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1.
Artículo en Inglés | MEDLINE | ID: mdl-38557778

RESUMEN

Patients with hypertension (HTN) are at increased risk of developing cardiovascular disease, which can be reduced with blood pressure (BP) control. Anxiety can contribute to high BP and low heart rate variability (HRV). Although relationships between social support, self-rated health-status (SRHS), anxiety and measures of HRV and BP have been suggested, they have not been clearly established. This cross-sectional correlational study aimed to 1) examine relationships between social support, SRHS, and anxiety; and 2) examine if HRV mediated relationships between anxiety symptoms and BP. Patients with primary HTN were recruited from a cardiovascular outpatient clinic using convenience sampling (N = 300). Data included scale scores for SRHS, social support, and anxiety (Hospital Anxiety and Depression Scale). A handheld limb-lead electrocardiogram monitor measured HRV, using the ratio of low-frequency bands to high-frequency bands; an automatic sphygmomanometer measured systolic and diastolic blood pressure (SBP and DBP, respectively). Path analysis of structural equation models examined relationships between variables; the bootstrap method examined the mediating effects of HRV. Analysis showed scores for SRHS and social support had a direct effect on anxiety scores. Scores for anxiety directly affected HRV and BP. HRV also had a direct effect on BP. Bootstrapping indicated HRV mediated the relationship between anxiety symptoms and BP. The final model indicated SRHS, social support, and anxiety symptoms together explained 80% of SBP and 33% of DBP. These findings suggest HRV could be used to measure the effectiveness of strategies aimed at reducing anxiety and improving control of BP.

2.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1485-1493, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621932

RESUMEN

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.


Asunto(s)
Ligusticum , Reproducción , Polen , Flores , Polisacáridos
3.
Food Microbiol ; 121: 104499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38637070

RESUMEN

In this study, we investigated the impact of microbial interactions on Monascus pigment (MP) production. We established diverse microbial consortia involving Monascus purpureus and Lactobacillus fermentum. The addition of Lactobacillus fermentum (4% at 48 h) to the submerged fermentation of M. purpureus resulted in a significantly higher MP production compared to that achieved using the single-fermentation system. Co-cultivation with immobilized L. fermentum led to a remarkable increase of 59.18% in extracellular MP production, while mixed fermentation with free L. fermentum caused a significant decrease of 66.93% in intracellular MPs, contrasting with a marginal increase of 4.52% observed during co-cultivation with immobilized L. fermentum and the control group respectively. The findings indicate an evident enhancement in cell membrane permeability of M. purpureus when co-cultivated with immobilized L. fementum. Moreover, integrated transcriptomic and metabolomic analyses were conducted to elucidate the regulatory mechanisms underlying MP biosynthesis and secretion following inoculation with immobilized L. fementum, with specific emphasis on glycolysis, steroid biosynthesis, fatty acid biosynthesis, and energy metabolism.


Asunto(s)
Monascus , Fermentación , Monascus/genética , Monascus/metabolismo , Pigmentos Biológicos/metabolismo , Consorcios Microbianos , Glucólisis
4.
Int J Cancer ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613405

RESUMEN

Chimeric RNAs, which can arise from gene recombination at the DNA level or non-canonical splicing events at the RNA level, have been identified as important roles in human tumors. Dysregulated gene expression caused by somatic mutations and altered splicing patterns of oncogenes or tumor suppressor genes can contribute to the development of tumors. Therefore, investigating the formation mechanism of chimeric RNAs via somatic mutations is critical for understanding tumor pathogenesis. This project is the first to propose studying the association between somatic single nucleotide variants and chimeric RNAs, identifying around 2900 somatic SNVs affecting chimeric RNAs in pan-cancer level. The somatic SNVs on chimeric RNAs were commonly observed in various types of tumor tissues, providing a valuable resource for future study. Additionally, these SNVs show distinct tumor specificity, and those with high frequency had a significant impact on the survival time of patients with tumors. Further research revealed that somatic SNVs associated with chimeric RNA (chiR-SNVs) were typically found within 10 nt of the junction site of chimeric RNAs and had a particularly significant effect on chimeric RNAs from different chromosomes. The enrichment analysis revealed that chiR-SNVs were significantly overrepresented in oncogenes and genes related to RNA binding proteins involved in RNA splicing, which could imply that chiR-SNVs may disrupt the process of RNA splicing and induce the occurrence of chimeric RNAs. This study sheds light on the potential molecular interaction mechanism between somatic SNVs and chimeric RNAs, which opens up a new avenue for researching disease pathway and tumorigenesis development.

5.
Inflammation ; 47(2): 696-717, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38319541

RESUMEN

The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1ß and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate. LCZ696 also reduces caspase-11 and GSDMD activation, lactate dehydrogenase release, propidium iodide uptake, and the extracellular release of NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in ATP-activated macrophages, suggesting a potential mitigation of pyroptosis. Mechanistically, LCZ696 lowers mitochondrial reactive oxygen species and preserves mitochondrial integrity. Importantly, it does not significantly impact NLRP3, proIL-1ß, inducible nitric oxide synthase, cyclooxygenase-2 expression, or NF-κB activation in lipopolysaccharide-activated macrophages. LCZ696 partially inhibits the NLRP3 inflammasome through the induction of autophagy. In an in vivo context, LCZ696 alleviates NLRP3-associated colitis in a mouse model by reducing colonic expression of IL-1ß and tumor necrosis factor-α. Collectively, these findings suggest that LCZ696 holds significant promise as a therapeutic agent for ameliorating NLRP3 inflammasome activation in various inflammatory diseases, extending beyond its established use in hypertension and heart failure treatment.


Asunto(s)
Aminobutiratos , Compuestos de Bifenilo , Colitis , Sulfato de Dextran , Modelos Animales de Enfermedad , Inflamasomas , Macrófagos , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Valsartán , Animales , Ratones , Aminobutiratos/farmacología , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/farmacología , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Sulfato de Dextran/toxicidad , Combinación de Medicamentos , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Valsartán/farmacología , Masculino
6.
Zhongguo Zhong Yao Za Zhi ; 49(1): 162-174, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403349

RESUMEN

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Pirazinas , Accidente Cerebrovascular , Ratas , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-sis , Sirtuina 1/genética , Sirtuina 1/metabolismo , Angiogénesis , Antígeno Ki-67/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/genética , Transducción de Señal , Infarto de la Arteria Cerebral Media
7.
Genome Med ; 16(1): 30, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347596

RESUMEN

BACKGROUND: Biological processes are controlled by groups of genes acting in concert. Investigating gene-gene interactions within different cell types can help researchers understand the regulatory mechanisms behind human complex diseases, such as tumors. METHODS: We collected extensive single-cell RNA-seq data from tumors, involving 563 patients with 44 different tumor types. Through our analysis, we identified various cell types in tumors and created an atlas of different immune cell subsets across different tumor types. Using the SCINET method, we reconstructed interactome networks specific to different cell types. Diverse functional data was then integrated to gain biological insights into the networks, including somatic mutation patterns and gene functional annotation. Additionally, genes with prognostic relevance within the networks were also identified. We also examined cell-cell communications to investigate how gene interactions modulate cell-cell interactions. RESULTS: We developed a data portal called CellNetdb for researchers to study cell-type-specific interactome networks. Our findings indicate that these networks can be used to identify genes with topological specificity in different cell types. We also found that prognostic genes can deconvolved into cell types through analyzing network connectivity. Additionally, we identified commonalities and differences in cell-type-specific networks across different tumor types. Our results suggest that these networks can be used to prioritize risk genes. CONCLUSIONS: This study presented CellNetdb, a comprehensive repository featuring an atlas of cell-type-specific interactome networks across 44 human tumor types. The findings underscore the utility of these networks in delineating the intricacies of tumor microenvironments and advancing the understanding of molecular mechanisms underpinning human tumors.


Asunto(s)
Neoplasias , Humanos , Neoplasias/genética , Redes Reguladoras de Genes , Microambiente Tumoral/genética
8.
J Nurs Res ; 32(1): e311, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38190326

RESUMEN

BACKGROUND: Poor functional status relating to heart failure (HF) negatively affects health-related quality of life (HRQOL). Patients with HF, especially those with New York Heart Association (NYHA) Class III or IV HF, often exhibit poor HRQOL because of physical limitations and HF-related symptoms. Although sense of coherence (SOC) has been reported to be a determinant of HRQOL, its role as a mediator between functional status and HRQOL remains unclear, and few studies have explored the prevalence of HF in patients in NYHA Classes I and II. PURPOSE: This study was designed to investigate SOC as a mediator between different functional status classes and HRQOL in patients with HF. METHODS: A cross-sectional study was conducted on patients with HF recruited from a hospital in northern Taiwan from April 2020 to September 2020. The Minnesota Living with Heart Failure Questionnaire and a questionnaire on sociodemographic characteristics; functional classification in terms of NYHA Classes I, II, and III; and SOC were administered. The PROCESS v3.5 (by Andrew F. Hayes) macro was applied to analyze the effects, and Model 4 was used to examine the mediating role of SOC on the relationship between NYHA functional class and HRQOL. RESULTS: Of the 295 participants, SOC was found to mediate the effects of functional status on HRQOL more significantly in patients in Class II than those in Class III but not more significantly in patients in Class I than those in Class III. A weaker mediating effect of SOC was noted on the relationship between functional status and HRQOL in patients with HF in NYHA Class II than those in Class III. CONCLUSIONS: In patients with HF, poor functional status often reduces HRQOL significantly. SOC mediates the relationship between functional status and HRQOL more significantly in those in NYHA Class II than those in Class III. Nursing staff should work to increase patients' SOC by strengthening their coping capacity and improving their functional status to improve their HRQOL.


Asunto(s)
Insuficiencia Cardíaca , Sentido de Coherencia , Humanos , Calidad de Vida , Estudios Transversales , Estado Funcional , Insuficiencia Cardíaca/complicaciones
9.
J Bioenerg Biomembr ; 56(1): 55-71, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38041751

RESUMEN

Circular RNAs (circRNAs) showing unusual expressions have been discovered in pancreatic adenocarcinoma (PAAD). However, the functions and underlying mechanisms of these circRNAs still remain largely unclear. Our current study discovered a notable increase in the expression of circRNA hsa_circ_0002395 (circ_0002395) in both PAAD tissues and cell lines. This up-regulation of circ_0002395 was found to be associated with larger tumor sizes and lymph node metastasis. Furthermore, our findings showed that circ_0002395 facilitated aerobic glycolysis and cell proliferation in PAAD cells by regulating the miR-548c-3p/PDK1 axis. Mechanistically, we identified circ_0002395 as a competing endogenous RNA (ceRNA) that sponged miR-548c-3p, thereby promoting PDK1 expression and aerobic glycolysis, and ultimately resulting in the enhancement of cell proliferation. Our findings found that circ_0002395 promoted proliferation of PAAD cells by enhancing PDK1 expression and aerobic glycolysis by sponging miR-548c-3p.


Asunto(s)
Adenocarcinoma , MicroARNs , Neoplasias Pancreáticas , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , Línea Celular Tumoral , Proliferación Celular , Glucólisis
10.
Drug Dev Res ; 85(1): e22128, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37984820

RESUMEN

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 µM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 µM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.


Asunto(s)
Inhibidores de Glicósido Hidrolasas , Tiazoles , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Tiazoles/farmacología , Tiazoles/química , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo , Estructura Molecular
11.
Eur J Pharm Sci ; 191: 106598, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37783378

RESUMEN

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.


Asunto(s)
COVID-19 , Inhibidores de Proteasas , Adulto , Humanos , Antivirales/efectos adversos , Inhibidores Enzimáticos , Voluntarios Sanos , Inhibidores de Proteasas/efectos adversos , Ritonavir/uso terapéutico , SARS-CoV-2
12.
J Med Chem ; 66(21): 14735-14754, 2023 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-37874867

RESUMEN

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.


Asunto(s)
Pseudomonas aeruginosa , Percepción de Quorum , Cumarinas/farmacología , Antibacterianos/farmacología , Biopelículas , Hierro/farmacología , Homeostasis , Factores de Virulencia , Proteínas Bacterianas
13.
Health Res Policy Syst ; 21(1): 95, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700266

RESUMEN

BACKGROUND: The dental workforce plays a crucial role in delivering quality oral healthcare services, requiring continuous training and education to meet evolving professional demands. Understanding the impact of dental workforce training and education programmes on policy evolution is essential for refining existing policies, implementing evidence-based reforms and ensuring the growth of the dental profession. Therefore, this study protocol aims to assess the influence of dental workforce training and education programmes on policy evolution in Malaysia. METHODS: A mixed-method research design will be employed, combining quantitative surveys and qualitative interviews. Stakeholder theory and policy change models will form the theoretical framework of the study. Participants from various stakeholder groups will be recruited using purposive sampling. Data collection will involve surveys and one-on-one semi-structured interviews. Descriptive statistics, inferential analysis and thematic analysis will be used to analyse the data. Integration of quantitative and qualitative data will be used to provide a comprehensive understanding of the data. DISCUSSION: This study will shed light on factors influencing policy decisions related to dental education and workforce development in Malaysia. The findings will inform evidence-based decision-making, guide the enhancement of dental education programmes and improve the quality of oral healthcare services. Challenges related to participant recruitment and data collection should be considered, and the study's unique contribution to the existing body of knowledge in the Malaysian context will be discussed.


Asunto(s)
Exactitud de los Datos , Proyectos de Investigación , Humanos , Recolección de Datos , Políticas , Recursos Humanos
14.
Mol Med ; 29(1): 113, 2023 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-37605109

RESUMEN

OBJECTIVE: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease. METHODS AND RESULTS: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE-/- mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE. CONCLUSION: AGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.


Asunto(s)
Aterosclerosis , FN-kappa B , Animales , Ratones , Receptor para Productos Finales de Glicación Avanzada/genética , Caveolina 1/genética , Células Endoteliales , Transcitosis , Productos Finales de Glicación Avanzada
15.
Angew Chem Int Ed Engl ; 62(38): e202309613, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37555781

RESUMEN

In situ polymerization of liquid electrolytes is currently the most feasible way for constructing solid-state batteries, which, however, is affected by various interfering factors of reactions and so the electrochemical performance of cells. To disclose the effects from polymerization conditions, two types of generally used in situ polymerizing reactions of ring-opening polymerization (ROP) and double bond radical polymerization (DBRP) were investigated on the aspects of monomer conversion and electrochemical properties (Li+ -conductivity and interfacial stability). The ROP generated poly-ester and poly-carbonate show a high monomer conversion of ≈90 %, but suffer a poor Li+ -conductivity of lower than 2×10-5  S cm-1 at room temperature (RT). Additionally, the terminal alkoxy anion derived from the ROP is not resistant to high-voltage cathodes. While, the DBRP produced poly-VEC(vinyl ethylene carbonate) and poly-VC(vinylene carbonate) show lower monomer conversions of 50-80 %, delivering relatively higher Li+ -conductivities of 2×10-4  S cm-1 at RT. Compared two polymerizing reactions and four monomers, the VEC-based F-containing copolymer possesses advantages in Li+ -conductivity and antioxidant capacity, which also shows simultaneous stability towards Li-metal with the help of LiF-based passivating layer, allowing a long-term stable cycling of high-voltage quasi solid-state cells.

16.
ACS Appl Mater Interfaces ; 15(36): 42603-42610, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37639524

RESUMEN

Organic materials have garnered intensive focus as a new group of electrodes for lithium-ion batteries (LIBs). However, many reported organic electrodes so far still exhibit unsatisfying cycling stability because of the dissolution in the electrolytes. Herein, a novel azo-linked hexaazatrianphthalene (HATN)-based polymer (AZO-HATN-AQ) is designed and fabricated by the polymerization of trinitrodiquinoxalino[2,3-a:2',3'-c]phenazine (HATNTN) and 2,6-diaminoanthraquinone (DAAQ). The abundant redox-active sites, extended π-conjugated planar conformation, and low energy gap endow the AZO-HATN-AQ electrode with high theoretical capacity, excellent solubility resistance, and fast Li-ion transport. In particular, the fully lithiated AZO-HATN-AQ still keeps the planar structure, contributing to the excellent cycling stability. As a result, AZO-HATN-AQ cathodes show high specific capacity (240 mAh g-1 at 0.05 A g-1), prominent rate capability (98 mAh g-1 at 8 A g-1), and outstanding cycling stability (120 mAh g-1 after 2000 cycles at 4 A g-1 with 85.7% capacity retention) simultaneously. This study demonstrates that rational structure design of the polymer electrodes is an effective approach to achieving excellent comprehensive electrochemical performance.

17.
Front Immunol ; 14: 1152295, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37483634

RESUMEN

Background: Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection). Methods: A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant. Results: Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1ß, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1ß, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05). Conclusion: This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs.


Asunto(s)
Antiinflamatorios , Citocinas , Receptores de Trasplantes , Vitamina D , Vitamina D/farmacología , Vitamina D/uso terapéutico , Humanos , Estudios Retrospectivos , Trasplante de Riñón/efectos adversos , Citocinas/efectos de los fármacos , Estudios de Casos y Controles , Masculino , Femenino , Adulto , Persona de Mediana Edad , Suplementos Dietéticos
18.
Nanomaterials (Basel) ; 13(7)2023 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-37049264

RESUMEN

Indium oxide (In2O3) is a widely used n-type semiconductor for detection of pollutant gases; however, its gas selectivity and sensitivity have been suboptimal in previous studies. In this work, zinc-doped indium oxide nanowires with appropriate morphologies and high crystallinity were synthesized using chemical vapor deposition (CVD). An accurate method for electrical measurement was attained using a single nanowire microdevice, showing that electrical resistivity increased after doping with zinc. This is attributed to the lower valence of the dopant, which acts as an acceptor, leading to the decrease in electrical conductivity. X-ray photoelectron spectroscopy (XPS) analysis confirms the increased oxygen vacancies due to doping a suitable number of atoms, which altered oxygen adsorption on the nanowires and contributed to improved gas sensing performance. The sensing performance was evaluated using reducing gases, including carbon monoxide, acetone, and ethanol. Overall, the response of the doped nanowires was found to be higher than that of undoped nanowires at a low concentration (5 ppm) and low operating temperatures. At 300 °C, the gas sensing response of zinc-doped In2O3 nanowires was 13 times higher than that of undoped In2O3 nanowires. The study concludes that higher zinc doping concentration in In2O3 nanowires improves gas sensing properties by increasing oxygen vacancies after doping and enhancing gas molecule adsorption. With better response to reducing gases, zinc-doped In2O3 nanowires will be applicable in environmental detection and life science.

19.
Nanomaterials (Basel) ; 13(7)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37049291

RESUMEN

We report an efficient method to synthesize undoped and K-doped rare cubic tungsten trioxide nanowires through the thermal evaporation of WO3 powder without a catalyst. The WO3 nanowires are reproducible and stable with a low-cost growth process. The thermal evaporation processing was conducted in a three-zone horizontal tube furnace over a temperature range of 550-850 °C, where multiple substrates were placed at different temperature zones. The processing parameters, including pressure, temperature, type of gas, and flow rate, were varied and studied in terms of their influence on the morphology, aspect ratio and density of the nanowires. The morphologies of the products were observed with scanning electron microscopy. High resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction studies were conducted to further identify the chemical composition, crystal structure and growth direction of the nanostructures. Additionally, the growth mechanism has been proposed. Furthermore, we investigated the potassium doping effect on the physical properties of the nanostructures. Photoluminescence measurements show that there were shorter emission bands at 360 nm and 410 nm. Field emission measurements show that the doping effect significantly reduced the turn-on electric field and increased the enhancement factor. Furthermore, as compared with related previous research, the K-doped WO3 nanowires synthesized in this study exhibited excellent field emission properties, including a superior field enhancement factor and turn-on electric field. The study reveals the potential of WO3 nanowires in promising applications for sensors, field emitters and light-emitting diodes.

20.
Front Endocrinol (Lausanne) ; 14: 1111152, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36875452

RESUMEN

Background: Remnant cholesterol (RC) has been correlated with a higher risk of atherosclerosis. It has been confirmed that in the general population, an elevated RC level is related to a 5-fold higher risk of peripheral arterial disease (PAD). Diabetes is one of the strongest risk factors for PAD development. However, the association between RC and PAD in the specific population of type 2 diabetes mellitus (T2DM) has not been investigated. Herein, the correlation was investigated between RC and PAD in T2DM patients. Methods: In the retrospective study, the hematological parameter data of 246 T2DM patients without PAD (T2DM - WPAD) and 270 T2DM patients with PAD (T2DM - PAD) was collected. Differences in RC levels between the two groups were compared, and the association between RC and PAD severity was examined. Multifactorial regression was used to determine whether RC was a significant contributor to the development of T2DM - PAD. The diagnostic potential of RC was tested using receiver operating characteristic (ROC) curve. Results: The RC levels in T2DM - PAD individuals were considerably greater than in T2DM - WPAD individuals (P < 0.001). RC had a positive correlation with disease severity. Further, multifactorial logistic regression analyses found that elevated RC levels were a major contributor to T2DM - PAD (P < 0.001). The area under the curve (AUC) of the RC for T2DM - PAD patients was 0.727. The cut-off value of RC was 0.64 mmol/L. Conclusion: The RC levels were higher in T2DM - PAD patients, and were independently linked with its severity. Diabetic patients with RC levels > 0.64 mmol/L had an elevated risk of developing PAD.


Asunto(s)
Aterosclerosis , Diabetes Mellitus Tipo 2 , Hipercolesterolemia , Enfermedad Arterial Periférica , Humanos , Estudios Retrospectivos , Colesterol
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