium surface respectively. This study provides theoretical basis for the clinical application of Er:YAG laser in the treatment of peri-implantitis.