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T cell-excluded tumors are less responsive to immunotherapies. In this issue of Immunity, Taifour et al. show that secretion of the cytokine Chi3l1 by tumor cells induces T cell exclusion via neutrophil extracellular trap (NET) formation. Chi3l1 depletion stimulates T cell infiltration and synergizes with PD-1 blockade.
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Neoplasias , Linfócitos T , Humanos , Neoplasias/terapia , Imunoterapia , CitocinasRESUMO
OBJECTIVES: We investigated the association between dietary flavonoids intake and periodontitis. MATERIALS AND METHODS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2010 on 3025 participants aged between 30 and 80 years who had full-mouth periodontal examination and dietary flavonoids intake data. This study used periodontal pocket depth (PPD) and clinical attachment loss (CAL) as periodontitis markers. Data were analyzed using multivariate linear regression. RESULTS: After adjusting confounders, the middle tertile of total dietary flavonoids was associated with decreased mean PPD (0.06 mm, P = 0.016) and mean CAL (0.13 mm, P = 0.001) and the top tertile of total dietary flavonoids was significantly associated with decreases in mean PPD (0.05 mm, P = 0.029) and mean CAL (0.11 mm, P = 0.010). Both the middle and top tertiles of total flavonoids intake were significantly related with decreased mean CAL in females, those flossing 0 days/week, overweight and non-diabetic population but not in males, smokers, those flossing 1-6 days/week and diabetic population. Higher anthocyanidins, flavones and flavonols intake was significantly associated with decreased mean PPD and mean CAL while higher flavanones intake was only significantly associated with decreased mean CAL. Higher anthocyanidins intake was particularly related with greatest decreases in mean CAL (top tertile: 0.22 mm, middle tertile: 0.17 mm, both P < 0.010). However, no significant associations were found between isoflavones and flavan_3_ols intake and mean CAL. CONCLUSIONS: Higher dietary flavonoids intake may be beneficial for periodontal health. CLINICAL RELEVANCE: Additional anthocyanidins, flavanones, flavones and flavonols intake was associated with improved periodontal health.
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Flavanonas , Flavonas , Periodontite , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Inquéritos Nutricionais , Antocianinas , Periodontite/epidemiologia , Periodontite/prevenção & controle , Flavonoides , Polifenóis , FlavonóisRESUMO
This study investigated the role of phospholipase D (PLD) in retinal ischemia-reperfusion (I/R) injury using an oxygen-glucose deprivation/reperfusion (OGD/R) model commonly used in retinal I/R injury research. To create an in vitro cellular I/R model, pharmacological inhibitors and small interfering RNA (siRNA) were used to target PLD1 and PLD2 in retinal pigment epithelial (RPE) cells. Treatment with PLD inhibitors and siRNA reduced reactive oxygen species (ROS) and malondialdehyde (MDA) induced by OGD/R in RPE cells and increased the levels of superoxide dismutase (SOD) and glutathione (GSH), indicating a reduction in oxidative damage and improvement in the antioxidant system. Next, we showed that inhibiting PLD1 or PLD2 reduced intracellular iron levels and lipid peroxidation, which are critical factors in ferroptosis. Additionally, PLD1 and PLD2 modulated the expression of proteins involved in the regulation of ferroptosis, including GPX4, SLC7A11, FTH1, and ACSL4. We also investigated the roles of PLD1 and PLD2 in preventing pyroptosis, another form of programmed cell death associated with inflammation. Our study found that OGD/R significantly increased the production of pro-inflammatory cytokines and activated caspase-1, NLRP3, ASC, cleaved-caspase 1 (C-caspase-1), and GSDMD-N in RPE cells, indicating pyroptosis induction. However, PLD1 and PLD2 inhibition or knockdown significantly inhibited the production of pro-inflammatory cytokines and activation of the NLRP3 inflammasome, Taken together, our findings support the hypothesis that the PLD signaling pathway plays a key role in OGD/R-induced ferroptosis and pyroptosis induction and may be a potential therapeutic target for preventing or treating retinal dysfunction and degeneration.
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Ferroptose , Traumatismo por Reperfusão , Humanos , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Epitélio Pigmentado da Retina/metabolismo , RNA Interferente Pequeno/metabolismo , Citocinas/metabolismo , Caspases/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controleRESUMO
OBJECTIVE: We investigated the association of severely damaged endodontically infected tooth with carotid artery plaque and abnormal mean carotid intima-media thickness (CIMT) ≥ 1.0 mm. METHODS: A retrospective analysis of 1502 control participants and 1552 participants with severely damaged endodontically infected tooth who received routine medical and dental checkup in Health Management Center, Xiangya Hospital was performed. Carotid plaque and CIMT were measured with B-mode tomographic ultrasound. Data were analyzed using logistic and linear regression. RESULTS: Severely damaged endodontically infected tooth group had a significantly higher prevalence of carotid plaque (41.62%) compared to 32.22% of carotid plaque in control group. Participants with severely damaged endodontically infected tooth had a significantly higher prevalence of abnormal CIMT (16.17%) and a significantly increased level of CIMT (0.79 ± 0.16 mm) in comparison to 10.79% of abnormal CIMT and 0.77 ± 0.14 mm CIMT in control participants. Severely damaged endodontically infected tooth was significantly related with formation of carotid plaque [1.37(1.18-1.60), P < 0.001], top quartile length [1.21(1.02-1.44), P = 0.029] and top quartile thickness [1.27(1.08-1.51), P = 0.005] of carotid plaque and abnormal CIMT [1.47(1.18-1.83), P < 0.001]. Severely damaged endodontically infected tooth was significantly associated with both single [1.277(1.056-1.546), P = 0.012] and multiple carotid plaques [1.488(1.214-1.825), P < 0.001] and instable carotid plaques [1.380(1.167-1.632), P < 0.001]. Presence of severely damaged endodontically infected tooth increased 0.588 mm of carotid plaque length (P = 0.001), 0.157 mm of carotid plaque thickness (P < 0.001) and 0.015 mm of CIMT (P = 0.005). CONCLUSION: Severely damaged endodontically infected tooth was associated with carotid plaque and abnormal CIMT. CLINICAL RELEVANCE: Early treatment of endodontically infected tooth is warranted.
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Doenças das Artérias Carótidas , Placa Dentária , Placa Aterosclerótica , Humanos , Espessura Intima-Media Carotídea , Estudos Retrospectivos , Placa Aterosclerótica/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Fatores de RiscoRESUMO
BACKGROUND: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD. METHODS: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used. RESULTS: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner. CONCLUSION: Betel nut chewing related severely worn dentition was associated with intra-articular TMD.
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Transtornos da Articulação Temporomandibular , Atrito Dentário , Desgaste dos Dentes , Humanos , Masculino , Feminino , Mastigação , Estudos Transversais , Areca/efeitos adversos , Dentição , Transtornos da Articulação Temporomandibular/etiologia , Desgaste dos Dentes/etiologiaRESUMO
BACKGROUND: Congenitally missing tooth is the most common dental abnormality which leaves spaces in the arch, leads to numerous forms of malocclusion due to the Bolton index discrepancy and is even associated with abnormal craniofacial morphology. Even though the roles of malocclusion and tooth loss in temporomandibular disorders (TMD) development remain controversial, basic researches have found some common molecules are involved in osteoarthritis and dental agenesis. However, the association of congenitally missing teeth with TMD is unknown. We hence investigated the association of congenitally missing teeth with TMD. METHODS: A cross-sectional analysis of 586 control participants (male: 287, female: 299, 38.33 ± 11.65 years) and 583 participants with non-third molar congenitally missing teeth (male: 238, female: 345, 39.13 ± 11.67 years) who consecutively received routine dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders Axis I in Health Management Center, Xiangya Hospital was performed. Logistic regression analysis was used to study the association of congenitally missing teeth with TMD. RESULTS: The congenitally missing teeth group included 581 hypodontia and 2 oligodontia participants. The congenitally missing anterior teeth participants, the congenitally missing posterior teeth participants and participants with both congenitally missing anterior and posterior teeth accounted for 88.34%, 8.40% and 3.26% of the congenitally missing teeth group respectively. Congenitally missing teeth group had greater ratios of females and orthodontic history. Participants with congenitally missing teeth had a significantly higher prevalence of overall TMD (67.24%) in comparison to control participants (45.90%). After adjusting age, gender, presence of congenitally missing teeth, number of congenitally missing teeth, number of non-congenitally missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, the variables of age, gender, presence of congenitally missing teeth and number of dental quadrants with missing teeth were significant for overall TMD. Multivariable logistic regression analysis showed congenitally missing tooth was significantly related with overall TMD [odds ratio (OR):1.689(1.080-2.642), P = 0.022], intra-articular TMD [OR: 1.711(1.103-2.656), P = 0.017] and pain-related TMD [OR: 3.093(1.321-7.239), P = 0.009]. CONCLUSION: Congenitally missing tooth is a risk factor for TMD. When treating the congenitally missing teeth population, TMJ evaluation and multidisciplinary strategies are necessary.
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Anodontia , Má Oclusão , Transtornos da Articulação Temporomandibular , Perda de Dente , Dente , Humanos , Masculino , Adulto , Feminino , Estudos Transversais , Saúde da População Urbana , Anodontia/complicações , Anodontia/epidemiologia , Perda de Dente/complicações , Perda de Dente/epidemiologia , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/epidemiologia , Má Oclusão/complicações , Má Oclusão/epidemiologiaRESUMO
Malformed fruits depreciate a plant's market value. In tomato (Solanum lycopersicum), fruit malformation is associated with the multi-locule trait, which involves genes regulating shoot apical meristem (SAM) development. The expression pattern of TOPLESS3 (SlTPL3) throughout SAM development prompted us to investigate its functional significance via RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (Cas9)-mediated gene editing. Lower SlTPL3 transcript levels resulted in larger fruits with more locules and larger SAMs at the 5 d after germination (DAG5) stage. Differentially expressed genes in the SAM of wild-type (WT) and SlTPL3-RNAi plants, identified by transcriptome deep sequencing (RNA-seq), were enriched in the gibberellin (GA) biosynthesis and plant hormone signaling pathways. Moreover, exogenous auxin and paclobutrazol treatments rescued the multi-locule phenotype, indicating that SlTPL3 affects SAM size by mediating auxin and GA levels in the SAM. Furthermore, SlTPL3 interacted with WUSCHEL (SlWUS), which plays an important role in SAM size maintenance. We conducted RNA-seq and DNA affinity purification followed by sequencing (DAP-seq) analyses to identify the genes regulated by SlTPL3 and SlWUS in the SAM and to determine how they regulate SAM size. We detected 24 overlapping genes regulated by SlTPL3 and SlWUS and harboring an SlWUS-binding motif in their promoters. Furthermore, functional annotation revealed a notable enrichment for functions in auxin transport, auxin signal transduction, and GA biosynthesis. Dual-luciferase assays also revealed that SlTPL3 enhances SlWUS-mediated regulation (repression and activation) of SlPIN3 and SlGA2ox4 transcription, indicating that the SlTPL3-SlWUS module regulates SAM size by mediating auxin distribution and GA levels, and perturbations of this module result in enlarged SAM. These results provide novel insights into the molecular mechanism of SAM maintenance and locule formation in tomato and highlight the SlTPL3-SlWUS module as a key regulator.
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Meristema , Solanum lycopersicum , Meristema/metabolismo , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20-59 years. METHODS: RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. RESULTS: The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32 and 10.83, 58.08 and 1.23, 11.75 and 0.25, 7.66 and 0.12 respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27) and female (20.50) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24) and oral leukoplakia (3.03) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71), oral leukoplakia (20.17) and oral leukoplakia combined with OSF (15.42) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. CONCLUSIONS: Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.
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Fibrose Oral Submucosa , Estomatite Aftosa , Areca , Estudos Transversais , Feminino , Humanos , Leucoplasia Oral/epidemiologia , Masculino , Fibrose Oral Submucosa/epidemiologia , Fibrose Oral Submucosa/patologia , Prevalência , Estomatite Aftosa/epidemiologiaRESUMO
BACKGROUND: Multiple organ failure (MOF) may lead to an increased mortality rate of moderately severe (MSAP) or severe acute pancreatitis (SAP). This study is aimed to use machine learning to predict the risk of MOF in the course of disease. METHODS: Clinical and laboratory features with significant differences between patients with and without MOF were screened out by univariate analysis. Prediction models were developed for selected features through six machine learning methods. The models were internally validated with a five-fold cross-validation, and a series of optimal feature subsets were generated in corresponding models. A test set was used to evaluate the predictive performance of the six models. RESULTS: 305 (68%) of 455 patients with MSAP or SAP developed MOF. Eighteen features with significant differences between the group with MOF and without it in the training and validation set were used for modeling. Interleukin-6 levels, creatinine levels, and the kinetic time were the three most important features in the optimal feature subsets selected by K-fold cross-validation. The adaptive boosting algorithm (AdaBoost) showed the best predictive performance with the highest AUC value (0.826; 95% confidence interval: 0.740 to 0.888). The sensitivity of AdaBoost (80.49%) and specificity of logistic regression analysis (93.33%) were the best scores among the six models in the test set. CONCLUSIONS: A predictive model of MOF complicated by MSAP or SAP was successfully developed based on machine learning. The predictive performance was evaluated by a test set, for which AdaBoost showed a satisfactory predictive performance. The study is registered with the China Clinical Trial Registry (Identifier: ChiCTR1800016079).
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Insuficiência de Múltiplos Órgãos , Pancreatite , Doença Aguda , Estudos de Coortes , Humanos , Aprendizado de Máquina , Insuficiência de Múltiplos Órgãos/etiologiaRESUMO
BACKGROUND: Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer. METHODS: A total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29-86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors' institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system. RESULTS: Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872). CONCLUSION: This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.
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Neoplasias da Mama/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Metástase Linfática/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos RetrospectivosRESUMO
Direct evidence is limited for the association between heart rate variability (HRV) indices and ventricular tachyarrhythmias (VTAs). While galectin-3 (Gal-3) is regarded as a causal factor for cardiac remodelling and a biomarker for arrhythmias, its regulation on VTAs and HVR is unknown. Using aged transgenic (TG) mice with cardiac overexpression of ß2 -adrenoceptors and spontaneous VTAs, we studied whether changes in HRV indices correlated with the severity of VTAs, and whether Gal-3 gene knockout (KO) in TG mice might limit VTA. Body-surface ECG was recorded (10-minute period) in 9- to 10-month-old mice of non-transgenic (nTG), TG and TG × Gal-3 knockout (TG/KO). Time-domain, frequency-domain and nonlinear-domain HRV indices were calculated using the R-R intervals extracted from ECG signals and compared with frequency of VTAs. TG and TG/KO mice developed frequent VTAs and showed significant changes in certain time-domain and nonlinear-domain HRV indices relative to nTG mice. The severity of VTAs in TG and TG/KO mice in combination, estimated by VTA counts and arrhythmia score, was significantly correlated with certain time-domain and nonlinear-domain HRV indices. In conclusion, significant changes in HRV indices were evident and correlated with the severity of spontaneous VTAs in TG mice. The frequency of VTA and HRV indices were largely comparable between TG and TG/KO mice. Deletion of Gal-3 in TG mice altered certain HRV indices implying influence by neuronally localized Gal-3 on autonomic nervous activity.
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Frequência Cardíaca , Taquicardia Ventricular/fisiopatologia , Animais , Eletrocardiografia , Feminino , Masculino , Camundongos , Camundongos TransgênicosRESUMO
The non-contact monitoring of vital signs by radar has great prospects in clinical monitoring. However, the accuracy of separated respiratory and heartbeat signals has not satisfied the clinical limits of agreement. This paper presents a study for automated separation of respiratory and heartbeat signals based on empirical wavelet transform (EWT) for multiple people. The initial boundary of the EWT was set according to the limited prior information of vital signs. Using the initial boundary, empirical wavelets with a tight frame were constructed to adaptively separate the respiratory signal, the heartbeat signal and interference due to unconscious body movement. To verify the validity of the proposed method, the vital signs of three volunteers were simultaneously measured by a stepped-frequency continuous wave ultra-wideband (UWB) radar and contact physiological sensors. Compared with the vital signs from contact sensors, the proposed method can separate the respiratory and heartbeat signals among multiple people and obtain the precise rate that satisfies clinical monitoring requirements using a UWB radar. The detection errors of respiratory and heartbeat rates by the proposed method were within ±0.3 bpm and ±2 bpm, respectively, which are much smaller than those obtained by the bandpass filtering, empirical mode decomposition (EMD) and wavelet transform (WT) methods. The proposed method is unsupervised and does not require reference signals. Moreover, the proposed method can obtain accurate respiratory and heartbeat signal rates even when the persons unconsciously move their bodies.
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Radar , Análise de Ondaletas , Algoritmos , Frequência Cardíaca , Humanos , Processamento de Sinais Assistido por Computador , Sinais VitaisRESUMO
BACKGROUND Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis. MATERIAL AND METHODS Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation. RESULTS Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro. CONCLUSIONS CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening.
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Adenoviridae/metabolismo , Osteoclastos/metabolismo , Osteólise/etiologia , RNA Interferente Pequeno/metabolismo , Receptores de Interleucina-8B/metabolismo , Titânio/efeitos adversos , Animais , Células da Medula Óssea/patologia , Feminino , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteólise/metabolismo , Osteólise/patologia , Osteoprotegerina/metabolismo , Ligante RANK/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
INTRODUCTION: Quantitative electrocardiographic (ECG) waveform analysis provides a noninvasive reflection of the metabolic milieu of the myocardium during resuscitation and is a potentially useful tool to optimize the defibrillation strategy. However, whether combining multiple ECG features can improve the capability of defibrillation outcome prediction in comparison to single feature analysis is still uncertain. METHODS: A total of 3828 defibrillations from 1617 patients who experienced out-of-hospital cardiac arrest were analyzed. A 2.048-s ECG trace prior to each defibrillation without chest compressions was used for the analysis. Sixteen predictive features were optimized through the training dataset that included 2447 shocks from 1050 patients. Logistic regression, neural network and support vector machine were used to combine multiple features for the prediction of defibrillation outcome. Performance between single and combined predictive features were compared by area under receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and prediction accuracy (PA) on a validation dataset that consisted of 1381 shocks from 567 patients. RESULTS: Among the single features, mean slope (MS) outperformed other methods with an AUC of 0.876. Combination of complementary features using neural network resulted in the highest AUC of 0.874 among the multifeature-based methods. Compared to MS, no statistical difference was observed in AUC, sensitivity, specificity, PPV, NPV and PA when multiple features were considered. CONCLUSIONS: In this large dataset, the amplitude-related features achieved better defibrillation outcome prediction capability than other features. Combinations of multiple electrical features did not further improve prediction performance.
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Diagnóstico por Computador/métodos , Eletrocardiografia/métodos , Parada Cardíaca Extra-Hospitalar/mortalidade , Equipamentos e Provisões , Humanos , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.
RESUMO
This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.
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Células 3T3-L1 , Adipogenia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Extratos Vegetais , Aumento de Peso , Animais , Dieta Hiperlipídica/efeitos adversos , Extratos Vegetais/farmacologia , Camundongos , Aumento de Peso/efeitos dos fármacos , Masculino , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Obesidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismoRESUMO
Accurate identification and localization of multiple abnormalities are crucial steps in the interpretation of chest X-rays (CXRs); however, the lack of a large CXR dataset with bounding boxes severely constrains accurate localization research based on deep learning. We created a large CXR dataset named CXR-AL14, containing 165,988 CXRs and 253,844 bounding boxes. On the basis of this dataset, a deep-learning-based framework was developed to identify and localize 14 common abnormalities and calculate the cardiothoracic ratio (CTR) simultaneously. The mean average precision values obtained by the model for 14 abnormalities reached 0.572-0.631 with an intersection-over-union threshold of 0.5, and the intraclass correlation coefficient of the CTR algorithm exceeded 0.95 on the held-out, multicentre and prospective test datasets. This framework shows an excellent performance, good generalization ability and strong clinical applicability, which is superior to senior radiologists and suitable for routine clinical settings.
Assuntos
Anormalidades Múltiplas , Aprendizado Profundo , Humanos , Estudos Prospectivos , Raios X , Cardiomegalia/diagnóstico por imagemRESUMO
This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.
Assuntos
Adiposidade , Cucumis melo , Animais , Camundongos , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversos , Extratos Vegetais/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Aumento de Peso , Fígado/metabolismo , Peso Corporal , Metabolismo dos Lipídeos , Triglicerídeos , Colesterol , Camundongos Endogâmicos C57BLRESUMO
Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, while metastasis is the main cause of OSCC-related death. There is an urgent need to explore novel prognostic biomarkers and identify biological targets related to metastasis in OSCC treatment. Methods: Analysis of differential expression was performed using datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) was conducted to assess the expression of betacellulin (BTC) in OSCC. SCC4 and CAL27 cells were used for in vitro experiments, in which CCK-8, transwell assays, and wounding healing assays were performed to verify the biological functions of BTC. The role of BTC in EMT was analyzed by EMT score and Western blot. Results: Through the analysis of the mRNA expression profile data from TCGA database in OSCC, we found that only low expression of BTC was significantly correlated with a poor prognosis in OSCC patients. The results of IHC assays and TCGA databases showed that the expression level of BTC was related to the tumor stage, histological grade, and metastasis status. In vitro analysis showed that overexpression of BTC significantly suppressed the proliferation and migration of OSCC cells. Furthermore, we confirmed that BTC could affect EMT through the PI3K-AKT signaling pathway. Conclusion: The overexpression of BTC suppresses the proliferation, migration, and EMT of OSCC cells via the PI3K-AKT pathways, leading to a better prognosis in OSCC. BTC may be used as a novel molecular marker to assess the prognosis of OSCC patients.
RESUMO
Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and antimelanogenic effects were investigated against the background of skin photoprotective and antimelanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVAand UVBirradiated keratinocytes and αmelanocyte stimulating hormone (αMSH)stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant antiapoptotic effects on UVAand UVBirradiated keratinocytes. After αMSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the αMSHinduced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmiaassociated transcription factor (MITF), tyrosinase, tyrosinaserelated protein (TRP)1 and TRP2 in αMSHstimulated melanocytes. In addition, gomisin D markedly downregulated αMSHinduced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP1 and TRP2 genes. Overall, gomisin D has photoprotective and antimelanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.