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The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.
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Antiinflamatorios , Medicamentos Herbarios Chinos , Lipopolisacáridos , Animales , Ratones , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células RAW 264.7 , Lipopolisacáridos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ratas , Cromatografía Liquida/métodos , Masculino , Óxido Nítrico/metabolismo , Espectrometría de Masas/métodos , Ratas Sprague-Dawley , Interleucina-6/sangreRESUMEN
BACKGROUND: Stroke is a leading cause of morbidity and mortality worldwide. Neuroinflammation plays a key role in acute brain injury of ischemic stroke. MicroRNA-210 (miR210) is the master hypoxamir and regulates microglial activation and inflammation in a variety of diseases. In this study, we uncovered the mechanism of miR210 in orchestrating ischemic stroke-induced neuroinflammation through repression of TET2 (ten-eleven translocation methylcytosine dioxygenase 2) in the adult mouse brain. METHODS: Ischemic stroke was induced in adult WT (wild type) or miR210 KO (miR210 deficient) mice by transient intraluminal middle cerebral artery occlusion. Injection of TET2 silencing RNA or miR210 complementary locked nucleic acid oligonucleotides, or miR210 KO mice were used to validate miR210-TET2 axis and its role in ischemic brain injury. Furthermore, the effect of TET2 overexpression on miR210-stimulated proinflammatory cytokines was examined in BV2 microglia. Post assays included magnetic resonance imaging scan for brain infarct size; neurobehavioral tests, reverse transcription-quantitative polymerase chain reaction, and Western blot for miR210; and TET2 levels, flow cytometry, and ELISA for neuroinflammation in the brain after stroke or microglia in vitro. RESULTS: miR210 injection significantly reduced TET2 protein abundance in the brain, while miR210 complementary locked nucleic acid oligonucleotides or miR210 KO preserved TET2 regardless of ischemic brain injury. TET2 knockdown reversed the protective effects of miR210 inhibition or miR210 KO on ischemic stroke-induced brain infarct size and neurobehavioral deficits. Moreover, flow cytometry and ELISA assays showed that TET2 knockdown also significantly dampened the anti-inflammatory effect of miR210 inhibition on microglial activation and IL (interleukin)-6 release after stroke. In addition, overexpression of TET2 in BV2 microglia counteracted miR210-induced increase in cytokines. CONCLUSIONS: miR210 inhibition reduced ischemic stroke-induced neuroinflammatory response via repression of TET2 in the adult mouse brain, suggesting that miR210 is a potential treatment target for acute brain injury after ischemic stroke.
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Lesiones Encefálicas , Isquemia Encefálica , Dioxigenasas , Accidente Cerebrovascular Isquémico , MicroARNs , Animales , Ratones , Lesiones Encefálicas/patología , Isquemia Encefálica/patología , Citocinas/metabolismo , Infarto/patología , Infarto de la Arteria Cerebral Media/patología , Inflamación/patología , Interleucina-6/metabolismo , Accidente Cerebrovascular Isquémico/patología , Ratones Endogámicos C57BL , Microglía/patología , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades NeuroinflamatoriasRESUMEN
A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c^{2}.
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We report a search for light dark matter produced through the cascading decay of η mesons, which are created as a result of inelastic collisions between cosmic rays and Earth's atmosphere. We introduce a new and general framework, publicly accessible, designed to address boosted dark matter specifically, with which a full and dedicated simulation including both elastic and quasielastic processes of Earth attenuation effect on the dark matter particles arriving at the detector is performed. In the PandaX-4T commissioning data of 0.63 tonne·year exposure, no significant excess over background is observed. The first constraints on the interaction between light dark matter generated in the atmosphere and nucleus through a light scalar mediator are obtained. The lowest excluded cross section is set at 5.9×10^{-37} cm^{2} for a dark matter mass of 0.1 MeV/c^{2} and mediator mass of 300 MeV/c^{2}. The lowest upper limit of η to the dark matter decay branching ratio is 1.6×10^{-7}.
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We report results of a search for dark-matter-nucleon interactions via a dark mediator using optimized low-energy data from the PandaX-4T liquid xenon experiment. With the ionization-signal-only data and utilizing the Migdal effect, we set the most stringent limits on the cross section for dark matter masses ranging from 30 MeV/c^{2} to 2 GeV/c^{2}. Under the assumption that the dark mediator is a dark photon that decays into scalar dark matter pairs in the early Universe, we rule out significant parameter space of such thermal relic dark-matter model.
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We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.
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Núcleo Celular , ElectronesRESUMEN
BACKGROUND: The reconstruction of large mandibular defects is a challenge, and free vascularized bone flaps are most commonly used. However, the precision and symmetry of this repair are deficient, and patients have a risk of vascular embolism, flap necrosis, and donor site complications. Therefore, to explore an ideal alternative in mandibular reconstruction with high surgical accuracy and low complications is indispensable. METHODS: Seven patients with recurrent or large-scope ameloblastoma were enrolled in this study. All patients were provided with a fully digital treatment plan, including the design of osteotomy lines, surgical guides, and three-dimensional printed titanium mesh for implantation. With the assistance of surgical guide, ameloblastomas were resected, and custom 3D printed titanium mesh combined with posterior iliac bone harvest was used in mandibular reconstruction. A comparison was made between the discrepant surgical outcomes and the intended surgical plan, as well as the average three-dimensional deviation of the mandible before and after the surgery. At the same time, the resorption rate of the implanted bone was evaluated. RESULTS: All patients completed the fully digital treatment process successfully without severe complications. Image fusion showed that the postoperative contour of the mandible was basically consistent with surgical planning, except for a slight increase in the inferior border of the affected side. The mean three-dimensional deviation of the mandible between the preoperative and postoperative periods was 0.78 ± 0.41 mm. The mean error between the intraoperative bone volume and the digital planning bone volume was 2.44%±2.10%. Furthermore, the bone resorption rates of the harvested graft 6 months later were 32.15%±6.95%. CONCLUSIONS: The use of digital surgical planning and 3D-printed templates can assist surgeons in performing surgery precisely, and the 3D-printed titanium mesh implant can improve the patient's facial symmetry. 3D printed titanium mesh combined with posterior iliac cancellous bone graft can be regarded as an ideal alternative in extensive mandibular reconstruction.
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Ameloblastoma , Implantes Dentales , Humanos , Ameloblastoma/cirugía , Titanio , Hueso Esponjoso , Mallas Quirúrgicas , Mandíbula/cirugíaRESUMEN
Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the 95.0-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be 1.5×10^{-50} cm^{2} for a fermionic dark matter mass of 40 MeV/c^{2} with 90% confidence level.
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We report a search on sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne year exposure collected by the PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and the electron. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such a dark matter candidate into photon final states. In particular, we present the first direct detection limits for a vector (axial-vector) interaction which are the strongest in the mass range from 35 to 55 (25 to 45) keV/c^{2} in comparison to other astrophysical and cosmological constraints.
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We report a novel search for the cosmic-ray boosted dark matter using the 100 tonne·day full dataset of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10^{-31} and 10^{-28} cm^{2} for dark matter masses from 0.1 MeV/c^{2} to 0.1 GeV/c^{2}, with a large parameter space previously unexplored by experimental collaborations.
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This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.
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Osteoclastos , Osteogénesis , Animales , Bovinos , Materiales Biocompatibles , Cementos para Huesos , Regeneración Ósea , Calcio , Fosfatos de Calcio/farmacología , Diferenciación Celular , Iones , Andamios del TejidoRESUMEN
Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone-like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx-Cre:FNDC5/irisin KO mice, in which FNDC5/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early-stage to adulthood. Our phenotypical analysis exhibited decreased osteoblast-related gene expression and increased osteoclast-related gene expression in bone tissues, and reduced adipose tissue browning due to bone-born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain-of-function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.
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Huesos , Fibronectinas , Músculo Esquelético , Osteoblastos , Osteogénesis , Animales , Huesos/metabolismo , Enfermedades Óseas Metabólicas/metabolismo , Fibronectinas/deficiencia , Fibronectinas/genética , Músculo Esquelético/metabolismo , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , RatonesRESUMEN
BACKGROUND: Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of acute mortality and chronic disability in newborns. Our previous studies demonstrated that HI insult significantly increased microRNA-210 (miR-210) in the brain of rat pups and inhibition of brain endogenous miR-210 by its inhibitor (LNA) provided neuroprotective effect in HI-induced brain injury. However, the molecular mechanisms underpinning this neuroprotection remain unclear. METHODS: We made a neonatal HI brain injury model in mouse pups of postnatal day 7 to uncover the mechanism of miR-210 in targeting the ten eleven translocation (TET) methylcytosine dioxygenase 2 that is a transcriptional suppressor of pro-inflammatory cytokine genes in the neonatal brain. TET2 silencing RNA was used to evaluate the role of TET2 in the neonatal HI-induced pro-inflammatory response and brain injury. MiR-210 mimic and inhibitor (LNA) were delivered into the brain of mouse pups to study the regulation of miR-210 on the expression of TET2. Luciferase reporter gene assay was performed to validate the direct binding of miR-210 to the 3' untranslated region of the TET2 transcript. Furthermore, BV2 mouse microglia cell line was employed to confirm the role of miR-210-TET2 axis in regulating pro-inflammatory response in microglia. Post-assays included chromatin immunoprecipitation (ChIP) assay, co-immunoprecipitation, RT-PCR, brain infarct assay, and neurobehavioral test. Student's t test or one-way ANOVA was used for statistical analysis. RESULTS: HI insult significantly upregulated miR-210, downregulated TET2 protein abundance, and increased NF-κB subunit p65 acetylation level and its DNA binding capacity to the interleukin 1 beta (IL-1ß) promoter in the brain of mouse pups. Inhibition of miR-210 rescued TET2 protein level from HI insult and miR-210 mimic decreased TET2 protein level in the brain of mouse pups, suggesting that TET2 is a functional target of miR-210. The co-immunoprecipitation was performed to reveal the role of TET2 in HI-induced inflammatory response in the neonatal brain. The result showed that TET2 interacted with NF-κB subunit p65 and histone deacetylase 3 (HDAC3), a co-repressor of gene transcription. Furthermore, TET2 knockdown increased transcriptional activity of acetyl-p65 on IL-1ß gene in the neonatal brain and enhanced HI-induced upregulation of acetyl-p65 level and pro-inflammatory cytokine expression. Of importance, TET2 knockdown exacerbated brain infarct size and neurological deficits and counteracted the neuroprotective effect of miR-210 inhibition. Finally, the in vitro results demonstrated that the miR-210-TET2 axis regulated pro-inflammatory response in BV2 mouse microglia cell line. CONCLUSIONS: The miR-210-TET2 axis regulates pro-inflammatory cytokine expression in microglia, contributing to neonatal HI brain injury.
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Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/biosíntesis , Regulación hacia Abajo/fisiología , Hipoxia-Isquemia Encefálica/metabolismo , Mediadores de Inflamación/metabolismo , MicroARNs/biosíntesis , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/biosíntesis , Animales , Animales Recién Nacidos , Línea Celular , Dioxigenasas , Femenino , Hipoxia-Isquemia Encefálica/patología , Masculino , RatonesRESUMEN
We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9 tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30 MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38} cm^{2}.
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We report the first dark matter search results using the commissioning data from PandaX-4T. Using a time projection chamber with 3.7 tonne of liquid xenon target and an exposure of 0.63 tonne·year, 1058 candidate events are identified within an approximate nuclear recoil energy window between 5 and 100 keV. No significant excess over background is observed. Our data set a stringent limit to the dark matter-nucleon spin-independent interactions, with a lowest excluded cross section (90% C.L.) of 3.8×10^{-47} cm^{2} at a dark matter mass of 40 GeV/c^{2}.
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INTRODUCTION: Corticotomy is widely used in clinical practice to accelerate tooth movement and shorten the duration of orthodontic treatment. It is effective, but an invasive surgery is needed to induce alveolar bone osteopenia that enable rapid tooth movement. In this study, we discovered the potential of 6-shogaol as a more patient-friendly non-invasive alternative to induce transient osteopenia and accelerate tooth movement. MATERIALS AND METHODS: The effects of 6-shogaol on the bone marrow macrophages (BMM) proliferation and osteoclast differentiation, and bone resorption were determined in vitro. Sprague-Dawley rats were distributed into three groups: CON, IPinj or Localinj and euthanized at day 28. Micro-CT, histology, immunohistological, and TUNEL analysis were performed to evaluate the tooth movement acceleration effect of 6-shogaol. RESULTS: In vitro, 6-shogaol promotes osteoclast differentiation and functional demineralization of alveolar bone. RANKL-induced mRNA expression of osteoclastic-specific genes was significantly higher in the presence of 6-shogaol. A dose-dependent increase in the area of TRAP-positive cells was observed with 6-shogaol treatment. F-actin ring formation and increased bone resorption confirmed that osteoclasts treated with 6-shogaol were mature and functional. 6-shogaol stimulated JNK activation and NFATc1 expression during osteoclast differentiation. In vivo, 6-shogaol promotes alveolar bone transient osteopenia and accelerates orthodontic tooth movement. Alveolar bone mass was reduced, more osteoclasts were observed in bone resorption lacunae on the compression side, and the expression of RANKL and sclerostin were higher than the control group. In conclusion, our results suggest that 6-shogoal accelerates tooth movement by inducing osteopenia by a mechanism similar to surgically induced bone injury.
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Resorción Ósea , Técnicas de Movimiento Dental , Animales , Catecoles , Humanos , Factores de Transcripción NFATC , Osteoclastos , Ratas , Ratas Sprague-DawleyRESUMEN
Cortical neurons oscillate synchronously between the Up and Down state during slow-wave sleep and general anesthesia. Using local-field-potential recording in the rat prefrontal cortex (PFC), we have shown that systemic administration of methylphenidate promotes PFC Up states and reduces PFC slow oscillation, suggesting a depolarizing effect of the drug on PFC neurons. Here, we report that systemic injection of d-amphetamine produced similar effects. Our evidence further suggests that norepinephrine (NE) plays a major role in the effects of d-amphetamine since they were mimicked by the NE reuptake inhibitors tomoxetine and nisoxetine and completely blocked by the α1 receptor antagonist prazosin. The effects of d-amphetamine persisted, however, in the presence of α2 or ß receptor blockade. Experiments with α1 subtype-selective antagonists further suggest that d-amphetamine's effects depend on activation of central, but not peripheral, α1A receptors. Unexpectedly, the putative α1 receptor agonist cirazoline failed to mimic the effects of d-amphetamine. Previous studies suggest that cirazoline is also an antagonist at α2 receptors. Furthermore, it is a partial, not full, agonist at α1B and α1D receptors. Whether or not these properties of cirazoline contribute to its failure to mimic d-amphetamine's effects remains to be determined. Methylphenidate and d-amphetamine are two most common medications for attention-deficit/hyperactivity disorder (ADHD). Both, however, are associated with adverse effects including abuse potential and psychotomimetic effects. Further understanding of their mechanisms of action will help develop safer treatments for ADHD and offer new insights into drug addiction and psychosis.
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Anfetamina/farmacología , Corteza Prefrontal/efectos de los fármacos , Receptores Adrenérgicos/fisiología , Animales , Clorhidrato de Atomoxetina/farmacología , Dextroanfetamina/farmacología , Dopamina , Masculino , Metilfenidato/farmacología , Neuronas/efectos de los fármacos , Norepinefrina/metabolismo , Prazosina , RatasRESUMEN
ABSTRACT: This study aimed to design and fabricate a customized distractor based on 3D printing technology and compare its mechanical properties with conventional distractor. The investigators designed and implemented a study composed of conventional and customized distractors. The design of customized distractor was based on the specification of conventional mandibular distractors and was fabricated using selective laser melting (SLM) technology. The same type of conventional distractors served as control group. Vickers-hardness test, three-point bending test and welding strength test were carried out for the conventional and customized distractor respectively and data was analyzed with t test using SPSS13.0 software package. The sample was composed of 18 distractors grouped as follows: customized distractor (nâ=â9) and conventional distractor (nâ=â9). The customized distractor showed better result than the conventional distractor in mechanical property tests, with statistically significant differences in Vickers-hardness and maximum load (Pâ<â0.05), and no significant differences in yield strength and welding strength (Pâ>â0.05). The results of this study suggest indicated that compared to the conventional distractor, the customized distractor had better mechanical properties and could be used in maxillofacial distraction osteogenesis.
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Mandíbula , Osteogénesis por Distracción , Humanos , Rayos Láser , Impresión TridimensionalRESUMEN
C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.
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Hipoxia-Isquemia Encefálica/patología , Péptido Natriurético Tipo-C/farmacología , Lesiones del Sistema Vascular/prevención & control , Animales , Animales Recién Nacidos , Encéfalo/metabolismo , Edema Encefálico/patología , Infarto Encefálico/metabolismo , Lesiones Encefálicas/patología , Células Cultivadas , Células Endoteliales/metabolismo , Femenino , Hipoxia-Isquemia Encefálica/metabolismo , Infusiones Intraventriculares , Masculino , Ratones , Péptido Natriurético Tipo-C/metabolismo , Péptido Natriurético Tipo-C/fisiología , Fármacos Neuroprotectores , Lesiones del Sistema Vascular/metabolismoRESUMEN
INTRODUCTION: This study aimed to evaluate the association of esthetic expectations with self-reported personal characteristics, anxiety, depression, self-esteem, oral health-related quality of life, and the Orthognathic Quality of Life Questionnaire (OQLQ) in Chinese adult patients before orthognathic treatment. METHODS: This study involved 213 patients with clinically significant skeletal deformity requiring orthognathic surgery for comprehensive treatment. Each patient completed a series of Chinese version scales, including the self-rating anxiety scale, self-rating depression scale, self-esteem scale, the Oral Health Impact Profile-14 questionnaire, and the OQLQ. The patients' self-reported personal characteristics were also recorded, including facial appearance ratings before and after orthognathic treatment, highest education level, mean monthly income, and enthusiasm toward orthodontic or orthognathic treatment. The Least Absolute Shrinkage and Selection Operator multivariate linear regression model was conducted for the selection of the above factors. The final multivariate linear regression model was built with variables identified under the optimal tuning parameter. RESULTS: A total of 213 patients (87 men and 126 women) were included in this study. The patients' esthetic expectation scores were significantly associated with their total scores, which encompassed the education level, mean monthly income, enthusiasm toward orthodontic or orthognathic treatment, self-esteem scale, the Chinese version of the 14-item Oral Health Impact Profile questionnaire, OQLQ, etc. In the multivariate linear regression model, the OQLQ, enthusiasm toward orthognathic treatment, depression, and expected facial appearance score after the treatment were the most important factors to predict esthetic expectation. CONCLUSIONS: High esthetic expectations for orthognathic treatment were mostly associated with higher expected facial appearance scores after the treatment, greater enthusiasm toward orthognathic treatment, worse depression (confusion), and 2 domains (social aspects of deformity and oral function) of OQLQ. Therefore, OQLQ, enthusiasm toward orthognathic treatment, and expected facial appearance score after treatment may be used to predict patients' esthetic expectations before commencing orthognathic treatment in daily clinical practice.