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1.
J Med Virol ; 96(9): e29921, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300802

RESUMEN

Severe fever with thrombocytopenia syndrome (SFTS) represents an emerging infectious disease characterized by a substantial mortality risk. Early identification of patients is crucial for effective risk assessment and timely interventions. In the present study, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was conducted to identify key risk factors associated with progression to critical illness at 7-day and 14-day. A nomogram was constructed and subsequently assessed for its predictive accuracy through evaluation and validation processes. The risk stratification of patients was performed using X-tile software. The performance of this risk stratification system was assessed using the Kaplan-Meier method. Additionally, a heat map was generated to visualize the results of these analyses. A total of 262 SFTS patients were included in this study, and four predictive factors were included in the nomogram, namely viral copies, aspartate aminotransferase (AST) level, C-reactive protein (CRP), and neurological symptoms. The AUCs for 7-day and 14-day were 0.802 [95% confidence interval (CI): 0.707-0.897] and 0.859 (95% CI: 0.794-0.925), respectively. The nomogram demonstrated good discrimination among low, moderate, and high-risk groups. The heat map effectively illustrated the relationships between risk groups and predictive factors, providing valuable insights with high predictive and practical significance.


Asunto(s)
Enfermedad Crítica , Nomogramas , Síndrome de Trombocitopenia Febril Grave , Humanos , Síndrome de Trombocitopenia Febril Grave/virología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Medición de Riesgo/métodos , Phlebovirus/genética , Proteína C-Reactiva/análisis , Adulto , Progresión de la Enfermedad , Aspartato Aminotransferasas/sangre
2.
BMC Infect Dis ; 24(1): 996, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294596

RESUMEN

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. METHODS: All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. RESULTS: 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017-1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003-1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175-2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005-1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035-26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096-10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/ . CONCLUSION: This study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.


Asunto(s)
Nomogramas , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/mortalidad , Femenino , Persona de Mediana Edad , Anciano , Modelos Logísticos , Pronóstico , Índice de Severidad de la Enfermedad , Curva ROC , Phlebovirus , Estimación de Kaplan-Meier , Estudios Retrospectivos , Adulto
3.
FASEB J ; 36(5): e22305, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35394692

RESUMEN

Identifying novel molecules involved in axon regeneration of neurons in the peripheral nervous system (PNS) will be of benefit in obtaining a therapeutic strategy for repairing axon damage both in the PNS and the central nervous system (CNS). Metabolism and axon regeneration are tightly connected. However, the overall metabolic processes and the landscape of the metabolites in axon regeneration of PNS neurons are uncovered. Here, we used an ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS)-based untargeted metabolomics to analyze dorsal root ganglia (DRG) metabolic characteristics at different time points post sciatic nerve injury and acquired hundreds of differentially changed metabolites. In addition, the results reveal that several metabolic pathways were significantly altered, such as 'Histidine metabolism', 'Glycine serine and threonine metabolism', 'Arginine and proline metabolism', 'taurine and hypotaurine metabolism' and so on. Given metabolite could alter a cell's or an organism's phenotype, further investigation demonstrated that N, N-dimethylglycine (DMG) has a promoting effect on the regenerative ability post injury. Overall, our data may serve as a resource useful for further understanding how metabolites contribute to axon regeneration in DRG during sciatic nerve regeneration and suggest DMG may be a candidate drug to repair nerve injury.


Asunto(s)
Ganglios Espinales , Regeneración Nerviosa , Axones/metabolismo , Ganglios Espinales/metabolismo , Metabolómica , Regeneración Nerviosa/fisiología , Neuronas , Sarcosina/análogos & derivados
4.
Allergol Immunopathol (Madr) ; 51(5): 29-32, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37695227

RESUMEN

Acquired angioedema (AAE) is a rare disease due to the C1 esterase inhibitor (C1-INH) deficiency. Clinically, its symptoms are similar to hereditary angioedema (HAE) with hereditary C1-INH deficiency. Both conditions have the potential to cause upper airway obstruction, which can be fatal in clinical practice and thus require intense attention. Here, we'd like to discuss the clinical presentation, diagnosis and follow up of a special case of AAE associated with monoclonal gammopathies of unknown significance (MGUS) with recurrent upper airway obstruction. The patient was regularly followed up after being discharged from our ward. Measurements of C3-C4 levels were carried out by a hematological test. Due to the rarity of such a disease, especially in Chinese people, relevant diagnosis methods are missing in this patient, so the patient was only diagnosed with AAE-C1-INH associated with MGUS clinically. The latest follow up showed that he still underwent recurrent upper airway obstruction; thus, he remained in a tracheostomy state due to a lack of proper medication prophylaxis and died eventually. This unusual case reminds emergency physicians to pay attention to such disease during clinical practice, and relevant diagnosis method should be improved.


Asunto(s)
Obstrucción de las Vías Aéreas , Angioedemas Hereditarios , Asma , Paraproteinemias , Masculino , Humanos
5.
BMC Cardiovasc Disord ; 22(1): 406, 2022 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-36089586

RESUMEN

BACKGROUND: Non-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF. METHODS: The study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death. RESULTS: A total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable. CONCLUSIONS: It is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.


Asunto(s)
Trombosis , Filtros de Vena Cava , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Humanos , Estudios Retrospectivos , Rivaroxabán/efectos adversos , Trombosis/etiología , Filtros de Vena Cava/efectos adversos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Warfarina
6.
Acta Pharmacol Sin ; 42(10): 1556-1566, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33495516

RESUMEN

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 µM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.


Asunto(s)
Autofagia/efectos de los fármacos , Gosipol/uso terapéutico , Proteína Huntingtina/metabolismo , Enfermedad de Huntington/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Animales , Drosophila , Inhibidores Enzimáticos/uso terapéutico , Femenino , Células HEK293 , Células HeLa , Humanos , Proteína Huntingtina/química , Proteína Huntingtina/genética , Masculino , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Mutación , Multimerización de Proteína/efectos de los fármacos , Proteolisis/efectos de los fármacos , Proteína que Contiene Valosina/antagonistas & inhibidores , Proteína que Contiene Valosina/metabolismo
7.
Nucleic Acids Res ; 46(2): 823-839, 2018 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-29228324

RESUMEN

Controlling translation initiation is an efficient way to regulate gene expression at the post-transcriptional level. However, current knowledge regarding regulatory proteins and their modes of controlling translation initiation is still limited. In this study, we employed tandem affinity purification and mass spectrometry to screen for unknown proteins associated with the translation initiation machinery. Ubiquitin specific peptidase 9, X-linked (USP9X), was identified as a novel binding partner, that interacts with the eukaryotic translation initiation factor 4B (eIF4B) in a mRNA-independent manner. USP9X-deficient cells presented significantly impaired nascent protein synthesis, cap-dependent translation initiation and cellular proliferation. USP9X can selectively alter the translation of pro-oncogenic mRNAs, such as c-Myc and XIAP. Moreover, we found that eIF4A1, which is primarily ubiquitinated at Lys-369, is the substrate of USP9X. USP9X dysfunction increases the ubiquitination of eIF4A1 and enhances its degradation. Our results provide evidence that USP9X is a novel regulator of the translation initiation process via deubiquitination of eIF4A1, which offers new insight in understanding the pivotal role of USP9X in human malignancies and neurodevelopmental disorders.


Asunto(s)
Factor 4A Eucariótico de Iniciación/metabolismo , Biosíntesis de Proteínas , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación , Proliferación Celular/genética , Factor 4A Eucariótico de Iniciación/genética , Factores Eucarióticos de Iniciación/genética , Factores Eucarióticos de Iniciación/metabolismo , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , Mutación , Unión Proteica , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especificidad por Sustrato , Ubiquitina Tiolesterasa/genética
8.
Int J Mol Sci ; 21(16)2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32806611

RESUMEN

Ion-exchange membranes are the core elements for an electrodialysis (ED) separation process. Phase inversion is an effective method, particularly for commercial membrane production. It introduces two different mechanisms, i.e., thermal induced phase separation (TIPS) and diffusion induced phase separation (DIPS). In this study, anion exchange membranes (AEMs) were prepared by grafting a quaternized moiety (QM,2-[dimethylaminomethyl]naphthalen-1-ol) through brominated poly (2,6-dimethyl-1,4-phenylene oxide) (BPPO) via the TIPS method. Those membranes were applied for selective bisulfite (HSO3-) anion separation using ED. The membrane surface morphology was characterized by SEM, and the compositions were magnified using a high-resolution transmission electron microscope (HRTEM). Notably, the membranes showed excellent substance stability in an alkali medium and in grafting tests performed in a QM-soluble solvent. The ED experiment indicated that the as-prepared membrane exhibited better HSO3- separation performance than the state-of-the-art commercial Neosepta AMX (ASTOM, Japan) membrane.


Asunto(s)
Membranas Artificiales , Transición de Fase , Éteres Fenílicos/química , Polímeros/química , Sulfitos/química , Temperatura , Aniones , Conductividad Eléctrica , Intercambio Iónico , Modelos Moleculares , Éteres Fenílicos/síntesis química , Polímeros/síntesis química , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier
9.
Angew Chem Int Ed Engl ; 58(36): 12646-12654, 2019 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-31290250

RESUMEN

Artificial counterparts of conical-shaped transmembrane protein channels are of interest in biomedical sciences for biomolecule detection and selective ion permeation based on ionic size and/or charge differences. However, industrial-scale applications such as seawater desalination, separation of mono- from divalent cations, and treatment of highly-saline industrial waste effluents are still big challenges for such biomimetic channels. A simple monomer seeding experimental approach is used to grow ionically conductive biomimetic charged nanocone pores at the surface of an acid-functionalized membrane. These readily scalable nanocone membranes enable ultra-fast cation permeation (Na+ =8.4× vs. Mg2+ =1.4×) and high ion charge selectivity (Na+ /Mg2+ =6×) compared to the commercial state-of-the-art permselective membrane (CSO, Selemion, Japan) owing to negligible surface resistance and positively charged conical pore walls.


Asunto(s)
Materiales Biomiméticos/química , Cationes Bivalentes/metabolismo , Permeabilidad de la Membrana Celular , Canales Iónicos/metabolismo , Nanoporos , Canales Iónicos/química , Porosidad
10.
Nucleic Acids Res ; 43(21): 10157-67, 2015 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-26464436

RESUMEN

Eukaryotic translation initiation factor eIF4AI, the founding member of DEAD-box helicases, undergoes ATP hydrolysis-coupled conformational changes to unwind mRNA secondary structures during translation initiation. However, the mechanism of its coupled enzymatic activities remains unclear. Here we report that a gating mechanism for Pi release controlled by the inter-domain linker of eIF4AI regulates the coupling between ATP hydrolysis and RNA unwinding. Molecular dynamic simulations and experimental results revealed that, through forming a hydrophobic core with the conserved SAT motif of the N-terminal domain and I357 from the C-terminal domain, the linker gated the release of Pi from the hydrolysis site, which avoided futile hydrolysis cycles of eIF4AI. Further mutagenesis studies suggested this linker also plays an auto-inhibitory role in the enzymatic activity of eIF4AI, which may be essential for its function during translation initiation. Overall, our results reveal a novel regulatory mechanism that controls eIF4AI-mediated mRNA unwinding and can guide further mechanistic studies on other DEAD-box helicases.


Asunto(s)
Factor 4A Eucariótico de Iniciación/química , Iniciación de la Cadena Peptídica Traduccional , ARN Mensajero/química , Adenosina Difosfato/química , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Secuencias de Aminoácidos , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , Simulación de Dinámica Molecular , Mutación , Fosfatos/química , Fosfatos/metabolismo , Unión Proteica , Conformación Proteica , ARN Mensajero/metabolismo
11.
Mol Biol Rep ; 42(2): 517-24, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25348602

RESUMEN

The Aurora kinase family, as a group of serine/threonine kinases regulating cell cycles, are frequently overexpressed or amplified in human tumors. Here, we showed that the small molecule S4 could inhibit Aurora kinase in both of biochemincal and cell-based levels. The Aurora B inhibition of S4 treatment inhibited the phosphorylation of Histone H3 at serine 10 in HeLa and SMMC7721 cells. Cell proliferation assay showed that inhibition of Aurora kinase led to reduced cancer cell growth. As assessed in colony formation experiment, S4 blocked the capability of the HeLa cells to develop colonies. Subsequently, S4 treatment blocked the mitotic G2/M-G1 phase progression which is characterized by the accumulations of cells with 4 N DNA content, induced a cell cycle arrest in a pseudo G1 phase and resulted in apoptotic cell death in a dose- and time-dependent manners. Taken together, this Aurora kinase inhibitor S4 induces growth inhibition of cancer cell line.


Asunto(s)
Antineoplásicos/farmacología , Aurora Quinasa B/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Activación Enzimática/efectos de los fármacos , Células HeLa , Histonas/metabolismo , Humanos , Inhibidores de Proteínas Quinasas/química
12.
Risk Manag Healthc Policy ; 17: 145-158, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250220

RESUMEN

Background: Acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) carries a substantial risk of mortality, emphasizing the need for effective risk assessment and timely interventions. This study aimed to develop and validate a practical dynamic nomogram for predicting 3-month mortality in AIS patients with AF. Methods: AIS patients with AF were enrolled and randomly divided into training and validation cohorts. The nomogram was developed based on independent risk factors identified by multivariate logistic regression analysis. The prediction performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, decision curve analysis (DCA), and Kaplan-Meier survival analysis. Results: A total of 412 patients with AIS and AF entered final analysis, 288 patients in the training cohort and 124 patients in the validation cohort. The nomogram was developed using age, baseline National Institutes of Health Stroke Scale score, early introduction of novel oral anticoagulants, and pneumonia as independent risk factors. The nomogram exhibited good discrimination both in the training cohort (AUC, 0.851; 95% CI, 0.802-0.899) and the validation cohort (AUC, 0.811; 95% CI, 0.706-0.916). The calibration plots, DCA and Kaplan-Meier survival analysis demonstrated that the nomogram was well calibrated and clinically useful, effectively distinguishing the 3-month survival status of patients with AIS and AF, respectively. The dynamic nomogram can be obtained at the website: https://yanxiaodi.shinyapps.io/3-monthmortality/. Conclusion: The dynamic nomogram represents the first predictive model for 3-month mortality and may contribute to managing the mortality risk of patients with AIS and AF.

14.
Water Res ; 255: 121530, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38564897

RESUMEN

A huge chemical potential difference exists between the acid mine drainage (AMD) and the alkaline neutralization solution, which is wasted in the traditional AMD neutralization process. This study reports, for the first time, the harvest of this chemical potential energy through a controlled neutralization of AMD using H+-conductive films. Polyamide films with controllable thickness achieved much higher H+ conductance than a commercially available cation exchange membrane (CEM). Meanwhile, the optimal polyamide film had an excellent H+/Ca2+ selectivity of 63.7, over two orders of magnitude higher than that of the CEM (0.3). The combined advantages of fast proton transport and high proton/ion selectivity greatly enhanced the power generation of the AMD battery. The power density was 3.1 W m-2, which is over one order of magnitude higher than that of the commercial CEM (0.2 W m-2). Our study provides a new sustainable solution to address the environmental issues of AMD while simultaneously enabling clean energy production.

15.
Int J Biol Macromol ; 254(Pt 1): 127806, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37918593

RESUMEN

Bacterial infection and chronic inflammation are two major risks in diabetic wound healing, which increase patient mortality. In this study, a multifunctional sprayable nanogel (Ag-G@CS) based on chitosan has been developed to synergistically inhibit bacterial infection, eradicate biofilm, and relieve inflammation of diabetic wounds. The nanogel is successfully crafted by encapsulating with a nitric oxide (NO) donor and performing in-situ reduction of silver nanoparticles (Ag). The released NO enhances the antibacterial efficacy of Ag, nearly achieving complete eradication of biofilms in vitro. Upon application on both normal or diabetic chronic wounds, the combination effects of released NO and Ag offer a notable antibacterial effect. Furthermore, after bacteria inhibition and biofilm eradication, the NO released by the nanogel orchestrates a transformation of M1 macrophages into M2 macrophages, significantly reducing tumor necrosis factor α (TNF-α) release and relieving inflammation. Remarkably, the released NO also promotes M2a to M2c macrophages, thereby facilitating tissue remodeling in chronic wounds. More importantly, it upregulates the expression of vascular endothelial growth factor (VEGF), further accelerating the wound healing process. Collectively, the formed sprayable nanogel exhibits excellent inhibition of bacterial infections and biofilms, and promotes chronic wound healing via inflammation resolution, which has excellent potential for clinical use in the future.


Asunto(s)
Infecciones Bacterianas , Quitosano , Diabetes Mellitus Experimental , Nanopartículas del Metal , Animales , Humanos , Quitosano/farmacología , Óxido Nítrico/farmacología , Nanogeles , Factor A de Crecimiento Endotelial Vascular/farmacología , Diabetes Mellitus Experimental/metabolismo , Plata/farmacología , Cicatrización de Heridas , Antibacterianos/farmacología , Macrófagos , Bacterias , Biopelículas , Inflamación
16.
Front Pharmacol ; 15: 1364121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962309

RESUMEN

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir's inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient's acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

17.
Mol Pharm ; 10(10): 3555-63, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-23679916

RESUMEN

Over recent years, cell surface nucleolin as an anticancer target has attracted many researchers' attentions. To improve the antitumor efficacy, we developed a nucleolin targeted protein nanoparticle (NTPN) delivery system in which human serum albumin (HSA) was used as drug carrier and a DNA aptamer named AS1411, which had high affinity to nucleolin, was used as a bullet. The HSA nanoparticles (NPs-PTX) were fabricated by a novel self-assembly method and then modified with AS1411 (Apt-NPs-PTX). The resulted Apt-NPs-PTX were spherical. Compared with NPs-PTX, the uptake of Apt-NPs-PTX displayed a significant increase in MCF-7 cells while there was a decrease in nontumor cell lines such as MCF-10A and 3T3 cells. In a cytotoxic study, Apt-NPs-PTX displayed an enhanced cytotoxicity in MCF-7 tumor cells while there was almost no cytotoxicity in MCF-10A cells. Endostatin, a nucleolin inhibitor, could significantly decrease the internalization of Apt-NPs-PTX, suggesting nucleolin mediates the transmembrane process of Apt-NPs-PTX. Therefore, the AS1411 modified NTPN delivery system might be a promising targeted drug delivery system.


Asunto(s)
Antineoplásicos/metabolismo , Nanopartículas/química , Fosfoproteínas/metabolismo , Proteínas de Unión al ARN/metabolismo , Células 3T3 , Animales , Antineoplásicos/farmacología , Línea Celular , Membrana Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Endostatinas/farmacología , Humanos , Células MCF-7 , Ratones , Paclitaxel/metabolismo , Paclitaxel/farmacología , Fosfoproteínas/antagonistas & inhibidores , Proteínas de Unión al ARN/antagonistas & inhibidores , Nucleolina
18.
Clin Appl Thromb Hemost ; 29: 10760296231213070, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37956462

RESUMEN

The efficacy and safety of anticoagulant therapy in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF) remain uncertain. This study enrolled 431 AIS and AF patients from Nanjing Drum Tower Hospital between January 2019 and December 2021 and followed for 365 days to determine the associations between anticoagulants and clinical outcomes by assessing modified Rankin Scale (mRS) score, recurrent ischemic stroke/systemic embolism (IS/SE), all-cause mortality, intracranial hemorrhage (ICH) and major bleeding. Final analysis included 400 eligible patients and divided them into antiplatelet group (n = 191) and anticoagulant group (n = 209). Anticoagulant therapy was associated with excellent (mRS 0-1; adjusted odds ratio (aOR), 2.63; 95% confidence interval (CI), 1.61-4.30) and favorable functional outcomes (mRS 0-2; aOR, 2.82; 95% CI, 1.69-4.70) and lower risk of all-cause mortality (adjusted hazard ratio (aHR), 0.35; 95% CI, 0.21-0.57), ICH (aHR, 0.45; 95% CI, 0.23-0.87) and major bleeding (aHR, 0.51; 95% CI, 0.28-0.94), without increasing the risk of recurrent IS/SE (aHR, 0.75; 95% CI, 0.45-1.24). In conclusion, anticoagulant therapy may be a more effective and safer option than antiplatelet therapy for AIS patients with AF.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Hemorragias Intracraneales/inducido químicamente , Administración Oral
19.
Front Immunol ; 14: 1118039, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37033957

RESUMEN

Background: Intravenous immunoglobulin (IVIG) has been reported to exert a beneficial effect on severe fever with thrombocytopenia syndrome (SFTS) patients with neurological complications. However, in clinical practice, the standard regime is unclear and there is a lack of evidence from large-scale studies. Methods: A single-center retrospective study was conducted to determine the influence of IVIG dosage and duration on SFTS patients with neurological complications. The primary outcome was 28-day mortality, and laboratory parameters before and after IVIG treatment were measured. Survival curves were generated using the Kaplan-Meier method and analyzed with the log-rank test according to the median IVIG dosage and IVIG duration. Besides, multivariate Cox regression analysis was performed to examine the association between the independent factors and 28-day mortality in SFTS patients. Results: Overall, 36 patients (58.06%) survived, while 26 (41.9%) patients died. The median age of the included patients was 70 (55-75) years, and 46.8% (29/62) were male. A significantly higher clinical presentation of dizziness and headache was observed in the survival group. The IVIG duration in the survival group was longer than in the death group (P <0.05). Additionally, the IVIG dosage was higher in the survival group than in the death group, but there was not a statistically significant difference between the two groups (P = 0.066). The mediating effect of IVIG duration was verified through the relationship between IVIG dosage and prognosis using the Sobel test. Univariate analysis revealed that IVIG dosage (HR: 0.98; 95% CI: 0.97-1.00; P = 0.007) and IVIG duration (HR: 0.54; 95% CI: 0.41-0.72; P <0.001) were significantly associated with risk of death. The multivariate analysis generated an adjusted HR value of 0.98 (95% CI: 0.96-1.00; P = 0.012) for IVIG dosage and 0.26 (95% CI: 0.09-0.78; P = 0.016) for dizziness and headache. Conclusion: Prolonged high-dose IVIG is beneficial to the 28-day prognosis in SFTS patients with neurological complications.


Asunto(s)
Inmunoglobulinas Intravenosas , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Anciano , Femenino , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Retrospectivos , Mareo/tratamiento farmacológico , Pronóstico , Cefalea/tratamiento farmacológico
20.
Water Res ; 240: 120079, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37224666

RESUMEN

Uranium extraction from seawater has become a crucial issue that has raised tremendous attention. The transport of water molecules along with salt ions through an ion-exchange membrane is a common phenomenon for typical electro-membrane processes such as selective electrodialysis (SED). In this study, a cascade electro-dehydration process was proposed for the simultaneous extraction and enrichment of uranium from simulated seawater by taking advantage of water transport through ion-exchange membranes and the high permselectivity of membranes for monovalent ions against uranate ions. The results indicated that the electro-dehydration effect in SED allowed 1.8 times the concentration of uranium with a loose structure CJMC-5 cation-exchange membrane at a current density of 4 mA/cm2. Thereafter, a cascade electro-dehydration by a combination of SED with conventional electrodialysis (CED) enabled approximately 7.5 times uranium concentration with the extraction yield rate reaching over 80% and simultaneously desalting the majority of salts. Overall, a cascade electro-dehydration is a viable approach, creating a novel route for highly effective uranium extraction and enrichment from seawater.


Asunto(s)
Uranio , Humanos , Uranio/análisis , Deshidratación , Agua de Mar/química , Cationes , Agua
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