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OBJECTIVES: The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) in vivo by using RNA sequencing. The maxillary and mandibular DP were additionally compared. METHODS: Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50-100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed. RESULTS: After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days. CONCLUSIONS: This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.
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Classifying individuals with neurological disorders and healthy subjects using EEG is a crucial area of research. The current feature extraction approach focuses on the frequency domain features in each of the EEG frequency bands and functional brain networks. In recent years, researchers have discovered and extensively studied stability differences in the electroencephalograms (EEG) of patients with neurological disorders. Based on this, this paper proposes a feature descriptor to characterize EEG instability. The proposed method starts by forming a signal point cloud through Phase Space Reconstruction (PSR). Subsequently, a pseudo-metric space is constructed, and pseudo-distances are calculated based on the consistent measure of the point cloud. Finally, Distance to Measure (DTM) Function are generated to replace the distance function in the original metric space. We calculated the relative distances in the point cloud by measuring signal similarity and, based on this, summarized the point cloud structures formed by EEG with different stabilities after PSR. This process demonstrated that Multivariate Kernel Density Estimation (MKDE) based on a Gaussian kernel can effectively separate the mappings of different stable components within the signal in the phase space. The two average DTM values are then proposed as feature descriptors for EEG instability.In the validation phase, the proposed feature descriptor is tested on three typical neurological disorders: epilepsy, Alzheimer's disease, and Parkinson's disease, using the Bonn dataset, CHB-MIT, the Florida State University dataset, and the Iowa State University dataset. DTM values are used as feature inputs for four different machine learning classifiers, and The results show that the best classification accuracy of the proposed method reaches 98.00 %, 96.25 %, 96.71 % and 95.34 % respectively, outperforming commonly used nonlinear descriptors. Finally, the proposed method is tested and analyzed using noisy signals, demonstrating its robustness compared to other methods.
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Background: Uterine Corpus Endometrial Carcinoma (UCEC) is the most common type of cancer that develops in the uterus, specifically originating from the endometrium, the inner lining of the uterus. Programmed cell death (PCD) is a highly regulated process that eliminates damaged, aged, or unwanted cells in the body. Dysregulation of PCD pathways can contribute to the formation and progression of various cancers, including UCEC. Methods: Fourteen PCD pathways (autophagy-dependent cell death, alkaliptosis, apoptosis, cuproptosis, entotic cell death, ferroptosis, immunogenic cell death, lysosome-dependent cell death, MPT-driven necrosis, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were involved in building a prognostic signature. The model was trained and tested using data from the TCGA-UCEC and validated with the GSE119041 dataset. Results: A 12-gene PCD signature (DRAM1, ELAPOR1, MAPT, TRIM58, UCHL1, CDKN2A, CYFIP2, AKT2, LINC00618, TTPA, TRIM46, and NOS2) was established and validated in an independent dataset. UCEC patients with a high PCD score (PCDS) exhibited worse prognosis. Furthermore, PCDS was found to be associated with immune related cells and key tumor microenvironment components through multiple methods. It was observed that UCEC patients with a high PCD score may not benefit from immunotherapy, but some chemo drugs like Bortezomib may be useful. Conclusion: In conclusion, a novel PCD model was established by comprehensively analyzing diverse cell death patterns. This model accurately predicts the clinical prognosis and drug sensitivity of UCEC. The findings suggest that the PCD signature can serve as a valuable tool in assessing prognosis and guiding treatment decisions for UCEC patients.
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BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by a poor prognosis and closely linked to tumor stemness. However, the key molecules that regulate ICC stemness remain elusive. Although Y-box binding protein 1 (YBX1) negatively affects prognosis in various cancers by enhancing stemness and chemoresistance, its effect on stemness and cisplatin sensitivity in ICC remains unclear. METHODS: Three bulk and single-cell RNA-seq datasets were analyzed to investigate YBX1 expression in ICC and its association with stemness. Clinical samples and colony/sphere formation assays validated the role of YBX1 in stemness and sensitivity to cisplatin. AZD5363 and KYA1979K explored the interaction of YBX1 with the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) and WNT/ß-catenin pathways. RESULTS: YBX1 was significantly upregulated in ICC, correlated with worse overall survival and shorter postoperative recurrence time, and was higher in chemotherapy-non-responsive ICC tissues. The YBX1-high group exhibited significantly elevated stemness scores, and genes linked to YBX1 upregulation were enriched in multiple stemness-related pathways. Moreover, YBX1 expression is significantly correlated with several stemness-related genes (SOX9, OCT4, CD133, CD44 and EPCAM). Additionally, YBX1 overexpression significantly enhanced the colony- and spheroid-forming abilities of ICC cells, accelerated tumor growth in vivo and reduced their sensitivity to cisplatin. Conversely, the downregulation of YBX1 exerted the opposite effect. The transcriptomic analysis highlighted the link between YBX1 and the PI3K/AKT and WNT/ß-catenin pathways. Further, AZD5363 and KYA1979K were used to clarify that YBX1 promoted ICC stemness through the regulation of the AKT/ß-catenin axis. CONCLUSIONS: YBX1 is upregulated in ICC and promotes stemness and cisplatin insensitivity via the AKT/ß-catenin axis. Our study describes a novel potential therapeutic target for improving ICC prognosis.
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Colangiocarcinoma , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Proteína 1 de Ligação a Y-Box , beta Catenina , Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , beta Catenina/metabolismo , beta Catenina/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína 1 de Ligação a Y-Box/metabolismo , Proteína 1 de Ligação a Y-Box/genéticaRESUMO
Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.
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Ácido Clodrônico , Células Estreladas do Fígado , Lipopolissacarídeos , Lipossomos , Cirrose Hepática , Macrófagos , Ratos Sprague-Dawley , Animais , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Lipossomos/química , Lipopolissacarídeos/farmacologia , Ácido Clodrônico/farmacologia , Ácido Clodrônico/química , Ácido Clodrônico/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/induzido quimicamente , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Células RAW 264.7 , Camundongos , Tetracloreto de Carbono/toxicidadeRESUMO
OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.
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Bibliometria , Quiroprática , Humanos , Pesquisa Biomédica , História do Século XX , História do Século XXIRESUMO
The efficient removal of 2-Methylisoborneol (2-MIB), a typical odour component, in water treatment plants (WTPs), poses a great challenge to conventional water treatment technology due to its chemical stability. In this study, the combination of ultraviolet light-emitting diode (UV-LED) and chlorine (UV-LED/chlorine) was exploited for 2-MIB removal, and the role of ultraviolet (UV) wavelength was investigated systematically. The results showed that UV or chlorination alone did not degrade 2-MIB effectively, and the UV/chlorine process could degrade 2-MIB efficiently, following the pseudo-first-order kinetic model. The 275â nm UV exhibited higher 2-MIB degradation efficiency in this UV-LED/chlorine system than 254â nm UV, 265â nm UV and 285â nm UV due to the highest mole adsorption coefficient and quantum yield of chlorine in 275â nm UV. ·OH and ·Cl produced in the 275â nm UV/chlorine system played major roles in 2-MIB degradation. HCO3- and Natural organic matter (NOM), prevalent in water, consumed ·OH and ·Cl, thus inhibiting the 2-MIB degradation by UV-LED/chlorine. In addition, NOM and 2-MIB could form a photonic competition effect. The degradation of 2-MIB by UV-LED/chlorine was done mainly through dehydration and demethylation, and odorous intermediates, such as camphor, were produced. 2-MIB was degraded through the α bond fracture and six-membered ring opening to form saturated or unsaturated hydrocarbons and aldehydes. Four DBPs, chloroform (CF), trichloroacetaldehyde (TCE), trichloroacetone (TCP) and dichloroacetone (DCP), were mainly generated, and CF was the most significant by-product.
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Poluentes Químicos da Água , Purificação da Água , Cloro/química , Desinfecção/métodos , Poluentes Químicos da Água/química , Raios Ultravioleta , Halogenação , Clorofórmio , Cinética , Purificação da Água/métodos , OxirreduçãoRESUMO
Hydrogels are attractive materials with structures and functional properties similar to biological tissues and widely used in biomedical engineering. However, traditional synthetic hydrogels possess poor mechanical strength, and their applications are limited. Herein, a multidimensional material design method is developed; it includes the in situ gelation of silk fabric and nacre-inspired layer-by-layer assembly, which is used to prepare silk fibroin (SF) hydrogels. The in situ gelation method of silk fabric introduces a directionally ordered fabric network in a silk substrate, considerably enhancing the strength of hydrogels. Based on the nacre structure, the layer-by-layer assembly method enables silk hydrogels to break through the size limit and increase the thickness, realizing the longitudinal extension of the hydrogels. The application of the combined biomineralization and hot pressing method can effectively reduce interface defects and improve the interaction between organic and inorganic interfaces. The multidimensional material design method helps increase the strength (287.78 MPa), toughness (18.43 MJ m-3), and fracture energy (50.58 kJ m-2) of SF hydrogels; these hydrogels can weigh 2000 times their own weight. Therefore, SF hydrogels designed using the aforementioned combined method can realize the combination of strength and toughness and be used in biological tissue engineering and structural materials.
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Fibroínas , Nácar , Fibroínas/química , Hidrogéis/química , Biomineralização , Nanopartículas em Multicamadas , Seda/químicaRESUMO
Aging is always accompanied by chronic diseases which probably attribute to long-term chronic inflammation in the aging body. Whereas, the mechanism of chronic inflammation in aging body is still obscure. Mesenchymal stem cells (MSCs) are capable of local chemotaxis to sites of inflammation and play a powerful role in immune regulation. Whether degeneration of MSCs in the aging body is associated with unbalanced inflammation is still not clear. In this study, immunosuppressive properties of aged MSCs are found to be repressed. The impaired immunosuppressive function of aged MSCs is associated with lower expression of the Hippo effector Yes-associated protein 1 (YAP1) and its target gene signal transducer and activator of transcription 1 (STAT1). YAP1 regulates the transcription of STAT1 through binding with its promoter. In conclusion, a novel YAP1/STAT1 axis maintaining immunosuppressive function of MSCs is revealed and impairment of this signal pathway in aged MSCs probably resulted in higher inflammation in aged mice liver.
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Via de Sinalização Hippo , Células-Tronco Mesenquimais , Camundongos , Animais , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/genética , Fatores de Transcrição/metabolismo , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismoRESUMO
Bioactive nanomaterials are increasingly being applied in oral health research. Specifically, they have shown great potential for periodontal tissue regeneration and have substantially improved oral health in translational and clinical applications. However, their limitations and side effects still need to be explored and elucidated. This article aims to review the recent advancements in nanomaterials applied for periodontal tissue regeneration and to discuss future research directions in this field, especially focusing on research using nanomaterials to improve oral health. The biomimetic and physiochemical properties of nanomaterials such as metals and polymer composites are described in detail, including their effects on the regeneration of alveolar bone, periodontal ligament, cementum and gingiva. Finally, the biomedical safety issues of their application as regenerative materials are updated, with a discussion about their complications and future perspectives. Although the applications of bioactive nanomaterials in the oral cavity are still at an initial stage, and pose numerous challenges, recent research suggests that they are a promising alternative in periodontal tissue regeneration.
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OBJECTIVES: To investigate the effect of three interceptive measures (slow maxillary expansion (SME) with removable plates (1), extraction of both upper deciduous canines (DC) (2) and no intervention (3)) on maxillary canine (MC) position in patients with early mixed dentition (EMD) and lack of upper arch space. These three groups were additionally compared to a control group (4) with adequate upper arch space. NULL HYPOTHESIS: None of the studied strategies outperforms the others regarding improvement of MC position. TRIAL DESIGN: Four-arm parallel group prospective randomized controlled trial. PARTICIPANTS: Patients in EMD with at least one impacted MC, non-resorbed DC, and no crossbite. INTERVENTIONS: Patients with a lack of space were randomly distributed to protocols (1), (2), and (3). PRIMARY OBJECTIVE: To assess the change in MC position after 18 months follow up. SECONDARY OBJECTIVES: To assess canine eruption and need for orthodontic intervention within 18-60 month follow up. OUTCOME ASSESSMENT: Five variables defined canine position: sector, canine-to-midline angle, canine-to-first-premolar angle, canine-cusp-to-midline distance, and canine-cusp-to-occlusal-plane distance on two panoramic radiographs at 0 (T1) and 18 months (T2). Mean differences between groups were compared with linear mixed models, corrected for age and sex. RANDOMIZATION: The patient allocation sequence was generated by an electronic randomization list. BLINDING: The operator taking the measurements was blinded to the groups. RESULTS: Seventy-six patients were included (142 canines, mean age 9.2 years, 60.5 per cent male, mean follow up 1.9 years), 19, 17, 14, and 26 patients in groups 1-4, respectively. In absence of dental crossbite in patients with lack of space and impacted MC, SME improved the canine sector (P = 0.040), compared to no intervention (P = 0.028). Canine-to-midline angle and canine-to-occlusal-plane distance significantly decreased in all groups at T2. Extraction improved the canine-to-first-premolar angle at T2 more than other strategies in EMD (P = 0.015-0.000). CONCLUSIONS: Early SME improves the canine sector and reduces the need for major orthodontic intervention in the long term. Taking a first panoramic radiograph in EMD allows timely intervention in case of MC impaction. TRIAL REGISTRATION NUMBER: NCT05629312 (Clinical Trials.org). Trial status: follow up ongoing.
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Má Oclusão , Erupção Ectópica de Dente , Dente Impactado , Humanos , Masculino , Criança , Resultado do Tratamento , Estudos Prospectivos , Extração Dentária/métodos , Dente Decíduo , Má Oclusão/prevenção & controle , Dente Canino/diagnóstico por imagem , Maxila , Dente Impactado/diagnóstico por imagem , Dente Impactado/terapiaRESUMO
Background: Babao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism. Methods: To verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS. Results: We observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway. Conclusion: In summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.
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As a rare and highly aggressive soft tissue sarcoma, the new immunophenotype, atypical FISH pattern and relevant molecular cytogenetics of synovial sarcoma (SS) remain less known, although it is characteristically represented by a pathognomonic chromosomal translocation t (X; 18) (p11.2; q11.2). Methodologically, the morphology was retrospectively analysed by using H&E staining, and immunohistochemical features were investigated by using markers that have been recently applied in other soft tissue tumors. Moreover, FISH signals for SS18 and EWSR-1 break-apart probes were examined. Finally, cytogenetic characteristics were analysed via RT-PCR and Sanger sequencing. Consequently, nine out of thirteen cases that were histologically highly suspected as SS were finally identified as SS via molecular analysis. Histologically, nine SS cases were divided into monophasic fibrous SS (4/9), biphasic SS (4/9) and poorly differentiated SS (1/9). Immunohistochemically, SOX-2 immunostaining was positive in eight cases (8/9) and PAX-7 immunostaining was diffusely positive in the epithelial component of biphasic SS (4/4). Nine cases showed negative immunostaining for NKX3.1 and reduced or absent immunostaining for INI-1. Eight cases showed typically positive FISH signalling for the SS18 break-apart probe, whereas one case exhibited an atypical FISH pattern (complete loss of green signalling, case 2). Furthermore, the SS18-SSX1 and SS18-SSX2 fusion genes were identified in seven cases and two cases, respectively. The fusion site in 8 out of 9 cases was common in the literature, whereas the fusion site in case 2 was involved in exon 10 codon 404 in SS18 and exon 7 codon 119 in SSX1 (which has not been previously reported), which notably corresponded to the complete loss of green signalling in the FISH pattern. Additionally, FISH analysis of the EWSR-1 gene in nine SS cases demonstrated aberrant signalling in three cases that were recognized as a monoallelic loss of EWSR-1 (1/9), an amplification of EWSR-1 (1/9) and a translocation of EWSR-1 (1/9). In conclusion, SS18-SSX fusion gene sequencing is obligatory for a precise diagnosis of SS when dealing with a confusing immunophenotype and atypical or aberrant FISH signalling for SS18 and EWSR-1 detection.
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Biomarcadores Tumorais , Sarcoma Sinovial , Humanos , Biomarcadores Tumorais/genética , Sarcoma Sinovial/patologia , Estudos Retrospectivos , Proteínas de Fusão Oncogênica/genética , Translocação Genética , Análise CitogenéticaRESUMO
OBJECTIVES: To prospectively follow up a previously reported sample, analyzing (1) changes in third molar (M3) position after completion of 2 different types of orthodontic treatment: (2) non-extraction treatment with (HG) vs without cervical headgear (non-HG) and (3) first or second premolar extractions (PM1-2) compared to a non-extraction group (NE). METHODS: A total of 474 patients were prospectively followed up. Panoramic radiographs were taken pre- (T1), post-treatment (T2) and at follow-up (T3). T3 records (a mean of three years after treatment) were available for 135 (HG vs non-HG) and 134 patients (PM1-2 vs NE), respectively. Angulation, vertical position, relation with the mandibular canal and mineralization status of M3 at T2 and T3 were statistically compared. RESULTS: The HG group presented more M3 with ideal vertical orientation at T3. In NE-cases, further improvement in angulation and orientation can be expected after debonding, as well as a deterioration in the relationship with the mandibular canal. Extractions accelerated upper M3 vertical eruption and PM2 extractions led to long-term larger lower retromolar spaces. CONCLUSIONS: The use of cervical headgear increased upper M3 uprighting three years after debonding, while little changes in M3 position were found after orthodontic treatment with extractions. However, PM2 extractions led to larger retromolar spaces and better M3 angulation in the long term.
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Dente Serotino , Ortodontia Corretiva , Humanos , Dente Serotino/diagnóstico por imagem , Seguimentos , Estudos Prospectivos , Radiografia Panorâmica , Extração Dentária , Erupção Dentária , Mandíbula/diagnóstico por imagemRESUMO
Stem cell therapy might be a promising method to stimulate alveolar bone regeneration, which is currently a major clinical challenge. However, its therapeutic features largely depend on pretreatment and transplantation preparation. Herein, a novel biomimetic periodontal ligament transplantation composed of human periodontal ligament stem cells (hPDLSCs) pretreated with gold nanocomplexes (AuNCs) and embedded in a type-I collagen hydrogel scaffold is developed to protect alveolar bone from resorption. AuNCs are readily absorbed by primary hPDLSCs, with limited cytotoxicity, and promote osteogenic differentiation of hPDLSCs effectively in vitro. In addition, the AuNCs-induced hPDLSCs are encapsulated with type-I collagen hydrogel scaffold to mimic their native physiological niche, and then are transplanted into a rat model of alveolar bone resorption. Both micro-computed tomography (micro-CT) and immunohistochemical assays demonstrate that alveolar bone loss is significantly prevented. Furthermore, the underlying therapeutic mechanism is elucidated, in which transplantation-activated osteogenesis is associated with autophagy, which enables bone remodeling and regeneration. This study provides critical insight into the role of PDLSCs in bone homeostasis and proposes an innovative AuNCs-based strategy for stem cell therapy in bone regeneration.
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Nanopartículas Metálicas , Ligamento Periodontal , Ratos , Humanos , Animais , Osteogênese , Ouro/farmacologia , Microtomografia por Raio-X , Biomimética , Diferenciação Celular , Colágeno Tipo I/farmacologia , Hidrogéis/farmacologia , Células Cultivadas , Proliferação de CélulasRESUMO
Hepatic fibrosis/cirrhosis is a significant health burden worldwide, resulting in liver failure or hepatocellular carcinoma (HCC) and accounting for many deaths each year. The pathogenesis of hepatic fibrosis/cirrhosis is very complex, which makes treatment challenging. Endogenous mesenchymal stromal cells (MSCs) have been shown to play pivotal roles in the pathogenesis of hepatic fibrosis. Paradoxically, exogenous MSCs have also been used in clinical trials for liver cirrhosis, and their effectiveness has been observed in most completed clinical trials. There are still many issues to be resolved to promote the use of MSCs in the clinic in the future. In this review, we will examine the controversial role of MSCs in the pathogenesis and treatment of hepatic fibrosis/cirrhosis. We also investigated the clinical trials involving MSCs in liver cirrhosis, summarized the parameters that need to be standardized, and discussed how to promote the use of MSCs from a clinical perspective.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Carcinoma Hepatocelular/patologia , Células Estreladas do Fígado/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Cirrose Hepática/terapia , Cirrose Hepática/patologia , Fibrose , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Accurate quantification of proprotein convertase subtilisin/kexin type 9 (PCSK9) in serum before and after the medication is helpful in grasping the evolution of PCSK9-related disease and evaluating the efficacy of PCSK9 inhibitors. Conventional approaches for PCSK9 quantification suffered from complicated operations and low sensitivity. By integrating stimuli-responsive mesoporous silica nanoparticles, dual-recognition proximity hybridization, and T7 exonuclease-assisted recycling amplification, a novel homogeneous chemiluminescence (CL) imaging approach was proposed for ultrasensitive and convenient immunoassay of PCSK9. Owing to the intelligent design and signal amplification property, the whole assay was conducted without separation and rinsing, significantly simplifying the procedure and eliminating the errors associated with the professional operation; meanwhile, it showed linear ranges over 5 orders of magnitude and detection limit as low as 0.7 pg mL-1. Parallel testing was allowed due to the imaging readout, which brought a maximum throughput of 26 tests h-1. The proposed CL approach was applied to analyze PCSK9 from hyperlipidemia mice before and after the intervention of the PCSK9 inhibitor. Serum PCSK9 levels in the model group and the intervention group could be distinguished efficiently. The results were reliable compared to commercial immunoassay results and histopathologic findings. Thus, it could facilitate the monitoring of the serum PCSK9 level and the lipid-lowering effect of the PCSK9 inhibitor, showing promising potential in bioanalysis and pharmaceuticals.
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Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Animais , Camundongos , Luminescência , Imunoensaio/métodosRESUMO
BACKGROUND: Balance training is the first choice of treatment for chronic ankle instability (CAI). However, there is a lack of research on the effects of balance training in CAI with generalized joint hypermobility (GJH). This study is to compare the outcomes of balance training in CAI patients with and without GJH. METHODS: Forty CAI patients were assigned into the GJH group (Beighton ≥ 4, 20) and non-GJH group (Beighton < 4, 20) and they received same 3-month supervised balance training. Repeated measure ANOVA and independent t test were used to analyze self-reported questionnaires (Foot and ankle ability measure, FAAM), the number of patients experiencing ankle sprain, isokinetic muscle strength and postural control tests (Star excursion balance test, SEBT and Balance errors system, BES) before training, post-training immediately, and post-training 3 months, respectively. RESULTS: At baseline, no differences were found between groups with except for GJH group having poorer SEBT in the posteromedial direction (83.6 ± 10.1 vs 92.8 ± 12.3, %) and in the posterolateral direction (84.7 ± 11.7 vs 95.7 ± 8.7, %). Following the balance training, GJH group demonstrated lower re-sprain ratio (immediately after training, 11.1% vs 23.5%, 3 month after training, 16.7% vs 29.4%) than non-GJH group, as well as greater FAAM-S score, plantarflexion strength and dorsiflexion strength at post-training immediately and 3 months, and both groups improved similarly in the FAAM-A score, muscle strength and balance control (SEBT in the posterior-lateral and posterior-medial directions, and BES scores) compared with baseline. CONCLUSIONS: CAI patients with GJH gained equally even better postural stability and muscle strength after the balance training than the non-GJH patients. Balance training could still be an effective treatment for CAI patients with GJH before considering surgery. TRIAL REGISTRATION: ChiCTR1900023999, June 21st, 2019.
Assuntos
Tornozelo , Instabilidade Articular , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/terapia , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Doença Crônica , Articulação do Tornozelo , Equilíbrio Postural/fisiologiaRESUMO
OBJECTIVE: To investigate the use of blended learning (BL) in Postgraduate Education in Orthodontics. METHODS: A self-developed online questionnaire was sent to 244 teaching staff members of the European Orthodontic Departments. They were asked to answer it and share it with their postgraduate students. 18 questions for teaching staff and 27 for postgraduate students evaluated the use, perceptions, feedback options, learning outcomes, and teacher's role in BL. The answers of teaching staff and students were statistically compared by Fisher's Exact Test, Chi-Square Test, Unpaired t-test, and Mann-Whitney Test. RESULTS: 124 completed questionnaires were received, 44 from teaching staff and 80 from postgraduate students. Teaching staff is more acquainted with BL than students (P = 0.001). Both groups found BL courses a good alternative to traditional courses (P = 0.654). The use of interactive multimedia was more appreciated by students (P = 0.015). Both groups found students' results not to change with BL, but teaching staff had a more negative perception (P = 0.012). In general, teaching staff perceived feedback and interaction as less essential than postgraduates in BL. Teaching staff felt more like coaches when using BL, while postgraduates did not perceive any changes in teachers' roles (P = 0.006). Limitations: Due to the General Data Protection Regulation it was not possible to directly contact the postgraduate students in Postgraduate Orthodontic Programs throughout Europe. Therefore, this study completely relied on the goodwill of the teaching staff being contacted. CONCLUSION: The main differences in perception between teaching staff and postgraduate students were student results, teachers' role, use, and importance of feedback and interactive multimedia. Although both groups found BL courses to stimulate students' learning and to be a relevant cost-effective addition to traditional courses, they were hesitant to fully replace them with BL.