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Although strongly influenced by environmental conditions, lateral root (LR) positioning along the primary root appears to follow obediently an internal spacing mechanism dictated by auxin oscillations that prepattern the primary root, referred to as the root clock. Surprisingly, none of the hitherto characterized PIN- and ABCB-type auxin transporters seem to be involved in this LR prepatterning mechanism. Here, we characterize ABCB15, 16, 17, 18, and 22 (ABCB15-22) as novel auxin-transporting ABCBs. Knock-down and genome editing of this genetically linked group of ABCBs caused strongly reduced LR densities. These phenotypes were correlated with reduced amplitude, but not reduced frequency of the root clock oscillation. High-resolution auxin transport assays and tissue-specific silencing revealed contributions of ABCB15-22 to shootward auxin transport in the lateral root cap (LRC) and epidermis, thereby explaining the reduced auxin oscillation. Jointly, these data support a model in which LRC-derived auxin contributes to the root clock amplitude.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Transporte Biológico , Proteínas de Membrana Transportadoras/genética , Ácidos Indolacéticos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: The structure and staffing of hospitals greatly impact patient outcomes, with frequent changes occurring during nights and weekends. This retrospective cohort study assessed the impact of admission timing on in-hospital management and outcomes for patients with stroke receiving reperfusion therapy in China using data from a nationwide registry. METHODS: Data from patients receiving reperfusion therapy were extracted from the Chinese Stroke Center Alliance. Hospital admission time was categorized according to day/evening versus night and weekday versus weekend. Primary outcomes were in-hospital death or discharge against medical advice, hemorrhage transformation, early neurological deterioration, and major adverse cardiovascular events. Logistic regression was performed to compare in-hospital management performance and outcomes based on admission time categories. RESULTS: Overall, 42â 381 patients received recombinant tissue-type plasminogen activator (r-tPA) therapy, and 5224 underwent endovascular treatment (EVT). Patients admitted during nighttime had a higher probability of receiving r-tPA therapy within 4.5 hours from onset or undergoing EVT within 6 hours from onset compared with those admitted during day/evening hours (adjusted odds ratio, 1.04 [95% CI, 1.01-1.08]; P=0.021; adjusted odds ratio, 1.72 [95% CI, 1.59-1.86]; P<0.001, respectively). However, no significant difference was observed between weekend and weekday admissions for either treatment. No notable differences were noted between weekends and weekdays or nighttime and daytime periods in door-to-needle time for r-tPA or door-to-puncture time for EVT initiation. Furthermore, weekend or nighttime admission did not have a significant effect on the primary outcomes of r-tPA therapy or EVT. Nevertheless, in patients undergoing EVT, a higher incidence of pneumonia was observed among those admitted at night compared with those admitted during day/evening hours (adjusted odds ratio, 1.22 [95% CI, 1.05-1.42]; P=0.011). CONCLUSIONS: Patients admitted at nighttime were more likely to receive r-tPA therapy or EVT within the time window recommended in the guidelines. However, patients receiving EVT admitted at night had an increased risk of pneumonia.
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BACKGROUND: Evidence of the effects of metabolically healthy obesity (MHO) on atherosclerosis is limited; the transition effects of metabolic health and obesity phenotypes have been ignored. We examined the association between metabolic health and the transition to atherosclerosis risk across body mass index (BMI) categories in a community population. METHODS: This cross-sectional study was based on a national representative survey that included 50,885 community participants aged ≥40 years. It was conducted from 01 December 2017 to 31 December 2020, in 13 urban and 13 rural regions across Hunan China. Metabolic health was defined as meeting less than three abnormalities in blood pressure, glucose, high-density lipoprotein cholesterol, triglycerides, or waist circumference. The participants were cross-classified at baseline based on their metabolic health and obesity. In addition, the relationship between atherosclerosis and transitions in metabolic health status based on 4733 participants from baseline to the second survey after 2 years was considered. The relationship between metabolic health status and the risk of transition to Carotid atherosclerosis (CA) was assessed using logistic regression and Cox proportional hazards regression analyses. RESULTS: In this study, the mean age of the participants was 60.7 years (standard deviation [SD], 10.91), 53.0% were female, and 51.2% had CA. As compared with metabolically healthy normal weight (MHN), those with MHO phenotype (odd ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.21), metabolically unhealthy normal weight (OR 1.27, 95% CI 1.19-1.35), metabolically unhealthy overweight (OR 1.41, 95% CI 1.33-1.48), and metabolically unhealthy obese (OR 1.54, 95% CI 1.44-1.64) had higher risk for CA. However, during the follow-up of 2 years, almost 33% of the participants transitioned to a metabolically unhealthy status. As compared with stable healthy normal weight, transition from metabolically healthy to unhealthy status (hazard ratios [HR] 1.21, 95% [CI] 1.02-1.43) and stable metabolically unhealthy overweight or obesity (MUOO) (HR 1.32, 95% CI 1.17-1.48) were associated with higher risk of CA. CONCLUSIONS: In the community population, obesity remains a risk factor for CA despite metabolic health. However, the risks were highest for metabolically unhealthy status across all BMI categories. A large proportion of metabolically healthy overweight or participants with obesity converts to an unhealthy phenotype over time, which is associated with an increased risk of CA.
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Aterosclerose , Doenças das Artérias Carótidas , Obesidade Metabolicamente Benigna , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Obesidade Metabolicamente Benigna/epidemiologia , Sobrepeso/complicações , Estudos Transversais , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Fatores de Risco , Índice de Massa Corporal , Nível de Saúde , Fenótipo , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Aterosclerose/epidemiologia , Aterosclerose/etiologiaRESUMO
Accumulating evidence suggests that human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exos) are a promising therapeutic strategy for cerebral ischemia-reperfusion injury (CIRI). However, the underlying mechanism remains unclear. hUC-MSCs-Exos were identified by electron microscopy, NTA, and Western blotting. In the hypoxia/reoxygenation (H/R) cell model, human brain microvascular endothelial cells (HBMECs) were cocultured with hUC-MSCs-Exos. Then, cell viability, migration, apoptosis, and tube formation were measured by MTT, flow cytometry, transwell, and tube formation assays. RT-qPCR and Western blotting were used to detect the changes in RNA and protein. RNA pull-down and dual luciferase reporter assays confirmed the relationship between circDLGAP4, miR-320, and KLF5. Ischemia-reperfusion (I/R) rat model was established for in vivo experiments. hUC-MSCs-Exos increased the expression levels of circDLGAP4 and KLF5 but decreased miR-320 in H/R-treated HBMECs by transferring exosomal circDLGAP4. Knockdown of circDLGAP4 in hUC-MSCs-Exos reversed the promoting effects of hUC-MSCs-Exos on cell viability, migration, and tube formation in H/R-treated HBMECs in vitro and also abolished the protective effects of hUC-MSCs-Exos on cerebrovascular injury in I/R rats. Mechanistically, exosomal circDLGAP4 negatively regulated miR-320 in HBMECs, which directly bound to KLF5. In addition, the downregulation of miR-320 could reverse the regulatory effect of exosomal shcircDLGAL5 in H/R-treated HBMECs by upregulating KLF5. hUC-MSCs-Exos-derived circDLGAP4 reduced cerebrovascular injury by regulating miR-320/KLF5 signaling. These results provide a stem cell-based approach to treat CIRI.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/metabolismo , Exossomos/genética , Exossomos/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismoRESUMO
Umbilical cord-mesenchymal stem cells (UC-MSCs)-derived exosomes have been considered as an effective treatment for ischemic stroke. CircRNA BBS2 (circBBS2) was demonstrated to be down-regulated in patients with ischemic stroke. However, the role of UC-MSCs-derived exosomal circBBS2 in ischemic stroke and potential mechanisms remain unclear. Hypoxia/reperfusion (H/R)-exposed SH-SY5Y cells and middle cerebral artery occlusion (MCAO)-treated rats were served as in vitro and in vivo models of ischemic stroke. Target gene expression was detected by qRT-PCR. Cell viability was assessed by MTT assay. Ferroptosis was determined by iron, MDA, GSH, and lipid ROS levels. Protein levels were measured by Western blotting. The target relationships among circBBS2, miR-494, and SLC7A11 were validated by RNA-pull down, RIP, and dual-luciferase reporter assays. TTC and HE staining were performed to evaluate cerebral infarction volume and neuropathological changes. circBBS2 was lowly expressed and ferroptosis was triggered in MCAO rats and H/R-stimulated SH-SY5Y cells. UC-MSCs-derived exosomes enhanced cell viability and restrained ferroptosis via increasing circBBS2 expression in SH-SY5Y cells. Mechanistically, circBBS2 sponged miR-494 to enhance the SLC7A11 level. Knockdown of miR-494 or SLC7A11 reversed the effects of silencing circBBS2 or miR-494 on ferroptosis of SH-SY5Y cells, respectively. Furthermore, UC-MSCs-derived exosomes attenuated ischemic stroke in rats via delivering circBBS2 to inhibit ferroptosis. UC-MSCs-derived exosomal circBBS2 enhanced SLC7A11 expression via sponging miR-494, therefore repressing ferroptosis and relieving ischemic stroke. Our findings shed light on a novel mechanism for UC-MSCs-derived exosomes in the treatment of ischemic stroke.
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Ferroptose , AVC Isquêmico , MicroRNAs , Neuroblastoma , Animais , Humanos , Ratos , Sistema y+ de Transporte de Aminoácidos/genética , Ferroptose/genética , Hipóxia , AVC Isquêmico/genética , MicroRNAs/genética , RNA Circular/genéticaRESUMO
PURPOSE: Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM. METHODS: Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions. RESULTS: The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90-1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97-1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM. CONCLUSIONS: The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM.
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Diabetes Gestacional , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Gravidez , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Índice de Massa CorporalRESUMO
PURPOSE: Pain is one of the most common and harmful symptoms experienced by individuals with acute herpetic neuralgia (AHN). In this population, studies to determine the causes that affect patients taking medications compliance are rare. This study aimed to construct a predictive model for medication compliance of patients with AHN and to verify its performance. DESIGN AND METHODS: In this prospective study of 398 patients with AHN who were discharged from a tertiary hospital with medications from July 2020 to October 2022, we used logistic regression analysis to explore the predictive factors of medication compliance of patients with AHN and to construct a nomogram. The area under the curve was used to evaluate the predictive effect of the model. RESULTS: A predictive model of drug compliance of patients with AHN was constructed based on the following four factors: disease duration, pain severity before treatment, medication beliefs, and comorbidity of chronic diseases. The area under the curve of the model was 0.766 (95% confidence interval [0.713, 0.819]), with a maximum Youden's index of 0.431, sensitivity of 0.776, and specificity of 0.655. A linear calibration curve was found with a slope close to 1. CONCLUSIONS: The prediction model constructed in this study had good predictive performance and provided a reference for early clinical screening of independent factors that affected the medication compliance of patients with AHN.
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BACKGROUND: The atherogenic index of plasma (AIP) is an important alternative metabolic biomarker of atherosclerosis and cardiovascular diseases. Nevertheless, the correlation between the AIP and carotid atherosclerosis is unknown among the general population. METHODS: A total of 52,380 community residents, aged ≥ 40 years who underwentcervical vascular ultrasound from December 2017 to December 2020 in Hunan China, were selected for retrospective analysis. The AIP was calculated as a logarithmically converted ratio of triglycerides (TG) to high-density lipoprotein-cholesterol (HDL-C). The participants were divided into AIP quartile groups (Q1-Q4). Logistic regression models and restricted cubic spline analyses were used to examine the association of the AIP with carotid atherosclerosis. Stratified analyses were applied to control for confounding factors. The incremental predictive value of the AIP was further assessed. RESULTS: After adjusting for traditional risk factors, an increased AIP was associated with a higher rate of carotid atherosclerosis (CA), increased carotid intima-media thickness (CIMT), and plaques [odds ratio, OR (95% confidence interval, CI): 1.06 (1.04, 1.08), 1.07 (1.05, 1.09), and 1.04 (1.02, 1.06) per 1-SD increase in the AIP, respectively]. Compared with those participants in the quartile 1 group, those in the quartile 4 group had a greater risk of CA [OR 1.18, 95% CI (1.12, 1.25)], increased CIMT [OR 1.20, 95% CI (1.13, 1.26)], and plaques [OR 1.13, 95% CI (1.06, 1.19)]. However, we did not observe an association between the AIP and stenosis [0.97 (0.77, 1.23), p for trend = 0.758]. Restricted cubic spline analyses also showed a cumulative increase in the risk of CA, increased CIMT, and plaques but not stenosis severity (> 50%) with an increase of the AIP. Subgroup analyses showed that a more significant association between the AIP and the prevalence of increased CA was detected in younger subjects (aged < 60 years) with a body mass index (BMI) of ≥ 24 and fewer comorbidities. Additionally, the AIP provided incremental predictive capacity over established risk factors for CA, as shown by an improvement in the net reclassification index (NRI) and integrated discrimination index (IDI) (all P < 0.05). CONCLUSIONS: An elevated AIP in a community-based population is associated with a higher rate of CA. the AIP could serve as a potential biomarker for CA risk assessment.
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Doenças das Artérias Carótidas , Placa Aterosclerótica , Humanos , Estudos Retrospectivos , Espessura Intima-Media Carotídea , Estudos de Coortes , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Triglicerídeos , Fatores de Risco , HDL-Colesterol , China/epidemiologia , BiomarcadoresRESUMO
Cell senescence is the growth arrest caused by the accumulation of irreparable cell damage, which is involved in physiological and pathological processes and regulated by the post-transcriptional level. This regulation is performed by transcriptional regulators and driven by aging-related small RNAs, long non-coding RNAs, and RNA-binding proteins. N6-methyladenosine (m6A) is the most common chemical modification in eukaryotic mRNA, which can enhance or reduce the binding of transcriptional regulators. Increasing studies have confirmed the crucial role of m6A in controlling mRNA in various physiological processes. Remarkably, recent reports have indicated that abnormal methylation of m6A-related RNA may affect cell senescence. In this review, we clarified the association between m6A modification and cell senescence and analyzed the limitations of the current research.
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Senescência Celular , Proteínas de Ligação a RNA , Metilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Senescência Celular/genéticaRESUMO
Ischemic stroke accounts for about 71% of strokes worldwide. Due to limited recommended therapeutics for ischemic stroke, more attention is focused on angiogenesis in ischemic stroke. Not long after ischemic stroke, angiogenesis arises and is vital for the prognosis. Various pro-angiogenic, anti-angiogenic factors and their downstream pathways engage in angiogenesis regulation. CircRNAs are differentially expressed after ischemic stroke. Up to now, circRNAs have been found to exert many functions in regulating apoptosis, autophagy, proliferation, and differentiation of neurons and neural stem cells mainly as miRNAs sponges or proteins decoy. Thus, many circRNAs are considered promising biomarkers or therapeutic targets for ischemic stroke. Besides, circRNAs participate in the modulation of endothelial-mesenchymal transition and blood-brain barrier maintenance. Moreover, circRNAs play significant roles in endothelial dysfunction concerning inflammation responses, apoptosis, proliferation, and migration. They correlate with many angiogenesis-related signaling pathways and genes via the circRNA/miRNA/mRNA network. Novel insights into circRNAs significance in angiogenesis regulation in ischemic stroke could be provided for further researches on the clinical application of circRNAs in ischemic stroke.
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AVC Isquêmico , MicroRNAs , Humanos , RNA Circular/genética , AVC Isquêmico/genética , AVC Isquêmico/terapia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , BiomarcadoresRESUMO
INTRODUCTION: Hayflick and Moorhead first demonstrated cell senescence as the irreversible growth arrest of cells after prolonged cultivation. Telomere shortening and oxidative stress are the fundamental mechanisms that drive cell senescence. Increasing studies have shown that TMAO is closely associated with cellular aging and age-related diseases. An emerging body of evidence from animal models, especially mice, has identified that TMAO contributes to senescence from multiple pathways and appears to accelerate many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. However, the specific mechanism of how TMAO speeds aging is still not completely clear. MATERIAL AND METHODS: In this review, we summarize some key findings in TMAO, cell senescence, and age-related diseases. We focused particular attention on the potential mechanisms for clinical transformation to find ways to interfere with the aging process. CONCLUSION: TMAO can accelerate cell senescence by causing mitochondrial damage, superoxide formation, and promoting the generation of pro-inflammatory factors.
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Envelhecimento , Senescência Celular , Camundongos , Animais , Metilaminas , Estresse OxidativoRESUMO
A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.
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Antozoários , Antineoplásicos , Diterpenos , Neoplasias , Animais , Antozoários/química , China , Diterpenos/farmacologia , Diterpenos/química , Estrutura Molecular , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/prevenção & controleRESUMO
Diabetic foot ulcer, is a chronic complication afflicting individuals with diabetes, continue to increase worldwide, immensely burdening society. Programmed cell death, which includes apoptosis, autophagy, ferroptosis, necroptosis and pyroptosis, has been increasingly implicated in the pathogenesis of diabetic foot ulcer. This review is based on an exhaustive examination of the literature on 'programmed cell death' and 'diabetic foot ulcers' via PubMed. The findings revealed that natural bioactive compounds, noncoding RNAs and certain proteins play crucial roles in the healing of diabetic foot ulcers through various forms of programmed cell death, including apoptosis, autophagy, ferroptosis and pyroptosis.
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Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.
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Edema Encefálico , Lesões Encefálicas , Curcumina , Apoptose , Edema Encefálico/metabolismo , Lesões Encefálicas/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/metabolismo , Curcumina/farmacologia , Humanos , Janus Quinase 1/metabolismo , Doenças Neuroinflamatórias , Neurônios/metabolismo , Fator de Transcrição STAT1/metabolismoRESUMO
BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) are key players in multicellular, stromal-dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor-associated neutrophils (TANs) during different stages of HCC pathogenesis. APPROACH AND RESULTS: In the HCC-TME, CAF-derived cardiotrophin-like cytokine factor 1 (CLCF1) increased chemokine (C-X-C motif) ligand 6 (CXCL6) and TGF-ß secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF-ß secreted by HCC cells activated extracellular signal-regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1-mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up-regulation of the CLCF1-CXCL6/TGF-ß axis exhibited a marked correlation with increased cancer stem cells, "N2"-polarized TANs, tumor stage, and poor prognosis. CONCLUSIONS: This study reveals a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1-CXCL6/TGF-ß axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.
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Fibroblastos Associados a Câncer/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimiocina CXCL6/metabolismo , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Microambiente TumoralRESUMO
The plant hormone auxin must be transported throughout plants in a cell-to-cell manner to affect its various physiological functions. ABCB transporters are critical for this polar auxin distribution, but the regulatory mechanisms controlling their function is not fully understood. The auxin transport activity of ABCB1 was suggested to be regulated by a physical interaction with FKBP42/Twisted Dwarf1 (TWD1), a peptidylprolyl cis-trans isomerase (PPIase), but all attempts to demonstrate such a PPIase activity by TWD1 have failed so far. By using a structure-based approach, we identified several surface-exposed proline residues in the nucleotide binding domain and linker of Arabidopsis ABCB1, mutations of which do not alter ABCB1 protein stability or location but do affect its transport activity. P1008 is part of a conserved signature D/E-P motif that seems to be specific for auxin-transporting ABCBs, which we now refer to as ATAs. Mutation of the acidic residue also abolishes auxin transport activity by ABCB1. All higher plant ABCBs for which auxin transport has been conclusively proven carry this conserved motif, underlining its predictive potential. Introduction of this D/E-P motif into malate importer, ABCB14, increases both its malate and its background auxin transport activity, suggesting that this motif has an impact on transport capacity. The D/E-P1008 motif is also important for ABCB1-TWD1 interactions and activation of ABCB1-mediated auxin transport by TWD1. In summary, our data imply a new function for TWD1 acting as a putative activator of ABCB-mediated auxin transport by cis-trans isomerization of peptidyl-prolyl bonds.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Nicotiana , Peptidilprolil Isomerase , Proteínas de Plantas , Proteínas de Ligação a Tacrolimo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Motivos de Aminoácidos , Peptidilprolil Isomerase/química , Peptidilprolil Isomerase/genética , Peptidilprolil Isomerase/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Ligação a Tacrolimo/química , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Nicotiana/química , Nicotiana/genética , Nicotiana/metabolismoRESUMO
PURPOSE: The aim of this study was screening for single nucleotide polymorphisms (SNPs) associated with white matter hyperintensities (WMHs) in symptomatic intracranial atherosclerotic stenosis (sICAS) patients and exploring a possible connection in the genetic background between macrovascular disease and small vessel disease. METHODS: There were 400 sICAS patients enrolled in the study. Fazekas scores were applied to WMH classification. Healthy controls were referred to 1,000 Genome Project and GeneSky company who provided 1,007 Chinese healthy controls. Fast target sequencing technology was used to select the SNPs of 102 genes related to the pathogenesis of sICAS in the sICAS patients. RESULTS: The allele frequencies of 88 SNPs were significantly different between the sICAS group and the healthy controls (p < 0.05). The allele frequencies of 53 SNPs were significantly different between the sICAS patients with and without WMHs (p < 0.05). Further analysis found that matrix metalloproteinase 9 (MMP9) rs17576 was simultaneously related to sICAS and WMHs. The frequency of the rs17576 A allele was significantly lower in sICAS patients when compared to the normal controls (p = 0.03, OR [95% CI] = 0.75 [0.625-0.91]). Also, the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.009), dominant (p = 0.014), and recessive (p= 0.023) models. The frequency of the rs17576 A allele was significantly higher in sICAS with WMH patients, compared to those without WMHs (p = 0.022, OR [95% CI] = 1.54 [1.06-2.22]); the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.019) and recessive (p = 0.032) models. Logistic regression analysis showed that age, hypertension, and MMP9 rs17576 AA genotype were independent risk factors for sICAS with WMHs. CONCLUSION: MMP9 rs17576 may be simultaneously associated with the risk of sICAS and WMHs.
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Arteriosclerose Intracraniana/genética , Ataque Isquêmico Transitório/genética , AVC Isquêmico/genética , Leucoencefalopatias/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/etnologia , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/etnologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/etnologia , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/etnologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
INTRODUCTION: Spinal subarachnoid haemorrhage is extremely rare in cases of subarachnoid haemorrhage and possesses servere characteristics. Additionally, spinal rheumatoid vasculitis is rare for spinal subarachnoid haemorrhage. The pathogenesis is unknown. CASE PRESENTATION: A 52-year-old woman with a 10-year history of seropositive rheumatoid arthritis was managed with leflunomide and celecoxib, and stable low disease activity was achieved. The patient had also been diagnosed with spinal subarachnoid haemorrhage secondary to isolated spinal rheumatoid vasculitis and obtained good therapeutic effects. CONCLUSION: This is the first case to describe spinal subarachnoid haemorrhage secondary to isolated spinal vasculitis in a patient with rheumatoid arthritis, which provides more proof of anomalous neovascularization in the central nervous system in rheumatoid arthritis.
Assuntos
Artrite Reumatoide , Vasculite Reumatoide , Hemorragia Subaracnóidea , Vasculite , Artrite Reumatoide/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Vasculite/complicaçõesRESUMO
BACKGROUND: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown. METHODS: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD). RESULTS: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees. CONCLUSIONS: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.
Assuntos
COVID-19 , Transtorno Depressivo/epidemiologia , Surtos de Doenças , Pessoal de Saúde/psicologia , Doenças Profissionais/epidemiologia , SARS-CoV-2 , Adulto , China/epidemiologia , Estudos Transversais , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/psicologia , Prevalência , Psicometria , Qualidade de Vida , Inquéritos e Questionários , Adulto JovemRESUMO
The van der Waals heterostructure (vdWH) has attracted widespread attention as a unique structure for future electronic and optoelectronic devices. In this paper, we constructed the ZnO-SeMoS and ZnO-SMoSe vdWHs and systematically investigated their electronic structures and band alignments considering vertical strain and external electric field effects. It is found that the ZnO-SeMoS and ZnO-SMoSe vdWHs both exhibit type-II band alignment with indirect band gaps of 1.31 and 0.63 eV respectively, depending on the interface characteristics. What's more, the band alignment of these two heterostructures can be tuned to type I or type III, and their band gap can be modified to direct feature by applying vertical strain and an electric field. The results reveal that ZnO/MoSSe vdWHs have promising potential in multi-functional nanodevices, and provide a way to modify the electronic properties of Janus-based heterojunctions using interface characteristics.