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Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1-like macrophages in tumors, promoted the activation of CD8+ T cells through PD-L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD-L1 and CD47 expressions by acting as a sponge of miR-141 and miR-340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD-L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD-L1 and CD47 in HCC tissues. Moreover, the combination of Tug1-siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.
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The rehabilitation robot can assist hemiplegic patients to complete the training program effectively, but it only focuses on helping the patient's training process and requires the rehabilitation therapists to manually adjust the training parameters according to the patient's condition. Therefore, there is an urgent need for intelligent training prescription research of rehabilitation robots to promote the clinical applications. This study proposed a decision support system for the training of upper limb rehabilitation robot based on hybrid reasoning with rule-based reasoning (RBR) and case-based reasoning (CBR). The expert knowledge base of this system is established base on 10 professional rehabilitation therapists from three different rehabilitation departments in Shanghai who are enriched with experiences in using desktop-based upper limb rehabilitation robot. The rule-based reasoning is chosen to construct the cycle plan inference model, which develops a 21-day training plan for the patients. The case base consists of historical case data from 54 stroke patients who underwent rehabilitation training with a desktop-based upper limb rehabilitation robot. The case-based reasoning, combined with a Random Forest optimized algorithm, was constructed to adjust the training parameters for the patients in real-time. The system recommended a rehabilitation training program with an average accuracy of 91.5%, an average AUC value of 0.924, an average recall rate of 88.7%, and an average F1 score of 90.1%. The application of this system in rehabilitation robot would be useful for therapists.
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BACKGROUND: Rehabilitation assessment is a critical component of rehabilitation treatment. OBJECTIVE: This study focuses on a comprehensive analysis of patients' movement performance using the upper limb rehabilitation robot. It quantitatively assessed patients' motor control ability and constructed an intelligent grading model of functional impairments. These findings contribute to a deeper understanding of patients' motor ability and provide valuable insights for personalized rehabilitation interventions. METHODS: Patients at different Brunnstrom stages underwent rehabilitation training using the upper limb rehabilitation robot, and data on the distal movement positions of the patients' upper limbs were collected. A total of 22 assessment metrics related to movement efficiency, smoothness, and accuracy were extracted. The performance of these assessment metrics was measured using the Mann-Whitney U test and Pearson correlation analysis. Due to the issue of imbalanced sample categories, data augmentation was performed using the Synthetic Minority Over-sampling Technique (SMOTE) algorithm based on weighted sampling, and an intelligent grading model of functional impairment based on the Extreme Gradient Boosting Tree (XGBoost) algorithm was constructed. RESULTS: Sixteen assessment metrics were screened. These metrics were effectively normalized to their maximum values, enabling the derivation of quantitative assessment scores for motor control ability across the three dimensions through a weighted fusion approach. Notably, when applied to the data-enhanced dataset, the intelligent grading model exhibited remarkable improvement, achieving an accuracy rate exceeding 0.98. Moreover, significant enhancements were observed in terms of precision, recall, and f1-score. CONCLUSION: The research findings demonstrate that this study enables the quantitative assessment of patients' motor control ability and intelligent grading of functional impairments, thereby contributing to the efficiency enhancement of clinical rehabilitation assessment. Moreover, this method resolves the issues associated with the subjectivity and prolonged periods of traditional rehabilitation assessment methods.
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Extremidade Superior , Humanos , Extremidade Superior/fisiopatologia , Extremidade Superior/fisiologia , Fenômenos Biomecânicos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Robótica/métodos , Algoritmos , Idoso , Movimento/fisiologiaRESUMO
BACKGROUND: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis. METHODS: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach. RESULTS: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects. CONCLUSIONS: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training. TRIAL REGISTRATION: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829.
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Exercícios Respiratórios , Fibrose Cística , Humanos , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Criança , Exercícios Respiratórios/métodos , Adolescente , Força Muscular , Músculos Respiratórios/fisiopatologia , Qualidade de Vida , Resultado do Tratamento , Tolerância ao ExercícioRESUMO
BACKGROUND: There are few isometric training systems based on upper limb rehabilitation robots. Its efficacy and neural mechanism are not well understood. OBJECTIVE: This study aims to investigate the cortex activation of dynamic resistance and static (isometric) training based on upper limb rehabilitation robot combined with virtual reality (VR) interaction by using functional near-infrared spectroscopy (fNIRS). METHODS: Twenty subjects were included in this study. The experiment adopts the block paradigm design. Experiment in dynamic and static conditions consisted of three trials, each consisting of task (60âs)-rest (40âs). The neural activities of the sensorimotor cortex (SMC), premotor cortex (PMC) and prefrontal cortex (PFC) were measured. The cortex activation and functional connectivity (FC) were analyzed. RESULTS: Both the dynamic and static training can activate SMC, PMC, and PFC. In SMC and PMC, the activation of static training was stronger than dynamic training, there were significant differences between the two modes of each region of interest (ROI) (pâ<â0.05) (SMC: pâ=â0.022, ESâ=â0.72, PMC: pâ=â0.039, ESâ=â0.63). Besides, the FC between all ROIs of the static training was stronger than that of the dynamic training. CONCLUSION: The static training based on upper limb rehabilitation robot may better facilitate the cortical activation associated with motor control.
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Treinamento Resistido , Robótica , Humanos , Projetos Piloto , Extremidade Superior , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologiaRESUMO
Significant improvement in wastewater treatment is the most effective way for eutrophication control, especially in semiarid regions. However, its effect on the nutrient status and stoichiometry of the receiving water body has remained poorly considered and understood at broad temporal scales. Taking Guanting Reservoir (GR) in Hebei-Beijing (P. R. China) as an example, we present a study that links a continuous monitoring dataset for GR with corresponding estimates of human-induced nutrient discharges in its watershed from the year 2006 to 2019. We find that current GR belongs to strict P limitation and the faster decrease of TP than TN concentrations and continuous increase of TN/TP mass ratios in GR are attributed to the water restoration investment-induced declining of nutrient loadings. The improved municipal wastewater treatment capacity is mainly responsible for these significant changes, due to the higher removal efficiency of TP than TN in municipal wastewater. Given the potential ecological impact on aquatic biodiversity as well as ecosystem function of changes in TN/TP ratios and higher retention rate of TP (97.4%) compared with TN (93.1%) in GR, our findings highlight that future strategy for water pollution control should not only concentrate on more nutrient reduction efficiencies but attach importance to their stoichiometric balance to reduce the potential risk of phytoplankton blooms and toxin production during the water quality recovery of lakes or reservoirs.
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Ecossistema , Monitoramento Ambiental , Humanos , Pequim , Nitrogênio/análise , Fósforo/análise , China , Qualidade da Água , Eutrofização , Lagos , NutrientesRESUMO
Aiming for treating decentralized domestic wastewater in rural China, this study evaluates the effects of ceramsite size and structure, and water recirculation parameters, upon the performance of recirculating biofilter (RBF). RBF shows stable capability of chemical oxygen demand (COD) remediation and ammonia nitrification. In addition, the microbial flora and structures of the various layers in the system are analyzed via high-throughput sequencing in order to study the microbial diversity. The results indicate that while the ceramic particle size has no significant influence on the COD remediation capacity, the ceramics with smaller particle sizes exhibit better ammonia nitrogen (NH4+-N) removal ability, with a first-order linear relationship between the influent ammonia nitrogen load and the effluent NH4+-N concentration in RBF (R2 > 0.64). An increased hydraulic load and intermittent operation are shown to deteriorate the water quality with respect to NH4+-N, while an increased recirculation ratio increases the removal rate of NH4+-N from the effluent. Further, the water distribution time has a stronger effect upon the NH4+-N concentration in the effluent than does the recirculation ratio. Moreover, the microbial structure of the multi-layer recirculating trickle biofilter varies significantly during the process. The results indicate that a high recirculation ratio, long water distribution time, and multi-layer structure will be beneficial for improving the pollutant treatment capacity of RBF.
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Amônia , Esgotos , Reatores Biológicos , Águas Residuárias , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodosRESUMO
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are commonly used in regenerative medicine. However, it is not clear whether transplantation of BMSCs can improve cardiac function of the X-Linked Muscular Dystrophy Mice (mdx) and how to detect it. We aimed to investigate the role of speckle tracking echocardiography (STE) in detecting cardiac function of the BMSCs-transplanted mdx in comparison with the untreated mdx. METHODS: The experimental mice were divided into the BMSCs-transplanted mdx, untreated mdx, and control mice groups (n = 6 per group). The BMSCs were transplanted via tail vein injections into a subset of mdx at 20 weeks of age. After four weeks, the cardiac functional parameters of all the mice in the 3 groups were analyzed by echocardiography. Then, all the mice were sacrificed, and the cardiac tissues were harvested and analyzed by immunofluorescence. The serum biochemical parameters were also analyzed to determine the beneficial effects of BMSCs transplantation. RESULTS: Traditional echocardiography parameters did not show statistically significant differences after BMSCs transplantation for the three groups of mice. In comparison with the control group, mdx showed significantly lower left ventricular (LV) STE parameters in both the long-axis and short-axis LV images (P < 0.05). However, BMSCs-transplanted mdx showed improvements in several STE parameters including significant increases in a few STE parameters (P < 0.05). Immunofluorescence staining of the myocardium tissues showed statistically significant differences between the mdx and the control mice (P < 0.05), and the mdx transplanted with BMSCs demonstrated significantly improvement compared with the untreated mdx (P < 0.05). CONCLUSION: This study demonstrated that the early reduction in the LV systolic and diastolic function in the mdx were accurately detected by STE. Furthermore, our study demonstrated that the transplantation of BMSCs significantly improved myocardial function in the mdx.
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Medula Óssea , Distrofia Muscular de Duchenne , Camundongos , Animais , Infusões Intravenosas , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/diagnóstico , Ecocardiografia/métodos , MiocárdioRESUMO
There is increasing concern about the adverse impact of exposure to microplastic, as an emerging pollutant, on wild organisms, and particularly on organisms co-exposed to microplastic and other environmental contaminants. It has been widely reported that the combination of microplastics and heavy metals showed obvious toxicity to organisms in terms their growth and development. The present study was performed to determine the impact of binary metal mixtures of cadmium (Cd) and polystyrene microplastic (PS-microplastic) on Tigriopus japonicus, a typical marine model organism, using a titration design. Increasing concentrations of PS-microplastic (2 µg/L, 20 µg/L, and 200 µg/L) were titrated against a constant concentration of Cd (15.2 µg/L). The results showed no significant impact of exposure to this dose of Cd or co-exposure to Cd and the lowest dose of PS-microplastic examined (2 µg/L). However, the feeding rate, filtration rate, oxygen consumption rate, and hatching number declined significantly in T. japonicus co-exposed to Cd and higher concentrations of PS-microplastic (20 µg/L and 200 µg/L) (p < 0.05). Furthermore, the development of F1 larvae from nauplius stage (N) to adult stage (A) was markedly delayed when co-exposed to Cd and higher doses of PS-microplastic (20 and 200 µg/L), and the effects persisted to the F2 larval stage. Interestingly, the present titration design did not affect the sex ratio or number of oocysts in either the F1 or F2 generation. These results indicated that the current marine environmental concentrations of Cd and microplastic are safe for wild organisms. Further studies are required to address the knowledge gap regarding toxicological effects at the cellular and molecular levels.
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Copépodes , Metais Pesados , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Cádmio/toxicidade , Plásticos/toxicidade , Poliestirenos , Poluentes Químicos da Água/toxicidade , Metais Pesados/toxicidade , Organismos AquáticosRESUMO
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. The aim of this study was to investigate the molecular epidemiological characteristic of the G6PD deficiency among newborn screening population in Wuhan region. A total of 430,806 healthy neonates in Wuhan area of China were screened for G6PD deficiency from November 2016 to December 2021. The positive samples were further detected with gene analysis. Among the 957 neonates with abnormal G6PD enzyme activity, the prevalence of G6PD deficiency in Wuhan was calculated as 0.22%. 38 genotypes were found and the top 5 frequencies of G6PD gene variants were c.1388G > A, c.1376G > T, c.95A > G, c.1024C > T and c.871G > A. Seven rare single variants (c.25C > T, c.152C > T, c.406C > T, c.497G > A, c.679C > T, c.854G > A and c.1057C > T) and two rare multiple variants (IVS-5 637/638T del/c.1311C > T/1365-13T > C and c.406C > T/c.1311C > T/1365-13T > C) were discovered in this study. In addition, four novel variants (c.49C > T, c.691G > A, c.857A > T and c.982G > A) were detected out in our cohort, which have never been reported before. The result indicated that a rich diversity of G6PD genetic variants in Wuhan region, also had its own regional characteristic. Our data provided the basic knowledge for future prevention and research of G6PD deficiency and the findings will be useful for genetic counseling and prenatal diagnosis of G6PD deficiency in the Wuhan region.
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Childhood obesity, as one of the potential risk factors of cardiovascular diseases, is closely associated with the incidence of cardiovascular disease at a younger age and has become a public health concern worldwide. However, its potential effects on the cardiovascular system have still remained elusive. In this study, we systematically evaluated the cardiovascular characteristics of 79 obese children and 161 normal weight children in Guangzhou (China) using the potential biomarkers for cardiovascular disease. Compared with normal weight children, obese children not only exhibited significantly higher levels of creatine kinase (CK), lactate dehydrogenase (LHD), soluble fms-like tyrosine kinase-1 (s-Flt-1), high-sensitivity C-reactive protein (hs-CRP), and uric acid (UA) (p = 0.0062, 0.0012, 0.0013, 0.0225, and <0.0001, respectively) but also significantly higher diastolic blood pressure (p = 0.0074) and the heart rate (p = 0.0049) were found in obese children. Of 79 obese children, cardiac functions of 40 cases were further assessed by color Doppler echocardiography. The results showed that there were significant differences between the obesity group and the healthy weight group in terms of interventricular septal wall thickness at end-diastolic (IVSd), the left ventricular posterior wall thickness at end-diastolic (LVPWD), and aortic annulus (AO) (p < 0.0001, 0.0003, and p < 0.0001, respectively). Besides, the left and/or right ventricular functions were declined in 52.4% of obese children. Correlation analysis revealed that the anthropometric parameters of obesity were not only significantly correlated with a blood lipid profile but also exhibited a more significant correlation with most of the parameters of cardiac dysfunction than a blood lipid profile. Therefore, our study indicated that obese children in Guangzhou suffered from functional damages related to cardiovascular events, which were characterized by cardiac dysfunction, and the anthropometric parameters of obesity could be economically alternative biomarkers for monitoring of cardiac dysfunction in obese children.
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Plastic pollution is a global crisis, especially in the marine environment. Excessive consumption and unsound disposal are responsible for the constant accumulation of plastic waste, resulting in plastic litter and microplastic contamination on a global scale. Establishing a new global framework is regarded as a promising tool to address plastic pollution, including marine plastic litter. However, there is a need to raise awareness of the role of consumers at individual and national levels in reducing the use of unnecessary plastics and increasing the recycling of plastic waste. The global framework should incorporate aspects of the importance of consumption responsibility in solutions addressing the issue of plastic pollution.
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Microplásticos , Plásticos , Poluição Ambiental/prevenção & controle , ReciclagemRESUMO
Objective: Pendrin is encoded by SLC26A4, which is expressed in the apical membrane of inner ear epithelial cells and drives chloride reabsorption in the apical septum. In the inner ear, pendrin dysfunction and hypofunctional mutations lead to vestibular aqueduct (EVA) enlargement and sensory neural hearing loss. Mutations in SLC26A4 are a common reason of deafness. However, the underlying mechanisms of SLC26A4 mutants in hearing loss remain unknown. Methods: In the present study, pEGFP-N1 carrying wild-type and mutant SLC26A4 (c.85G>A, c.2006A>T, and c.853G>A) were transfected into HEK-293T cells. GFP fluorescence and GFP levels were determined. SLC26A4 mRNA levels were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the expression of chloride intracellular channel 1 (CLIC1) and CLIC2 was measured by Immunofluorescence assay. Intracellular chloride concentration and apoptotic rate were analyzed by flow cytometry. The levels of membrane/cytoplasmic pendrin, apoptosis-associated proteins, and the PI3K/Akt/mTOR pathway members were determined by Western blot. Results: Constructed SLC26A4 mutant 1 (c.85G>A), SLC26A4 mutant 2 (c.2006A>T), and SLC26A4 mutant 3 (c.853G>A). The wild-type and 3 mutations were stably expressed in HEK-293T. SLC26A4 mRNA expression was significantly increased after transfection with wild-type SLC26A4 and mutant SLC26A4 compared with the untransfected vector group (P < 0.01). Compared with the vector group, the expression levels of membrane pendrin, cytoplasmic pendrin, CLIC1, CLIC2, Bcl-2, p-PI3K, p-Akt, and p-mTOR were upregulated. Compared with the vector group, the chloride concentration, cell apoptotic rate, and the expression levels of caspase-3, caspase-9, and Bax were downregulated. Compared with the vector group, the above effects of SLC26A4 were reversed after the SLC26A4 mutant. Conclusion: After SLC26A4 mutation, pendrin was transferred from the membrane, the chloride intracellular channel function was reduced, and the excessive accumulation of chloride in the cytoplasm induced cell apoptosis by inhibited PI3K/Akt/mTOR pathway phosphorylation.
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Cloretos , Perda Auditiva , Transportadores de Sulfato , Apoptose/genética , Canais de Cloreto/genética , Cloretos/metabolismo , Células HEK293 , Perda Auditiva/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Mutação/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transportadores de Sulfato/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Ischemic heart disease is a major global public health challenge, and its functional outcomes remain poor. Lysine crotonylation (Kcr) was recently identified as a post-translational histone modification that robustly indicates active promoters. However, the role of Kcr in myocardial injury is unknown. In this study, we aimed to clarify the pathophysiological significance of Kcr in cardiac injury and explore the underlying mechanism. METHODS: We investigated the dynamic change of both the Kcr sites and protein level in left ventricular tissues at 2 time points following sham or cardiac ischemia-reperfusion injury, followed by liquid chromatography-coupled tandem mass tag mass spectrometry. After validation of the enriched protein Kcr by immunoprecipitation and Western blot, the function and mechanism of specific Kcr sites were further investigated in vitro and in vivo by gain- or loss-of-function mutations targeting Kcr sites of selected proteins. RESULTS: We found that cardiac ischemia-reperfusion injury triggers preferential Kcr of proteins required for cardiomyocyte contractility, including mitochondrial and cytoskeleton proteins, which occurs largely independently of protein-level changes in the same proteins. Those exhibiting Kcr changes were associated not only with disruption of cardiomyocyte mitochondrial, sarcomere architecture, and gap junction but also with cardiomyocyte autophagy and apoptosis. Modulating site-specific Kcr of selected mitochondrial protein IDH3a (isocitrate dehydrogenase 3 [NAD+] alpha) at K199 and cytoskeletal protein TPM1 (tropomyosin alpha-1 chain) at K28/29 or enhancing general Kcr via sodium crotonate provision not only protects cardiomyocyte from apoptosis by inhibiting BNIP3 (Bcl-2 adenovirus E18 19-kDa-interacting protein 3)-mediated mitophagy or cytoskeleton structure rearrangement but also preserves postinjury myocardial function by inhibiting fibrosis and apoptosis. CONCLUSIONS: Our results indicate that Kcr modulation is a key response of cardiomyocytes to ischemia-reperfusion injury and may represent a novel therapeutic target in the context of ischemic heart disease.
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Isquemia Miocárdica , Traumatismo por Reperfusão , Humanos , Lisina/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismoRESUMO
Rational: Wnt4 plays a critical role in development and is reactivated during fibrotic injury; however, the role of Wnt4 in cardiac repair remains unclear. In this study, our aim was to clarify the pathophysiological role and mechanisms of Wnt4 following acute cardiac ischemic reperfusion injury. Methods and results: We investigated the spatio-temporal expression of Wnt4 following acute cardiac ischemic reperfusion injury and found that Wnt4 was upregulated as an early injury response gene in cardiac fibroblasts near the injury border zone and associated with mesenchymal-endothelial transition (MEndoT), a beneficial process for revascularizing the damaged myocardium in cardiac repair. Using ChIP assay and in vitro and in vivo loss- and gain-of-function, we demonstrated that Wnt4 served as a crucial downstream target gene of p53 during MEndoT. Wnt4 knockdown in cardiac fibroblasts led to decreased MEndoT and worsened cardiac function. Conversely, Wnt4 overexpression in cardiac fibroblasts induced MEndoT in these cells via the phospho-JNK/JNK signaling pathway; however, both the p53 and Wnt4 protein levels were dependent on the ß-catenin signaling pathway. JNK activation plays a critical role in the induction of MEndoT and is crucial for Wnt4 regulated MEndoT. Moreover, Wnt4 overexpression specifically in cardiac fibroblasts rescued the cardiac function worsening due to genetic p53 deletion by decreasing fibrosis and increasing MEndoT and vascular density. Conclusion: Our study revealed that Wnt4 plays a pivotal role in cardiac repair with involvement of phospho-JNK mediated MEndoT and is a crucial gene for cardiac fibroblast-targeted therapy in heart disease.
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MAP Quinase Quinase 4/metabolismo , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53 , Endotélio/metabolismo , Fibroblastos/metabolismo , Fibrose , Humanos , Fosforilação , Traumatismo por Reperfusão/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Wnt4/genética , Proteína Wnt4/metabolismoAssuntos
Ambliopia , Estrabismo , Criança , Humanos , Ambliopia/diagnóstico , Ambliopia/terapia , Acuidade VisualRESUMO
BACKGROUND: Hypothyroidism is a systemic metabolic deficiency syndrome caused by a deficiency in thyroid hormone or a decrease in the action of thyroid hormones. It has a high incidence among women of child-bearing age, and pregnant women with hypothyroidism may have a higher risk of birth defects. OBJECTIVE: To explore the specific biological mechanism affecting the occurrence of hypothyroidism. METHODS: This study determined key molecules by comparing and analyzing the difference in methylation levels between pre-pregnancy women and normal controls using the Illumina Infinium MethylationEPIC BeadChip. RESULTS: 3493 Differential methylation positions (DMPs) related genes and 47 differentially methylated regions (DMRs) related genes were found between the Hypothyroidism group and the control group. Among them, miR-21 has been found to be closely related to thyroid hormone regulation. The results of enrichment analysis showed that the DMPs or DMRs-related genes are both significantly enriched in human T-cell leukemia virus 1 infection, osteoclast differentiation and sphingolipid signaling pathway, which were also closely related to the occurrence and development of hypothyroidism. In addition, the combined analysis of CNVs and DMRs showed that significant differences occurred near the regions of 16 M bp in chromosome 1 between the two groups, and the genes involved in these regions included NDUFS2, FCER1G and SHC1. CONCLUSION: This work screened molecular markers and key signaling pathways that are involved in the development of hypothyroidism in pre-pregnancy women, which may provide new targets for the research and diagnosis of hypothyroidism in the future.
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Hipotireoidismo , Complicações na Gravidez , Humanos , Feminino , Gravidez , Hipotireoidismo/complicações , Hipotireoidismo/genética , Hipotireoidismo/diagnóstico , Metilação de DNA , Complicações na Gravidez/genética , Hormônios TireóideosRESUMO
Heavy metal pollution has become a great concern due to its adverse effects on the ecological system and human health. The present study investigated the concentrations of six common heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the Tianjin coastal area to understand their distribution, enrichment, sources, and potential ecological risk levels, focusing on the main contributors. The results showed that the concentration of Cu was high in the surface seawater (6.89 µg/L for the average), while Cd was the main contaminating metal in the sediments, with an average concentration of 0.77 mg/kg. The potential ecological risk index (RI) implied that the heavy metals in the sediments could cause considerable ecological risk, and Cd was the major contributor to ecological risk in this area. In particular, the field investigation showed that Cd contamination occurred as a result of anthropogenic activities, including port transportation, mariculture, and metal fabrication along the coastal area. Therefore, it is necessary to control Cd contamination in the future to improve the quality of the marine environment in Bohai Bay.
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Metais Pesados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Metais Pesados/análise , Medição de Risco , Água do Mar , Poluentes Químicos da Água/análiseRESUMO
The molecular mode of action underpinning the response of mollusks exposure to endocrine disrupting chemicals (EDCs) remains unclear due to a lack of available information regarding their genome. Single molecule real-time (SMRT) sequencing makes it possible to reveal molecular mechanisms by direct sequencing of full-length transcripts. In the present study, the transcriptome profile of the freshwater snail Parafossarulus striatulus after exposure to 17ß-estradiol (E2) or 17α-methyltestosterone (MT) was evaluated using SMRT sequencing strategy. In total, 216,598 non-redundant and full-length gene isoforms were generated and 106,266 isoforms were predicted with a complete open reading frame (ORF). Moreover, 60.36% of the isoforms were matched to known proteins in at least one of six databases. Differential gene expression analyses showed significantly different patterns in paired samples with different treatments. The expression levels of several membrane receptor isoforms of P. striatulus including dopamine receptor (DR), FMRFamide receptor (FMRFaR), neuropeptide Y receptor (NYR) and neuropeptide FF receptor (NFFR), but not estrogen receptor (ER) or estrogen-related receptor (ERR), were significantly affected by E2 and MT. These findings suggest that activation of membrane receptors, as well as other signaling pathways, might be critical for mediating the effects of endocrine disruption in mollusks. The transcriptome information obtained from the SMRT sequencing provides a significant contribution to the investigation of the molecular mode of action of endocrine disrupting chemicals on P. striatulus.