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1.
Psychiatry Res ; 336: 115893, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38657475

ABSTRACT

Abnormal emotion processing is a core feature of schizophrenia spectrum disorders (SSDs) that encompasses multiple operations. While deficits in some areas have been well-characterized, we understand less about abnormalities in the emotion processing that happens through language, which is highly relevant for social life. Here, we introduce a novel method using deep learning to estimate emotion processing rapidly from spoken language, testing this approach in male-identified patients with SSDs (n = 37) and healthy controls (n = 51). Using free responses to evocative stimuli, we derived a measure of appropriateness, or "emotional alignment" (EA). We examined psychometric characteristics of EA and its sensitivity to a single-dose challenge of oxytocin, a neuropeptide shown to enhance the salience of socioemotional information in SSDs. Patients showed impaired EA relative to controls, and impairment correlated with poorer social cognitive skill and more severe motivation and pleasure deficits. Adding EA to a logistic regression model with language-based measures of formal thought disorder (FTD) improved classification of patients versus controls. Lastly, oxytocin administration improved EA but not FTD among patients. While additional validation work is needed, these initial results suggest that an automated assay using spoken language may be a promising approach to assess emotion processing in SSDs.


Subject(s)
Emotions , Oxytocin , Schizophrenia , Humans , Male , Adult , Schizophrenia/physiopathology , Emotions/physiology , Middle Aged , Oxytocin/administration & dosage , Deep Learning , Schizophrenic Psychology
2.
J Biomed Inform ; 150: 104598, 2024 02.
Article in English | MEDLINE | ID: mdl-38253228

ABSTRACT

OBJECTIVES: We aimed to investigate how errors from automatic speech recognition (ASR) systems affect dementia classification accuracy, specifically in the "Cookie Theft" picture description task. We aimed to assess whether imperfect ASR-generated transcripts could provide valuable information for distinguishing between language samples from cognitively healthy individuals and those with Alzheimer's disease (AD). METHODS: We conducted experiments using various ASR models, refining their transcripts with post-editing techniques. Both these imperfect ASR transcripts and manually transcribed ones were used as inputs for the downstream dementia classification. We conducted comprehensive error analysis to compare model performance and assess ASR-generated transcript effectiveness in dementia classification. RESULTS: Imperfect ASR-generated transcripts surprisingly outperformed manual transcription for distinguishing between individuals with AD and those without in the "Cookie Theft" task. These ASR-based models surpassed the previous state-of-the-art approach, indicating that ASR errors may contain valuable cues related to dementia. The synergy between ASR and classification models improved overall accuracy in dementia classification. CONCLUSION: Imperfect ASR transcripts effectively capture linguistic anomalies linked to dementia, improving accuracy in classification tasks. This synergy between ASR and classification models underscores ASR's potential as a valuable tool in assessing cognitive impairment and related clinical applications.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Speech Perception , Humans , Speech , Language , Alzheimer Disease/diagnosis
3.
Dalton Trans ; 52(44): 16085-16102, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37814810

ABSTRACT

Metal-organic frameworks (MOFs) have received extensive attention in tumor therapy because of their advantages, including large specific surface area, regular pore size, adjustable shape, and facile functionalization. MOFs are porous materials formed by the coordination bonding of metal clusters and organic ligands. This review summarized the most recent advancements in tumor treatment based on nMOFs. First, we discuss the classification of MOFs, which primarily include the series of isoreticular MOF (IRMOF), zeolitic imidazolate framework (ZIF), coordination pillared-layer (CPL), Materials of Institute Lavoisier (MIL), porous coordination network (PCN), University of Oslo (UiO) and Biological metal-organic frameworks (BioMOFs). Then, we discuss the use of nMOFs in antitumor therapy, including drug delivery strategies, photodynamic therapy (PDT), photothermal therapy (PTT), and combination therapy. Finally, the obstacles and opportunities in nMOFs are discussed.


Subject(s)
Metal-Organic Frameworks , Neoplasms , Photochemotherapy , Humans , Phototherapy , Drug Delivery Systems , Neoplasms/drug therapy
4.
AMIA Jt Summits Transl Sci Proc ; 2023: 360-369, 2023.
Article in English | MEDLINE | ID: mdl-37350929

ABSTRACT

The evidence is growing that machine and deep learning methods can learn the subtle differences between the language produced by people with various forms of cognitive impairment such as dementia and cognitively healthy individuals. Valuable public data repositories such as TalkBank have made it possible for researchers in the computational community to join forces and learn from each other to make significant advances in this area. However, due to variability in approaches and data selection strategies used by various researchers, results obtained by different groups have been difficult to compare directly. In this paper, we present TRESTLE (Toolkit for Reproducible Execution of Speech Text and Language Experiments), an open source platform that focuses on two datasets from the TalkBank repository with dementia detection as an illustrative domain. Successfully deployed in the hackallenge (Hackathon/Challenge) of the International Workshop on Health Intelligence at AAAI 2022, TRESTLE provides a precise digital blueprint of the data pre-processing and selection strategies that can be reused via TRESTLE by other researchers seeking comparable results with their peers and current state-of-the-art (SOTA) approaches.

5.
Article in English | MEDLINE | ID: mdl-37040674

ABSTRACT

Civil aviation flight crew and civil aviation air traffic controllers are prone to circadian rhythm abnormalities, which can lead to a slew of other maladies. It could endanger people's health and provide a serious threat to the safety of civil aviation flights if it is not appropriately evaluated and addressed. Early detection of rhythm irregularities and prompt treatment for particular populations that are vulnerable to rhythm disorders are crucial for enhancing civil aviation safety. In general, monitoring of the classical circadian rhythm biomarkers (melatonin or cortisol) in plasma or saliva is an effective way to evaluate the rhythm status. Due to the challenging sample procedure and the trauma of plasma, urine sample testing has received an increasing amount of attention. While, urine circadian rhythm biomarkers have seldom been examined, and the relationship between urinary steroid hormones and melatonin is still poorly understood. In most cases, hormones are determined by immunoassays respectively, mainly enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). There are also reports describing the liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique as a method of melatonin or few steroid hormones quantification, however, the simultaneous detection of multiple rhythmic hormones in human urine is rarely reported. For the quantification of the rhythmic hormones in human urine, an accurate approach using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was devised in this work. Nine endogenous hormones (melatonin, 6-hydroxymelatonin, 6-sulfatoxymelatonin, cortisol, corticosterone, cortisone, testosterone, epitestosterone and androsterone), in human overnight urine, were quantified after solid phase extraction (SPE). A reverse phase HSS C18 column was used for chromatographic separation with a 9-minute gradient elution and deuterated analogues of each analyte were applied as internal standards. This method was successfully applied to the analysis of 596 overnight urine samples (23:00-9:00) collected from 84 air traffic controllers in the Beijing area during shift work. This study's findings showed a clear correlation not only between melatonin and its metabolites; cortisol-related metabolites, but also between melatonin metabolites and endogenous metabolites upstream and downstream of cortisol, implying that these two categories of hormones can be used as potential biological rhythm indicators to provide circadian rhythm data support for future studies on circadian rhythm disorders.


Subject(s)
Hydrocortisone , Melatonin , Humans , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Circadian Rhythm , Steroids , Biomarkers , Chromatography, High Pressure Liquid/methods
6.
Int J Mol Sci ; 23(24)2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36555703

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is recognized as a metabolic disease characterized by hepatic steatosis. Despite the growing burden of NAFLD, approved pharmacological treatment is lacking. As an inhibitor of androgen receptor (AR), EPI-001 is being explored for the treatment of prostate cancer. This study aimed to investigate the potential of EPI-001 for treating NAFLD in free fatty acids (FFAs)-induced human hepatic cells and high-fat-high-sugar (HFHS)-feeding mice. Our results showed that EPI-001 reduced lipid accumulation in hepatic cells and ameliorated hepatic steatosis in mouse livers. Further exploration suggested that the effect of EPI-001 was associated with CYP2E1-mediated reduction of reactive oxygen species (ROS). This provides encouraging evidence for further studies on EPI-001 therapy for NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Humans , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Cytochrome P-450 CYP2E1/metabolism , Receptors, Androgen/metabolism , Liver/metabolism , Hepatocytes/metabolism , Lipid Metabolism , Mice, Inbred C57BL , Diet, High-Fat/adverse effects
7.
Mar Drugs ; 20(11)2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36354990

ABSTRACT

Aphrocallistes vastus lectin (AVL) is a C-type marine lectin derived from sponges. Our previous study demonstrated that oncolytic vaccinia virus carrying AVL (oncoVV-AVL) significantly enhanced the cytotoxicity of oncoVV in cervical cancer, colorectal cancer and hepatocellular carcinoma through the activation of Ras/ERK, MAPK/ERK and PI3K/Akt signaling pathways. In this study, the inflammatory response induced by oncoVV-AVL in a hepatocellular carcinoma cell (HCC) model was investigated. The results showed that oncoVV-AVL increased the levels of inflammatory cytokines including IL-6, IL-8 and TNF-α through activating the AP-1 signaling pathway in HCC. This study provides novel insights into the utilization of lectin AVL in the field of cancer therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Porifera , Animals , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Vaccinia virus , Lectins/pharmacology , Oncolytic Virotherapy/methods , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Phosphatidylinositol 3-Kinases , Cell Line, Tumor
8.
Front Chem ; 10: 1031811, 2022.
Article in English | MEDLINE | ID: mdl-36277335

ABSTRACT

Tumor immunotherapy mainly relies on activating the immune system to achieve antitumor treatment. However, the present tumor immunotherapy used in the clinic showed low treatment efficacy with high systematic toxicity. To overcome the shortcomings of traditional drugs for immunotherapy, a series of antitumor immunotherapies based on nanomaterials have been developed to enhance the body's antitumor immune response and reduce systematic toxicity. Due to the noninvasiveness, remote controllability, and high temporal and spatial resolution of light, photocontrolled nanomaterials irradiated by excitation light have been widely used in drug delivery and photocontrolled switching. This review aims to highlight recent advances in antitumor immunotherapy based on photocontrolled nanomaterials. We emphasized the advantages of nanocomposites for antitumor immunotherapy and highlighted the latest progress of antitumor immunotherapy based on photoactivated nanomaterials. Finally, the challenges and future prospects of light-activated nanomaterials in antitumor immunity are discussed.

9.
Cytokine ; 158: 155983, 2022 10.
Article in English | MEDLINE | ID: mdl-35930964

ABSTRACT

The key to prevent pulp necrosis in the early stage of pulpitis is to promote tissue repair, which begins with cell migration. Stromal cell-derived factor 1α (SDF-1α) has been proven to promote cell migration. Related research has so far concentrated on the biological effects of SDF-1α while its expression in pulpitis is still unclear. We investigated the effect of inflammation on SDF-1α in dental pulp and the underlying regulatory mechanisms. First, rat pulpitis models were established by exposing pulp. SDF-1α was decreased on the 3rd day but increased on the 7th day. Next, lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) was applied to dental pulp cells (DPCs). Within 24 h, SDF-1α decreased, but after 48 h, it steadily increased. Similarly, SDF-1α expression in human chronic pulpitis tissues was also increased. To investigate the effect of altered SDF-1α on DPC migration, cell supernatants collected following Pg.LPS treatment were utilized to stimulate DPCs, and the number of migrated cells was correlated with changes in SDF-1α secretion. Finally, we explored the regulatory mechanisms of SDF-1α down-regulation in the early phase of pulpitis. Within 24 h, JNK/c-Jun pathway was activated in DPC inflammation. When JNK pathway was suppressed, SDF-1α rose. Furthermore, tumor necrosis factor receptor 2 (TNFR2) and apoptosis signal-regulated kinase-interacting protein 1 (AIP1) were up-regulated. Knockdown of them abolished Pg.LPS-induced activation of JNK and c-Jun(Ser63) and significantly enhanced SDF-1α. Our findings indicated that in the early phase of pulpitis, inflammation suppressed SDF-1α by up-regulating TNFR2 and AIP1, which activated JNK/c-Jun(Ser63) pathway.


Subject(s)
Chemokine CXCL12/metabolism , Pulpitis , Animals , Humans , Inflammation , Lipopolysaccharides , Rats , Receptors, Tumor Necrosis Factor, Type II , Stromal Cells/metabolism
10.
J Healthc Eng ; 2022: 1560438, 2022.
Article in English | MEDLINE | ID: mdl-35388324

ABSTRACT

Achieving automatic classification of femur trochanteric fracture from the edge computing device is of great importance and value for remote diagnosis and treatment. Nevertheless, designing a highly accurate classification model on 31A1/31A2/31A3 fractures from the X-ray is still limited due to the failure of capturing the scale-variant and contextual information. As a result, this paper proposes a deep scale-variant (DSV) network with a hybrid and progressive (HP) loss function to aggregate more influential representations of the fracture regions. More specifically, the DSV network is based on the ResNet and integrated with the designed scale-variant (SV) layer and HP loss, where the SV layer aims to enhance the representation ability to extract the scale-variant features, and HP loss is intended to force the network to condense more contextual clues. Furthermore, to evaluate the effect of the proposed DSV network, we carry out a series of experiments on the real X-ray images for comparison and evaluation, and the experimental results demonstrate that the proposed DSV network could outperform other classification methods on this classification task.


Subject(s)
Hip Fractures , Femur/diagnostic imaging , Hip Fractures/diagnostic imaging , Humans , Radiography , X-Rays
11.
J Periodontal Res ; 57(3): 461-469, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35137408

ABSTRACT

BACKGROUND AND OBJECTIVE: Occlusal trauma is one of the most important local contributing factors of periodontitis. It has been reported that Wnt4, a noncanonical Wnt ligand, can inhibit osteoclast formation and inflammation and promote bone formation in vivo. However, the prospects of Wnt4 application in occlusal trauma and periodontitis have not yet been described. This study aimed to investigate the function and the corresponding mechanism of Wnt4 to regulate bone metabolism in occlusal trauma and periodontitis. MATERIAL AND METHODS: Osteogenic-induced MC3T3-E1 cells were treated with or without Porphyromonas gingivalis lipopolysaccharide (Pg. LPS) under cyclic uniaxial compressive stress. After treatment with mouse recombinant protein Wnt4 (rWnt4), the expression of osteogenic markers and activation of the IKK-NF-κB signaling pathway were evaluated in vitro. To investigate whether Wnt4 can promote osteogenesis via the ROCK signaling pathway, the expression of RhoA was evaluated in vitro. Finally, we evaluated the change in bone quantity and the activation of the IKK-NF-κB and ROCK signaling in mice with occlusal trauma and periodontitis to demonstrate the therapeutic efficacy of rWnt4 injection. RESULTS: Stimulation of traumatic force and Pg. LPS stimulation suppressed the expression of osteoblast markers, but their expression was rescued after rWnt4 treatment in vitro. In addition, the inhibition of the ROCK signaling pathway induced by force loading was reversed when rWnt4 was applied in vitro. Micro-CT, H&E, and TRAP staining of the mandibles showed increased bone loss in the occlusal trauma-aggravated periodontitis group, whereas it was rescued after rWnt4 injection. The expression levels of IκBα and p65 were upregulated in occlusal trauma and periodontitis-bearing mice, whereas the expression levels of Runx2 and RhoA were downregulated. After rWnt4 injection, remarkably upregulation of Runx2 and RhoA expression was observed in occlusal trauma and periodontitis- bearing mice. CONCLUSION: Wnt4 not only inhibits IKK-NF-κB signaling but also activates ROCK signaling to inhibit osteoclast formation and promote bone regeneration in occlusal trauma and periodontitis-bearing mice.


Subject(s)
Dental Occlusion, Traumatic , Periodontitis , Animals , Core Binding Factor Alpha 1 Subunit , I-kappa B Kinase/metabolism , Lipopolysaccharides , Mice , NF-kappa B/metabolism , Periodontitis/drug therapy , Signal Transduction , Wnt4 Protein , rho-Associated Kinases/metabolism
12.
J Biomed Inform ; 126: 103998, 2022 02.
Article in English | MEDLINE | ID: mdl-35063668

ABSTRACT

Formal thought disorder (ThD) is a clinical sign of schizophrenia amongst other serious mental health conditions. ThD can be recognized by observing incoherent speech - speech in which it is difficult to perceive connections between successive utterances and lacks a clear global theme. Automated assessment of the coherence of speech in patients with schizophrenia has been an active area of research for over a decade, in an effort to develop an objective and reliable instrument through which to quantify ThD. However, this work has largely been conducted in controlled settings using structured interviews and depended upon manual transcription services to render audio recordings amenable to computational analysis. In this paper, we present an evaluation of such automated methods in the context of a fully automated system using Automated Speech Recognition (ASR) in place of a manual transcription service, with "audio diaries" collected in naturalistic settings from participants experiencing Auditory Verbal Hallucinations (AVH). We show that performance lost due to ASR errors can often be restored through the application of Time-Series Augmented Representations for Detection of Incoherent Speech (TARDIS), a novel approach that involves treating the sequence of coherence scores from a transcript as a time-series, providing features for machine learning. With ASR, TARDIS improves average AUC across coherence metrics for detection of severe ThD by 0.09; average correlation with human-labeled derailment scores by 0.10; and average correlation between coherence estimates from manual and ASR-derived transcripts by 0.29. In addition, TARDIS improves the agreement between coherence estimates from manual transcripts and human judgment and correlation with self-reported estimates of AVH symptom severity. As such, TARDIS eliminates a fundamental barrier to the deployment of automated methods to detect linguistic indicators of ThD to monitor and improve clinical care in serious mental illness.


Subject(s)
Schizophrenia , Speech , Hallucinations , Humans , Linguistics , Machine Learning
13.
Adv Healthc Mater ; 10(11): e2001986, 2021 06.
Article in English | MEDLINE | ID: mdl-33876580

ABSTRACT

The development of 3D printing has significantly advanced the field of bone tissue engineering by enabling the fabrication of scaffolds that faithfully recapitulate desired mechanical properties and architectures. In addition, computer-based manufacturing relying on patient-derived medical images permits the fabrication of customized modules in a patient-specific manner. In addition to conventional 3D fabrication, progress in materials engineering has led to the development of 4D printing, allowing time-sensitive interventions such as programed therapeutics delivery and modulable mechanical features. Therapeutic interventions established via multi-dimensional engineering are expected to enhance the development of personalized treatment in various fields, including bone tissue regeneration. Here, recent studies utilizing 3D printed systems for bone tissue regeneration are summarized and advances in 4D printed systems are highlighted. Challenges and perspectives for the future development of multi-dimensional printed systems toward personalized bone regeneration are also discussed.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Bone Regeneration , Bone and Bones , Humans , Printing, Three-Dimensional
14.
J Endod ; 47(3): 458-465, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33352150

ABSTRACT

INTRODUCTION: Dentin regeneration is one of the main goals of vital pulp treatment in which the biological properties of dental pulp cells (DPCs) need to be considered. In our previous study, we showed that EDTA could enhance the stromal cell-derived factor 1 alpha-induced migration of DPCs. The purpose of this study was to explore the effects of EDTA on the mineralization of dental pulp in vitro and in vivo. METHODS: DPCs were obtained from human premolars or third molars. Alkaline phosphatase assays and alizarin red S staining were used to examine the degree of differentiation and mineralized nodule formation of DPCs. Real-time polymerase chain reaction and Western blot analysis were performed to detect the messenger RNA and protein expressions of mineralization-related markers in DPCs. Extracellular-regulated protein kinase and Smad inhibitors were used to study the roles of these 2 signaling pathways in this process. In addition, pulp exposures were created on 18 premolars of 2 beagle dogs (>12 months) using a high-speed dental handpiece. The experimental group (n = 9) was treated with 12% EDTA for 5 minutes, and the control group (n = 9) was treated with sterile saline for the same duration. Mineral trioxide aggregate was used for direct pulp capping followed by glass ionomer cement sealing. Samples were collected 3 months later, and the regenerated dentin was assessed by micro-computed tomographic and histologic analyses. RESULTS: Exposure to 12% EDTA promoted the activity of alkaline phosphatase, the formation of mineralized nodules, and the messenger RNA and protein expressions of mineralization-related markers in DPCs. Furthermore, the process of 12% EDTA enhancing the differentiation of DPCs was mediated by the extracellular-regulated protein kinase 1/2 signaling pathway and inhibited by the Smad2/3 signaling pathway. In vivo, compared with the control group, more regenerated dentin that had fewer tunnel defects was formed in the 12% EDTA-treated group. CONCLUSIONS: Our results showed that 12% EDTA could promote the mineralization of dental pulp in vitro and in vivo.


Subject(s)
Dental Pulp , Extracellular Matrix Proteins , Alkaline Phosphatase , Animals , Cell Differentiation , Cells, Cultured , Dogs , Edetic Acid/pharmacology
15.
Article in English | MEDLINE | ID: mdl-32673834

ABSTRACT

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a "false-positive" urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as "Target-metabolites". Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant "biomarkers" in workplace or mandatory drug screenings. This approach encourages further studies on the development of the "false-positive" identification system.


Subject(s)
Heroin Dependence/metabolism , Heroin Dependence/urine , Heroin/metabolism , Heroin/urine , Substance Abuse Detection/methods , Chromatography, High Pressure Liquid/methods , Data Mining/methods , Female , Humans , Male , Mass Spectrometry/methods , Morphine Derivatives/metabolism , Morphine Derivatives/urine , Reproducibility of Results
16.
J Periodontol ; 91(11): 1532-1540, 2020 11.
Article in English | MEDLINE | ID: mdl-32160313

ABSTRACT

BACKGROUND: Occlusal trauma is an important local contributing factor aggravating periodontal pocket and alveolar bone absorption in periodontal diseases. Our previous studies have found that occlusal trauma inhibited osteogenic differentiation through nuclear factor (NF)-κB signaling. To further investigate the underlying mechanism, the aim of this study was to explore the role of long chain non-coding differentiation antagonizing non-protein coding RNA (Dancr) in the inhibitory effect of traumatic stress on osteoblast differentiation. METHODS: We took the MC3T3-E1 cells as object in vitro research and stimulated cells with simple stress load, Dancr-siRNA + stress load, Dancr overexpression-plasmid + stress load. Quantitative real-time polymerase chain reaction was used to detect the RNA expression levels of Dancr, alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2). The protein expressions of Alp and Runx2 were tested by Western blot and the activity of Alp was qualitatively demonstrated by Alp staining. In addition, Western blot was performed to investigate the role of Dancr in affecting NF-κB signaling pathway. RESULTS: Traumatic compressive stress inhibited the expressions of Alp, Runx2, andDancr in MC3T3-E1 cells. Stress-induced inhibition of osteoblast differentiation was promoted after silencing Dancr. Overexpression of Dancr could alleviate the inhibitory effect of traumatic force on osteoblast differentiation to some extent. Furthermore, NF-κB signaling was activated after silencing Dancr, and the activated effect of traumatic force on NF-κB signaling could be alleviated through overexpression of Dancr to some extent. CONCLUSION: Traumatic compressive stress can indirectly activate the NF-κB signaling through downregulation of Dancr, thereby inhibiting osteogenic differentiation.


Subject(s)
Osteogenesis , RNA, Long Noncoding , Cell Differentiation , NF-kappa B , Osteoblasts , Osteogenesis/genetics , RNA, Long Noncoding/genetics
17.
Adv Protein Chem Struct Biol ; 120: 45-84, 2020.
Article in English | MEDLINE | ID: mdl-32085888

ABSTRACT

Periodontitis is an infection-driven inflammatory disease, which is characterized by gingival inflammation and bone loss. Periodontitis is associated with various systemic diseases, including cardiovascular, respiratory, musculoskeletal, and reproductive system related abnormalities. Recent theory attributes the pathogenesis of periodontitis to oral microbial dysbiosis, in which Porphyromonas gingivalis acts as a critical agent by disrupting host immune homeostasis. Lipopolysaccharide, proteases, fimbriae, and some other virulence factors are among the strategies exploited by P. gingivalis to promote the bacterial colonization and facilitate the outgrowth of the surrounding microbial community. Virulence factors promote the coaggregation of P. gingivalis with other bacteria and the formation of dental biofilm. These virulence factors also modulate a variety of host immune components and subvert the immune response to evade bacterial clearance or induce an inflammatory environment. In this chapter, our focus is to discuss the virulence factors of periodontal pathogens, especially P. gingivalis, and their roles in regulating immune responses during periodontitis progression.


Subject(s)
Periodontitis/immunology , Porphyromonas gingivalis/immunology , Virulence Factors/immunology , Humans , T-Lymphocytes/immunology
18.
AMIA Annu Symp Proc ; 2020: 1315-1324, 2020.
Article in English | MEDLINE | ID: mdl-33936508

ABSTRACT

Thought disorder (TD) as reflected in incoherent speech is a cardinal symptom of schizophrenia and related disorders. Quantification of the degree ofTD can inform diagnosis, monitoring, and timely intervention. Consequently, there has been an interest in applying methods ofdistributional semantics to quantify incoherence ofspoken language. Prior studies have generally involved few participants and utilized speech data collected in on-site structured interviews. In this paper we conduct a comprehensive evaluation ofapproaches to quantify incoherence using distributional semantics, including a novel variant that measures the global coherence oftext. This evaluation is conducted in the context of "audio diaries" collected from participants experiencing auditory verbal hallucinations using a smartphone application. Results reveal our novel global coherence metric using the centroid (weighted vector average) outperforms established approaches in their agreement with human annotators, supporting their preferential use in the context of short recordings ofunstructured and largely spontaneous speech.


Subject(s)
Semantics , Adult , Female , Hallucinations , Humans , Male , Middle Aged , Schizophrenia , Sense of Coherence , Speech , Young Adult
19.
J Periodontol ; 91(5): 683-692, 2020 05.
Article in English | MEDLINE | ID: mdl-31487049

ABSTRACT

BACKGROUND: Occlusal trauma is an important factor promoting bone loss caused by periodontal diseases. Although there are reports of traumatic force promoting bone resorption in periodontal diseases, no studies examining the inhibition of bone formation by traumatic force and the underlying mechanism have been reported. The aim of this study was to investigate the mechanism whereby traumatic force inhibits bone formation. METHODS: MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without stimulation with Pg. LPS. The expression of osteoblast markers and the activation of IKK-NF-κB signaling were evaluated in vitro. Then, MC3T3-E1 cells were induced to undergo osteogenic differentiation and subjected to cyclic uniaxial compressive stress with or without IKK-2 Inhibitor VI. The expression of osteoblast markers was determined. Then, the classic Wnt signaling pathway (ß-catenin, Gsk3ß, p-Gsk3ß, and Dkk1) was further evaluated in vitro. Finally, occlusal trauma was induced in Wistar rats with or without the injection of IKK-2 Inhibitor VI, to evaluate changes in bone mass and IKK-NF-κB and Wnt/ß-catenin signaling in vivo. RESULTS: After stimulation with Pg. LPS and traumatic force, IKK-NF-κB signaling was significantly activated in vitro. The expression of osteoblast markers and the activity of alkaline phosphatase in MC3T3-E1 cells declined after traumatic force loading and were rescued when IKK-NF-κB signaling was blocked. Wnt/ß-catenin signaling was accordingly inhibited upon force loading, but this inhibition was reversed when IKK-NF-κB was antagonized in vitro. X-ray and Micro-CT analysis of the mandibles of the rats as well as HE and TRAP staining showed that bone loss induced by occlusal trauma declined after IKK-NF-κB was inhibited. The expression of p65 and IκBα was increased when occlusal trauma was induced in Wistar rats, whereas ß-catenin, OCN, and Runx2 levels were decreased. After blocking IKK-NF-κB, significant upregulation of ß-catenin, OCN, and Runx2 was observed in rats suffering from occlusal trauma. CONCLUSIONS: IKK-NF-κB signaling could be activated by traumatic force or occlusal trauma. Its activation promoted the degradation of ß-catenin, ultimately inhibiting osteogenic differentiation in vitro and bone formation in vivo.


Subject(s)
Dental Occlusion, Traumatic , Osteogenesis , Animals , Cell Differentiation , NF-kappa B , Osteoblasts , Rats , Rats, Wistar , Wnt Signaling Pathway , beta Catenin
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-829936

ABSTRACT

Objective@#To investigate the diagnosis, treatment and prognosis of nonodontogenic periapical lesions and to provide a reference for clinical diagnosis and treatment.@*Methods@# A case of a patient with right upper molar pulp with apical penetration and local occlusion admitted to the West China Stomatological Hospital of Sichuan University was retrospectively analyzed, and the curative effect of microapical surgery and pith preservation was also analyzed.@*Results @#The imaging features of tooth 16 showed periradicular radiolucency combined with local radiopaque lesions around the distal buccal apical area. Endodontic microsurgery was performed under local anesthesia. Soft tissue coverage was observed in the distal buccal apical area during the surgery, and no radiopaque tissue was detected. The distal buccal root apex was cut by 3 mm, and mineral trioxide aggregate was used for root-end backfilling. The postoperative pathological results revealed fibrous connective tissue. One-week recall X-ray examination showed tight root-end backfilling and no periradicular radiolucency; an electrical test of pulp vitality showed positive results. The four-year follow-up showed that there was no discoloration in tooth 16 and no significant difference in thermal and electrical tests of pulp vitality compared with control teeth. Combining the clinical manifestations, imaging features, surgical exploration results and pathological reports, the case was most likely to be cemental hypoplasia. Through the literature review, the treatment and healthy pulp preservation of such cases by endodontic microsurgery under the premise of preserving teeth has not been reported.@*Conclusion@#For maxillary posterior teeth with periapical lesions but healthy pulp, accurate estimation of pulp status, endodontic microsurgical exploration and application of bioactive materials can achieve vital pulp preservation while removing the lesions.

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