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1.
Curr Res Toxicol ; 7: 100193, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39381497

RESUMEN

Excessive long-term manganese intake can inflict irreversible damage to the nervous system, with a predominant effect on the substantia nigra-striatum pathway. Through a mouse model simulating manganese exposure, we delved into its implications on the central nervous motor system, uncovering autophagy-lysosome dysfunction as a pivotal factor in manganese-induced neurotoxicity. Our research illuminated the molecular mechanisms behind TFEB's role in manganese-triggered neuronal autophagy dysfunction, offering insights into the cellular and molecular mechanisms of manganese-induced abnormal protein accumulation. This study lays a significant theoretical foundation for future endeavors aimed at safeguarding against manganese neurotoxicity. Furthermore, TFEB emerges as a potential early molecular biomarker for manganese exposure, providing a solid basis for preemptive protection and clinical treatment for populations exposed to manganese.

2.
BMC Oral Health ; 24(1): 1156, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39343901

RESUMEN

BACKGROUND: Previous studies have reported the link between hypoxic conditions and NLRP3 inflammasome-mediated pulpal inflammation in the progression of pulpitis. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the role of HIF-1α in the regulation of NLRP3 inflammasome pathway via NF-κB signaling under hypoxic conditions with or without LPS in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. METHODS: HIF-1α plasmids or siRNAs were used to upregulate or downregulate HIF-1α in HDPFs, respectively. The effect of hypoxia with or without LPS on the NF-κB signaling and NLRP3 inflammasome pathway was analyzed by immunofluorescence staining, qRT-PCR, western blotting and ELISA. RESULTS: The hypoxic conditions alone induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling in a time-dependent manner in HDPFs. The upregulation of HIF-1α further promoted hypoxia-induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. In comparison, downregulation of HIF-1α inhibited ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Additionally, LPS plus hypoxia further promoted HIF-1α expression and NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. CONCLUSIONS: HIF-1α served as a positive regulator of NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling in HDPFs in the sterile pulpal inflammation and caries-related pulpitis microenvironment. The finding of a novel functional HIF-1α-NF-κB-NLRP3 axis provides insight into the link between the hypoxic microenvironment and pulpal inflammation, thus supporting a promising therapeutic strategy for the control of pulpal inflammation.


Asunto(s)
Pulpa Dental , Fibroblastos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Inflamasomas , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Humanos , Pulpa Dental/citología , Pulpa Dental/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fibroblastos/metabolismo , FN-kappa B/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamasomas/metabolismo , Hipoxia/metabolismo , Lipopolisacáridos/farmacología , Pulpitis/metabolismo , Células Cultivadas , Western Blotting , Ensayo de Inmunoadsorción Enzimática
3.
Oral Oncol ; 159: 107015, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39270497

RESUMEN

BACKGROUND: The internal jugular vein (IJV) plays a major role in collecting venous blood from the cranium, face, and neck. Preserving or reconstructing at least one IJV during bilateral radical neck dissection (RND) allows preventing severe complications. The aim of this report was to present a variant of IJV reconstruction in bilateral radical neck dissection. CASE SUMMARY: A 55-year-old male complained for a gingival mass for about 2 months, which was approximately 4 × 2 cm in size with a surface ulceration, located in the anterior mandibular area. There were bilateral cervical adenopathy. The computed tomography (CT) scan revealed mandibular bone destruction with surrounding soft tissue masse, multiple enlarged lymph nodes around bilateral submandibular space and bilateral carotid sheath, with obvious necrosis in the center. The preoperative diagnosis was mandibular gingiva squamous cell carcinoma (SCC), staged T4aN2bM0. Under general anesthesia, the patient underwent bilateral RND with sacrifice of right IJV and reconstruction of left IJV by anastomosis of IJV to the ipsilateral EJV using the common facial vein as a communicating way, followed by an expanded resection of mandibular gingiva SCC via marginal mandibulectomy, left anterolateral thigh (ALT) free flap reconstruction of the resulting defects, and tracheotomy. The patient's post-operative course was uneventfully. CONCLUSION: In our case report, the immediate IJV reconstruction by the W method was performed without compromising oncologic principles and was found feasible, safe and effective to prevent the occurrence of severe postoperative complications related to bilateral RND with sacrifice of both IJV.

4.
Sci Total Environ ; 951: 175681, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173756

RESUMEN

Manganese (Mn) is an environmental pollutant, and overexposure can cause neurodegenerative disorders similar to Alzheimer's disease and Parkinson's disease that are characterized by ß-amyloid (Aß) overexpression, Tau hyperphosphorylation and neuroinflammation. However, the mechanisms of Mn neurotoxicity are not clearly defined. In our study, a knockout mouse model of Mn exposure combined with gut flora-induced neurotoxicity was constructed to investigate the effect of gut flora on Mn neurotoxicity. The results showed that the levels of Tau, p-Tau and Aß in the hippocampus of C57BL/6 mice were greater than those in the hippocampus of control mice after 5 weeks of continuous exposure to manganese chloride (Mn content of 200 mg/L). Transplanted normal and healthy fecal microbiota from mice significantly downregulated Tau, p-Tau and Aß expression and ameliorated brain pathology. Moreover, Mn exposure activated the cGAS-STING pathway and altered the cecal microbiota profile, characterized by an increase in Clostridiales, Pseudoflavonifractor, Ligilactobacillus and Desulfovibrio, and a decrease in Anaerotruncus, Eubacterium_ruminantium_group, Fusimonas and Firmicutes, While fecal microbiome transplantation (FMT) treatment inhibited this pathway and restored the microbiota profile. FMT alleviated Mn exposure-induced neurotoxicity by inhibiting activation of the NLRP3 inflammasome triggered by overactivation of the cGAS-STING pathway. Deletion of the cGAS and STING genes and FMT altered the gut microbiota composition and its predictive function. Phenotypic prediction revealed that FMT markedly decreased the abundances of anaerobic and stress-tolerant bacteria and significantly increased the abundances of facultative anaerobic bacteria and biofilm-forming bacteria after blocking the cGAS-STING pathway compared to the Mn-exposed group. FMT from normal and healthy mice ameliorated the neurotoxicity of Mn exposure, possibly through alterations in the composition and function of the microbiome associated with the cGAS-STING/NLRP3 pathway. This study provides a prospective direction for future research on the mechanism of Mn neurotoxicity.


Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Microbioma Gastrointestinal/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas de la Membrana/metabolismo , Manganeso/toxicidad , Síndromes de Neurotoxicidad , Ratones Noqueados , Transducción de Señal , Nucleotidiltransferasas
5.
Trials ; 25(1): 538, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143596

RESUMEN

BACKGROUND: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers. METHODS/DESIGN: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. DISCUSSION: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.


Asunto(s)
Cuidadores , Accidente Cerebrovascular Isquémico , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Cuidadores/educación , Accidente Cerebrovascular Isquémico/rehabilitación , Accidente Cerebrovascular Isquémico/enfermería , Accidente Cerebrovascular Isquémico/fisiopatología , Femenino , Persona de Mediana Edad , Masculino , Carga del Cuidador , Factores de Tiempo , Resultado del Tratamiento , China , Adulto , Actividades Cotidianas , Anciano , Actividad Motora , Calidad de Vida , Estado Funcional
6.
Int Immunopharmacol ; 136: 112370, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823174

RESUMEN

Reperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1ß were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.


Asunto(s)
Antiinflamatorios , Daño por Reperfusión Miocárdica , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Ratas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Línea Celular , Cinamatos/farmacología , Cinamatos/uso terapéutico , Ratas Sprague-Dawley , Peróxido de Hidrógeno/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Apoptosis/efectos de los fármacos , Inflamasomas/metabolismo , Modelos Animales de Enfermedad
7.
IEEE Trans Biomed Eng ; 71(11): 3123-3133, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38829760

RESUMEN

Retinal microvascular disease has caused serious visual impairment widely in the world, which can be hopefully prevented via early and precision microvascular hemodynamic diagnosis. Due to artifacts from choroidal microvessels and tiny movements, current fundus microvascular imaging techniques including fundus fluorescein angiography (FFA) precisely identify retinal microvascular microstructural damage and abnormal hemodynamic changes difficulty, especially in the early stage. Therefore, this study proposes an FFA-based multi-parametric retinal microvascular functional perfusion imaging (RM-FPI) scheme to assess the microstructural damage and quantify its hemodynamic distribution precisely. Herein, a spatiotemporal filter based on singular value decomposition combined with a lognormal fitting model was used to remove the above artifacts. Dynamic FFAs of patients (n = 7) were collected first. The retinal time fluorescence intensity curves were extracted and the corresponding perfusion parameters were estimated after decomposition filtering and model fitting. Compared with in vivo results without filtering and fitting, the signal-to-clutter ratio of retinal perfusion curves, average contrast, and resolution of RM-FPI were up to 7.32 ± 0.43 dB, 14.34 ± 0.24 dB, and 11.0 ± 2.0 µm, respectively. RM-FPI imaged retinal microvascular distribution and quantified its spatial hemodynamic changes, which further characterized the parabolic distribution of local blood flow within diameters ranging from 9 to 400 µm. Finally, RM-FPI was used to quantify, visualize, and diagnose the retinal hemodynamics of retinal vein occlusion from mild to severe. Therefore, this study provided a scheme for early and precision diagnosis of retinal microvascular disease, which might be beneficial in preventing its development.


Asunto(s)
Angiografía con Fluoresceína , Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Femenino , Masculino , Microvasos/diagnóstico por imagen , Microvasos/fisiología , Imagen de Perfusión/métodos , Persona de Mediana Edad , Adulto
8.
Med Phys ; 51(6): 4243-4257, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38436433

RESUMEN

BACKGROUND: Breast tumor is a fatal threat to the health of women. Ultrasound (US) is a common and economical method for the diagnosis of breast cancer. Breast imaging reporting and data system (BI-RADS) category 4 has the highest false-positive value of about 30% among five categories. The classification task in BI-RADS category 4 is challenging and has not been fully studied. PURPOSE: This work aimed to use convolutional neural networks (CNNs) for breast tumor classification using B-mode images in category 4 to overcome the dependence on operator and artifacts. Additionally, this work intends to take full advantage of morphological and textural features in breast tumor US images to improve classification accuracy. METHODS: First, original US images coming directly from the hospital were cropped and resized. In 1385 B-mode US BI-RADS category 4 images, the biopsy eliminated 503 samples of benign tumor and left 882 of malignant. Then, K-means clustering algorithm and entropy of sliding windows of US images were conducted. Considering the diversity of different characteristic information of malignant and benign represented by original B-mode images, K-means clustering images and entropy images, they are fused in a three-channel form multi-feature fusion images dataset. The training, validation, and test sets are 969, 277, and 139. With transfer learning, 11 CNN models including DenseNet and ResNet were investigated. Finally, by comparing accuracy, precision, recall, F1-score, and area under curve (AUC) of the results, models which had better performance were selected. The normality of data was assessed by Shapiro-Wilk test. DeLong test and independent t-test were used to evaluate the significant difference of AUC and other values. False discovery rate was utilized to ultimately evaluate the advantages of CNN with highest evaluation metrics. In addition, the study of anti-log compression was conducted but no improvement has shown in CNNs classification results. RESULTS: With multi-feature fusion images, DenseNet121 has highest accuracy of 80.22 ± 1.45% compared to other CNNs, precision of 77.97 ± 2.89% and AUC of 0.82 ± 0.01. Multi-feature fusion improved accuracy of DenseNet121 by 1.87% from classification of original B-mode images (p < 0.05). CONCLUSION: The CNNs with multi-feature fusion show a good potential of reducing the false-positive rate within category 4. The work illustrated that CNNs and fusion images have the potential to reduce false-positive rate in breast tumor within US BI-RADS category 4, and make the diagnosis of category 4 breast tumors to be more accurate and precise.


Asunto(s)
Neoplasias de la Mama , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Neoplasias de la Mama/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Femenino , Ultrasonografía/métodos , Ultrasonografía Mamaria/métodos
9.
Heliyon ; 9(9): e19503, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37810031

RESUMEN

In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.

10.
J Acoust Soc Am ; 154(3): 1757-1769, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37721402

RESUMEN

In underwater acoustic (UWA) communications, channels often exhibit a clustered-sparse structure, wherein most of the channel impulse responses are near zero, and only a small number of nonzero taps assemble to form clusters. Several algorithms have used the time-domain sparse characteristic of UWA channels to reduce the complexity of channel estimation and improve the accuracy. Employing the clustered structure to enhance channel estimation performance provides another promising research direction. In this work, a deep learning-based channel estimation method for UWA orthogonal frequency division multiplexing (OFDM) systems is proposed that leverages the clustered structure information. First, a cluster detection model based on convolutional neural networks is introduced to detect the cluster of UWA channels. This method outperforms the traditional Page test algorithm with better accuracy and robustness, particularly in low signal-to-noise ratio conditions. Based on the cluster detection model, a cluster-aware distributed compressed sensing channel estimation method is proposed, which reduces the noise-induced errors by exploiting the joint sparsity between adjacent OFDM symbols and limiting the search space of channel delay spread. Numerical simulation and sea trial results are provided to illustrate the superior performance of the proposed approach in comparison with existing sparse UWA channel estimation methods.

11.
Phys Med Biol ; 68(16)2023 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-37419124

RESUMEN

Objective. Three-dimensional (3D) ultrasound (US) is needed to provide sonographers with a more intuitive panoramic view of the complex anatomical structure, especially the musculoskeletal system. In actual scanning, sonographers may perform fast scanning using a one-dimensional (1D) array probe .at random angles to gain rapid feedback, which leads to a large US image interval and missing regions in the reconstructed volume.Approach.In this study, a 3D residual network (3D-ResNet) modified by a 3D global residual branch (3D-GRB) and two 3D local residual branches (3D-LRBs) was proposed to retain detail and reconstruct high-quality 3D US volumes with high efficiency using only sparse two-dimensional (2D) US images. The feasibility and performance of the proposed algorithm were evaluated onex vivoandin vivosets.Main results. High-quality 3D US volumes in the fingers, radial and ulnar bones, and metacarpophalangeal joints were obtained by the 3D-ResNet, respectively. Their axial, coronal, and sagittal slices exhibited rich texture and speckle details. Compared with kernel regression, voxel nearest-neighborhood, squared distance weighted methods, and a 3D convolution neural network in the ablation study, the mean peak-signal-to-noise ratio and mean structure similarity of the 3D-ResNet were up to 28.53 ± 1.29 dB and 0.98 ± 0.01, respectively, and the corresponding mean absolute error dropped to 0.023 ± 0.003 with a better resolution gain of 1.22 ± 0.19 and shorter reconstruction time.Significance.These results illustrate that the proposed algorithm can rapidly reconstruct high-quality 3D US volumes in the musculoskeletal system in cases of a large amount of data loss. This suggests that the proposed algorithm has the potential to provide rapid feedback and precise analysis of stereoscopic details in complex and meticulous musculoskeletal system scanning with a less limited scanning speed and pose variations for the 1D array probe.


Asunto(s)
Imagenología Tridimensional , Sistema Musculoesquelético , Imagenología Tridimensional/métodos , Ultrasonografía , Algoritmos , Sistema Musculoesquelético/diagnóstico por imagen , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos
12.
Ecotoxicol Environ Saf ; 255: 114828, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36989949

RESUMEN

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.


Asunto(s)
Disfunción Cognitiva , Inflamasomas , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedades Neuroinflamatorias , Antioxidantes , Ratones Noqueados , Disfunción Cognitiva/etiología , Hipoxia
13.
Elife ; 122023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36655976

RESUMEN

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.


Asunto(s)
Memoria Inmunológica , Células T Auxiliares Foliculares , Humanos , Animales , Ratones , Células Th17/metabolismo , Linfocitos B , Linfocitos T Colaboradores-Inductores
14.
Ultrasonics ; 127: 106833, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36070635

RESUMEN

High-frame-rate plane wave (PW) imaging suffers from unsatisfactory image quality due to the absence of focus in transmission. Although coherent compounding from tens of PWs can improve PW image quality, it in turn results in a decreased frame rate, which is limited for tracking fast moving tissues. To overcome the trade-off between frame rate and image quality, we propose a progressively dual reconstruction network (PDRN) to achieve adaptive beamforming and enhance the image quality via both supervised and transfer learning in the condition of single or a few PWs transmission. Specifically, the proposed model contains a progressive network and a dual network to form a close loop and provide collaborative supervision for model optimization. The progressive network takes the channel delay of each spatial point as input and progressively learns coherent compounding beamformed data with increased numbers of steered PWs step by step. The dual network learns the downsampling process and reconstructs the beamformed data with decreased numbers of steered PWs, which reduces the space of the possible learning functions and improves the model's discriminative ability. In addition, the dual network is leveraged to perform transfer learning for the training data without sufficient steered PWs. The simulated, in vivo, vocal cords (VCs), and public available CUBDL dataset are collected for model evaluation.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Ultrasonografía/métodos
15.
Artículo en Inglés | MEDLINE | ID: mdl-36269911

RESUMEN

Objective myocardial contractility assessment during stress tests aims to improve the diagnosis of myocardial ischemia. Tissue Doppler imaging (TDI) or optical flow (OF) speckle tracking echocardiography (STE) has been used to quantify myocardial contractility at rest. However, this is more challenging during stress tests due to image decorrelation at high heart rates. Moreover, stress tests imply a high frame rate which leads to a limited lateral field of view. Therefore, a large lateral field-of-view robust ultrafast myocardial regularized OF-TDI principal strain estimator has been developed for high-frame-rate echocardiography of coherently compounded transmitted diverging waves. The feasibility and accuracy of the proposed estimator were validated in vitro (using sonomicrometry as the gold standard) and in vivo stress experiments. Compared with OF strain imaging, the proposed estimator improved the accuracy of principal major and minor strains during stress tests, with an average contrast-to-noise ratio improvement of 4.4 ± 2.7 dB ( p -value < 0.01). Moreover, there was a significant correlation and a very close agreement between the proposed estimator and sonomicrometry for tested heart rates between 60 and 180 beats per minute (bpm). The averages ± standard deviations (STD) of R2 and biases ± STD between them were 0.96 ± 0.04 ( p -value < 0.01) and 0.01 ± 0.03% in the axial direction, respectively; and 0.94 ± 0.02 ( p -value < 0.01) and 0.04 ± 0.06% in the lateral direction, respectively. These results suggest that the proposed estimator could be useful clinically to provide an accurate and quantitative 2-D large lateral field-of-view myocardial strain assessment at high heart rates during stress echocardiography.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Humanos , Ecocardiografía/métodos , Ecocardiografía de Estrés/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Estudios de Factibilidad
16.
Int J Mol Sci ; 23(19)2022 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-36232745

RESUMEN

Lead exposure may weaken the ability of learning and memory in the nervous system through mitochondrial paramorphia and dysfunction. However, the underlying mechanism has not been fully elucidated. In our works, with SD rats, primary culture of hippocampal neuron and PC12 cell line model were built up and behavioral tests were performed to determine the learning and memory insults; Western blot, immunological staining, and electron microscope were then conducted to determine endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Co-immunoprecipitation were performed to investigate potential protein-protein interaction. The results show that lead exposure may cripple rats' learning and memory capability by inducing endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Furthermore, we clarify that enhanced MFN2 ubiquitination degradation mediated by PINK1 may account for mitochondrial paramorphia and endoplasmic reticulum stress. Our work may provide important clues for research on the mechanism of how Pb exposure leads to nervous system damage.


Asunto(s)
Plomo , Síndromes de Neurotoxicidad , Animales , Apoptosis , Estrés del Retículo Endoplásmico , Plomo/metabolismo , Plomo/toxicidad , Mitocondrias/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Proteínas Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley
17.
Oxid Med Cell Longev ; 2022: 7676872, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36238644

RESUMEN

Numerous studies have examined the effects of lead (Pb) on cognitive ability. It is essential for the brain to maintain its functions through the differentiation of neural stem cells into various types of cells. Despite this, it remains unclear how Pb exposure affects neural stem cells and how it does, so the Pb-exposed mice were treated with the Notch inhibitor DAPT after we established the Pb exposure models. Neuronal stem cells and autophagy were assessed by immunofluorescence staining and western blot. The microbiota of the feces was also analyzed using the 16S rRNA amplicon sequencing technique. In this study, we found that Pb exposure caused neural injuries and deficits in neural stem cells, whereas DAPT rescued the damage. With DAPT, Pb-induced autophagy was partially reversed. Exposure to Pb also reduced inflammation and damaged gut barrier function. Furthermore, Pb exposure led to low bacterial diversity, an increase in pathogen abundance, and an unusual mode of interaction. Taken together, this study revealed that damages in neural stem cells contributed largely to cognitive impairment during Pb exposure, and this process was partially dependent on the Notch pathway and gut dysbiosis.


Asunto(s)
Plomo , Células-Madre Neurales , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Eje Cerebro-Intestino , Plomo/toxicidad , Ratones , Células-Madre Neurales/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Transducción de Señal
18.
Int Endod J ; 55(11): 1225-1240, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35979583

RESUMEN

AIM: To investigate the synergetic regulatory effect of miR-22 on HIF-1α and NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1ß and IL-18 in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. METHODOLOGY: Fluorescence in situ hybridization (FISH) and immunofluorescence (IF) were performed to determine the localization of miR-22-3p, NLRP3 and HIF-1α in human dental pulp tissues (HDPTs). The miR-22 mimics and inhibitor or plasmid of NLRP3 or HIF-1α were used to upregulate or downregulate miR-22 or NLRP3 or HIF-1α in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of HIF-1α, NLRP3, caspase-1, IL-1ß and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1ß and IL-18 was analysed by ELISA. The significance of the differences between the experimental and control groups was determined by one-way analysis of variance, p < .05 indicated statistical significance. RESULTS: A decrease in miR-22 and an increase in HIF-1α and NLRP3 in HDPTs occurred during the transformation of reversible pulpitis into irreversible pulpitis compared with that in the healthy pulp tissues (p < .05). In the normal HDPTs, miR-22-3p was extensively expressed in dental pulp cells. HIF-1α and NLRP3 were mainly expressed in the odontoblasts and vascular endothelial cells. Whereas in the inflamed HDPTs, the odontoblast layers were disrupted. HDPFs were positive for miR-22-3p, HIF-1α and NLRP3. Computational prediction via TargetScan 5.1 and luciferase reporter assays confirmed that both NLRP3 and HIF-1α were direct targets of miR-22 in HDPFs. The miR-22 inhibitor further promoted the activation of NLRP3/CASP1 inflammasome pathway induced by ATP plus LPS and hypoxia (p < .05). In contrast, the miR-22 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS and hypoxia (p < .05). CONCLUSION: MiR-22, as a synergetic negative regulator, is involved in controlling the secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3 and HIF-1α. These results provide a novel function and mechanism of miR-22-HIF-1α-NLRP3 signalling in the control of proinflammatory cytokine secretion, thus indicating a potential therapeutic strategy for future endodontic treatment.


Asunto(s)
MicroARNs , Pulpitis , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/farmacología , Caspasa 1/metabolismo , Citocinas/metabolismo , Pulpa Dental , Células Endoteliales/metabolismo , Fibroblastos , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hibridación Fluorescente in Situ , Inflamasomas/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-18/farmacología , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pulpitis/metabolismo , ARN Mensajero/metabolismo
19.
J Alzheimers Dis ; 87(2): 619-633, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35367965

RESUMEN

BACKGROUND: Early-life Pb exposure can cause behavioral and cognitive problems and induce symptoms of hyperactivity, impulsivity, and inattention in children. Studies showed that blood lead levels were highly correlated with neuropsychiatric disorders, and effects of neurotoxicity might persist and affect the incidence of neurodegenerative diseases, for example Alzheimer's disease (AD). OBJECTIVE: To explore possible mechanisms of developmental Pb-induced neuropsychiatric dysfunctions. METHODS: Children were divided into low blood lead level (BLL) group (0-50.00µg/L) and high BLL group (> 50.00µg/L) and blood samples were collected. miRNA array was used to testify miRNA expression landscape between two groups. Correlation analysis and real-time PCR were applied to find miRNAs that altered in Pb and neuropsychiatric diseases. Animal models and cell experiments were used to confirm the effect of miRNAs in response to Pb, and siRNA and luciferase experiments were conducted to examine their effect on neural functions. RESULTS: miRNA array data and correlation analysis showed that miR-34b was the most relevant miRNA among Pb neurotoxicity and neuropsychiatric disorders, and synapse-associated membrane protein 2 (VAMP2) was the target gene regulating synapse function. In vivo and in vitro studies showed Pb exposure injured rats' cognitive abilities and induced upregulation of miR-34b and downregulation of VAMP2, resulting in decreases of hippocampal synaptic vesicles. Blockage of miR-34b mitigated Pb's effects on VAMP2 in vitro. CONCLUSION: Early-life Pb exposure might exert synapse-toxic effects via inhibiting VAMP2 mediated by upregulation of miR-34b and shed a light on the underlying relationship between Pb neurotoxicity and developmental neuropsychiatric disorders.


Asunto(s)
Plomo , MicroARNs , Animales , Humanos , Plomo/metabolismo , Plomo/toxicidad , MicroARNs/metabolismo , Ratas , Sinapsis/metabolismo , Regulación hacia Arriba , Proteína 2 de Membrana Asociada a Vesículas/genética , Proteína 2 de Membrana Asociada a Vesículas/metabolismo
20.
Med Phys ; 49(4): 2452-2461, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35137426

RESUMEN

PURPOSE: Owing to acoustic-pressure dependence, amplitudes of backscattered-echoes of encapsulated microbubbles (MBs) are unavoidably regulated by an uneven acoustic field, resulting in the misestimation of hemodynamics in conventional amplitude-coding dynamic contrast-enhanced ultrasound (DCEUS) with focused pulse transmission. This study aimed to investigate the feasibility and performance of Nakagami statistical-feature parametric imaging to recover the above misestimation. METHODS: Logarithmic Nakagami parameter (m)-coding DCEUS scheme was investigated via simulation and in vitro MB phantoms as well as in vivo kidney-perfusion experiments of four rabbits in the uneven acoustic fields with two different focal depths. In vivo tissue artifacts for m estimation were suppressed by pulse-inversion second-harmonic imaging and its robustness was enhanced by multiscale moment-estimation strategy. Time-Nakagami-m curves and the corresponding perfusion metrics of intensity and volume were calculated from the logarithmic m-coding DCEUS images within the prefocal and focal regions. These curves and metrics were further compared with the perfusion curves and metrics estimated from the conventional amplitude-coding images within the same regions. RESULTS: Compared with amplitudes of nonlinear scattering MB echoes, their logarithmic m values were relatively independent of the changes in acoustics pressures. Compared with the fixed-scale moment-estimation, the perfusion intensity estimated from logarithmic m-coding DCEUS scheme using multiscale statistical moment-estimation had smaller differences between the prefocal and focal regions. The differences of perfusion intensity induced by an uneven acoustic field decreased to 3.47% ± 1.58 %. The differences decreased by the logarithmic m-coding DCEUS scheme were further regulated by threshold values of m estimation. CONCLUSIONS: The logarithmic m-coding DCEUS scheme could recover the underestimated MB backscattered-echoes and the misestimated perfusion intensity induced by the uneven acoustic field. The scheme had the potential to weaken the limitation of microvasculature identification and hemodynamic characterization marked by MBs within tissues or tumors in the uneven acoustic field.


Asunto(s)
Acústica , Benchmarking , Animales , Estudios de Factibilidad , Perfusión , Conejos , Ultrasonografía/métodos
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