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1.
Tissue Eng Regen Med ; 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39400879

RESUMO

OBJECTIVE: Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing. APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. RESULTS: PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate > 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells. INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. CONCLUSION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

2.
J Am Heart Assoc ; 13(19): e032269, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39291497

RESUMO

BACKGROUND: Hypertension is a significant risk factor for cardiovascular and chronic kidney diseases. Its management in young people remains limited. Device-based therapies, such as low-level tragus stimulation (LL-TS), a noninvasive method that reduces sympathetic activity, have recently been explored for resistant hypertension. METHODS AND RESULTS: This trial involved patients with Grade 1 hypertension with no other medical history. LL-TS (20 Hz, 1 mA, 1 h/day) was applied for 3 months on the tragus (Intervention group [IG]) or earlobe (Control group [CG]). Blood pressure and outcomes were assessed at the first, second, and third months. Among 40 patients, 21 were in IG and 19 in CG. Baseline systolic blood pressure was similar between IG (142.62±8.18 mm Hg) and CG (143.00±8.61 mm Hg), P=0.89. Post-LL-TS, systolic blood pressure showed significant reductions in IG compared with CG at the first (IG: 134.47±5.95 mm Hg, CG: 141.28±6.78 mm Hg, P=0.002), second (IG: 132.50±7.51 mm Hg, CG: 140.62±7.15 mm Hg, P=0.001), and third months (IG: 128.81±7.13 mm Hg, CG: 136.51±7.96 mm Hg, P=0.003). diastolic blood pressure also differed significantly: first month (IG: 85.34±5.81 mm Hg, CG: 89.74±6.32 mm Hg, P=0.03), second month (IG: 82.12±5.22 mm Hg, CG: 88.57±7.11 mm Hg, P=0.002), and third month (IG: 80.71±5.96 mm Hg, CG: 87.55±5.26 mm Hg, P=0.001). Heart rate was unchanged (P>0.05). Only 0.01% of IG subjects reported site irritation, with no serious adverse events. CONCLUSIONS: LL-TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and efficacy of LL-TS. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2000038448.


Assuntos
Pressão Sanguínea , Hipertensão , Humanos , Masculino , Feminino , Hipertensão/fisiopatologia , Hipertensão/terapia , Hipertensão/diagnóstico , Pressão Sanguínea/fisiologia , Método Simples-Cego , Adulto , Resultado do Tratamento , Terapia por Estimulação Elétrica/métodos , Pessoa de Meia-Idade , Adulto Jovem , Fatores de Tempo
3.
Int Immunopharmacol ; 142(Pt B): 113136, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39293316

RESUMO

Hyper-activations of monocytes/macrophages and dendritic cells (DCs) contribute to the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE). Fatty acid synthase (FASN) is essential for the de novo synthesis of long-chain fatty acids, which play a key role in controlling the activation, differentiation, and function of immune cells. However, the role of FASN in regulating the activations of monocytes/macrophages and DCs has not been studied. In this study, we investigated the involvement of the FASN in modulating the activations of macrophages and DCs, as well as the pathogenesis of SLE. Importantly, we observed a significant upregulation of FASN expression in monocytes and DCs from patients with SLE. This increase is strongly correlated with disease severity and activation status of the immune cells. Furthermore, overexpression of FASN significantly boosts the TLR4/7/9-mediated activation of macrophages and DCs, while knockdown of FASN markedly inhibits this activation. Notably, knockdown of FASN alleviates TLR7 agonist imiquimod (IMQ)-induced lupus in mice and the activation of macrophages and DCs. It makes more sense that pharmaceutical targeting of FASN by using TVB-2640 significantly alleviates IMQ-induced lupus in mice and the activation of macrophages and DCs, as well as in spontaneous lupus MRL/lpr mice. Thus, FASN contributes to the TLRs-mediated activation of macrophages and DCs, as well as the pathogenesis of SLE. More importantly, FASN inhibitor TVB-2640 is expected to be an effective drug in the treatment of SLE.


Assuntos
Células Dendríticas , Ácido Graxo Sintase Tipo I , Lúpus Eritematoso Sistêmico , Macrófagos , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Feminino , Camundongos , Ácido Graxo Sintase Tipo I/metabolismo , Ácido Graxo Sintase Tipo I/genética , Imiquimode , Adulto , Masculino , Receptores Toll-Like/metabolismo , Células Cultivadas , Ativação de Macrófagos , Modelos Animais de Doenças
4.
Int J Mol Sci ; 25(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39126116

RESUMO

Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.


Assuntos
Hiperuricemia , Ácido Oxônico , Plantago , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Animais , Ratos , Ácido Oxônico/efeitos adversos , Masculino , Plantago/química , Ácido Úrico/sangue , Extratos Vegetais/farmacologia , Rim/metabolismo , Rim/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Xantina Oxidase/metabolismo
5.
JCI Insight ; 9(18)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115936

RESUMO

The interleukin 17 (IL-17) family of cytokines has emerged as a critical player in autoimmune disease, including systemic lupus erythematosus (SLE). However, the role of IL-17B, a poorly understood cytokine, in the pathogenesis of SLE is still not known. In this study, we investigated the role of IL-17B in the activation and differentiation of B cells, and the pathogenesis of SLE. Intriguingly, IL-17B deficiency aggravated disease in lupus-prone mice and promoted the activation of B cells and the differentiation of germinal center B cells and plasma cells, while recombinant mouse IL-17B (rmIL-17B) significantly alleviated disease in lupus-prone mice. Mechanistically, rmIL-17B inhibited the activation of the Toll-like receptor and interferon pathways in B cells by downregulating fatty acid synthase-mediated (FASN-mediated) lipid metabolism. Loss of FASN significantly alleviated the disease in lupus-prone mice and inhibited the activation and differentiation of B cells. In addition, B cells had greater FASN expression and lower IL-17RB levels in patients with SLE than in healthy controls. Our study describes the role of IL-17B in regulating B cell activation and differentiation, and alleviating the onset of SLE. These findings will lay a theoretical foundation for further understanding of the pathogenesis of SLE.


Assuntos
Linfócitos B , Diferenciação Celular , Interleucina-17 , Lúpus Eritematoso Sistêmico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Animais , Camundongos , Interleucina-17/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Humanos , Feminino , Ácido Graxo Sintase Tipo I/metabolismo , Ácido Graxo Sintase Tipo I/genética , Modelos Animais de Doenças , Masculino , Ativação Linfocitária/imunologia , Camundongos Knockout , Metabolismo dos Lipídeos
6.
Lipids Health Dis ; 23(1): 226, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049120

RESUMO

BACKGROUND: The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap. METHODS: A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL. RESULTS: This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)). CONCLUSIONS: This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.


Assuntos
Exercício Físico , Metabolismo dos Lipídeos , Intervenção Coronária Percutânea , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos , Humanos , Exercício Físico/fisiologia , Triglicerídeos/sangue , Medicina Esportiva , HDL-Colesterol/sangue , Colesterol/sangue , Masculino , LDL-Colesterol/sangue , Terapia por Exercício
7.
Heliyon ; 10(13): e33688, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39044991

RESUMO

Primary aldosteronism (PA), often due to aldosteronoma, commonly causes secondary hypertension and typically requires surgery. We present a case of an elderly man with longstanding hypertension, complicated by cerebral hemorrhage and myocardial infarction. Enhanced CT imaging identified a right-sided aldosteronoma and left adrenal gland fullness. Combined with upright supine aldosterone ratio, captopril challenge test, bilateral adrenal venous sampling, and CYP11B1/CYP11B2 fusion gene testing, the diagnosis of PA was confirmed. Despite the absence of surgical intervention in this patient, pharmacotherapy effectively managed hypertension and enhanced cardiac function, thereby underscoring the advantageous utilization of aldosterone antagonists in non-surgical candidates diagnosed with PA.

8.
Ecotoxicol Environ Saf ; 280: 116579, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38865940

RESUMO

Environmental exposure to the cadmium (Cd) has been shown to be a risk factor for colorectal cancer (CRC) progression, but the exact mechanism has not been fully elucidated. In this study, we found that chronic Cd (3 µM) exposure promoted the proliferation, adhesion, migration, and invasion of CRC cells in vitro, as well as lung metastasis in vivo. RNA-seq and TCGA-COAD datasets revealed that decreased hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB) expression may be a crucial factor in Cd-induced CRC progression. Further analysis using qRT-PCR and tissue microarrays from CRC patients showed that HADHB expression was significantly reduced in CRC tissues compared to adjacent normal tissues, and low HADHB expression was associated with adverse clinical features and poor overall survival, either directly or through TNM stage. Furthermore, HADHB was found to play an important role in the Cd-induced malignant metastatic phenotype of CRC cells and lung metastasis in mice. Mechanistically, we discovered that chronic Cd exposure resulted in hypermethylation of the HADHB promoter region via inhibition of DNA demethylase tet methylcytosine dioxygenase 2 (TET2), which then led to decreased HADHB expression and activation of the FAK signaling pathway, and ultimately contributed to CRC progression. In conclusion, this study provided a new potential insight and evaluable biomarker for Cd exposure-induced CRC progression and treatment.


Assuntos
Cádmio , Neoplasias Colorretais , Proteínas de Ligação a DNA , Dioxigenases , Progressão da Doença , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/induzido quimicamente , Humanos , Dioxigenases/genética , Animais , Camundongos , Cádmio/toxicidade , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Linhagem Celular Tumoral , Masculino , Proliferação de Células/efeitos dos fármacos , Feminino , Camundongos Nus , Metilação de DNA/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos
9.
Infect Drug Resist ; 17: 2089-2098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828375

RESUMO

Background: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 ß, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group. Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.

11.
Adv Mater ; 36(27): e2401772, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634168

RESUMO

High-performance covalent organic framework (COF) fibers are demanded for an efficient capturing of blue osmotic power because of their excellent durability, simple integration, and large scalability. However, the scalable production of COF fibers is still very challenging due to the poor solubility and fragile structure of COFs. Herein, for the first time, it is reported that COF dispersions can be continuously processed into macroscopic, meter-long, and pure COF fibers using a wet spinning approach. The two presented COF fibers can be directly used for capturing of osmotic energy, avoiding the production of composite materials that require other additives and face challenges such as phase separation and environmental issues induced by the additives. A COF fiber exhibits power densities of 70.2 and 185.3 W m-2 at 50-fold and 500-fold salt gradients, respectively. These values outperform those of most reported systems, which indicate the high potential of COF fibers for capturing of blue osmotic energy.

12.
Sci Total Environ ; 927: 172219, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38580120

RESUMO

Nature-based solutions (NBS) have great potential for achieving urban sustainability. While several reviews have comprehensively examined NBS, few have focused on its role in addressing urban sustainability challenges. Here we present a systematic review of 142 case studies selected from English papers published in SCI journals (i.e., indexed by Web of Science) during 2016-2022, whose titles, abstracts or keywords contain both urban-related terms and NBS-related terms. Using multiple methods, including statistical analysis, deductive content analysis, and inductive content analysis, we found that: (1) NBS have primarily been utilized to address urban flooding (43 %) and heat stress (21 %), with green roofs (24 %) and urban forests (16 %) being the most extensively studied NBS for tackling these challenges. (2) The ecosystem services (ES) capacity of NBS has been heavily researched (57 %), while studies addressing ES flows (7 %) and ES demand (18 %) are limited. (3) Most studies involved at least one NBS implementation process (83 %), but primarily focused on selecting and assessing NBS and related actions (66 %), with fewer studies on designing and implementing NBS and transferring & upscale NBS. We suggest that future research should contribute to the establishment of a checklist to assist in identifying which NBS types are effective in addressing specific urban sustainability challenges in varying contexts. Integrating the science and practice of NBS for urban sustainability is also crucial for advancing this field.

13.
BMC Med Educ ; 24(1): 388, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594653

RESUMO

BACKGROUND: Flexible hybrid teaching has become the new normal of basic medical education in the postepidemic era. Identifying ways to improve the quality of curriculum teaching and achieve high-level talent training is a complex problem that urgently needs to be solved. Over the course of the past several semesters, the research team has integrated design thinking (DT) into undergraduate teaching to identify, redesign and solve complex problems in achieving curriculum teaching and professional talent training objectives. METHODS: This study is an observational research. A total of 156 undergraduate stomatology students from Jining Medical University in 2021 were selected to participate in two rounds of online flipped teaching using the design thinking EDIPT (empathy, definition, idea, prototype, and test) method. This approach was applied specifically to the chapters on the respiratory system and female reproductive system. Data collection included student questionnaires, teacher-student interviews, and exam scores. GraphPad Prism software was used for data analysis, and the statistical method was conducted by multiple or unpaired t test. RESULTS: According to the questionnaire results, the flipped classroom teaching design developed using design thinking methods received strong support from the majority of students, with nearly 80% of students providing feedback that they developed multiple abilities during the study process. The interview results indicated that teachers generally believed that using design thinking methods to understand students' real needs, define teaching problems, and devise instructional design solutions, along with testing and promptly adjusting the effectiveness through teaching practices, played a highly positive role in improving teaching and student learning outcomes. A comparison of exam scores showed a significant improvement in the exam scores of the class of 2021 stomatology students in the flipped teaching chapters compared to the class of 2020 stomatology students, and this difference was statistically significant. However, due to the limitation of the experimental chapter scope, there was no significant difference in the overall course grades. CONCLUSION: The study explores the application of design thinking in histology and embryology teaching, revealing its positive impact on innovative teaching strategies and students' learning experience in medical education. Online flipped teaching, developed through design thinking, proves to be an effective and flexible method that enhances student engagement and fosters autonomous learning abilities.


Assuntos
Currículo , Aprendizagem Baseada em Problemas , Humanos , Feminino , Aprendizagem Baseada em Problemas/métodos , Aprendizagem , Estudantes , Inquéritos e Questionários , Ensino
14.
Acta Pharmacol Sin ; 45(7): 1477-1491, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538716

RESUMO

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Diabetes Mellitus Experimental , Transdução de Sinais , Cicatrização , Quinases Associadas a rho , Animais , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Cicatrização/efeitos dos fármacos , Humanos , Diabetes Mellitus Experimental/metabolismo , Masculino , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Feminino
15.
Nat Commun ; 15(1): 2729, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548716

RESUMO

The United Nations' Sustainable Development Goal (SDG) 3.9 calls for a substantial reduction in deaths attributable to PM2.5 pollution (DAPP). However, DAPP projections vary greatly and the likelihood of meeting SDG3.9 depends on complex interactions among environmental, socio-economic, and healthcare parameters. We project potential future trends in global DAPP considering the joint effects of each driver (PM2.5 concentration, death rate of diseases, population size, and age structure) and assess the likelihood of achieving SDG3.9 under the Shared Socioeconomic Pathways (SSPs) as quantified by the Scenario Model Intercomparison Project (ScenarioMIP) framework with simulated PM2.5 concentrations from 11 models. We find that a substantial reduction in DAPP would not be achieved under all but the most optimistic scenario settings. Even the development aligned with the Sustainability scenario (SSP1-2.6), in which DAPP was reduced by 19%, still falls just short of achieving a substantial (≥20%) reduction by 2030. Meeting SDG3.9 calls for additional efforts in air pollution control and healthcare to more aggressively reduce DAPP.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluição Ambiental , Conservação dos Recursos Naturais , Material Particulado/efeitos adversos , Atenção à Saúde , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise
16.
J Hazard Mater ; 467: 133692, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38341886

RESUMO

Cigarette smoking substantially promotes tumorigenesis and progression of colorectal cancer; however, the underlying molecular mechanism remains unclear. Among 662 colorectal cancer patients, our investigation revealed a significant correlation between cigarette smoking and factors, such as large tumor size, poor differentiation, and high degree of invasion. Among the nicotine-derived nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) emerged as the most critical carcinogen, which significantly promoted the malignant progression of colorectal cancer both in vivo and in vitro. The results of methylated RNA immunoprecipitation and transcriptome sequencing indicated that NNK upregulated transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) via N6-adenosine methylation, which was regulated by methyltransferase-like 14 (METTL14) and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Elevated TMUB1 levels were associated with a higher risk of cancer invasion and metastasis, leading to a high mortality risk in patients with colorectal cancer. Additionally, TMUB1 promoted lysine63-linked ubiquitination of AKT by interacting with AMFR, which led to the induction of malignant proliferation and metastasis in colorectal cancer cells exposed to NNK. In summary, this study provides a new insight, indicating that targeting TMUB1 expression via METTL14/YTHDF2 mediated N6-adenosine methylation may be a potential therapeutic and prognostic target for patients with colorectal cancer who smoke.


Assuntos
Adenina/análogos & derivados , Neoplasias Colorretais , Nicotina , Humanos , Proteínas Proto-Oncogênicas c-akt , Adenosina , Proteínas de Ligação a RNA , Metiltransferases/genética
17.
ACS Nano ; 18(8): 6570-6578, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38349220

RESUMO

Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target-probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target-probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.


Assuntos
Técnicas Biossensoriais , Masculino , Humanos , Transporte de Íons , Eletricidade
18.
Anal Chem ; 96(6): 2445-2454, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38293730

RESUMO

Artificial solid-state nanochannels featuring precise partitions present a highly promising platform for biomarker detection. While the significance of probes on the outer surface (POS) has been relatively overlooked in the past, our research highlights their crucial role in biosensing. Furthermore, the contribution of POS on the bullet-shaped asymmetric nanochannels has not been extensively explored until now. Here, we fabricated a series of bullet-shaped nanochannels, each featuring a distinct asymmetric structure characterized by different tip- and base-pore diameters. These nanochannels were further modified with explicit distributions at the inner wall (PIW), the outer surface (POS), and their combination (POS + PIW) for lysozyme sensing. The impact of diameters, structural asymmetry, and surface charge density on the sensing efficacy of POS and PIW was thoroughly examined through experimental investigations and numerical simulations. POS demonstrates great individual sensing performance for lysozyme within a broad concentration range, spanning from 10 nM to 1 mM. Furthermore, it improves the sensitivity when combined with PIW, particularly within the nanochannels featuring the smaller base-pore diameter, resulting in a 2-fold increase in sensing performance for POS + PIW compared to PIW at a concentration of 10 nM. These findings are substantiated by numerical simulations that closely align with the experimental parameters. The contributions of POS are notably amplified in the presence of smaller base pores and a higher degree of asymmetry within the bullet-shaped nanochannels. These findings elucidate the mechanism underlying the role of POS within bullet-shaped asymmetric nanochannels and open up new avenues for manipulating and enhancing the sensing efficiency.


Assuntos
Nanoestruturas , Nanoestruturas/química , Muramidase , Proteínas
19.
Medicine (Baltimore) ; 102(50): e36511, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115268

RESUMO

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.


Assuntos
Reabilitação Cardíaca , Doença das Coronárias , Humanos , Terapia por Exercício , Exercício Físico , Bibliometria
20.
Biochem Biophys Res Commun ; 682: 335-342, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37837754

RESUMO

Seed dormancy and germination determine the beginning of the life cycle of plants, and the phytohormone ABA plays a crucial role in regulation of seed dormancy and germination. However, the upstream regulatory mechanism of ABA metabolism during dormancy releasing is still remain elusive. In this paper, we present a novel mechanism of OsNAC2 in controlling ABA metabolism and regulation of seed dormancy. OsNAC2 highly expressed during seed development and germination, and overexpression of OsNAC2 strengthened seed dormancy and suppressed germination. Moreover, exogenous phytohormone treatment showed that OsNAC2 acted upstream of GA signaling and downstream of ABA signaling. Additionally, overexpression of OsNAC2 inhibited ABA degradation and increased ABA content during early germination. Further molecular analysis revealed that OsNAC2 directly bound to the ABA metabolism genes promoter and inhibits their transcription in rice protoplasts. These finding could help us explain the genetic regulation mechanism of ABA metabolism during dormancy release and germination in rice.


Assuntos
Oryza , Dormência de Plantas , Dormência de Plantas/genética , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Germinação/genética , Sementes/metabolismo , Regulação da Expressão Gênica de Plantas
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