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1.
Cancer Lett ; 584: 216618, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211652

RESUMO

As an immune checkpoint protein expressed by diverse cancer cells, programmed death ligand 1 (PD-L1) facilitates immune evasion by interacting with programmed cell death-1 (PD-1) on T cells. Despite the clinical benefits observed in various cancer types, strategies targeting PD-1/PD-L1 have demonstrated limited efficacy in gastric cancer (GC). Furthermore, the regulation of PD-L1, especially at post-translational modification levels, remains largely unknown. Therefore, it is crucial to elucidate the mechanisms governing PD-L1 expression to enhance anti-tumor immunity. In this study, we have identified that IKAROS family zinc finger 4 (IKZF4) and Non-POU domain-containing octamer-binding (NONO) synergistically regulate and enhance the expression of RAB11 family-interacting protein 3 (RAB11FIP3) in GC. The IKZF4/NONO-RAB11FIP3 axis facilitates the endosomal recycling of PD-L1, particularly on the cell membrane of GC cells. Moreover, overexpression of RAB11FIP3 mitigates the hypo-expression of PD-L1 protein resulting from IKZF4 or NONO deletion. Functionally, the silencing of RAB11FIP3 or IKZF4 promotes T cell proliferation, and enhances T-cell cytotoxicity towards GC cells in vitro, which further inhibits tumor immune evasion in mice via increasing the infiltration of CD8+ T cells into the tumor microenvironment (TME) to suppress GC progression. Our study suggests that the IKZF4/NONO-RAB11FIP3 axis promotes immune evasion by facilitating PD-L1 endosome recycling, thus presenting a potential therapeutic target for GC treatment.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Gástricas , Animais , Camundongos , Antígeno B7-H1 , Endossomos/metabolismo , Evasão da Resposta Imune , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Humanos
3.
Sci Total Environ ; 904: 166750, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659537

RESUMO

This study presents a novel method for producing acicular aragonite using argon oxygen decarburization (AOD) slag while controlling the reaction temperature, reaction time, stirring speed, and the magnesium-to­calcium stoichiometric ratio. This approach provides steel plants with an opportunity to decrease their CO2 emissions and promote efficient resource utilization and CO2 storage through the production of high-quality value-added products. The experimental results showed that reaction temperature was the most significant factor affecting the carbonation efficiency of AOD slag, followed by reaction time, stirring speed, CO2 partial pressure, and the liquid-to-solid ratio (L/S). The study also found that elevated temperature and prolonged reaction duration favored the preferential precipitation of aragonite. Additionally, raising the temperature and the magnesium-to­calcium stoichiometric ratio was shown to enhance the formation of aragonite, affecting its crystal growth orientation and dimensions. The optimal combination of reaction parameters for the preparation of acicular aragonite was found to be the reaction time of 8 h, the magnesium-to­calcium stoichiometric ratio of 0.8, the reaction temperature of 120 °C, and the stirring speed of 200 r·min-1. Under these conditions, the resulting acicular aragonite exhibited excellent overall uniformity, a large aspect ratio, and a smooth crystal surface, with a content of 91.49 %, a single crystal length ranging from 9.86 to 32.6 µm, and a diameter ranging from 0.63 to 2.15 µm. This study provides valuable insights into the efficient production of acicular aragonite from steel slag while reducing CO2 emissions and promoting the sustainable use of resources.

4.
CNS Neurosci Ther ; 29(12): 3980-3994, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37402694

RESUMO

AIMS: As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin. METHODS: Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins. RESULTS: The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons. CONCLUSION: Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.


Assuntos
Ansiedade , Neuroproteção , Humanos , Camundongos , Animais , Feminino , Osteocalcina/metabolismo , Osteocalcina/farmacologia , Bromodesoxiuridina/metabolismo , Ansiedade/induzido quimicamente , Menopausa , Hipocampo/metabolismo , Neurogênese/fisiologia
5.
J Bone Miner Metab ; 41(5): 606-620, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37418073

RESUMO

INTRODUCTION: The increase of ATP concentration in the extracellular space represents one of the effective signals that stimulate the physiological activities of cells when the bone is exposed to external mechanical stimulation such as stretching and shear stress force throughout life. However, the effects of ATP on osteoblast differentiation and related mechanisms are not well understood. MATERIALS AND METHODS: In this study, the roles of extracellular ATP on osteoblast differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. RESULTS: Our results showed that 100 µM extracellular ATP initiated intracellular calcium ([Ca2+]i) oscillations via the calcium-sensing receptor (P2R) and promoted the differentiation of MC3T3-E1 cells. Metabolomics analysis showed that the differentiation of MC3T3-E1 cells depended on aerobic oxidation, but little glycolysis. Moreover, the differentiation of MC3T3-E1 cells and aerobic oxidation were suppressed with the inhibition of AMP-activated protein kinase (AMPK). CONCLUSION: These results indicate that calcium oscillations triggered by extracellular ATP can activate aerobic oxidation through AMPK-related signaling pathways and thus promote osteoblast differentiation.


Assuntos
Sinalização do Cálcio , Cálcio , Cálcio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Diferenciação Celular , Osteoblastos/metabolismo , Trifosfato de Adenosina/metabolismo
6.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36902420

RESUMO

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca2+]i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.


Assuntos
Cálcio , Osteoblastos , Proteínas Proto-Oncogênicas c-akt , Cálcio/metabolismo , Cálcio da Dieta/farmacologia , Diferenciação Celular , Proliferação de Células , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Camundongos , Linhagem Celular
7.
Arterioscler Thromb Vasc Biol ; 43(5): 726-738, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36951065

RESUMO

BACKGROUND: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. METHODS: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. RESULTS: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. CONCLUSIONS: This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.


Assuntos
Hipertensão , Vasodilatação , Camundongos , Humanos , Animais , Pressão Sanguínea , Endotélio/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Homeostase , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
8.
J Exerc Sci Fit ; 21(1): 147-156, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36688000

RESUMO

Background: Considerable attention has been paid to interindividual differences in the cardiorespiratory fitness (CRF) response to exercise. However, the complex multifactorial nature of CRF response variability poses a significant challenge to our understanding of this issue. We aimed to explore whether unsupervised clustering can take advantage of large amounts of clinical data and identify latent subgroups with different CRF exercise responses within a healthy population. Methods: 252 healthy participants (99 men, 153 women; 36.8 ± 13.4 yr) completed moderate endurance training on 3 days/week for 4 months, with exercise intensity prescribed based on anaerobic threshold (AT). Detailed clinical measures, including resting vital signs, ECG, cardiorespiratory parameters, echocardiography, heart rate variability, spirometry and laboratory data, were obtained before and after the exercise intervention. Baseline phenotypic variables that were significantly correlated with CRF exercise response were identified and subjected to selection steps, leaving 10 minimally redundant variables, including age, BMI, maximal oxygen uptake (VO2max), maximal heart rate, VO2 at AT as a percentage of VO2max, minute ventilation at AT, interventricular septal thickness of end-systole, E velocity, root mean square of heart rate variability, and hematocrit. Agglomerative hierarchical clustering was performed on these variables to detect latent subgroups that may be associated with different CRF exercise responses. Results: Unsupervised clustering revealed two mutually exclusive groups with distinct baseline phenotypes and CRF exercise responses. The two groups differed markedly in baseline characteristics, initial fitness, echocardiographic measurements, laboratory values, and heart rate variability parameters. A significant improvement in CRF following the 16-week endurance training, expressed by the absolute change in VO2max, was observed only in one of the two groups (3.42 ± 0.4 vs 0.58 ± 0.65 ml⋅kg-1∙min-1, P = 0.002). Assuming a minimal clinically important difference of 3.5 ml⋅kg-1∙min-1 in VO2max, the proportion of population response was 56.1% and 13.9% for group 1 and group 2, respectively (P<0.001). Although group 1 exhibited no significant improvement in CRF at group level, a significant decrease in diastolic blood pressure (70.4 ± 7.8 vs 68.7 ± 7.2 mm Hg, P = 0.027) was observed. Conclusions: Unsupervised learning based on dense phenotypic characteristics identified meaningful subgroups within a healthy population with different CRF responses following standardized aerobic training. Our model could serve as a useful tool for clinicians to develop personalized exercise prescriptions and optimize training effects.

9.
Cells ; 11(18)2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-36139403

RESUMO

Gastric cancer (GC) was the fourth deadliest cancer in the world in 2020, and about 770,000 people died from GC that year. The death of patients with GC is mainly caused by the metastasis, recurrence, and chemotherapy resistance of GC cells. The cancer stem cell theory defines cancer stem cells (CSCs) as a key factor in the metastasis, recurrence, and chemotherapy resistance of cancer. It considers targeting gastric cancer stem cells (GCSCs) to be an effective method for the treatment of GC. For GCSCs, genes or noncoding RNAs are important regulatory factors. Many experimental studies have found that some drugs can target the stemness of gastric cancer by regulating these genes or noncoding RNAs, which may bring new directions for the clinical treatment of gastric cancer. Therefore, this review mainly discusses related genes or noncoding RNAs in GCSCs and drugs that target its stemness, thereby providing some information for the treatment of GC.


Assuntos
Neoplasias Gástricas , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
10.
Phys Ther ; 102(10)2022 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-35906872

RESUMO

OBJECTIVE: Physical factors have been used to address disuse osteoporosis, but their effects and mechanism remain unclear. The purpose of this study was to determine the effects of pulsed electromagnetic field (PEMF) and whole-body vibration (WBV) on disuse osteoporosis to increase knowledge about treating osteoporosis. METHODS: A disuse osteoporosis rat model was developed by hind-limb unloading (HU) for 6 weeks. Forty 4-month-old female Sprague-Dawley rats were divided into 5 groups and given the following interventions: HU, HU treated with PEMF (HUP), HU treated with WBV (HUW), HU treated with both PEMF and WBV (HUPW), and no intervention (controls). After 8 weeks of intervention, measurements were taken. RESULTS: HU induced a decrease in bone mineral density (BMD), whereas HUP, HUW, and HUPW increased it. Moreover, the bone resorption markers tartrate-resistant acid phosphatase (TRAP) and C-terminal peptide of type 1 collagen in the HU group significantly increased, whereas the osteogenesis markers osteocalcin and N-terminal propeptide of type 1 procollagen significantly decreased. The markers osteocalcin and N-terminal propeptide of type 1 procollagen significantly increased, but TRAP and C-terminal peptide of type 1 collagen significantly decreased in the HUPW, HUP, and HUW groups compared with the HU group. In particular, HUPW effectively increased osteocalcin and decreased TRAP compared with HUP and WBV. Microcomputed tomography analysis of the femur indicated that HUPW improved trabecular number, bone volume over total volume, bone surface over bone volume, trabecular separation, and the structure model index compared with HUP and that it improved bone surface over bone volume, trabecular separation, and structure model index compared with HUW. The HUPW group showed a significant increase in maximum load compared with the HUW group and a significant increase in elastic modulus compared with the HUP group. CONCLUSION: PEMF, WBV, and their combination all attenuated bone resorption and enhanced osteogenesis. WBV and the combination of treatments have great potential to improve osteogenesis compared with PEMF. In addition, HUPW significantly attenuated bone resorption compared with HUW and HUP. IMPACT: The results of this study indicated that HUPW could effectively improve disuse osteoporosis compared with HUP, given that trabecular number and bone volume over total volume are associated with disuse osteoporosis. Moreover, BMD recovered well with HUP, HUW, and HUPW but the bone structure-especially mechanical performance-did not, indicating that osteoporosis should be evaluated with BMD and mechanical performance, not with BMD in isolation.


Assuntos
Reabsorção Óssea , Osteoporose , Ratos , Feminino , Animais , Campos Eletromagnéticos , Microtomografia por Raio-X , Osteocalcina , Colágeno Tipo I , Vibração/uso terapêutico , Fosfatase Ácida Resistente a Tartarato , Pró-Colágeno , Ratos Sprague-Dawley , Osteoporose/terapia , Densidade Óssea , Peptídeos
11.
Materials (Basel) ; 15(4)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35207849

RESUMO

The undercooling (∆T) dependencies of the solidification pathways, microstructural evolution, and recalescence behaviors of undercooled Co-18.5at.%B eutectic alloys were systematically explored. Up to four possible solidification pathways were identified: (1) A lamellar eutectic structure consisting of the FCC-Co and Co3B phase forms, with extremely low ΔT; (2) The FCC-Co phase primarily forms, followed by the eutectic growth of the FCC-Co and Co2B phases when ΔT < 100 K; (3) As the ΔT increases further, the FCC-Co phase primarily forms, followed by the metastable Co23B6 phase with the trace of an FCC-Co and Co23B6 eutectic; (4) When the ΔT increases to 277 K, the FCC-Co phase primarily forms, followed by an FCC-Co and Co3B eutectic, which is similar in composition to the microstructure formed with low ΔT. The mechanisms of the microstructural evolution and the phase selection are interpreted on the basis of the composition segregation, the skewed coupled zone, the strain-induced transformation, and the solute trapping. Moreover, the prenucleation of the primary FCC-Co phase was also detected from an analysis of the different recalescence behaviors. The present work not only enriches our knowledge about the phase selection behavior in the undercooled Co-B system, but also provides us with guidance for controlling the microstructures and properties practically.

12.
J Biomed Opt ; 27(2)2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35212200

RESUMO

SIGNIFICANCE: Functional near-infrared spectroscopy (fNIRS) is a promising optical neuroimaging technique, measuring the hemodynamic signals from the cortex. However, improving signal quality and reducing artifacts arising from oscillation and baseline shift (BS) are still challenging up to now for fNIRS applications. AIM: Considering the advantages and weaknesses of the different algorithms to reduce the artifact effect in fNIRS signals, we propose a hybrid artifact detection and correction approach. APPROACH: First, distinct artifact detection was realized through an fNIRS detection strategy. Then the artifacts were divided into three categories: BS, slight oscillation, and severe oscillation. A comprehensive correction was applied through three main steps: severe artifact correction by cubic spline interpolation, BS removal by spline interpolation, and slight oscillation reduction by dual-threshold wavelet-based method. RESULTS: Using fNIRS data acquired during whole night sleep monitoring, we compared the performance of our approach with existing algorithms in signal-to-noise ratio (SNR) and Pearson's correlation coefficient (R). We found that the proposed method showed improvements in performance in SNR and R with strong stability. CONCLUSIONS: These results suggest that the new hybrid artifact detection and correction method enhances the viability of fNIRS as a functional neuroimaging modality.


Assuntos
Artefatos , Espectroscopia de Luz Próxima ao Infravermelho , Algoritmos , Neuroimagem Funcional/métodos , Movimento (Física) , Espectroscopia de Luz Próxima ao Infravermelho/métodos
13.
Front Genet ; 12: 747581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721537

RESUMO

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated. Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0. Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers. Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.

14.
Front Physiol ; 12: 733264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630151

RESUMO

Noninvasive assessment of autonomic nervous system (ANS) activity is of great importance, but the accuracy of the method used, which is primarily based on electrocardiogram-derived heart rate variability (HRV), has long been suspected. We investigated the feasibility of photoplethysmography (PPG) in ANS evaluation. Data of 32 healthy young men under four different ANS activation patterns were recorded: baseline, slow deep breathing (parasympathetic activation), cold pressor test (peripheral sympathetic activation), and mental arithmetic test (cardiac sympathetic activation). We extracted 110 PPG-based features to construct classification models for the four ANS activation patterns. Using interpretable models based on random forest, the main PPG features related to ANS activation were obtained. Results showed that pulse rate variability (PRV) exhibited similar changes to HRV across the different experiments. The four ANS patterns could be better classified using more PPG-based features compared with using HRV or PRV features, for which the classification accuracies were 0.80, 0.56, and 0.57, respectively. Sensitive features of parasympathetic activation included features of nonlinear (sample entropy), frequency, and time domains of PRV. Sensitive features of sympathetic activation were features of the amplitude and frequency domain of PRV of the PPG derivatives. Subsequently, these sensitive PPG-based features were used to fit the improved HRV parameters. The fitting results were acceptable (p < 0.01), which might provide a better method of evaluating ANS activity using PPG.

15.
Biochim Biophys Acta Mol Cell Res ; 1868(5): 118970, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33529640

RESUMO

Sphingosine-1-phosphate (S1P) has been shown to possess pro-hypertrophic properties in the heart, but the detailed molecular mechanism that underlies the pathological process is rarely explored. In the present study, we aim to explore the role of S1P-mediated intracellular Ca2+ signaling, with a focus on sarcoplasmic reticulum (SR)-mitochondria communication, in cardiomyocyte hypertrophy. Cultured neonatal rat ventricular myocytes (NRVMs) displayed significantly hypertrophic growth after treatment with 1 µmol/L S1P for 48 h, as indicated by the cell surface area or mRNA expressions of hypertrophic marker genes (ANP, BNP and ß-MHC). Importantly, mitochondrial Ca2+ and reactive oxygen species (ROS) levels were dramatically elevated upon S1P stimulation, and pharmacological blockage of which abolished NRVM hypertrophy. 0.5 Hz electrical pacing induced similar cytosolic Ca2+ kinetics to S1P stimulation, but unaffected the peak of mitochondrial [Ca2+]. With interference of the expression of type 2 inositol 1,4,5-trisphosphate receptors (IP3R2), which are unemployed in electrical paced Ca2+ activity but may be activated by S1P, alteration in mitochondrial Ca2+ as well as the hypertrophic effect in NRVMs under S1P stimulation were attenuated. The hypertrophic effect of S1P can also be abolished by pharmacological block of S1PR1 or Gi signaling. Collectively, our study highlights the mechanistic role of IP3R2-mediated excess SR-mitochondria Ca2+ transport in S1P-induced cardiomyocyte hypertrophy.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Lisofosfolipídeos/farmacologia , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/patologia , Retículo Sarcoplasmático/metabolismo , Esfingosina/análogos & derivados , Animais , Animais Recém-Nascidos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertrofia , Receptores de Inositol 1,4,5-Trifosfato/genética , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Esfingosina/farmacologia
16.
Cardiovasc Res ; 117(4): 1091-1102, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32531044

RESUMO

AIMS: Despite numerous reports documenting an important role of hypertension in the development of atrial fibrillation (AF), the detailed mechanism underlying the pathological process remains incompletely understood. Here, we aim to test the hypothesis that diastolic sarcoplasmic reticulum (SR) Ca2+ leak in atrial myocytes, induced by mechanical stretch due to elevated pressure in the left atrium (LA), plays an essential role in the AF development in pressure-overloaded hearts. METHODS AND RESULTS: Isolated mouse atrial myocytes subjected to acute axial stretch displayed an immediate elevation of SR Ca2+ leak. Using a mouse model of transverse aortic constriction (TAC), the relation between stretch, SR Ca2+ leak, and AF susceptibility was further tested. At 36 h post-TAC, SR Ca2+ leak in cardiomyocytes from the LA (with haemodynamic stress), but not right atrium (without haemodynamic stress), significantly increased, which was further elevated at 4 weeks post-TAC. Accordingly, AF susceptibility to atrial burst pacing in the 4-week TAC mice were also significantly increased, which was unaffected by inhibition of atrial fibrosis or inflammation via deletion of galectin-3. Western blotting revealed that type 2 ryanodine receptor (RyR2) in left atrial myocytes of TAC mice was oxidized due to activation and up-regulation of Nox2 and Nox4. Direct rescue of dysfunctional RyR2 with dantrolene or rycal S107 reduced diastolic SR Ca2+ leak in left atrial myocytes and prevented atrial burst pacing stimulated AF. CONCLUSION: Our study demonstrated for the first time the increased SR Ca2+ leak mediated by enhanced oxidative stress in left atrial myocytes that is causatively associated with higher AF susceptibility in pressure-overloaded hearts.


Assuntos
Fibrilação Atrial/metabolismo , Sinalização do Cálcio , Cálcio/metabolismo , Mecanorreceptores/metabolismo , Miócitos Cardíacos/metabolismo , Retículo Sarcoplasmático/metabolismo , Potenciais de Ação , Animais , Antiarrítmicos/farmacologia , Aorta/fisiopatologia , Aorta/cirurgia , Pressão Arterial , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/prevenção & controle , Função do Átrio Esquerdo , Pressão Atrial , Remodelamento Atrial , Bloqueadores dos Canais de Cálcio/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Galectina 3/genética , Galectina 3/metabolismo , Frequência Cardíaca , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/efeitos dos fármacos
17.
Orthop Surg ; 12(4): 1182-1189, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32618427

RESUMO

OBJECTIVE: To assess whether the computed tomography (CT)-based method of three-dimensional (3D) analysis (Mimics) was accurate and reliable for spine surgical anatomical measurements. METHODS: A total of 40 lumbar segments and 32 inter-vertebral discs from eigth adult male cadavers without fractures or deformities fixed with the classical formaldehyde method were included in this research on 5 June 2017. CT scans including seven dimensions: anterior height of the vertebral body (VBHa), middle height of the vertebral body (VBHm), posterior height of the vertebral body (VBHp), width of the upper endplate (EPWu), depth of the upper endplate (EPDu), anterior height of the inter-vertebral disc in the median sagittal plane (IDHa), and posterior height of the inter-vertebral disc in the median sagittal plane (IDHp). They were performed based on uniform conditions (slice thickness: 0.625 mm) using a CT scanner on 8 June 2017. Afterwards, the surgical anatomical measurements were conducted with a Vernier caliper on 12 June 2017. The computer-aided anatomical measurements were conducted by three investigators using Mimics 16.0 to perform 3D reconstructions of CT bone on 16 June 2017. Finally, the length and angle were measured with associated measurement tools, yielding a verified accuracy of 0.01 mm and 0.01°, respectively. Each measurement was repeated three times, and all anatomical data was analyzed using the statistical software and P-value < 0.05 was considered statistically significant. RESULTS: The results showed no statistically significant difference was observed between the surgical anatomical and computer-aided anatomical measurements (P > 0.05) for lumbar vertebra measurements, and the absolute difference between surgical and computer-aided data were all less than 1.0 mm (for the VBHa, VBHm, VBHp, EPWu, and EPDu were 0.12, 0.03, 0.03, 0.31, and 0.03 mm, respectively). Moreover, although the absolute differences of discs was larger than those of lumbar vertebras, no significant differences were detected between the computer-aided and surgical anatomical measurements for the IDHa, as well as IDHp in the vast majority of measurements (P = 0.543, 0.079 or 0.052 for IDHa, and P = 0.212, 0.133 or 0.042 for IDHp). In addition, excellent reliability correlation was observed between the measurements of each investigator, and the reliability coefficients in the intra-groups were all greater than 0.9 except for IDHp (reliability coefficient = 0.892). Additionally, the reliability coefficients were greater than 0.9 for the all between-group correlations, and a significant correlation was also observed. Furthermore, no statistically significant difference for three anatomical values was found in the computer-assisted measurements of the lumbar bone structure (P > 0.05). Similarly, we did not observe a statistical difference in the anatomical data of the lumbar discs from the three measures (P > 0.05). CONCLUSIONS: Computer-aided anatomical measurement for spine based on CT scans presents the high accuracy and reliability for improving spinal surgical procedures.


Assuntos
Imageamento Tridimensional , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Corpo Vertebral/diagnóstico por imagem , Adulto , Cadáver , Humanos , Disco Intervertebral/anatomia & histologia , Vértebras Lombares/anatomia & histologia , Masculino , Reprodutibilidade dos Testes , Corpo Vertebral/anatomia & histologia
18.
ACS Appl Mater Interfaces ; 12(11): 13265-13274, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32105063

RESUMO

E-textile consisting of natural fabrics has become a promising material to construct wearable sensors due to its comfortability and breathability on the human body. However, the reported fabric-based e-textile materials, such as graphene-treated cotton, silk, and flax, generally suffer from the electrical and mechanical instability in long-term wearing. In particular, fabrics on the human body have to endure heat variation, moisture evaporation from metabolic activities, and even the immersion with body sweat. To face the above challenges, here we report a wool-knitted fabric sensor treated with graphene oxide (GO) dyeing followed by l-ascorbic acid (l-AA) reduction (rGO). This rGO-based strain sensor is highly stretchable, washable, and durable with rapid sensing response. It exhibits excellent linearity with more than 20% elongation and, most importantly, withstand moisture from 30 to 90% (or even immersed with water) and still maintains good electrical and mechanical properties. We further demonstrate that, by integrating this proposed material with the near-field communication (NFC) system, a batteryless, wireless wearable body movement sensor can be constructed. This material can find wide use in smart garment applications.


Assuntos
Grafite/química , Dispositivos Eletrônicos Vestíveis , Fibra de Lã , Teste de Materiais , Fenômenos Mecânicos , Molhabilidade
19.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3368-3373, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602897

RESUMO

Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.


Assuntos
Medicamentos de Ervas Chinesas/normas , Controle de Qualidade , Tripterygium/química , Comprimidos
20.
Pflugers Arch ; 471(11-12): 1397-1406, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31624956

RESUMO

Accumulating evidence has demonstrated a significant relationship between prefrontal lobe and hypertension. Elevated blood pressure is usually associated with a prefrontal hemodynamic abnormality. However, the detailed process is still unclear. In this study, we designed a startle protocol and tested the response of the cerebral cortex and cardiovascular system in young normotensive subjects with a family history of hypertension (FH+). Additionally, the cold forehead test (CFT) was performed in hypertensive subjects. In total, 40 young normotensive subjects (21 with FH+ and 19 without a family history of hypertension (FH-)) and 49 middle-aged subjects (21 normotensives (NT) and 28 hypertensives (HT)) were recruited. Our results showed that the magnitude of startle-evoked alpha oscillation at the parasympathetic-related prefrontal cortex (FP1 and FP2) in the FH+ group was significantly smaller than in the FH- group. Acute bradycardia (RRI increase) was observed in FH- subjects but disappeared in the FH+ group. The coupling between instant cardiac acute response (increased RRI) and prefrontal arousal (magnitude of evoked oscillation) was significantly weakened in the FH+ group compared with the FH- group. Furthermore, the decrease in HR induced by parasympathetic outflow during CFT was absent in HT subjects. Hence, we concluded that the impairment of parasympathetic outflow derived from the prefrontal lobe occurs in both healthy young offspring of hypertensive and hypertensive patients.


Assuntos
Hipertensão/fisiopatologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Pressão Sanguínea/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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