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Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.
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Cardiomiopatías , MicroARNs , ARN Largo no Codificante , Animales , Ratas , Apoptosis , Cardiomiopatías/metabolismo , Depresión , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/genética , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Miocitos Cardíacos/metabolismo , Piroptosis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Waste polystyrene contributes considerably to environmental pollution due to its persistent nature, prompting a widespread consensus on the urgent need for viable recycling solutions. Owing to the aromatic groups structure of polystyrene, hyper-cross-linked polymers can be synthesized through the Friedel-Crafts cross-linking reaction using Lewis acids as catalysts. In addition, hyper-cross-linked polystyrene and its carbonaceous counterparts can be used in several important applications, which helps in their efficient recycling. This review systematically explores methods for preparing multifunctional hyper-cross-linked polymers from waste polystyrene and their applications in sustainable recycling. We have comprehensively outlined various synthetic approaches for these polymers and investigated their physical and chemical properties. These multifunctional polymers not only exhibit structural flexibility but also demonstrate diversity in performance, making them suitable for various applications. Through a systematic examination of synthetic methods, we showcase the cutting-edge positions of these materials in the field of hyper-cross-linked polymers. Additionally, we provide in-depth insights into the potential applications of these hyper-cross-linked polymers in intentional recycling, highlighting their important contributions to environmental protection and sustainable development. This research provides valuable references to the fields of sustainable materials science and waste management, encouraging further exploration of innovative approaches for the utilization of discarded polystyrene.
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Microbial contamination has profoundly impacted human health, and the effective eradication of widespread microbial issues is essential for addressing serious hygiene concerns. Taking polystyrene (PS) membrane as an example, we herein developed report a robust strategy for the in situ preparation of chlorine-regenerable antimicrobial polymer molecular sieve membranes through combining post-crosslinking and nucleophilic substitution reaction. The cross-linking PS membranes underwent a reaction with 5,5-dimethylhydantoin (DMH), leading to the formation of polymeric N-halamine precursors (PS-DMH). These hydantoinyl groups within PS-DMH were then efficiently converted into biocidal N-halamine structures (PS-DMH-Cl) via a simple chlorination process. ATR-FTIR and XPS spectra were recorded to confirm the chemical composition of the as-prepared PS-DMH-Cl membranes. SEM analyses revealed that the chlorinated PS-DMH-Cl membranes displayed a rough surface with a multitude of humps. The effect of chlorination temperature and time on the oxidative chlorine content in the PS-DMH-Cl membranes was systematically studied. The antimicrobial assays demonstrated that the PS-DMH-Cl membranes could achieve a 6-log inactivation of E. coli and S. aureus within just 4 min of contact time. Additionally, the resulting PS-DMH-Cl membranes exhibited excellent stability and regenerability of the oxidative chlorine content.
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Cloro , Escherichia coli , Membranas Artificiales , Staphylococcus aureus , Cloro/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Halogenación , Polímeros/química , Poliestirenos/química , Hidantoínas/química , Hidantoínas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , AminasRESUMEN
BACKGROUND: Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arterial diseases, especially in arterial restenosis after angioplasty or stent placement. VSMCs reprogram their metabolism to meet the increased requirements of lipids, proteins, and nucleotides for their proliferation. De novo purine synthesis is one of critical pathways for nucleotide synthesis. However, its role in proliferation of VSMCs in these arterial diseases has not been defined. METHODS: De novo purine synthesis in proliferative VSMCs was evaluated by liquid chromatography-tandem mass spectrometry. The expression of ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase), the critical bifunctional enzyme in the last 2 steps of the de novo purine synthesis pathway, was assessed in VSMCs of proliferative arterial neointima. Global and VSMC-specific knockout of Atic mice were generated and used for examining the role of ATIC-associated purine metabolism in the formation of arterial neointima and atherosclerotic lesions. RESULTS: In this study, we found that de novo purine synthesis was increased in proliferative VSMCs. Upregulated purine synthesis genes, including ATIC, were observed in the neointima of the injured vessels and atherosclerotic lesions both in mice and humans. Global or specific knockout of Atic in VSMCs inhibited cell proliferation, attenuating the arterial neointima in models of mouse atherosclerosis and arterial restenosis. CONCLUSIONS: These results reveal that de novo purine synthesis plays an important role in VSMC proliferation in arterial disease. These findings suggest that targeting ATIC is a promising therapeutic approach to combat arterial diseases.
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Aterosclerosis , Transferasas de Hidroximetilo y Formilo , Humanos , Ratones , Animales , Neointima , Purinas , Proliferación Celular , Miocitos del Músculo Liso , Aterosclerosis/genéticaRESUMEN
BACKGROUND: Coronary allograft vasculopathy (CAV) is a devastating sequela of heart transplant in which arterial intimal thickening limits coronary blood flow. There are currently no targeted therapies to prevent or reduce this pathology that leads to transplant failure. Vascular smooth muscle cell (VSMC) phenotypic plasticity is critical in CAV neointima formation. TET2 (TET methylcytosine dioxygenase 2) is an important epigenetic regulator of VSMC phenotype, but the role of TET2 in the progression of CAV is unknown. METHODS: We assessed TET2 expression and activity in human CAV and renal transplant samples. We also used the sex-mismatched murine aortic graft model of graft arteriopathy (GA) in wild-type and inducible smooth muscle-specific Tet2 knockout mice; and in vitro studies in murine and human VSMCs using knockdown, overexpression, and transcriptomic approaches to assess the role of TET2 in VSMC responses to IFNγ (interferon γ), a cytokine elaborated by T cells that drives CAV progression. RESULTS: In the present study, we found that TET2 expression and activity are negatively regulated in human CAV and renal transplant samples and in the murine aortic graft model of GA. IFNγ was sufficient to repress TET2 and induce an activated VSMC phenotype in vitro. TET2 depletion mimicked the effects of IFNγ, and TET2 overexpression rescued IFNγ-induced dedifferentiation. VSMC-specific TET2 depletion in aortic grafts, and in the femoral wire restenosis model, resulted in increased VSMC apoptosis and medial thinning. In GA, this apoptosis was tightly correlated with proliferation. In vitro, TET2-deficient VSMCs undergo apoptosis more readily in response to IFNγ and expressed a signature of increased susceptibility to extrinsic apoptotic signaling. Enhancing TET2 enzymatic activity with high-dose ascorbic acid rescued the effect of GA-induced VSMC apoptosis and intimal thickening in a TET2-dependent manner. CONCLUSIONS: TET2 is repressed in CAV and GA, likely mediated by IFNγ. TET2 serves to protect VSMCs from apoptosis in the context of transplant vasculopathy or IFNγ stimulation. Promoting TET2 activity in vivo with systemic ascorbic acid reduces VSMC apoptosis and intimal thickening. These data suggest that promoting TET2 activity in CAV may be an effective strategy for limiting CAV progression.
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Apoptosis/genética , Proteínas de Unión al ADN/genética , Dioxigenasas/genética , Miocitos del Músculo Liso/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/metabolismo , Aloinjertos , Animales , Biomarcadores , Proteínas de Unión al ADN/metabolismo , Dioxigenasas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Trasplante de Corazón/efectos adversos , Humanos , Inmunohistoquímica , Interferón gamma/metabolismo , Ratones , Ratones Noqueados , Factor de Transcripción STAT1 , Transducción de Señal , Enfermedades Vasculares/patologíaRESUMEN
BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).
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Antihipertensivos/administración & dosificación , Combinación de Medicamentos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Área sin Atención Médica , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Alabama , Amlodipino/administración & dosificación , Atorvastatina/administración & dosificación , LDL-Colesterol/sangre , Centros Comunitarios de Salud , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Hipertensión/complicaciones , Losartán/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
Major depressive disorder (MDD) and loneliness are phenotypically and genetically correlated with coronary artery disease (CAD), but whether these associations are explained by pleiotropic genetic variants or shared comorbidities is unclear. To tease apart these scenarios, we first assessed the medical morbidity pattern associated with genetic risk factors for MDD and loneliness by conducting a phenome-wide association study in 18,385 European-ancestry individuals in the Vanderbilt University Medical Center biobank, BioVU. Polygenic scores for MDD and loneliness were developed for each person using previously published meta-GWAS summary statistics, and were tested for association with 882 clinical diagnoses ascertained via billing codes in electronic health records. We discovered strong associations with heart disease diagnoses, and next embarked on targeted analyses of CAD in 3893 cases and 4197 controls. We found odds ratios of 1.11 (95% CI, 1.04-1.18; P 8.43 × 10-4) and 1.13 (95% CI, 1.07-1.20; P 4.51 × 10-6) per 1-SD increase in the polygenic scores for MDD and loneliness, respectively. Results were similar in patients without psychiatric symptoms, and the increased risk persisted in females even after adjusting for multiple conventional risk factors and a polygenic score for CAD. In a final sensitivity analysis, we statistically adjusted for the genetic correlation between MDD and loneliness and re-computed polygenic scores. The polygenic score unique to loneliness remained associated with CAD (OR 1.09, 95% CI 1.03-1.15; P 0.002), while the polygenic score unique to MDD did not (OR 1.00, 95% CI 0.95-1.06; P 0.97). Our replication sample was the Atherosclerosis Risk in Communities (ARIC) cohort of 7197 European-ancestry participants (1598 incident CAD cases). In ARIC, polygenic scores for MDD and loneliness were associated with hazard ratios of 1.07 (95% CI, 0.99-1.14; P = 0.07) and 1.07 (1.01-1.15; P = 0.03), respectively, and we replicated findings from the BioVU sensitivity analyses. We conclude that genetic risk factors for MDD and loneliness act pleiotropically to increase CAD risk in females.
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Enfermedad de la Arteria Coronaria , Trastorno Depresivo Mayor , Enfermedad de la Arteria Coronaria/genética , Trastorno Depresivo Mayor/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Soledad , Masculino , Herencia Multifactorial/genética , Factores de RiesgoRESUMEN
This study presents an efficient and systematic approach to synthesize bioapplicable porous hollow polymeric capsules (HPCs). The hydroxyl-functionalized nanoporous polymers with hollow capsular shapes could be generated via the moderate Friedel-Crafts reaction without using any hard or soft template. The numerous primitive hydroxyl groups on these HPCs were further converted to carboxyl groups. Owing to the abundance of highly branched carboxyl groups on the surface of the HPCs, biomolecules [such as folic acid (FA)] could be covalently decorated on these organic capsules (FA-HPCs) for drug delivery applications. The intrinsic hollow porosities and specific targeting agent offered a maximum drug encapsulation efficiency of up to 86% and drug release of up to 50% in 30 h in an acidic environment. The in vitro studies against cancer cells demonstrated that FA-HPCs exhibited a more efficient cellular uptake and intracellular doxorubicin release than bare HPCs. This efficient approach to fabricate carbonyl-functionalized hollow organic capsules may open avenues for a new type of morphological-controlled nanoporous polymers for various potential bioengineering applications.
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Ácido Fólico , Neoplasias , Cápsulas , Línea Celular Tumoral , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico , PolímerosRESUMEN
The lipid aldehyde 4-oxo-2-nonenal (ONE) is a highly reactive protein crosslinker derived from peroxidation of n-6 polyunsaturated fatty acids and generated together with 4-hydroxynonenal (HNE). Lipid peroxidation product-mediated crosslinking of proteins in high-density lipoprotein (HDL) causes HDL dysfunction and contributes to atherogenesis. Although HNE is relatively well-studied, the role of ONE in atherosclerosis and in modifying HDL is unknown. Here, we found that individuals with familial hypercholesterolemia (FH) had significantly higher ONE-ketoamide (lysine) adducts in HDL (54.6 ± 33.8 pmol/mg) than healthy controls (15.3 ± 5.6 pmol/mg). ONE crosslinked apolipoprotein A-I (apoA-I) on HDL at a concentration of > 3 mol ONE per 10 mol apoA-I (0.3 eq), which was 100-fold lower than HNE, but comparable to the potent protein crosslinker isolevuglandin. ONE-modified HDL partially inhibited HDL's ability to protect against lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) and interleukin-1ß (IL-1ß) gene expression in murine macrophages. At 3 eq, ONE dramatically decreased apoA-I exchange from HDL, from â¼46.5 to â¼18.4% (p < 0.001). Surprisingly, ONE modification of HDL or apoA-I did not alter macrophage cholesterol efflux capacity. LC-MS/MS analysis revealed that Lys-12, Lys-23, Lys-96, and Lys-226 in apoA-I are modified by ONE ketoamide adducts. Compared with other dicarbonyl scavengers, pentylpyridoxamine (PPM) most efficaciously blocked ONE-induced protein crosslinking in HDL and also prevented HDL dysfunction in an in vitro model of inflammation. Our findings show that ONE-HDL adducts cause HDL dysfunction and are elevated in individuals with FH who have severe hypercholesterolemia.
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Aldehídos/metabolismo , Hiperlipoproteinemia Tipo II/metabolismo , Lipoproteínas HDL/metabolismo , Lisina/metabolismo , Aldehídos/análisis , Animales , Apolipoproteína A-I/metabolismo , Aterosclerosis/metabolismo , Células Cultivadas , Femenino , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
BACKGROUND: Fruit set after successful pollination is key for the production of sweet cherries, and a low fruit-setting rate is the main problem in production of this crop. As gibberellin treatment can directly induce parthenogenesis and satisfy the hormone requirement during fruit growth and development, such treatment is an important strategy for improving the fruit-setting rate of sweet cherries. Previous studies have mainly focused on physiological aspects, such as fruit quality, fruit size, and anatomical structure, whereas the molecular mechanism remains clear. RESULTS: In this study, we analyzed the transcriptome of 'Meizao' sweet cherry fruit treated with gibberellin during the anthesis and hard-core periods to identify genes associated with parthenocarpic fruit set. A total of 25,341 genes were identified at the anthesis and hard-core stages, 765 (681 upregulated, 84 downregulated) and 186 (141 upregulated, 45 downregulated) of which were significant differentially expressed genes (DEGs) at the anthesis and the hard-core stages after gibberellin 3 (GA3) treatment, respectively. Based on DEGs between the control and GA3 treatments, the GA3 response mainly involves parthenocarpic fruit set and cell division. Exogenous gibberellin stimulated sweet cherry fruit parthenocarpy and enlargement, as verified by qRT-PCR results of related genes as well as the parthenocarpic fruit set and fruit size. Based on our research and previous studies in Arabidopsis thaliana, we identified key genes associated with parthenocarpic fruit set and cell division. Interestingly, we observed patterns among sweet cherry fruit setting-related DEGs, especially those associated with hormone balance, cytoskeleton formation and cell wall modification. CONCLUSIONS: Overall, the result provides a possible molecular mechanism regulating parthenocarpic fruit set that will be important for basic research and industrial development of sweet cherries.
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Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Prunus avium/efectos de los fármacos , Prunus avium/genética , Transcriptoma , Xantonas/farmacología , Biología Computacional/métodos , Frutas/genética , Perfilación de la Expresión Génica , Ontología de Genes , Giberelinas/metabolismo , Redes y Vías Metabólicas , Fenotipo , Transducción de Señal , Factores de Transcripción/metabolismoRESUMEN
Hybrid polymeric micelles self-assembled from a mixture containing poly(3,4-dihydroxy-L-Phenylalanine)-Block-poly(γ-benzyl-L-glutamate) diblock copolymer bioconjugates and silver nanoparticles were reported. A series of amphiphilic copolymers with different molecular weights were synthesized via ring-opening polymerization of α-amino acid N-carboxyanhydrides. The polymer backbone was demonstrated via proton nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy. It was observed that the resulting amphiphilic copolymer can self-assemble into rod-like micelles in dimethyl formamide/ethanol mixtures as confirmed via transmission electron microscopy. In addition, the formed rod-like micelles transformed to vesicular micelles upon introducing silver nanoparticles into the amphiphilic copolymer solution. The effect of silver nanoparticles content on the vesicle formation process was also studied. Spindle-like micelles were observed sequentially before the formation of the vesicles.
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Ácido Glutámico , Nanopartículas del Metal , Dihidroxifenilalanina/análogos & derivados , Espectroscopía de Resonancia Magnética , Micelas , Polímeros , PlataRESUMEN
A facile technique for the preparation of a multicomponent electrocatalyst that shows promising activity for the electrooxidation of alcohol has been demonstrated. The synthesis involves the preparation of hyper-crosslinked polydichloroxylene solid nanoflakes that are hybridized with PdCl2. The hybrid is reduced in an aqueous NaBH4 solution to fabricate Pd nanoparticle-decorated hyper-crosslinked polydichloroxylene. Finally, the polymer-supported palladium nanoparticles are subjected to thermal pyrolysis to form Pd-decorated carbon nanoflakes. The unique porous construction of these carbon nanoflakes result in high surface area and robust stability. The evaluation of the Pd-decorated carbon nanoflakes electrocatalyst shows improved performance and stability with high reaction efficiency for the electrooxidation of alcohols such as methanol.
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Prostaglandin (PG) D2 is formed by two distinct PGD synthases (PGDS): lipocalin-type PGDS (L-PGDS), which acts as a PGD2-producing enzyme and as extracellular lipophilic transporter, and hematopoietic PGDS (H-PGDS), a σ glutathione-S-transferase. PGD2 plays an important role in the maintenance of vascular function; however, the relative contribution of L-PGDS- and H-PGDS-dependent formation of PGD2 in this setting is unknown. To gain insight into the function played by these distinct PGDS, we assessed systemic blood pressure (BP) and thrombogenesis in L-Pgds and H-Pgds knockout (KO) mice. Deletion of L-Pgds depresses urinary PGD2 metabolite (PGDM) by â¼35%, whereas deletion of H-Pgds does so by â¼90%. Deletion of L-Pgds, but not H-Pgds, elevates BP and accelerates the thrombogenic occlusive response to a photochemical injury to the carotid artery. HQL-79, a H-PGDS inhibitor, further depresses PGDM in L-Pgds KO mice, but has no effect on BP or on the thrombogenic response. Gene expression profiling reveals that pathways relevant to vascular function are dysregulated in the aorta of L-Pgds KOs. These results indicate that the functional impact of L-Pgds deletion on vascular homeostasis may result from an autocrine effect of L-PGDS-dependent PGD2 on the vasculature and/or the L-PGDS function as lipophilic carrier protein.
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Hipertensión/genética , Oxidorreductasas Intramoleculares/genética , Lipocalinas/genética , Prostaglandina D2/genética , Eliminación de Secuencia/genética , Animales , Arterias Carótidas/patología , Glutatión Transferasa/genética , Masculino , Ratones , Ratones NoqueadosRESUMEN
Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and rubor, as well as dolor, tumor, and calor, and systemically, heat loss, frigor, chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured rubor by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and calor/frigor by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Hipolipemiantes/efectos adversos , Irritantes/efectos adversos , Niacina/efectos adversos , Piel/fisiopatología , Biomimética , Colorimetría , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico , Rubor/inducido químicamente , Rubor/patología , Humanos , Hipolipemiantes/química , Hipolipemiantes/uso terapéutico , Irritantes/química , Irritantes/uso terapéutico , Flujometría por Láser-Doppler , Niacina/química , Niacina/uso terapéutico , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Piel/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVE: To study the risk factors for the development of acute respiratory distress syndrome (ARDS) in children with measles. METHODS: The clinical data of 55 children with measles were retrospectively studied. Of the 55 children, 11 were complicated by ARDS. The risk factors for the development of ARDS were investigated by univariate analysis and multivariate non-conditional logistic regression analysis. RESULTS: The univariate analysis showed that there were significant differences in the oxygen inhalation mode (nasal catheter/mask), the rate of sepsis, blood C-reactive protein (CRP) levels and lymphocyte counts at admission between the ARDS and non-ARDS groups (P<0.05). The presence of sepsis and higher blood CRP levels were identified as the major risk factors for the development of ARDS by the multivariate logistic regression analysis (OR=116.444, 1.050 respectively; P<0.05). CONCLUSIONS: The children with measles who have sepsis and higher blood CRP levels are at risk of ARDS.
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Proteína C-Reactiva/análisis , Sarampión/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Preescolar , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Factores de Riesgo , Sepsis/complicacionesRESUMEN
OBJECTIVE: To investigate the factors that influence the short-term (6 months) prognosis in children with acute liver failure. METHODS: The clinical information of 53 children with acute liver failure treated between June 2008 and September 2013 was retrospectively analyzed. The patients were divided into survival group (n=21) and death group (n=32) according to their outcomes. The liver function parameters and incidence of complications were compared between the two groups, and multivariate logistic regression analysis was used to identify major factors affecting the short-term prognosis in these patients. RESULTS: There were significant differences between the death and survival groups in the indices of international normalized ratio (INR), blood ammonia and serum albumin (Alb), and complications such as hepatic encephalopathy, gastrointestinal hemorrhage, and multiple organ failure (P<0.05). Multivariate logistic regression analysis demonstrated that serum Alb, INR, and hepatic encephalopathy were the major factors affecting the short-term prognosis of acute liver failure (OR=0.616, 75.493 and 1210.727 respectively; P<0.05). CONCLUSIONS: INR, hepatic encephalopathy and serum Alb are the major factors that influence the short-term prognosis in children with acute liver failure.
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Fallo Hepático Agudo/mortalidad , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Relación Normalizada Internacional , Fallo Hepático Agudo/sangre , Modelos Logísticos , Masculino , Pronóstico , Estudios Retrospectivos , Albúmina Sérica/análisisRESUMEN
OBJECTIVE: To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients. METHODS: A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients. RESULTS: A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (µg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF (r = -0.377, P = 0.014) and 4DEF (r = -0.697, P = 0.000), while no correlation was found with RVEF (r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score (r = 0.306, P = 0.033), while LVEF (r = 0.112, P = 0.481), RVEF (r = -0.134, P = 0.595), and 4DEF (r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. CONCLUSIONS: GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.
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Unidades de Cuidados Intensivos , Sepsis , Humanos , Estudios Prospectivos , Pronóstico , Sepsis/diagnóstico , Sepsis/mortalidad , Sepsis/fisiopatología , Troponina T/sangre , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Biomarcadores/sangre , Ecocardiografía , Función Ventricular Izquierda , Volumen Sistólico , Masculino , Femenino , Péptido Natriurético Encefálico/sangre , Curva ROC , Fragmentos de Péptidos/sangre , Valor Predictivo de las Pruebas , Persona de Mediana EdadRESUMEN
Vanadium nitride (VN) is a potential cathode material with high capacity and high energy density for aqueous zinc batteries (AZIBs). However, the slow kinetics resulting from the strong electrostatic interaction of the electrode materials with zinc ions is a major challenge for fast storage. Here, VN clusters with nitrogen-vacancy embedded in carbon (C) (Nv-VN/C-SS-2) are prepared for the first time to improve the slow reaction kinetics. The nitrogen vacancies can effectively accelerate the reaction kinetics, reduce the electrochemical polarization, and improve the performance. The density functional theory (DFT) calculations also prove that the rapid adsorption and desorption of zinc ions on Nv-VN/C-SS-2 can release more electrons to the delocalized electron cloud of the material, thus adding more active sites. The Nv-VN/C-SS-2 exhibits a specific capacity and outstanding cycle life. Meanwhile, the quasi-solid-state battery exhibits a high capacity of 186.5 mAh g-1, ultra-high energy density of 278.9 Wh kg-1, and a high power density of 2375.1 W kg-1 at 2.5 A g-1, showing excellent electrochemical performance. This work provides a meaningful reference value for improving the comprehensive electrochemical performance of VN through interface engineering.
RESUMEN
Cancer is a serious threat to human health because of its high annual mortality rate. It has attracted significant attention in healthcare, and identifying effective strategies for the treatment and relief of cancer pain requires urgency. Drug delivery systems (DDSs) offer the advantages of excellent efficacy, low cost, and low toxicity for targeting drugs to tumor sites. In recent decades, copolymer carriers based on poly(phenylalanine) (PPhe) and poly(3,4-dihydroxy-L-phenylalanine) (PDopa) have been extensively investigated owing to their good biocompatibility, biodegradability, and controllable stimulus responsiveness, which have resulted in DDSs with loading and targeted delivery capabilities. In this review, we introduce the synthesis of PPhe and PDopa, highlighting the latest proposed synthetic routes and comparing the differences in drug delivery between PPhe and PDopa. Subsequently, we summarize the various applications of PPhe and PDopa in nanoscale-targeted DDSs, providing a comprehensive analysis of the drug release behavior based on different stimulus-responsive carriers using these two materials. In the end, we discuss the challenges and prospects of polypeptide-based DDSs in the field of cancer therapy, aiming to promote their further development to meet the growing demands for treatment.
Asunto(s)
Portadores de Fármacos , Humanos , Portadores de Fármacos/química , Animales , Sistemas de Liberación de Medicamentos , Péptidos/química , Péptidos/administración & dosificación , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Polímeros/química , Liberación de Fármacos , Fenilalanina/química , Fenilalanina/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Materiales Biocompatibles/químicaRESUMEN
Microporous organic polymers (MOPs) and metal oxide hybrid composites are considered valuable coating materials because of their versatility derived from the synergistic combination of MOPs' inherent dispersibility and the distinctive properties of metal oxides. In this study, we present the synthesis of sea-urchin-like MOPs hybridised with silver oxide nanoparticles (Ag2O NPs) to fabricate antibacterial composites suitable for potential antibacterial coating applications. Ag2O NP-decorated urchin-like MOPs (Ag2O@UMOPs) were synthesised by employing a combination of two methods: a one-pot Lewis acid-base interaction-mediated self-assembly and a straightforward impregnation process. The as-prepared Ag2O@UMOPs demonstrated high antibacterial efficacy against both E. coli (G-) and S. aureus (G+). The antibacterial mechanism of Ag2O@UMOPs mainly involved the synergistic effects of accumulation of Ag2O@UMOPs, the release of Ag+ ions, and the generation of reactive oxygen species. The exceptional processability and biosafety of Ag2O@UMOPs make them ideal organic coating materials for convenient application on various substrates. These remarkable features of Ag2O@UMOPs provide an effective platform for potential antibacterial applications in biological sciences.