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Acute lung injury (ALI) is featured with a robust inflammatory response. Angiopoietin-like protein 2 (ANGPTL2), a pro-inflammatory protein, is complicated with various disorders. However, the role of ANGPTL2 in ALI remains to be further explored. The mice and MH-S cells were administrated with lipopolysaccharide (LPS) to evoke the lung injury in vivo and in vitro. The role and mechanism of ANGPTL was investigated by haematoxylin-eosin, measurement of wet/dry ratio, cell count, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling, reverse transcription quantitative polymerase chain reaction, immunofluorescence, enzyme-linked immunosorbent assay, detection of autophagic flux and western blot assays. The level of ANGPTL2 was upregulated in lung injury. Knockout of ANGPTL2 alleviated LPS-induced pathological symptoms, reduced pulmonary wet/dry weight ratio, the numbers of total cells and neutrophils in BALF, apoptosis rate and the release of pro-inflammatory mediators, and modulated polarization of alveolar macrophages in mice. Knockdown of ANGPTL2 downregulated the level of pyroptosis indicators, and elevated the level of autophagy in LPS-induced MH-S cells. Besides, downregulation of ANGPTL2 reversed the LPS-induced the expression of leukocyte immunoglobulin (Ig)-like receptor B2 (LILRB2) and triggering receptor expressed on myeloid cells 2 (TREM2), which was reversed by the overexpression of LILRB2. Importantly, knockdown of TREM2 reversed the levels of autophagy- and pyroptosis-involved proteins, and the contents of pro-inflammatory factors in LPS-induced MH-S cells transfected with si ANGPTL2, which was further inverted with the treatment of rapamycin. Therefore, ANGPTL2 silencing enhanced autophagy to alleviate alveolar macrophage pyroptosis via reducing LILRB2-mediated inhibition of TREM2.
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Lesión Pulmonar Aguda , Proteína 2 Similar a la Angiopoyetina , Autofagia , Macrófagos Alveolares , Piroptosis , Receptores Inmunológicos , Animales , Masculino , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/patología , Autofagia/genética , Técnicas de Silenciamiento del Gen , Lipopolisacáridos , Macrófagos Alveolares/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Piroptosis/genética , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genéticaRESUMEN
Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation model was established by applying LPS to the pulp of SD rats. We found that the increased expression of P2X3 was induced by acute pulpitis. A selective P2X3 inhibitor (A-317491) reduced pain-like behavior in the maxillofacial region of rats and depressed the activation of neurons in the trigeminal ganglion induced by pulpitis. The upregulated MAPK signaling (p-p38, p-ERK1/2) expression in the ipsilateral TG induced by pulpitis could also be depressed by the application of the P2X3 inhibitor. Furthermore, the expression of markers of inflammatory processes, such as NF-κB, TNF-α and IL-1ß, could be induced by acute pulpitis and deduced by the intraperitoneal injection of P2X3 antagonists. Our findings demonstrate that purinergic P2X3 receptor signaling in TG neurons contributes to pulpitis-induced pain in rats and that P2X3 signaling may be a potential therapeutic target for tooth pain.
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Pulpitis , Ratas , Animales , Pulpitis/metabolismo , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Dolor/metabolismo , Transducción de Señal , Inflamación/complicaciones , Inflamación/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Ganglio del Trigémino/metabolismoRESUMEN
OBJECTIVES: Malnutrition is prevalent in geriatric patients and associated with poor prognosis. This study aimed to evaluate the incremental prognostic value of different nutritional assessment tools in patients (90 years and older) with multimorbidity in China. METHODS: Patients aged ≥90 years with multimorbidity from the Geriatric Research Center in Nanjing Jinling Hospital from January 1, 2008 to December 31, 2018 were analyzed. Patients were followed until December 31,2022. The nutrition status was assessed according to the mini nutritional assessment (MNA), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. The outcome was all-cause death. Kaplan-Meier method was used to draw the survival curve, and univariate and multivariate Cox proportional risk regression analysis was used to explore the influencing factors of all-cause death in the patients. RESULTS: 160 participants aged 90(90,91) years were included. During a median follow-up of 5.41(3.12-7.64) years, 106(66.25 %) patients died. Deceased patients had lower MNA [20.75(16.75,23.00) vs. 26.00(24.00,26.00); p < 0.001], lower GNRI [96.21±8.75 vs. 100.94±6.80; p = 0.001] and lower PNI [46.16(40.77,49.57) vs. 47.75(45.36,51.53); p = 0.010] than did survivors. According to MNA, GNRI, and PNI score, 93(58.1 %), 72(45.0 %) and 41(25.6 %) of participants were at risk of malnutrition. Multivariate analysis revealed that malnutrition was independently associated with increased risk for mortality by MNA score (adjusted hazard ratio [HR] 2.502, 95 % confidence interval [CI] 1.561-4.009, p<0.001), GNRI score (adjusted HR 1.650, 95 % CI, 1.117-2.438, p = 0.012), and PNI score (adjusted HR 2.894, 95 % CI, 1.891-4.431, p<0.001). Furthermore, the inclusion of malnutrition indicators in the survival prediction model significantly improved the predictive power of mortality. CONCLUSION: The risk of malnutrition, as assessed by MNA, GNRI and PNI, in long-lived patients with multimorbidity is a strong independent predictor of mortality and adds significant prognostic information to the survival models.
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Titanium nitride (TiN) nanoparticles have recently been considered as potential candidate plasmonic materials; such materials support localized surface plasmon resonances (LSPRs) and show excellent thermal stability with a high melting point. The electromagnetic (EM) field coupling and gap distance between components of individual TiN nanosphere multimers are critical parameters affecting their plasmonic sensitivity and surface-enhanced Raman scattering (SERS) performance, both of which are numerically investigated by the finite element method. It is demonstrated that the fractional shifts of both the dipolar LSPR wavelength [Formula: see text] and the refractive index sensitivity factor S follow the universal 'plasmon ruler' behavior, which is explained well in terms of EM field distribution. The response of the obtained S to [Formula: see text] is also presented and elucidated in terms of the optical response of the dielectric constants of TiN. The maximum S and SERS enhancement (excited by three normally available lasers in experiments) are also predicted; both are comparable to the values for Au dimeric nanoparticles. The present work holds great promise for the development of non-noble metal plasmonic materials in both SERS and plasmonic sensing applications.
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Acute lower extremity ischemia (ALEXI) is known worldwide as an urgent condition, occurring when there is an abrupt interruption in blood flow into an extremity. This study aims to investigate whether microRNA-224 (miR-224) affects the ALEXI mice and the underlying mechanism. The miR-224 expression and C/EBP homologous protein (CHOP), mammalian target of rapamycin (mTOR), translation initiation factor 4E-binding protein 1 (4E-BP1), and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) messenger RNA (mRNA), as well as protein expressions, were determined. The target gene of miR-224 was also verified by using a luciferase reporter gene assay. The vascular endothelial cells from the ALEXI mice were transfected with miR-224 mimics, miR-224 inhibitors, or small-interfering RNA against CHOP. Cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle distribution along with the cell apoptosis were both evaluated by using a flow cytometry. The muscle fibers of the lower extremities found in the ALEXI mice were evidently swollen and rounded, presenting with a remarkably narrowed gap. The positive CHOP expression increased in ALEXI mice than normal mice, while the miR-224 expression and mTOR, 4E-BP1, and p70S6K mRNA, as well as the protein expression, decreased. Luciferase reporter gene assay validated that the miR-224 gene directly targeted CHOP. MiR-224 facilitated cell proliferation but inhibited cell apoptosis; by contrast, CHOP increased cell apoptosis. Moreover, the cells transfected along with miR-224 mimic exhibited a lower CHOP expression as well as increased mTOR, 4E-BP1, and p70S6K expression. Our study provided evidence that miR-224 could alleviate the occurrence and development of ALEXI in mice through activation of the mTOR signaling pathway by downregulating CHOP.
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Isquemia/metabolismo , MicroARNs/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factor de Transcripción CHOP/metabolismo , Animales , Regulación de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular , Extremidad Inferior , Ratones , Ratones Desnudos , MicroARNs/genética , Organismos Libres de Patógenos Específicos , Serina-Treonina Quinasas TOR/genética , Factor de Transcripción CHOP/genéticaRESUMEN
OBJECTIVE: Leptin, through binding to its special receptor (Ob-Rb), has potent effects on immunity and inflammation. This study aimed to investigate the expression of leptin receptor Ob-Rb in human dental pulp fibroblasts (HDPFs) and the effects of leptin on the production of proinflammatory cytokines of IL-6 and IL-8 by HDPFs. METHODS: Ob-Rb expression was determined by quantitative real-time PCR (real-time PCR), Western blot and immunofluorescence analyses in cultured HDPFs. Small interfering RNA (siRNA) was transfected into HDPFs to down-regulate the expression of Ob-Rb. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were used to determine the proinflammatory cytokines of IL-6 and IL-8 levels in leptin-stimulated HDPFs. The involved signalling pathways that mediate the leptin-stimulated production of proinflammatory cytokines were investigated using Western blot and specific signalling inhibitor analyses. RESULTS: The expression levels of Ob-Rb mRNA and protein were detected in HDPFs. Leptin could stimulate mRNA and protein expression of IL-6 and IL-8 in HDPFs in a concentration-dependent and time-dependent manner. Transfection with siRNA targeting Ob-Rb resulted in remarkable reduction of IL-6 and IL-8 expressions by HDPFs. In accordance with the enhanced expression of proinflammatory cytokines, leptin stimulation resulted in rapid phosphorylation of STAT3, p38 MAPK, ERK and Akt in HDPFs. Inhibiting JAK2/STAT3, p38 MAPK or PI3K/Akt substantially decreased leptin-induced IL-6 production, whereas blocking ERK and p38 MAPK substantially suppressed IL-8 production from leptin-stimulated HDPFs. CONCLUSIONS: Leptin may up-regulate IL-6 and IL-8 production through binding with Ob-Rb in HDPFs via the activation of different intracellular signalling pathways.
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Pulpa Dental/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , ARN Mensajero/metabolismo , Receptores de Leptina/metabolismo , Western Blotting , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/efectos de los fármacos , Humanos , Leptina , Reacción en Cadena de la Polimerasa , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: The purpose of this study is to compare the clinical outcomes of endovascular versus open revascularization for chronic mesenteric ischemia (CMI). METHODS: Published studies that investigated endovascular versus open revascularization for CMI were identified, and meta-analysis was used for statistical analysis. RESULTS: Eight studies were analyzed by meta-analysis method, cumulative 569 cases were included. Endovascular treatments were performed in 209 cases, and open repairs were performed in 360 cases. Meta-analysis showed that there was no difference in 30-day mortality and 3-year cumulative survival rate between the endovascular group and the open group (P = 0.55 and P = 0.56); compared with the open revascularization group, the endovascular revascularization group resulted in significantly lower rate of in-hospital complication (P = 0.002), while recurrence rate within 3 years after revascularization was significantly greater in the endovascular revascularization group (P < 0.00001). CONCLUSION: Endovascular treatment offers a benefit of lower in-hospital complication rate, but a greater recurrence rate within 3 years after revascularization compared with the open revascularization, and both groups have similar 30-day mortality and 3-year cumulative survival rate.
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Procedimientos Endovasculares , Isquemia Mesentérica/cirugía , Oclusión Vascular Mesentérica/cirugía , Procedimientos Quirúrgicos Vasculares , Distribución de Chi-Cuadrado , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Humanos , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/mortalidad , Isquemia Mesentérica/fisiopatología , Oclusión Vascular Mesentérica/diagnóstico , Oclusión Vascular Mesentérica/mortalidad , Oclusión Vascular Mesentérica/fisiopatología , Oportunidad Relativa , Complicaciones Posoperatorias/etiología , Recurrencia , Factores de Riesgo , Circulación Esplácnica , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
Isoenzyme c of horseradish peroxidase (HRP-C) is widely used in enzyme immunoassay combined with chemiluminescence (CL) detection. For this application, HRP-C activity measurement is usually based on luminol oxidation in the presence of hydrogen peroxide (H2O2). However, this catalysis reaction was enhancer dependent. In this study, we demonstrated that Jatropha curcas peroxidase (JcGP1) showed high efficiency in catalyzing luminol oxidation in the presence of H2O2. Compared with HRP-C, the JcGP1-induced reaction was enhancer independent, which made the enzyme-linked immunosorbent assay (ELISA) simpler. In addition, the JcGP1 catalyzed reaction showed a long-term stable CL signal. We optimized the conditions for JcGP1 catalysis and determined the favorable conditions as follows: 50 mM Tris buffer (pH 8.2) containing 10 mM H2 O2, 14 mM luminol and 0.75 M NaCl. The optimum catalysis temperature was 30°C. The detection limit of JcGP1 under optimum condition was 0.2 pM. Long-term stable CL signal combined with enhancer-independent property indicated that JcGP1 might be a valuable candidate peroxidase for clinical diagnosis and enzyme immunoassay with CL detection.
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Jatropha/enzimología , Mediciones Luminiscentes/métodos , Luminol/química , Peroxidasa/química , Catálisis , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/química , Cinética , Límite de Detección , Luminiscencia , Oxidación-Reducción , Peroxidasa/metabolismo , Hojas de la Planta/enzimología , TemperaturaRESUMEN
INTRODUCTION: Enamel demineralization and gingival inflammation are the most prevalent consequences of biofilm formation in orthodontics. Our hypothesis was that educating patients about the severe consequences of biofilm accumulation could enhance their oral hygiene while wearing fixed appliances. METHODS: This study was designed as a randomized controlled 4-arm parallel trial. A total of 148 participants in Chengdu, China, matching the eligibility criteria of 11 to 25 years of age, at least 20 natural teeth, and a treatment plan that included conventional stainless steel brackets, were randomly assigned to 4 intervention groups based on computer-generated random sequencing using simple randomization without blocking. In group A (n = 37), the subjects were shown images illustrating the severe consequences of biofilm formation, including enamel demineralization and gingival inflammation; subjects in group B (n = 40) were given biofilm disclosing tablets; those in group C (n = 38) received a combination of A and B; the subjects in group D (n = 33) served as the controls. The investigators were blinded to the allocations, and the researcher managing the random sequence did not participate in allocation or measurement. All groups received routine oral hygiene instructions. Plaque index and gingival index scores were recorded at each appointment during a 6-month follow-up. RESULTS: Eighteen participants were lost during follow-up, resulting in a total of 130 participants after the trial (group A, 35; group B, 32; group C, 34; group D, 29). No adverse events were recorded. Groups A and C exhibited a significantly lower plaque index scores (parameter-estimate [95% confidence interval] = -1.20 [-1.76 to -0.63] for group A, and -1.12 [-1.69 to -0.56] for group C) and gingival index scores (-0.13 [-0.21 to -0.04], and -0.19 [-0.28 to -0.10]), respectively, compared with group D (P <0.001 for all), whereas no significant difference was found between groups B and D, or between groups A and C (P >0.05). The adults had significantly lower plaque index (0.48 [0.13-0.84], P <0.001) and gingival index (0.06 [0.01-0.11], P = 0.018) scores than did the teenagers, and the female subjects had significantly higher gingival index (-0.06 [-0.11 to -0.01], P = 0.040) scores than did the male subjects. CONCLUSIONS: The use of images showing the severe consequences of biofilm accumulation enhanced the oral hygiene of patients treated with fixed appliances.
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Recursos Audiovisuales , Colorantes , Placa Dental/diagnóstico , Higiene Bucal/educación , Educación del Paciente como Asunto/métodos , Adolescente , Adulto , Biopelículas/clasificación , Niño , Esmalte Dental/patología , Placa Dental/complicaciones , Índice de Placa Dental , Femenino , Estudios de Seguimiento , Gingivitis/etiología , Humanos , Masculino , Soportes Ortodóncicos/microbiología , Índice Periodontal , Estudios Prospectivos , Método Simple Ciego , Desmineralización Dental/etiología , Cepillado Dental/instrumentación , Pastas de Dientes/uso terapéutico , Adulto JovenRESUMEN
The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.
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Hiperalgesia , Pulpitis , Ratas , Animales , Hiperalgesia/metabolismo , Ratas Sprague-Dawley , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ganglio del Trigémino , Neuronas/metabolismo , Dolor Facial/metabolismo , Dolor Facial/patología , Receptores PurinérgicosRESUMEN
Odontogenesis consists of a series of consecutive tooth morphogenesis stages, in which apoptosis is involved to eliminate the unnecessary cells. Autophagy, a lysosome or endosome-mediated self-degradation process, is indicated to participate in embryogenesis and tissue morphogenesis associated with apoptosis. This study hypothesized that autophagy may be involved and associated with apoptosis in odontogenesis. The transcripts of autophagy-related genes (Atg5, Atg7, and Atg12) were positively detected in tooth germs at embryonic day (E) 14.5 and postnatal day (P) 5.5 by quantitative real-time PCR. The protein expression of Atg5-Atg12 conjugate and lipidation of LC3 (microtubule-associated protein 1 light chain 3, autophagic marker) were revealed in the developing tooth germs by western blot. Meanwhile, LC3 was immunolocalized in the enamel organ and dental papilla at embryonic stages (E13.5-E18.5), especially stage E14.5 cervical loop and the PEK that facing the mesenchyme. At postnatal stages (P1.5-P15.5), besides the dental epithelium cells, LC3 was detected in the differentiating and differentiated odontoblasts, dental follicle cells, and Hertwig's epithelium root sheath cells. Moreover, double-immunofluorescence analysis revealed the partial colocalization of LC3 and TUNEL signal in the E14.5 PEK that facing the mesenchyme, the E16.5 stratum intermedium and outer enamel epithelium, the P5.5 stratum intermedium and stellate reticulum. Nevertheless, LC3 was also found in non-apoptotic cells. Furthermore, the transmission electron microscopic images revealed the presence of autophagy, as well as the partial colocalization of autophagic vacuoles and apoptotic nuclei during tooth development. Our findings imply the developmental appearance of autophagy and its partial colocalization with apoptosis during odontogenesis.
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Autofagia , Diente Molar/embriología , Odontogénesis , Germen Dentario , Animales , Apoptosis , Autofagia/genética , Proteína 12 Relacionada con la Autofagia , Proteína 5 Relacionada con la Autofagia , Proteína 7 Relacionada con la Autofagia , Western Blotting , Regulación del Desarrollo de la Expresión Génica , Edad Gestacional , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ratones , Ratones Endogámicos ICR , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Diente Molar/metabolismo , Diente Molar/ultraestructura , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Germen Dentario/metabolismo , Germen Dentario/ultraestructuraRESUMEN
RATIONALE: Calciphylaxis, known as calcific uremic arteriolopathy, is a rare cause of dry gangrene. Despite an increase in the clinical recognition of demographic characteristics and risk factors associated with calciphylaxis, it remains a poorly understood disease with high mortality. PATIENT CONCERNS AND DIAGNOSES: We present a 45-year-old man, who was diagnosed with calciphylaxis disease, with a history of diabetes mellitus, end-stage renal disease and cirrhosis with a half-month evolution of painful dry gangrene on his glans penis and scrotum. The patient also presented with gangrene of fingers. INTERVENTIONS AND OUTCOMES: The patient and his family opted for palliative care. However, he died eventually. LESSONS: This case contributed to the current understanding of calciphylaxis. Since no standard treatment is available and the prognosis remained poor, early, and accurate diagnosis of calciphylaxis is important. We here report the current case and provide data for the diagnosis and treatment of this kind of disease.
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Calcifilaxia , Fallo Renal Crónico , Masculino , Humanos , Persona de Mediana Edad , Gangrena , Calcifilaxia/complicaciones , Calcifilaxia/diagnóstico , Pene , Necrosis/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapiaRESUMEN
A modified numerical procedure for the shakedown analysis of structures under dual cyclic loadings, based on the Abdalla method, is proposed in this paper. Based on the proposed numerical procedure, the shakedown analysis of the thick cylindrical vessels with crossholes (TCVCs) under cyclic internal pressure and cyclic thermal loading was carried out. The effects of material parameters (elastic modulus and thermal expansion coefficient) and crosshole radius on the elastic shakedown limit of TCVCs are discussed and, finally, normalized and formularized. Furthermore, the obtained shakedown limit boundary formulation is compared with FEA results and is verified to evaluate the shakedown behavior of TCVCs under cyclic internal pressure and cyclic thermal loading.
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BACKGROUND: Osteoclast differentiation plays a key role in orthodontic tooth movement (OTM). We aimed to explore the role of human periodontal ligament (hPDL) extracellular vesicles (EVs) in osteoclast differentiation and OTM. METHODS: The hPDL cells were exposed to 4.0 g/cm2 compression force (CF) and the hPDL-EVs were collected. The peripheral blood mononuclear cells were isolated, purified, and induced osteoclast differentiation. The OTM rat model was established through excess orthodontic force. Dual-luciferase reporter gene assay verified the targeting effect of miR-28 on RUNX1. In addition, tartrate-resistant acid phosphase (TRAP) staining, immunofluorescence, western blot, and quantitative real-time PCR were also carried out. RESULTS: CF pretreated hPDL-EVs promoted osteoclast differentiation and down-regulated RUNX1 levels in in vitro and in vivo experiments. The addition of CF-hPDL-EVs also elevated tooth movement in OTM rats. Besides, miR-28 was significantly up-regulated in CF-pretreated hPDL-EVs. In addition, RUNX1 was negatively regulated by miR-28. Moreover, the addition of CF-lenti-miR-28 inhibitor-Evs down-regulated the expression of osteoclast marker genes and the number of TRAP positive (+) multinucleated cells (MNCs) in vitro. Furthermore, in vivo experiments confirmed that CF-lenti-miR-28 inhibitor-Evs injection down-regulated the number of TRAP (+) MNCs and inhibited tooth movement of OTM rats. CONCLUSION: CF-treated hPDL-EVs promoted osteoclast differentiation by transporting miR-28 and inhibiting the expression of RUNX1, which provides new insight into the specific mechanism of hPDL-Evs affecting osteoclast differentiation.
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Vesículas Extracelulares , MicroARNs , Humanos , Ratas , Animales , Ligamento Periodontal , Técnicas de Movimiento Dental , Osteoclastos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucocitos Mononucleares , MicroARNs/genéticaRESUMEN
The purpose of the present study was to evaluate histologically in beagle dogs the healing in acute dehiscence type defects following treatment with open flap debridement (OFD) with or without porous biphasic calcium phosphate (PBCP). Alveolar bone dehiscence defects were surgically created bilaterally at the labial aspects of maxillary third incisors in 12 beagle dogs. After root conditioning with ethylenediaminetetraacetate, PBCP was filled in the defects and the contralaterals were cured with OFD. Two fluorochrome labelings were administered at the 7th and 11th weeks, respectively. Four dogs were killed at the 12, 16, and 24 weeks, respectively. Histological observations were processed through microcomputed tomographic imaging, fluorescence microscope, and light microscopy. The formation of new regenerated tissues was assessed histomorphometrically. The results revealed the healing after treatments with PBCP evidenced a new attachment apparatus and that with OFD supported periodontal repair. In PBCP groups, the amount of new bone varied from 1.15 to 3.86 mm (23-77.2% of the original defect size), while only 0.3 to 1.04 mm (6-20.8%) in OFD group. The amount of new cementum in PBCP varied from 1.18 to 4.16 mm (23.6-82.3%), while only 0.67 to 1.15 mm (13.4-23%) in OFD group. The amount of periodontal ligament in PBCP varied from 1.03 to 4.12 mm (20.6-82.4%), while only 0 to 0.93 mm (0-18.6%) in OFD group. There was significantly more regenerated tissue in PBCP groups compared to OFD procedures (p < 0.01). The present results indicate that PBCP may enhance periodontal regeneration in acute-type labial dehiscence defects.
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Pérdida de Hueso Alveolar/cirugía , Sustitutos de Huesos/uso terapéutico , Cerámica , Hidroxiapatitas/uso terapéutico , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/patología , Animales , Regeneración Ósea/efectos de los fármacos , Quelantes/uso terapéutico , Desbridamiento , Cemento Dental/efectos de los fármacos , Cemento Dental/patología , Perros , Ácido Edético/uso terapéutico , Colorantes Fluorescentes , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Incisivo/patología , Masculino , Microscopía Fluorescente , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/patología , Fenoles , Regeneración/efectos de los fármacos , Sulfóxidos , Colgajos Quirúrgicos , Tetraciclina , Factores de Tiempo , Raíz del Diente/efectos de los fármacos , Cicatrización de Heridas/fisiología , Microtomografía por Rayos X , XilenosRESUMEN
BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of osteoclast biology and several pathogenic progression. This study aimed to identify the role of miR-26a in osteoclastogenesis and orthodontically induced inflammatory root resorption(OIIRR). METHODS: Rat orthodontic tooth movement (OTM) model was established by ligating a closed coil spring between maxillary first molar and incisor, and 50 g orthodontic force was applied to move upper first molar to middle for 7 days. Human periodontal ligament (hPDL) cells were isolated from periodontium of healthy donors, and then subjected to compression force (CF) for 24 h to mimic an in vitro OTM model. The levels of associated factors in vivo and in vitro were measured subsequently. RESULT: The distance of tooth movement was increased and root resorption pits were occurred in rat OTM model. The expression of miR-26a was decreased in vivo and vitro experiments. CF treatment enhanced the secretion of inflammatory factors receptor activator of nuclear factor-kappa B ligand (RANKL) and IL-6, osteoclast marker levels, and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, while miR-26a overexpression reversed these results. Furthermore, miR-26a overexpression inhibited the osteoclastogenesis and rescued the root resorption in OTM rats through inhibition of Jagged1. Additionally, Runx1 could bind to miR-26a promoter and promote its expression, thereby suppressing the osteoclastogenesis. CONCLUSION: We concluded that Runx1/miR-26a/Jagged1 signaling axis restrained osteoclastogenesis and alleviated OIIRR.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , Resorción Radicular/inmunología , Técnicas de Movimiento Dental/efectos adversos , Adolescente , Adulto , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo/inmunología , Femenino , Humanos , Proteína Jagged-1/genética , Masculino , Osteoclastos , Osteogénesis/inmunología , Ligamento Periodontal/citología , Ligamento Periodontal/patología , Cultivo Primario de Células , Regiones Promotoras Genéticas/genética , Ratas , Resorción Radicular/genética , Resorción Radicular/patología , Regulación hacia Arriba/inmunología , Adulto JovenRESUMEN
Embedded noble metal nanostructures and surface anti-reflection (AR) layers affect the optical properties of methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells significantly. Herein, by employing a combined finite element method and genetic algorithm approach, we report five different types of CH3NH3PbI3 perovskite solar cells by introducing embedded Ag nanoparticles within the CH3NH3PbI3 layer and/or top ITO cylinder grating as an AR layer. The maximum photocurrent was optimized to reach 23.56 mA/cm2, which was 1.09/1.17 times higher than Tran's report/ flat cases. It is also comparable with values (23.6 mA/cm2) reported in the literature. The calculations of the electric field and charge carrier generation rate of the optimized solar cell further confirms this improvement than flat cases. It attributes to the synergistic effect of the embedded Ag nanoparticles and ITO AR layer. The results obtained herein hold great promise for future boosting the optical efficiency of perovskite solar cells.
RESUMEN
The objectives of this study were to investigate the early response to mechanical stress in neonatal rat mandibular chondrocytes by proteomic analysis. To evaluate its molecular mechanism, chondrocytes were isolated and cultured in vitro, then loaded mechanical stress by four-point bending system on different patterns. Morphological observation, flow cytometric analysis, and MTT assays indicated that 4,000 microstrain loading for 60 min was an appropriate mechanical stimulus for the following proteome analysis, which produced a transient but obvious inhibitory effect on the cell cycle. Therefore, we took a proteomic approach to identify significantly differential expression proteins in chondrocytes under this mechanical stress. Using 2-DE and MALDI-TOF, we identified seven differentially expressed proteins including the MAPK pathway inhibitor RKIP, cytoskeleton proteins, actin and vimentin, and other selected proteins. Some differentially expressed proteins were validated by both Western blot analysis and fluorescent staining of cytoskeleton at different loading times. The vimentin and RKIP responsive expression were also proven in vivo in oral orthopedic treatment rats, which was in line with the result in vitro. The histological changes in cartilage also showed the inhibition effect. Furthermore, the expressional level of phosphorylated ERK was increased, which demonstrates the changes in MAPK activity. Taken together, these data indicate that mechanical stress resulted in vimentin expression changes first and then led to the subsequent changes in actin expression, MAPK pathway regulated by RKIP and heat shock protein GRP75. All those changes contributed to the cytoskeleton remolding and cell cycle inhibition, finally led to condylar remodeling.
Asunto(s)
Condrocitos/citología , Condrocitos/metabolismo , Cóndilo Mandibular/citología , Proteómica/métodos , Estrés Mecánico , Actinas/metabolismo , Animales , Animales Recién Nacidos , Western Blotting , Ciclo Celular , Forma de la Célula , Condrocitos/ultraestructura , Citoesqueleto/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Inmunohistoquímica , Espectrometría de Masas , Modelos Biológicos , Ratas , Ratas Sprague-Dawley , Vimentina/metabolismoRESUMEN
Bacterial adhesion to biomaterial surfaces constituting the bracket-adhesive-enamel junction represents a growing problem in orthodontics, because bacteria can adversely affect treatment by causing demineralization of the enamel surface around the brackets. It is important to know the forces with which bacteria adhere to the surfaces of these junction materials, as the strength of these forces will determine how easy it will be to remove the bacteria. We compared the adhesion forces of five initially colonizing and four cariogenic strains of bacteria to an orthodontic adhesive, stainless steel, and enamel, with and without a salivary conditioning film. Adhesion forces were determined using atomic force microscopy and a bacterial probe. In the absence of a salivary conditioning film, the strongest bacterial adhesion forces occurred to the adhesive surface (-2.9 to -6.9 nN), while adhesion forces to the enamel surfaces were lowest (-0.8 to -2.7 nN). In the presence of a salivary conditioning film, adhesion forces were reduced strongly, to less than 1 nN, and the differences between the various materials were reduced. Generally, however, initial colonizers of dental hard surfaces presented stronger adhesion forces to the different materials (-4.7 and -0.6 nN in the absence and presence of a salivary conditioning film, respectively) than cariogenic strains (-1.8 and -0.5 nN).
Asunto(s)
Adhesión Bacteriana/fisiología , Materiales Biocompatibles/química , Biopelículas , Esmalte Dental/microbiología , Boca/microbiología , Soportes Ortodóncicos/microbiología , Ortodoncia Correctiva/instrumentación , Cementos de Resina/química , Actinomyces/fisiología , Animales , Fenómenos Biomecánicos , Bovinos , Aleaciones Dentales/química , Película Dental/microbiología , Película Dental/fisiología , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Lactobacillus acidophilus/fisiología , Masculino , Ensayo de Materiales , Acero Inoxidable/química , Streptococcus/fisiología , Streptococcus mitis/fisiología , Streptococcus mutans/fisiología , Streptococcus oralis/fisiología , Streptococcus sobrinus/fisiología , Estrés Mecánico , HumectabilidadRESUMEN
INTRODUCTION: Length of treatment is a complaint of many orthodontic patients. The purpose of this study was to evaluate the security and feasibility of rapid tooth movement with periodontal ligament distraction. METHODS: Eight male beagles, aged 13 to 16 months, were used in this study. Extraction of the mandibular second premolar and alveolar surgery to reduce the osteal resistance on the mesial side of the extraction socket were performed on the experimental side. Then a device was placed to distract the first premolars distally on the experimental side; on the control side, the first premolars were distalized with nickel-titanium coil springs. The beagles were killed in the first, second, fourth, and eighth weeks after orthodontic force application. RESULTS: The first premolar on the experimental side moved more rapidly than that on the control side (P <0.05). Histologic data indicated that more new bone was deposited on tension area of the experimental side than on the control side. Active and extensive bone resorption in the compressive area and bone deposition in the tension area were observed on the experimental side. CONCLUSIONS: These results suggest that the periodontal ligament can be rapidly distracted without complications. The rapid orthodontic tooth movement by distracting the periodontal ligament cannot be emulated by current conventional orthodontic concepts and methods.